WO2000060066A1 - Protein-protein from s. cerevisiae and methods of using same - Google Patents

Protein-protein from s. cerevisiae and methods of using same Download PDF

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Publication number
WO2000060066A1
WO2000060066A1 PCT/US2000/008399 US0008399W WO0060066A1 WO 2000060066 A1 WO2000060066 A1 WO 2000060066A1 US 0008399 W US0008399 W US 0008399W WO 0060066 A1 WO0060066 A1 WO 0060066A1
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Prior art keywords
polypeptide
protein
complex
cellular
column
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PCT/US2000/008399
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French (fr)
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WO2000060066A8 (en
Inventor
Loic Giot
Traci A. Mansfield
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Curagen Corporation
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Priority to CA002365548A priority Critical patent/CA2365548A1/en
Priority to EP00921513A priority patent/EP1165772A1/en
Priority to AU41820/00A priority patent/AU4182000A/en
Priority to JP2000609558A priority patent/JP2003524400A/en
Publication of WO2000060066A1 publication Critical patent/WO2000060066A1/en
Publication of WO2000060066A8 publication Critical patent/WO2000060066A8/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
    • C07K14/39—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts
    • C07K14/395—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts from Saccharomyces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • the invention relates generally to polypeptides and complexes of two or more polypeptides, as well as to methods of use thereof.
  • biologically important activities are mediated at the tissue, cellular, and subcellular level at least in part by interactions between one o? more proteins.
  • biologically important activities can include, e.g., cell division, cell differentiation, anabolic activities, and catabolic activities.
  • Interacting proteins or polypeptides can form a complex. Accordingly, failure to form a given polypeptide complex can result in deleterious consequences to a cell or individual. Conversely, the inappropriate formation of a given polypeptide complex can likewise be undesirable.
  • the identification of protein complexes associated with specific biological activities can be used to identify or prevent conditions associated with the absence or presence of these complexes.
  • the invention is based, in part, upon the identification of protein-protein interactions in the yeast S. cerevisiae and humans. Interacting proteins present in complexes according to the invention are shown in, e.g., Table 3.
  • the invention provides a purified complex including a first polypeptide that includes the amino acid sequence encoded by the open reading frame ("ORF") listed in Table 3, column 1, and a second polypeptide that includes the amino acid sequence of the corresponding polypeptide encoded by the ORF recited in column 5 of Table 3.
  • ORF open reading frame
  • column 1 Gene names for the ORFs recited in Table 3, column 1 , and Table 3, column 5 are provided in Table 3, columns 2 and 6, respectively.
  • the invention provides a purified complex including a first polypeptide and a second polypeptide selected from, or including, the human polypeptides recited in Table 7, column 2, and the corresponding polypeptides recited in Table 7, column 6.
  • a purified complex including a first polypeptide and a second polypeptide selected from, or including, the human polypeptides recited in Table 7, column 2, and the corresponding polypeptides recited in Table 7, column 6.
  • Complexes of polypeptides including the binding domains of such polypeptides, and complexes having labeled polypeptide, are also provided.
  • the invention also provides purified complexes of a first and a second polypeptide.
  • the first polypeptide is a polypeptide functionally classified in the MIPS database as a
  • the second polypeptide is the corresponding polypeptide recited in Table 3, column 5 or Table 7, column 6, respectively.
  • the invention also provides a purified complex of a first and second polypeptide, where at least one of the polypeptides is a microtubule or microtubule-associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein.
  • the invention further provides purified chimeric complexes including a yeast polypeptide and a human ortholog polypeptide.
  • the yeast polypeptide includes the amino acid sequence of the polypeptides recited in Table 7, column 1
  • the human polypeptide includes the amino acid sequence of the corresponding polypeptides recited in Table 7, column 6.
  • the yeast polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 5
  • the human ortholog polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2.
  • the invention provides chimeric polypeptides having six or more amino acids of a first polypeptide covalently linked to six or more amino acids of a second polypeptide.
  • the chimeric polypeptides are yeast-yeast chimeras, while in others the chimeric polypeptides are human-human or yeast-human chimera.
  • the first polypeptide is selected from the polypeptides recited in Table 3, column 1, and the second polypeptide is selected from the polypeptides recited in Table 3, column 5.
  • the first polypeptide is selected from polypeptides recited in Table 7, columns 1 or 2
  • the second polypeptide is selected from the polypeptides recited in Table 7, columns 5 or 6.
  • Nucleic acids encoding chimeric polypeptides, and vectors and cells containing the same, are also provided.
  • the invention provides an antibody which specifically binds polypeptide complexes according to the invention.
  • the antibody preferably binds to a complex comprising one or more polypeptides with greater affinity than its affinity for either polypeptide that is not present in the complex.
  • kits containing reagent which can specifically detect the complexes of the invention.
  • the reagent is a complex-specific antibody, while in other embodiments the reagent is an antibody specific for the first or second polypeptides of the complex.
  • the invention provides pharmaceutical compositions including the . complexes described herein.
  • Such compositions are formulated to be suitable for therapeutic administration in the treatment of deficiencies or diseases involving altered levels of the complexes of the invention.
  • the invention provides methods of identifying an agent which disrupts a polypeptide complex by providing a complex described herein, contacting the complex with a test agent, and detecting the presence of a polypeptide displaced from the complex.
  • the complex includes at least one polypeptide comprising a microtubule or microtubule-associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein.
  • the invention provides a method for inhibiting the interaction of a protein with a ligand by contacting a complex of the protein and ligand with an agent that disrupts the complex.
  • the protein is a microtubule or microtubule associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein
  • the ligand is a corresponding interacting polypeptide described herein.
  • the invention provides a method of identifying a polypeptide complex in a subject by providing a biological sample from the subject and detecting, if present, the level of a complex, described herein, in the subject.
  • Also provided by the invention is a method for detecting a polypeptide in a biological sample by providing a biological sample containing a first polypeptide, and contacting the sample with a second polypeptide under conditions suitable to form a polypeptide complex.
  • the invention provides a method for removing a first polypeptide from a biological sample by providing a biological sample including the first polypeptide, contacting the sample with a second polypeptide under conditions suitable for formation of a polypeptide complex, and removing the complex, thereby effectively removing the first polypeptide.
  • the first polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2
  • the second polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 6.
  • the first polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 6
  • the second polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2.
  • the invention provides a method for determining altered expression of a polypeptide in a subject by providing a biological sample from the subject, measuring the level of polypeptide complex in the sample, and comparing the level of the complex in the sample to the level of complex in a reference sample with a known polypeptide expression level.
  • the invention provides a method of treating or preventing a disease or disorder involving altered levels of a complex described herein or a polypeptide described herein, by administering, to a subject in need thereof, a therapeutically-effective amount of at least one molecule that modulates the function of the complex or polypeptide.
  • the agent modulates the function of a polypeptide selected from the polypeptides recited in Table 7, columns 2 or 6.
  • the invention provides complexes of interacting polypeptides which have not heretofore been shown to interact directly, as well as methods of using these complexes.
  • Some interacting polypeptides were identified by identifying which of the predicted open-reading frames (ORFs) of the yeast S. cerevisiae encode polypeptides that interact in a yeast two-hybrid system. In one screen, 692 discrete interacting protein pairs were discovered. These interacting pairs include (i) interactions that place functionally unclassified proteins in a biological context, (ii) novel interactions between proteins involved in the same biological function, and (iii) novel interactions that link together biological functions into larger cellular processes.
  • ORFs predicted open-reading frames
  • yeast ORF activation domain construct was excluded from the pool due to self-activation in a test screen (YJR009C - glyceraldehyde-3 -phosphate dehydrogenase and YNL333W - Snz2) and three yeast ORF activation domain constructs were excluded because they encoded proteins that could affect the selection process (YPL248C - Gal4, YML051 W - Gal80 and YEL021 W - Ura3).
  • the total number of yeast ORFs found as an interacting binding domain clone and/or an interacting activation domain clone in the screens. d All screening experiments were performed in duplicate.
  • Table 2 indicates that the interacting proteins disclosed herein can be grouped by functional roles using the Kunststoff Information Center for Protein Sequences (“MIPS”) classification system.
  • Unclassified Proteins 2593 313 388 1 10 a In the MIPS database, proteins have been classified into at least one category, and one third of proteins have been placed in more than one category. See MIPS Yeast Genome Database (MYGD)
  • two proteins of unknown function YGROlOWp and YLR328Wp (77% identical) were observed to interact with each other, and also to bind to ornithine aminotransferase (Car2p), which catalyzes a step in arginine metabolism.
  • Car2p ornithine aminotransferase
  • YGROIOWP and YLR328Wp are implicated in arginine metabolism.
  • YGROlOWp and YLR328Wp are 40% identical to the human protein KLAA0479 (Genbank accession number AB007948)
  • the interactive data further suggest tha the human protein KIAA0479 is also involved in arginine metabolism.
  • proteins involved in autophagy e.g., Apgl3p
  • proteins of the Cvt (cytoplasm-to-vacuole targeting) pathway e.g., Lap4p.
  • Cvt cytoplasm-to-vacuole targeting pathway
  • Autophagy is a degradation pathway used under conditions of nutrient stress to non- selectively recycle cytoplasmic proteins and organelles to their constituent components, while the Cvt pathway is a biosynthetic pathway that transports the vacuolar enzyme aminopeptidase I (API, encoded by LAP4) specifically to the vacuole.
  • API vacuolar enzyme aminopeptidase I
  • Lap4p is a self-interactor, corroborating previous evidence that Lap4p assembles into a dodecamer (see Funakoshi et al., Gene 192: 207 (1997)), and the observed interaction between Apgl and Apg 13 lends support to previous genetic evidence suggesting that APG1 is a high-copy suppressor of apgl 3 (Kim et al., J. Cell. Biol. 137: 609 (1997)).
  • Nab2p and Nab4p bind to the 3' end of mRNA, but have distinct roles. See Kessler et al., Genes Dev. 11: 2545 (1997).
  • Nab2p is required for the regulation of poly(A) tail length and export of mRNA from the nucleus, and Nab4p is essential for the cleavage of pre-mRNA at the correct 3 ' site.
  • the newly described interaction between Nab2p and Nab4p suggests that they may act in concert.
  • Ypt53p a rab5-like GTPase involved in vacuolar protein sorting and endocytosis
  • Siw4p a putative tyrosine phosphatase which acts in a complex to control nutrient-dependent cell proliferation.
  • Siw4p a putative tyrosine phosphatase which acts in a complex to control nutrient-dependent cell proliferation.
  • NPC nuclear pore complex
  • SPB spindle pole body
  • Msh5p meiosis-specific protein
  • Msh5p meiosis-specific protein
  • S synaptonemal complex
  • Mrel lp is part of a complex that participates in DSB formation. See Usui et al, Cell 95: 705 (1998). It is also known that Tid3p helps form the spindle pole body and interacts with Dmclp, a protein required for the formation of the SC.
  • the present invention identifies at least two interactions that tie cycle regulation to microtubule assembly. The first is between a microtubule checkpoint protein, Bub3p and a spindle pole body checkpoint protein, Mad3p.
  • the complexes disclosed herein are useful, inter alia, in identifying agents which modulate cellular processes in which one or more members of the complex have previously been associated.
  • interacting Pro-Pairs la- lb (representing open reading frames YGR108W and YBR135W, or genes CLB1 and CKS1, respectively) as shown in Table 3, have both been previously implicated in cell growth, cell division, and /or DNA synthesis.
  • new agents which modulate cell growth, cell division, and/or DNA synthesis can be identified by evaluating the ability of a test agent to affect formation or dissolution of a complex of the Pro-Pairs la and lb.
  • Complexes according to the invention can also be used in methods for identifying a desired polypeptides in a biological sample by forming a complex of a first polypeptide and a second polypeptide that interacts with the first polypeptide. The presence of the complex indicates that the sample contains the first polypeptide.
  • the invention includes a purified complex that includes two or more polypeptides.
  • the invention provides purified complexes of two or more polypeptides.
  • One of the polypeptides includes a polypeptide selected from the polypeptides recited in Table 3, column 1 (referenced as ProPair la-692a) and another includes a polypeptide selected from the polypeptides recited in Table 3, column 5 (referenced as ProPair lb-692b).
  • the first and second polypeptides of the complex are the polypeptides enumerated in Table 3.
  • a first polypeptide is listed as a “bait” polypeptide and a second polypeptide is denoted as “prey” polypeptide, while in other embodiments the first polypeptide corresponds to a “prey” polypeptide and the second is a “bait” polypeptide.
  • corresponding polypeptide is meant, with reference to Tables 3-7, the polypeptide recited in the same row, reading across from left-to-right or right-to-left, as a specific selected peptide.
  • Table 3 in the first row, the corresponding polypeptide of YGR108W is YBR135W. These protein pairs are designated as la and lb, as is indicated in Table 3.
  • the corresponding polypeptide of YBR135W is
  • YBR108W ProPair la
  • the corresponding polypeptide of YBR135W is YPR119W (a bait protein; ProPair 2a).
  • protein and protein complex are used synonymously with “polypeptide” and “polypeptide complex.”
  • a “purified” polypeptide, protein or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the polypeptide is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized.
  • substantially free of cellular material includes preparations of protein in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly produced.
  • the language "substantially free of cellular material” includes preparations of polypeptide complex having less than about 30% (by dry weight) of non- complex proteins (also referred to herein as a "contaminating protein”), more preferably less than about 20% of contaminating protein, still more preferably less than about 10% of contaminating protein, and most preferably less than about 5% non-complex protein.
  • contaminating protein also referred to herein as a "contaminating protein”
  • the polypeptide or complex is recombinantly produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the protein preparation.
  • culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the protein preparation.
  • YGL229C SAP4 7a Cell Growth, Cell Division And YJL030W MAD2 7b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis,
  • YGL229C SAP4 9a Cell Growth, Cell Division And YJL013C MAD3 9b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis, Cellular Organization,
  • YDR108W GSG1 11a Cell Growth, Cell Division And YGR234W YHB1 11b Cell Rescue, Defense, Cell DNA Synthesis, Death And Aging, Cellular Organization,
  • YER180C ISC10 14a Cell Growth, Cell Division And YGL026C TRP5 14b Metabolism, Cellular DNA Synthesis, Organization,
  • YGL229C SAP4 15a Cell Growth, Cell Division And YBR196C PGI1 15b Metabolism, Energy, Cellular DNA Synthesis, Organization;
  • YGL158W RCK1 16a Cell Growth, Cell Division And YLR113W HOG1 16b Metabolism, Signal Transduction, DNA Synthesis, Cell Rescue, Defense, Cell Death And Aging,
  • YPR119W CLB2 19a Cell Growth, Cell Division And YNL135C FPR1 19b Protein Destination, Cellular
  • YGL229C SAP4 33a Cell Growth, Cell Division And YJL211C 33b Unclassified Proteins,
  • YDR076W RAD55 40a Cell Growth, Cell Division And YER095W RAD51 40b Cell Growth, Cell Division And DNA Synthesis, Cell Rescue, DNA Synthesis, Cell Rescue, Defense, Cell Death And Aging, Defense, Cell Death And Aging, Cellular Organization, Cellular Organization,
  • YOR368W RAD 17 41a Cell Growth, Cell Division And YLR288C MEC3 41b Cell Growth, Cell Division And DNA Synthesis, Cell Rescue, DNA Synthesis, Cellular Defense, Cell Death And Aging, Biogenesis, Cell Rescue, Defense, Cell Death And Aging,
  • YLR288C MEC3 45a Cell Growth, Cell Division And YMR159C SAP18 45b Unclassified Proteins,
  • YER179W DMC1 51a Celt Growth, Cell Division And YER179W DMC1 51b Cell Growth, Cell Division And
  • YHR184W SSP1 54a Cell Growth, Cell Division And YHR184W SSP1 54b Cell Growth, Cell Division And
  • YDR388W RVS167 55a Cell Growth Cell Division And YCR009C RVS161 55b Cell Growth, Cell Division And
  • YGR014W MSB2 56a Cell Growth, Cell Division And YDL165W CDC36 56b Cell Growth, Cell Division And
  • YML031W NDC1 59a Cell Growth, Cell Division And YDL088C ASM4 59b Cell Rescue, Defense, Cell
  • YDR218C SPR28 65a Cell Growth Cell Division And YJR076C CDC11 65b Metabolism, Cell Growth, Cell
  • YNL189W SRP1 80a Cell Growth, Cell Division And YML028W TSA1 80b Cell Rescue, Defense, Cell
  • YNL189W SRP1 84a Cell Growth, Cell Division And YPR062W FCY1 84b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YNL189W SRP1 85a Cell Growth, Cell Division And YJR159W SOR1 85b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YNL189W SRP1 86a Cell Growth, Cell Division And YPL214C THI6 86b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YNL189W SRP1 87a Cell Growth, Cell Division And YFL061W 87b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YNL189W SRP1 88a Cell Growth, Cell Division And YOL058W ARG1 88b Metabolism, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization,
  • YNL189W SRP1 89a Cell Growth, Cell Division And YPL111W CAR1 89b Metabolism, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization,
  • YNL154C YCK2 93a Cell Growth, Cell Division And YMR267W PPA2 93b Metabolism, Energy, Cellular DNA Synthesis, Intracellular Organization, Transport, Cell Rescue Defense, Cell Death And Aging, Cellular Organization,
  • YNL189W SRP1 94a Cell Growth, Cell Division And YGL221C NIF3 94b Transcription, DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YNL189W SRP1 95a Cell Growth, Cell Division And YHL009C YAP3 95b Transcription, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization,
  • YNL154C YCK2 96a Cell Growth, Cell Division And YCL054W 96b Transcription, Cellular DNA Synthesis, Intracellular Organization, Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YNL154C YCK2 97a Cell Growth, Cell Division And YCR011C ADP1 97b Transport Facilitation, Cellular DNA Synthesis, Intracellular Organization, Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YCR009C RVS161 98a Cell Growth, Cell Division And YBR108W 98b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YNL189W SRP1 100a Cell Growth, Cell Division And YGR024C 100b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YNL154C YCK2 101a Cell Growth, Cell Division And YER079W 101b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YNL154C YCK2 102a Cell Growth, Cell Division And YKL204W 102b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YNL154C YCK2 103a Cell Growth, Cell Division And YMR180C 103b Unclassified Proteins, DNA Synthesis, Intracellular
  • YGL116W CDC20 104a Cell Growth, Cell Division And YJL030W MAD2 104b Cell Growth, Cell Division And DNA Synthesis, Protein DNA Synthesis; Destination, Cellular Organization,
  • YJL001W PRE3 105a Cell Growth, Cell Division And YLR386W 105b Unclassified Proteins, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YFR052W RPN12 106a Cell Growth, Cell Division And YDR273W 106b Unclassified Proteins, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YFR052W RPN12 107a Cell Growth, Cell Division And YJR133W 107b Unclassified Proteins, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YBL105C PKC1 108a Cell Growth, Cell Division And YML109W ZDS2 108b Cell Growth, Cell Division And DNA Synthesis, Signal DNA Synthesis; Transduction, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YPR054W SMK1 109a Cell Growth Cell Division And YFL029C CAK1 109b Cell Growth, Cell Division And
  • YLR229C CDC42 110a Cell Growth, Cell Division And YDL135C RDM 110b Cell Growth, Cell Division And
  • YLR362W STE11 111a Cell Growth Cell Division And YCL032W STE50 111b Cell Growth, Cell Division And
  • YJR086W STE18 112a Cell Growth Cell Division And YOR212W STE4 112b Cell Growth, Cell Division And
  • YLR305C STT4 114a Cell Growth Cell Division And YOR047C STD1 114b Metabolism, Transcription,
  • YCL055W KAR4 119a Cell Growth, Cell Division And YBR057C MUM2 119b Cell Growth, Cell Division And
  • YNL210W MER1 120a Cell Growth Cell Division And YKL142W MRP8 120b Protein Synthesis, Cellular
  • YOL006C TOP1 124a Cell Growth, Cell Division And YMR233W 124b Unclassified Proteins
  • YLR433C CNA1 125a Cell Growth, Cell Division And YNL047C 125b Unclassified Proteins, DNA Synthesis, Transcription, Ionic Homeostasis, Cellular Organization,
  • YGL058W RAD6 126a Cell Growth, Cell Division And YCR066W RAD 18 126b Cell Growth, Cell Division And DNA Synthesis, Transcription, DNA Synthesis, Protein Protein Destination, Cell Rescue, Destination, Cell Rescue, Defense, Cell Death And Aging, Defense, Cell Death And Aging, Cellular Organization, Cellular Organization,
  • YPR018W RLF2 127a Cell Growth, Cell Division And YBR195C MSI1 127b Cell Growth, Cell Division And DNA Synthesis, Transcription, DNA Synthesis, Transcription, Protein Destination, Cellular Protein Destination, Cellular Organization, Biogenesis, Signal Transduction,
  • YBR244W 129a Cell Rescue, Defense, Cell Death YLR117C SYF3 129b Cell Growth, Cell Division And Aging, DNA Synthesis,
  • YLL057C 130a Cell Rescue, Defense, Cell Death YLL057C 130b Cell Rescue, Defense, Cell And Aging, Death And Aging;
  • YGR213C RTA1 133a Cell Rescue, Defense, Cell Death YHR134W 133b Unclassified Proteins, And Aging,
  • YDR077W SED1 137a Cell Rescue, Defense, Cell Death YDR044W HEM13 137b Metabolism, Cellular And Aging, Cellular Organization, Organization;
  • YJL092W HPR5 138a Cell Rescue, Defense, Cell Death YDR510W SMT3 138b Protein Destination, And Aging, Cellular Organization
  • YJL092W HPR5 139a Cell Rescue, Defense, Cell Death YBR184W MEL1 139b Unclassified Proteins, And Aging, Cellular Organization,
  • YJL092W HPR5 140a Cell Rescue, Defense, Cell Death YDR078C PUN1 140b Unclassmed Proteins, And Aging, Cellular Organization,
  • YCL059C KRR1 146a Cellular Organization
  • YGL201C MCM6 146b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization
  • YDR106W ARP10 147a Cellular Organization
  • YHR129C ARP1 147b Cell Growth, Cell Division And DNA Synthesis, Intracellular Transport, Cellular Organization,
  • YMR092C AIP1 148a Cellular Organization
  • YLR102C APC9 148b Cell Growth, Cell Division And DNA Synthesis, Protein Destination
  • YER018C 150a Cellular Organization YMR117C 150b Cellular Organization
  • YLR429W CRN1 152a Cellular Organization
  • YDR328C SKP1 152b Metabolism, Cell Growth, Cell Division And DNA Synthesis, Protein Destination, Cellular Organization,
  • YCL024W 158a Classification Not Yet Clear-Cut, YKR048C NAP1 158b Cell Growth, Cell Division And
  • YFR024C-A 159a Classification Not Yet Clear-Cut, YBL007C SLA1 159b Cell Growth, Cell Division And
  • YGR057C LST7 180a Intracellular Transport YKL015W PUT3 180b Metabolism, Transcription,
  • YFR002W NIC96 183a Intracellular Transport Cellular YGR120C 183b Intracellular Transport, Cellular Organization, Organization,
  • YGR119C NUP57 186a Intracellular Transport, Cellular YJL041W NSP1 186b Transcription, Intracellular Organization, Transport, Cellular Organization,
  • YGR119C NUP57 187a Intracellular Transport, Cellular YGL172W NUP49 187b Transcription, Intracellular Organization, Transport, Cellular Organization,
  • YER105C NUP157 190a Intracellular Transport, Cellular YMR153W 190b Unclassified Proteins, Organization,
  • YMR129W POM152 191a Intracellular Transport Cellular YJL057C IKS1 191b Unclassified Proteins, Organization,
  • YMR129W POM 152 192a Intracellular Transport Cellular YMR153W 192b Unclassified Proteins, Organization,
  • YOR128C ADE2 196a Metabolism, YCR066W RAD 18 196b Cell Growth, Cell Division And DNA Synthesis, Protein Destination, Cell Rescue, Defense Cell Death And Aging, Cellular Organization,
  • YOR128C ADE2 198a Metabolism, YCR067C SED4 198b Intracellular Transport, Cellular Organization,
  • YCL040W GLK1 292a Metabolism Energy Intracellular YML099C ARG81 292b Metabolism, Transcription, Transport, Cellular Organization, Cellular Organization, tsj YMR079W SEC14 293a Metabolism, Intracellular YDL001W 293b Unclassified Proteins, Transport, Cellular Organization,
  • YOR348C PUT4 307a Metabolism, Transport Facilitation, YMR228W MTF1 307b Cell Growth, Cell Division And
  • YMR091C NPL6 311a Protein Destination, YFR037C RSC8 311b Cell Growth Cell Division And
  • YML094W GIM5 320a Protein Destination, YLR200W YKE2 320b Unclassified Proteins, YOL111C 321a Protein Destination, YOR007C SGT2 321b Unclassified Proteins, YHR057C CYP2 322a Protein Destination, Cell Rescue, YJR091C JSN1 322b Cell Growth', Cell Division And
  • YPL149W APG5 324a Protein Destination, Cellular YMR159C SAP18 324b Unclassified Proteins, Biogenesis, Cellular Organization, YBR217W 325a Protein Destination, Cellular YMR159C SAP 18 325b Unclassified Proteins, Biogenesis, Cellular Organization,
  • YMR314W PRE5 326a Protein Destination, Cellular YKL130C SHE2 326b Cell Growth, Cell Division And Organization, DNA Synthesis, Cellular Organization,
  • YPR185W APG13 339a Protein Destination, Intracellular YGR253C PUP2 339b Cell Growthi Cell Division And Transport, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YPR185W APG13 340a Protein Destination Intracellular YGR120C 340b Intracellular Transport, Cellular
  • YPL259C APM1 345a Protein Destination Intracellular YKL135C APL2 345b Protein Destination, Intracellular Transport, Cellular Biogenesis, Transport, Cellular Organization, Cellular Organization
  • YDR142C PEX7 349a Protein Destination, Intracellular YGR239C 349b Unclassified Proteins, Transport, Cellular Organization,
  • YDR142C PEX7 350a Protein Destination, Intracellular YHR160C 350b Unclassified Proteins, Transport, Cellular Organization,
  • YER102W RPS8B 353a Protein Synthesis, Cellular YBR135W CKS1 353b Cell Growth, Cell Division And
  • YKL166C TPK3 374a Signal Transduction, Cellular YIL033C SRA1 374b Metabolism, Cell Growth, Cell Organization, Division And DNA Synthesis, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YDR017C KCS1 375a Transcription, YDR099W BMH2 375b Cell Growth, Cell Division And DNA Synthesis,
  • YOR025W HST3 376a Transcription, YLR403W SFP1 376b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
  • YDR026C 378a Transcription, YDR110W FOB1 378b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
  • YIL105C 379a Transcription, YKL130C SHE2 379b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
  • YPR107C YTH1 387a Transcription, YJR093C FIP1 387b Transcription, Cellular Organization,
  • YDR311W TFB1 393a Transcription, Cell Rescue, YGR120C 393b Intracellular Transport, Cellular Defense, Cell Death And Aging, Organization, Cellular Organization,
  • YDR311W TFB1 394a Transcription, Cell Rescue, YKL103C LAP4 394b Protein Destination, Cellular Defense, Cell Death And Aging, Organization, Cellular Organization,
  • YDR311W TFB1 395a Transcription, Cell Rescue, YOL082W 395b Unclassified Proteins, Defense, Cell Death And Aging, Cellular Organization,
  • YDR225W HTA1 396a Transcription, Cellular YKR048C NAP1 396b Cell Growth, Cell Division And Organization, DNA Synthesis, Protein Destination, Cellular Biogenesis, Cellular Organization,
  • YMR112C 397a Transcription, Cellular YBR253W SRB6 397b Metabolism, Cell Growth, Cell Organization, Division And DNA Synthesis, Transcription, Cellular Organization,
  • YGL208W SIP2 398a Transcription, Cellular YGL115W SNF4 398b Metabolism, Transcription, Cell Organization, Rescue, Defense, Cell Death And Aging, Cellular Organization,
  • YDL160C DHH1 400a Transcription, Cellular YOL149W DCP1 400b Transcription, Organization,
  • YKL028W TFA1 402a Transcription, Cellular YDR311W TFB1 402b Transcription, Cell Rescue, 1 Organization, Defense, Cell Death And Aging,
  • YGL237C HAP2 403a Transcription, Cellular YBL021C HAP3 403b Transcription, Cellular Organization, Organization,
  • YGL237C HAP2 404a Transcription, Cellular YOR358W HAP5 404b Transcription, Cellular Organization, Organization,
  • YBL021C HAP3 405a Transcription, Cellular YOR358W HAP5 405b Transcription, Cellular Organization, Organization,
  • YOL123W HRP1 406a Transcription, Cellular YGL122C NAB2 406b Transcription, Cellular Organization, Organization,
  • YOL135C MED7 407a Transcription, Cellular YOR174W MED4 407b Transcription, Cellular Organization, Organization,
  • YPR110C RPC40 408a Transcription, Cellular YNL113W RPC19 408b Transcription, Cellular Organization, Organization,
  • YJL025W RRN7 409a Transcription, Cellular YBL014C RRN6 409b Transcription, Cellular Organization, Organization,
  • YMR270C RRN9 410a Transcription, Cellular YBL025W RRN10 410b Transcription, Cellular Organization, Organization,
  • YOR159C SME1 411a Transcription, Cellular YPR182W SMX3 411b Transcription, Cellular Organization, Organization,
  • YPR182W SMX3 412a Transcription, Cellular YLR275W SMD2 412b Transcription, Cellular Organization, Organization,
  • YGR104C SRB5 413a Transcription, Cellular YBR193C MED8 413b Transcription, Cellular Organization, Organization,
  • YDR308C SRB7 415a Transcription, Cellular YOL135C MED7 415b Transcription, Cellular
  • YKL028W TFA1 417a Transcription, Cellular YKR062W TFA2 417b Transcription, Cellular
  • YOR210W RPB10 418a Transcription, Cellular YGL166W CUP2 418b Transcription, Ionic Homeostasis,
  • YIR018W YAP5 419a Transcription, Cellular YGL071W RCS1 419b Transcription, Ionic Homeostasis,
  • YDR002W 426a Transcription, Intracellular YKR048C NAP1 426b Cell Growth, Cell Division And
  • YLR293C GSP1 427a Transcription, Intracellular YJR074W MOG1 427b Unclassified Proteins, Transport, Cellular Organization,
  • YLR216C CPR6 429a Transcription, Protein Destination, YIR037W HYR1 429b Cell Rescue, Defense, Cell Cellular Organization, Death And Aging,
  • YBR237W PRP5 430a Transcription, Protein Destination, YDR073W SNF11 430b Metabolism; Cell Growth, Cell Cellular Organization, Division And DNA Synthesis, Transcription, Cellular Organization,
  • YGR252W GCN5 431a Transc ⁇ ption, Protein Destination, YDR448W ADA2 431b Transcription, Cellular
  • YFL060C SN03 441a Unclassified Proteins, YMR096W SNZ1 441b Cell Growth, Cell Division And
  • YDL012C 442a Unclassified Proteins, YDR151C CTH1 442b Cell Growth, Cell Division And DNA Synthesis,
  • YIL065C 443a Unclassified Proteins, YJR091C JSN1 443b Cell Growth, Cell Division And DNA Synthesis,
  • YLR392C 444a Unclassified Proteins YJR091C JSN1 444b Cell Growth, Cell Division And DNA Synthesis,
  • YDR214W 445a Unclassified Proteins, YJL030W MAD2 445b Cell Growth, Cell Division And DNA Synthesis,
  • YGR278W 447a Unclassified Proteins, YGR049W SCM4 447b Cell Growth, Cell Division And DNA Synthesis;
  • YMR322C 448a Unclassified Proteins YMR096W SNZ1 448b Cell Growth, Cell Division And DNA Synthesis,
  • YBR190W 449a Unclassified Proteins YLR117C SYF3 449b Cell Growth, Cell Division And DNA Synthesis,
  • YDL012C 450a Unclassified Proteins, YJL065C 450b Cell Growth, Cell Division And DNA Synthesis,
  • YNR029C 451a Unclassified Proteins, YJL065C 451b Cell Growth, Cell Division And DNA Synthesis,
  • YGL061C DU01 452a Unclassified Proteins, YER016W BIM1 452b Cell Growth, Cell Division And
  • YOR353C 453a Unclassified Proteins, YHR102W NRK1 453b Cell Growth, Cell Division And
  • YBR141C 454a Unclassified Proteins, YGL091C NBP35 454b Cell Growth, Cell Division And
  • YGR154C 455a Unclassified Proteins, YCR057C PWP2 455b Cell Growth, Cell Division And
  • YGR017W 456a Unclassified Proteins, YLR403W SFP1 456b Cell Growth, Cell Division And
  • YJL048C 457a Unclassified Proteins, YKL130C SHE2 457b Cell Growth, Cell Division And
  • YPR020W 458a Unclassified Proteins, YKL130C SHE2 458b Cell Growth, Cell Division And
  • YDL239C 459a Unclassified Proteins, YHR184W SSP1 459b Cell Growth, Cell Division And
  • YNL078W 460a Unclassified Proteins, YKR048C NAP1 460b Cell Growth, Cell Division And
  • YDR315C 461a Unclassified Proteins, YJR117W STE24 461b Cell Growth, Cell Division And
  • YLR200W YK ⁇ 2 462a Unclassified Proteins, YMR052W FAR3 462b Cell Growth, Cell Division And
  • YDR200C 463a Unclassified Proteins, YMR052W FAR3 463b Cell Growth, Cell Division And
  • YIL132C 467a Unclassified Proteins, YLR321C SFH1 467b Cell Growth, Cell Division And DNA Synthesis, Transcription, Cellular Biogenesis, Cellular Organization,
  • YGL230C 468a Unclassified Proteins, YKL110C KTI12 468b Cell Rescue, Defense, Cell Death And Aging,
  • YBL101W- 469a Unclassified Proteins, YBL043W ECM13 469b Cellular Biogenesis,
  • YGR068C 470a Unclassified Proteins, YBL102W SFT2 470b Cellular Organization,
  • YPL260W 472a Unclassified Proteins, YIL144W TID3 472b Cellular Organization,
  • YMR322C 480a Unclassified Proteins, YNL333W SNZ2 480b Classification Not Yet Clear-Cut,
  • YMR322C 481a Unclassified Proteins, YFL059W SNZ3 481b Classification Not Yet Clear-Cut,
  • YJL112W 485a Unclassified Proteins, YLL001W DNM1 485b Intracellular Transport, Cellular Biogenesis,
  • YDR472W 486a Unclassified Proteins, YKR068C BET3 486b Intracellular Transport, Cellular Organization,
  • YDR128W 487a Unclassified Proteins, YLR208W SEC13 487b Intracellular Transport, Cellular Organization,
  • YPR105C 488a Unclassified Proteins, YGL145W TIP20 488b Intracellular Transport, Cellular Organization,
  • YDR472W 490a Unclassified Proteins, YBR254C 490b Intracellular Transport, Cellular Organization,
  • YER157W 491a Unclassified Proteins, YGR120C 491b Intracellular Transport, Cellular Organization,
  • YNR025C 492a Unclassified Proteins, YGR120C 492b Intracellular Transport, Cellular Organization,
  • YOR353C 493a Unclassified Proteins, YGR120C 493b Intracellular Transport, Cellular Organization,
  • YEL041W 496a Unclassified Proteins, YJR049C UTR1 496b Ionic Homeostasis,
  • YGR163W GTR1 497a Unclassified Proteins, YML121W GTR1 497b Metabolism,
  • YLL062C 500a Unclassified Proteins, YOL143C RIB4 500b Metabolism,
  • YGR294W 504a Unclassified Proteins, YHL018W 504b Metabolism,
  • YIL008W 505a Unclassified Proteins, YHR111W 505b Metabolism,
  • YFR042W 507a Unclassified Proteins, YPR159W KRE6 507b Metabolism,
  • YML088W 508a Unclassified Proteins, YDR328C SKP1 508b Metabolism, Cell Growth, Cell
  • YGR122W 509a Unclassified Proteins, YLR025W SNF7 509b Metabolism, Cell Growth, Cell
  • YMR025W 510a Unclassified Proteins, YNR052C POP2 510b Metabolism, Cell Growth, Cell cr> Division And DNA Synthesis,
  • YML068W 511a Unclassified Proteins, YDR073W SNF11 511b Metabolism, Cell Growth, Cell
  • YNL094W 512a Unclassified Proteins, YNL025C SSN8 512b Metabolism, Cell Growth, Cell
  • YDR215C 513a Unclassified Proteins, YPL175W SPT14 513b Metabolism, Cellular Biogenesis,
  • YLR465C 515a Unclassified Proteins, YML035C AMD1 515b Metabolism, Energy,
  • YML053C 518a Unclassified Proteins, YJR009C TDH2 518b Metabolism, Energy, Cellular
  • YGR058W 519a Unclassified Proteins, YLR113W HOG1 519b Metabolism, Signal Transduction,
  • YCL046W 520a Unclassified Proteins, YGL115W SNF4 520b Metabolism, Transcription, Cell
  • YPL039W MET31 521a Unclassified Proteins, YEL009C GCN4 521b Metabolism, Transcription,
  • YGL242C 522a Unclassified Proteins, YKR099W BAS1 522b Metabolism, Transcription,
  • YDL110C 526a Unclassified Proteins, YKL015W PUT3 526b Metabolism, Transcription,
  • YLL049W 530a Unclassified Proteins, YNR069C 530b Protein Destination,
  • YAR031W 532a Unclassified Proteins, YBR217W 532b Protein Destination, Cellular
  • YAL034W- 533a Unclassified Proteins, YKL103C LAP4 533b Protein Destination, Cellular
  • YPL019C 534a Unclassified Proteins, YHR060W VMA22 534b Protein Destination, Cellular
  • YPR105C 535a Unclassified Proteins, YHR060W VMA22 535b Protein Destination, Cellular
  • YOL105C WSC3 536a Unclassified Proteins, YGL153W PEX14 536b Protein Destination, Intracellular

Abstract

The invention provides complexes of at least two polypeptides from the yeast S. cerevisiae and methods of using the same. Purified complexes of two polypeptides are provided, including chimeric complexes, and chimeric polypeptides and complexes thereof are also provided, as are nucleic acids encoding chimeric polypeptides and vectors and cells containing the same. Also provided are methods of identifying agents that disrupt polypeptide complexes, methods of identifying complex or polypeptide in a sample, and for removing the same, methods of determining altered expression of a polypeptide in a subject and methods of treating/preventing disorders involving altered levels of complex or polypeptide.

Description

PROTEIN-PROTEIN FROM S. CEREVISIAE AND METHODS OF USING SAME
FIELD OF THE INVENTION
The invention relates generally to polypeptides and complexes of two or more polypeptides, as well as to methods of use thereof.
BACKGROUND OF THE INVENTION
Most, if not all, biologically important activities are mediated at the tissue, cellular, and subcellular level at least in part by interactions between one o? more proteins. These biologically important activities can include, e.g., cell division, cell differentiation, anabolic activities, and catabolic activities. Interacting proteins or polypeptides can form a complex. Accordingly, failure to form a given polypeptide complex can result in deleterious consequences to a cell or individual. Conversely, the inappropriate formation of a given polypeptide complex can likewise be undesirable.
The identification of protein complexes associated with specific biological activities can be used to identify or prevent conditions associated with the absence or presence of these complexes.
SUMMARY OF THE INVENTION
The invention is based, in part, upon the identification of protein-protein interactions in the yeast S. cerevisiae and humans. Interacting proteins present in complexes according to the invention are shown in, e.g., Table 3.
In one aspect, the invention provides a purified complex including a first polypeptide that includes the amino acid sequence encoded by the open reading frame ("ORF") listed in Table 3, column 1, and a second polypeptide that includes the amino acid sequence of the corresponding polypeptide encoded by the ORF recited in column 5 of Table 3. Gene names for the ORFs recited in Table 3, column 1 , and Table 3, column 5 are provided in Table 3, columns 2 and 6, respectively.
In another aspect, the invention provides a purified complex including a first polypeptide and a second polypeptide selected from, or including, the human polypeptides recited in Table 7, column 2, and the corresponding polypeptides recited in Table 7, column 6. Complexes of polypeptides including the binding domains of such polypeptides, and complexes having labeled polypeptide, are also provided.
The invention also provides purified complexes of a first and a second polypeptide. The first polypeptide is a polypeptide functionally classified in the MIPS database as a
Cell/Growth/Cell Division/DNA Synthesis protein; a Cell Rescue/Cell Defense/Cell Death and Aging Protein; a Cellular Biogenesis protein; a Cellular Organization protein; a Classification Not-Yet Clear Cut protein; an Energy Protein; an Intracellular Transport protein; an Ionic Homeostasis protein, a Metabolism protein; a Protein Destination protein; a Protein Synthesis protein; a Retrotransposon/Plasmid protein; a Signal Transduction protein; a Transcription protein; a Transport Facilitation protein, or an Unclassified protein. The second polypeptide is the corresponding polypeptide recited in Table 3, column 5 or Table 7, column 6, respectively.
The invention also provides a purified complex of a first and second polypeptide, where at least one of the polypeptides is a microtubule or microtubule-associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein.
The invention further provides purified chimeric complexes including a yeast polypeptide and a human ortholog polypeptide. In some embodiments the yeast polypeptide includes the amino acid sequence of the polypeptides recited in Table 7, column 1, and the human polypeptide includes the amino acid sequence of the corresponding polypeptides recited in Table 7, column 6. In other embodiments the yeast polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 5, and the human ortholog polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2.
In a further aspect, the invention provides chimeric polypeptides having six or more amino acids of a first polypeptide covalently linked to six or more amino acids of a second polypeptide. In some embodiments, the chimeric polypeptides are yeast-yeast chimeras, while in others the chimeric polypeptides are human-human or yeast-human chimera. In some embodiments, the first polypeptide is selected from the polypeptides recited in Table 3, column 1, and the second polypeptide is selected from the polypeptides recited in Table 3, column 5. In other embodiments, the first polypeptide is selected from polypeptides recited in Table 7, columns 1 or 2, and the second polypeptide is selected from the polypeptides recited in Table 7, columns 5 or 6. Nucleic acids encoding chimeric polypeptides, and vectors and cells containing the same, are also provided. In yet another aspect, the invention provides an antibody which specifically binds polypeptide complexes according to the invention. The antibody preferably binds to a complex comprising one or more polypeptides with greater affinity than its affinity for either polypeptide that is not present in the complex. Also provided by the invention are kits containing reagent which can specifically detect the complexes of the invention. In one embodiment, the reagent is a complex-specific antibody, while in other embodiments the reagent is an antibody specific for the first or second polypeptides of the complex.
In another aspect, the invention provides pharmaceutical compositions including the . complexes described herein. Such compositions are formulated to be suitable for therapeutic administration in the treatment of deficiencies or diseases involving altered levels of the complexes of the invention.
In still another aspect, the invention provides methods of identifying an agent which disrupts a polypeptide complex by providing a complex described herein, contacting the complex with a test agent, and detecting the presence of a polypeptide displaced from the complex. In certain embodiments, the complex includes at least one polypeptide comprising a microtubule or microtubule-associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein.
In a further aspect, the invention provides a method for inhibiting the interaction of a protein with a ligand by contacting a complex of the protein and ligand with an agent that disrupts the complex. In certain embodiments, the protein is a microtubule or microtubule associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein, and the ligand is a corresponding interacting polypeptide described herein.
In yet another aspect, the invention provides a method of identifying a polypeptide complex in a subject by providing a biological sample from the subject and detecting, if present, the level of a complex, described herein, in the subject.
Also provided by the invention is a method for detecting a polypeptide in a biological sample by providing a biological sample containing a first polypeptide, and contacting the sample with a second polypeptide under conditions suitable to form a polypeptide complex. In another aspect, the invention provides a method for removing a first polypeptide from a biological sample by providing a biological sample including the first polypeptide, contacting the sample with a second polypeptide under conditions suitable for formation of a polypeptide complex, and removing the complex, thereby effectively removing the first polypeptide. In certain embodiments, the first polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2, and the second polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 6. In another embodiment, the first polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 6, and the second polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2.
In a further aspect, the invention provides a method for determining altered expression of a polypeptide in a subject by providing a biological sample from the subject, measuring the level of polypeptide complex in the sample, and comparing the level of the complex in the sample to the level of complex in a reference sample with a known polypeptide expression level.
In a still further aspect, the invention provides a method of treating or preventing a disease or disorder involving altered levels of a complex described herein or a polypeptide described herein, by administering, to a subject in need thereof, a therapeutically-effective amount of at least one molecule that modulates the function of the complex or polypeptide. In one embodiment, the agent modulates the function of a polypeptide selected from the polypeptides recited in Table 7, columns 2 or 6.
In the specification and the appended claims, the singular forms include plural referents unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications cited in this specification are incorporated by reference herein in their entirety.
DETAILED DESCRIPTION OF THE INVENTION The invention provides complexes of interacting polypeptides which have not heretofore been shown to interact directly, as well as methods of using these complexes.
Some interacting polypeptides were identified by identifying which of the predicted open-reading frames (ORFs) of the yeast S. cerevisiae encode polypeptides that interact in a yeast two-hybrid system. In one screen, 692 discrete interacting protein pairs were discovered. These interacting pairs include (i) interactions that place functionally unclassified proteins in a biological context, (ii) novel interactions between proteins involved in the same biological function, and (iii) novel interactions that link together biological functions into larger cellular processes.
A summary of the screening used to identify interacting yeast ORFS is shown in Table 1.
Table 1 : Screen Summary
Description τ0tal
Yeast ORF PCR Products 6144 Yeast ORFs cloned3 5345
ORFs pooled to generate the activation domain library 5341°
Yeast ORFs identified to have interactions0 817
Total discrete interacting protein pairs 692
Interactions identified in independent experiments'1 286 Interactions identified multiple times in a single experiment 186
Interactions identified only once 220
^Number of PCR products giving transformants in both plasmids (pOBD2 and pOAD). bOne yeast ORF activation domain construct was excluded from the pool due to self-activation in a test screen (YJR009C - glyceraldehyde-3 -phosphate dehydrogenase and YNL333W - Snz2) and three yeast ORF activation domain constructs were excluded because they encoded proteins that could affect the selection process (YPL248C - Gal4, YML051 W - Gal80 and YEL021 W - Ura3). c The total number of yeast ORFs found as an interacting binding domain clone and/or an interacting activation domain clone in the screens. d All screening experiments were performed in duplicate.
Table 2 indicates that the interacting proteins disclosed herein can be grouped by functional roles using the Munich Information Center for Protein Sequences ("MIPS") classification system.
Table 2: Interactions grouped by Protein Functional Roles (as classified by the MIPS database) '
MIPS Results from the screen
Classification
Proteins in Proteins with Total Interactions
MIPS classification Category Interactions Interactions within a Category
Metabolism 1023 133 189 40
Energy 239 29 39 3
Cell Growth, Cell Division and DNA Synthesis 767 138 227 46
Transcription 734 134 185 38
Protein Synthesis 345 18 37 5
Protein Destination 525 76 98 15
Transport Facilitation 302 14 20 0
Intraceilular Transport 438 50 99 8
Cellular Biogenesis 185 23 35 3
Signal Transduction 122 25 32 4
Cell Rescue, Defense, Cell
Death and Aging 341 48 69 7
Ionic Homeostasis 120 8 18 0
Cellular Organization 2144 290 388 130
Retrotransposons and
Plasmid Proteins'1 1 13 1 1 0
Classification Not Yet
Clear-Cut 151 22 42 1
Unclassified Proteins 2593 313 388 1 10 aIn the MIPS database, proteins have been classified into at least one category, and one third of proteins have been placed in more than one category. See MIPS Yeast Genome Database (MYGD)
Functional Catalogue, www.mips.biochem.mpg.de/proi/yeast; Mewes et al., Nucl Acid. Res. 25.
28 (1997); Mewes et al., Nucl. Acid. Res. 26: 33 (1998). lumbers based on 6234 ORFs. cTotal based on 885 ORFs. Total interactions with at least one protein in the category. dOnly eight of the yeast ORFs in this category were contained in the original 6144 ORF screening population.
Some newly disclosed interactions place functionally unclassified proteins from the yeast genome in a biological context. For example, two proteins of unknown function, YGROlOWp and YLR328Wp (77% identical), were observed to interact with each other, and also to bind to ornithine aminotransferase (Car2p), which catalyzes a step in arginine metabolism. This observation suggests that YGROIOWP and YLR328Wp are implicated in arginine metabolism. In addition, because YGROlOWp and YLR328Wp are 40% identical to the human protein KLAA0479 (Genbank accession number AB007948), the interactive data further suggest tha the human protein KIAA0479 is also involved in arginine metabolism. Also included in the interactions are complexes of two or more proteins involved in functional pathways for which direct interactions have not been described previously. For example, proteins involved in autophagy, e.g., Apgl3p, are shown herein to interact with proteins of the Cvt (cytoplasm-to-vacuole targeting) pathway, e.g., Lap4p. Previously, direct interactions between proteins involved in autophagy and the Cvt pathway had not been reported. Autophagy is a degradation pathway used under conditions of nutrient stress to non- selectively recycle cytoplasmic proteins and organelles to their constituent components, while the Cvt pathway is a biosynthetic pathway that transports the vacuolar enzyme aminopeptidase I (API, encoded by LAP4) specifically to the vacuole. See Scott et al, Curr. Opin. Cell. Biol. 10: 523 (1998). Several mutants in the Cvt pathway (cvt) and autophagocytosis (aut and apg) are allelic, suggesting that both pathways utilize some of the same molecular components. See Tsukada et al., FEBS Letters 333: 169 (1993); Thumm et al., FEBS Letters 349: 275 (1994); Harding et al., J. Cell. Biol. 131: 17621 (1996); Scott et al., Proc. Natl. Acad. Sci. USA 93: 12304 (1996). A number of ORFs encoding proteins of unknown functions have been identified as components of autophagy. Since several of the genes altered in apg, aut, and cvt mutants have not yet been cloned, ORFs found in these interactions can be examined to determine if they encode any of these altered genes. It has also been shown that Lap4p is a self-interactor, corroborating previous evidence that Lap4p assembles into a dodecamer (see Funakoshi et al., Gene 192: 207 (1997)), and the observed interaction between Apgl and Apg 13 lends support to previous genetic evidence suggesting that APG1 is a high-copy suppressor of apgl 3 (Kim et al., J. Cell. Biol. 137: 609 (1997)).
An interaction was also identified between YDR201 Wp and YKR037Cp, two proteins known to be localized to the spindle pole body by mass spectrometry. See Wigge et al., J. Cell Biol. 141: 967 (1998). The interaction of these proteins may indicate their involvement in the regulation of mitotic events.
New insights into novel interactions between proteins involved in the same biological function are also provided. For example, the nuclear polyadenylated RNA-binding proteins Nab2p and Nab4p bind to the 3' end of mRNA, but have distinct roles. See Kessler et al., Genes Dev. 11: 2545 (1997). Nab2p is required for the regulation of poly(A) tail length and export of mRNA from the nucleus, and Nab4p is essential for the cleavage of pre-mRNA at the correct 3 ' site. The newly described interaction between Nab2p and Nab4p suggests that they may act in concert. Similarly, in yeast, diverse cyclins bind to Cdc28p in a coordinated manner to modulate its kinase activity during the cell cycle. The B-type cyclins play a critical role in the induction of bipolar mitotic spindle formation. See Nasmyth, Cwrr. Opin. Cell. Biol. 5: 166 (1993). Each of the B-type cyclins, Clblp, Clb2p and Clb3p, has presently been observed to form a complex with Ckslp and Cdc28p. The identification of interactions between Ckslp and each of Clblp, Clb2p and Clb3p, suggests that the kinase activity of Cdc28p could be mediated by cyclin Bs through their interaction with Ckslp.
In another example, Ypt53p, a rab5-like GTPase involved in vacuolar protein sorting and endocytosis, has presently been shown to interact with Siw4p, a putative tyrosine phosphatase which acts in a complex to control nutrient-dependent cell proliferation. See Singer-Kruger et al, J. Cell. Biol. 125: 283 (1994); Saul et al., Gen. Microbiol. 131: 1797 (1985). One possible explanation for the observed interaction is that Ypt53p senses nutrient availability to coordinate cell cycle progression.
The newly identified protein-protein interactions connect biological functions into larger cellular processes. For example, the nuclear pore complex (NPC), consisting of as many as 50 different subunits, is the macromolecular-conducting channel between the nucleus and the cytoplasm. See Fabre et al., Ann. Rev. Genet. 31 : 277 (1997); Marelli et al., J. Cell Biol. 143: 1813 (1998). Two newly identified NPC components, Nup53p and Nup59p/Asm4p, interact with Ndclp, a protein required for spindle pole body (SPB) duplication and component of the nuclear envelope. Evidence of a physical interaction between components of the NPC and SPB suggests that these two structures located in the nuclear envelope may coordinate communication between the nucleus and the cytoplasm.
Another interaction involves the meiosis-specific protein, Msh5p, which is required for the resolution of cross-overs during meiosis. Hollingsworth et al., Genes Dev. 9: 1728 (1995). Meiotic recombination is initiated by double-strand breaks (DSBs), a prerequisite to crossover formation that is resolved in a structure called the synaptonemal complex (SC). Mrel lp is part of a complex that participates in DSB formation. See Usui et al, Cell 95: 705 (1998). It is also known that Tid3p helps form the spindle pole body and interacts with Dmclp, a protein required for the formation of the SC. See Bishop et al, Cell 69: 439-56 (1992). It has presently been shown that Msh5p interacts with both Mrel lp and Tid3p. These novel associations tie DSB formation and the resolution of cross-overs with Msh5p as the linking protein. Similarly, to exit the cell cycle, cells must undergo a series of checkpoints that monitor correct microtubule and spindle formation. See Guenette et al, J. Cell. Sci. 108: 195 (1995). The present invention identifies at least two interactions that tie cycle regulation to microtubule assembly. The first is between a microtubule checkpoint protein, Bub3p and a spindle pole body checkpoint protein, Mad3p. This observation mirrors the recent interaction described between the human homologs of Bub3p and Mad3p. See Hoyt et al, Cell 66: 507-17 (1991); Hwang et al, Science 279: 1041 (1998); Taylor et al, J. Cell Biol. 142: 1 (1998). Interestingly, the second is between Mad3p and a known regulator of the Cdc28p kinase, Cln3p, See Cvrckova et al, EMBO J. 12: 5277 (1993). These interactions could give rise to a cascade Bub3->Mad3->Cln3p- Cdc28p, and may suggest a pathway to propagate the signal of incorrect microtubule formation during early events at the cell cycle arrest in Gl phase.
The complexes disclosed herein are useful, inter alia, in identifying agents which modulate cellular processes in which one or more members of the complex have previously been associated. For example, interacting Pro-Pairs la- lb (representing open reading frames YGR108W and YBR135W, or genes CLB1 and CKS1, respectively) as shown in Table 3, have both been previously implicated in cell growth, cell division, and /or DNA synthesis. Accordingly, new agents which modulate cell growth, cell division, and/or DNA synthesis can be identified by evaluating the ability of a test agent to affect formation or dissolution of a complex of the Pro-Pairs la and lb.
Complexes according to the invention can also be used in methods for identifying a desired polypeptides in a biological sample by forming a complex of a first polypeptide and a second polypeptide that interacts with the first polypeptide. The presence of the complex indicates that the sample contains the first polypeptide. These utilities, as well as additional utilities, are discussed in greater detail below
Purified Polypeptide Complexes
In one aspect, the invention includes a purified complex that includes two or more polypeptides. In one embodiment, the invention provides purified complexes of two or more polypeptides. One of the polypeptides includes a polypeptide selected from the polypeptides recited in Table 3, column 1 (referenced as ProPair la-692a) and another includes a polypeptide selected from the polypeptides recited in Table 3, column 5 (referenced as ProPair lb-692b). In some embodiments the first and second polypeptides of the complex are the polypeptides enumerated in Table 3. In some embodiments a first polypeptide is listed as a "bait" polypeptide and a second polypeptide is denoted as "prey" polypeptide, while in other embodiments the first polypeptide corresponds to a "prey" polypeptide and the second is a "bait" polypeptide. By "corresponding polypeptide" is meant, with reference to Tables 3-7, the polypeptide recited in the same row, reading across from left-to-right or right-to-left, as a specific selected peptide. For example, in Table 3, in the first row, the corresponding polypeptide of YGR108W is YBR135W. These protein pairs are designated as la and lb, as is indicated in Table 3. Similarly, in the first row, the corresponding polypeptide of YBR135W (ProPair lb) is
YBR108W (ProPair la). In the second row, however, the corresponding polypeptide of YBR135W (a prey protein; ProPair 2b) is YPR119W (a bait protein; ProPair 2a).
Also as used herein, "protein" and "protein complex" are used synonymously with "polypeptide" and "polypeptide complex." A "purified" polypeptide, protein or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the polypeptide is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language "substantially free of cellular material" includes preparations of protein in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly produced. In one embodiment, the language "substantially free of cellular material" includes preparations of polypeptide complex having less than about 30% (by dry weight) of non- complex proteins (also referred to herein as a "contaminating protein"), more preferably less than about 20% of contaminating protein, still more preferably less than about 10% of contaminating protein, and most preferably less than about 5% non-complex protein. When the polypeptide or complex is recombinantly produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the protein preparation. Table 3. Protein Pairs Identified in the Screen.
Figure imgf000013_0001
Binding Binding Pro-Pair Functional Classification Activation Activation Pro-Pair Functional Classification
Domain Domain Ref. No. (MIPS) Domain Domain Ref. No. . (MIPS)
Fusion Fusion Fusion Fusion
"Bait" "Prey"
[ORF] [Gene] [ORF] [Gene]
YGR108W CLB1 1a Cell Growth, Cell Division And YBR135W CKS1 1b Cell Growth, Cell Division And DNA Synthesis; DNA Synthesis,
YPR119W CLB2 2a Cell Growth, Cell Division And YBR135W CKS1 2b Cell Growth, Cell Division And DNA Synthesis; DNA Synthesis,
YDL155W CLB3 3a Cell Growth, Cell Division And YBR135W CKS1 3b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis,
YDR206W EBS1 4a Cell Growth, Cell Division And YJL030W MAD2 4b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis;
YDR206W EBS1 5a Cell Growth, Cell Division And YBR057C UM2 5b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis,
YGL175C SAE2 6a Cell Growth, Cell Division And YGL175C SAE2 6b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis,
YGL229C SAP4 7a Cell Growth, Cell Division And YJL030W MAD2 7b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis,
YOR026W BUB3 8a Cell Growth, Cell Division And YJL013C MAD3 8b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis, Cellular Organization;
YGL229C SAP4 9a Cell Growth, Cell Division And YJL013C MAD3 9b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis, Cellular Organization,
YDL127W PCL2 10a Cell Growth, Cell Division And YDR146C SWI5 10b Cell Growth, Cell Division And DNA Synthesis, DNA Synthesis; Transcription, Cellular Organization,
YDR108W GSG1 11a Cell Growth, Cell Division And YGR234W YHB1 11b Cell Rescue, Defense, Cell DNA Synthesis, Death And Aging, Cellular Organization,
YDR099W BMH2 12a Cell Growth, Cell Division And YBL043W ECM13 12b Cellular Biogenesis, DNA Synthesis,
YOL034W 13a Cell Growth, Cell Division And Y R117C 13b Cellular Organization, DNA Synthesis,
YER180C ISC10 14a Cell Growth, Cell Division And YGL026C TRP5 14b Metabolism, Cellular DNA Synthesis, Organization,
YGL229C SAP4 15a Cell Growth, Cell Division And YBR196C PGI1 15b Metabolism, Energy, Cellular DNA Synthesis, Organization;
YGL158W RCK1 16a Cell Growth, Cell Division And YLR113W HOG1 16b Metabolism, Signal Transduction, DNA Synthesis, Cell Rescue, Defense, Cell Death And Aging,
YDR206W EBS1 17a Cell Growth, Cell Division And YER027C GAL83 17b Metabolism, Transcription,
DNA Synthesis,
YDR206W EBS1 18a Cell Growth, Cell Division And YOR047C STD1 18b Metabolism, Transcription,
DNA Synthesis,
YPR119W CLB2 19a Cell Growth, Cell Division And YNL135C FPR1 19b Protein Destination, Cellular
DNA Synthesis, Organization,
YDR206W EBS1 20a Cell Growth, Cell Division And YOL149W DCP1 20b Transcription,
DNA Synthesis,
YLR117C SYF3 21a Cell Growth, Cell Division And YBR188C NTC20 21b Transcription,
DNA Synthesis,
YFL035C M0B2 22a Cell Growth, Cell Division And YOL036W 22b Unclassified Proteins,
DNA Synthesis,
YDR099W BMH2 23a Cell Growth, Cell Division And YNL042W 23b Unclassified Proteins,
DNA Synthesis,
YPR119W CLB2 24a Cell Growth, Cell Division And YDR386W MUS81 24b Unclassified Proteins,
DNA Synthesis,
YPR119W CLB2 25a Cell Growth, Cell Division And YDR412W 25b Unclassified Proteins,
DNA Synthesis,
YPR119W CLB2 26a Cell Growth, Cell Division And YHR035W 26b Unclassified Proteins,
DNA Synthesis,
YPR119W CLB2 27a Cell Growth, Cell Division And YNR022C 27b Unclassified Proteins,
DNA Synthesis,
YPR046W MCM16 28a Cell Growth, Cell Division And YJR135C MCM22 28b Unclassified Proteins,
DNA Synthesis,
YOR127W RGA1 29a Cell Growth, Cell Division And YHL042W 29b Unclassified Proteins,
DNA Synthesis,
YOR127W RGA1 30a Cell Growth, Cell Division And YJL185C 30b Unclassified Proteins,
DNA Synthesis,
YGL175C SAE2 31a Cell Growth, Cell Division And YCR086W 31b Unclassified Proteins,
DNA Synthesis,
YGL229C SAP4 32a Cell Growth, Cell Division And YJL178C 32b Unclassified Proteins,
DNA Synthesis, I
YGL229C SAP4 33a Cell Growth, Cell Division And YJL211C 33b Unclassified Proteins,
DNA Synthesis,
YGL229C SAP4 34a Cell Growth, Cell Division And YMR181C 34b Unclassified Proteins,
DNA Synthesis,
YGL229C SAP4 35a Cell Growth, Cell Division And YOR062C 35b Unclassified Proteins,
DNA Synthesis,
YGL229C SAP4 36a Cell Growth, Cell Division And YPR040W 36b Unclassified Proteins,
DNA Synthesis,
YMR096W SNZ1 37a Cell Growth, Cell Division And YMR095C SN01 37b Unclassified Proteins,
DNA Synthesis,
YHR014W SP013 38a Cell Growth, Cell Division And YHR185C 38b Unclassified Proteins,
DNA Synthesis,
YLR215C 39a Cell Growth, Cell Division And YLR386W 39b Unclassified Proteins,
DNA Synthesis,
YDR076W RAD55 40a Cell Growth, Cell Division And YER095W RAD51 40b Cell Growth, Cell Division And DNA Synthesis, Cell Rescue, DNA Synthesis, Cell Rescue, Defense, Cell Death And Aging, Defense, Cell Death And Aging, Cellular Organization, Cellular Organization,
YOR368W RAD 17 41a Cell Growth, Cell Division And YLR288C MEC3 41b Cell Growth, Cell Division And DNA Synthesis, Cell Rescue, DNA Synthesis, Cellular Defense, Cell Death And Aging, Biogenesis, Cell Rescue, Defense, Cell Death And Aging,
YPL204W HRR25 42a Cell Growth, Cell Division And YHR185C 42b Unclassified Proteins,
DNA Synthesis, Cell Rescue,
Defense, Cell Death And Aging,
Cellular Organization,
YJL160C 43a Cell Growth, Cell Division And YCR059C 43b Unclassified Proteins,
DNA Synthesis, Cell Rescue,
Defense, Cell Death And Aging,
YPL140C MKK2 44a Cell Growth, Cell Division And YHR030C SLT2 44b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Signal
Biogenesis, Signal Transduction, Transduction, Cell Rescue,
Cell Rescue, Defense, Cell Death Defense, Cell Death And Aging,
And Aging,
YLR288C MEC3 45a Cell Growth, Cell Division And YMR159C SAP18 45b Unclassified Proteins,
DNA Synthesis, Cellular
Biogenesis, Cell Rescue, ) Defense, Cell Death And Aging, I YGR014W MSB2 46a Cell Growth, Cell Division And YJL030W MAD2 46b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis,
Organization,
YDL154W MSH5 47a Cell Growth, Cell Division And YBR133C HSL7 47b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis,
Organization,
YDL154W MSH5 48a Cell Growth, Cell Division And YMR224C MRE11 48b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Cellular
Organization, Biogenesis, Cell Rescue,
Defense, Cell Death And Aging,
Cellular Organization,
YAL040C CLN3 49a Cell Growth, Cell Division And YJL013C MAD3 49b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Cellular
Organization, Organization;
YPL049C DIG1 50a Cell Growth, Cell Division And YDR480W DIG2 50b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis; Cellular
Organization, Organization;
YER179W DMC1 51a Celt Growth, Cell Division And YER179W DMC1 51b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Cellular
Organization, Organization;
YIL150C DNA43 52a Cell Growth, Cell Division And YGL201C MCM6 52b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Cellular
Organization, Organization,
YGR014W MSB2 53a Cell Growth, Cell Division And YJL013C MAD3 53b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Cellular
Organization, Organization,
YHR184W SSP1 54a Cell Growth, Cell Division And YHR184W SSP1 54b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Cellular
Organization, Organization,
YDR388W RVS167 55a Cell Growth Cell Division And YCR009C RVS161 55b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Intracellular
Organization, Transport, Cellular Organization,
YGR014W MSB2 56a Cell Growth, Cell Division And YDL165W CDC36 56b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Transcription,
Organization, Cellular Organization,
YDL154W MSH5 57a Cell Growth Cell Division And YGL025C PGD1 57b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Transcription,
Organization, Cellular Organization,
YMR139W RIM11 58a Cell Growth, Cell Division And YJR094C IME1 58b Cell Growth, Cell Division And
DNA Synthesis, Cellular DNA Synthesis, Transcription,
Organization, Cellular Organization,
YML031W NDC1 59a Cell Growth, Cell Division And YDL088C ASM4 59b Cell Rescue, Defense, Cell
DNA Synthesis, Cellular Death And Aging,
Organization,
YDL017W CDC7 60a Cell Growth, Cell Division And YGR099W TEL2 60b Cellular Organization,
DNA Synthesis, Cellular
Organization,
YGR014W MSB2 61a Cell Growth, Cell Division And YIL144W TID3 61b Cellular Organization,
DNA Synthesis, Cellular
Organization,
YDL154W MSH5 62a Cell Growth, Cell Division And YI 144W TID3 62b Cellular Organization,
DNA Synthesis, Cellular
Organization,
YDL017W CDC7 63a Cell Growth Cell Division And YKL039W PTM1 63b Classification Not Yet Clear-Cut,
DNA Synthesis, Cellular
Organization,
YOL069W NUF2 64a Cell Growth, Cell Division And YER099C PRS2 64b Metabolism,
DNA Synthesis, Cellular
Organization,
YDR218C SPR28 65a Cell Growth Cell Division And YJR076C CDC11 65b Metabolism, Cell Growth, Cell
DNA Synthesis, Cellular Division And DNA Synthesis,
Organization, Cellular Organization,
YDL017W CDC7 66a Cell Growth, Cell Division And YJL088W ARG3 66b Metabolism, Cellular
DNA Synthesis, Cellular Organization,
Organization,
YDL017W CDC7 67a Cell Growth Cell Division And YDL160C DHH1 67b Transcription, Cellular
DNA Synthesis, Cellular Organization,
Organization,
YGR014W MSB2 68a Cell Growth, Cell Division And YPL211W NIP7 68b Transcription, Cellular
DNA Synthesis, Cellular Organization,
Organization,
YLR319C BUD6 69a Cell Growth, Cell Division And YGL015C 69b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YDL017W CDC7 70a Cell Growth, Cell Division And YCR022C 70b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YDL017W CDC7 71a Cell Growth, Cell Division And YCR050C 71b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YDL017W CDC7 72a Cell Growth, Cell Division And YEL023C 72b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YDL017W CDC7 73a Cell Growth, Cell Division And YFR057W 73b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YDL017W CDC7 74a Cell Growth, Cell Division And YNR048W 74b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YDL017W CDC7 75a Cell Growth, Cell Division And YOR006C 75b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YDL154W MSH5 76a Cell Growth, Cell Division And YGL170C 76b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YML031W NDC1 77a Cell Growth Cell Division And YMR153W 77b Unclassified Proteins,
DNA Synthesis, Cellular
Organization,
YNL189W SRP1 78a Cell Growth, Cell Division And YKL130C SHE2 78b Cell Growth, Cell Division And
DNA Synthesis, Intracellular DNA Synthesis, Cellular
Transport, Cellular Organization, Organization,
YDR335W MSN5 79a Cell Growth, Cell Division And YDR146C SWI5 79b Cell Growth, Cell Division And
DNA Synthesis, Intracellular DNA Synthesis, Transcription,
Transport, Cellular Organization,
YNL189W SRP1 80a Cell Growth, Cell Division And YML028W TSA1 80b Cell Rescue, Defense, Cell
DNA Synthesis, Intracellular Death And Aging, Cellular
Transport, Cellular Organization, Organization,
YNL189 SRP1 81a Cell Growth, Cell Division And YMR226C 81b Classification Not Yet Clear-Cut,
DNA Synthesis, Intracellular
Transport, Cellular Organization,
YNL154C YCK2 82a Cell Growth, Cell Division And YOR355W GDS1 82b Classification Not Yet Clear-Cut,
DNA Synthesis, Intracellular
Transport, Cell Rescue Defense,
Cell Death And Aging Cellular
Organization,
YNL189W SRP1 83a Cell Growth, Cell Division And YBR252W DUT1 83b Metabolism,
DNA Synthesis, Intracellular
Transport, Cellular Organization,
YNL189W SRP1 84a Cell Growth, Cell Division And YPR062W FCY1 84b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
YNL189W SRP1 85a Cell Growth, Cell Division And YJR159W SOR1 85b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
YNL189W SRP1 86a Cell Growth, Cell Division And YPL214C THI6 86b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
YNL189W SRP1 87a Cell Growth, Cell Division And YFL061W 87b Metabolism, DNA Synthesis, Intracellular Transport, Cellular Organization,
YNL189W SRP1 88a Cell Growth, Cell Division And YOL058W ARG1 88b Metabolism, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization,
YNL189W SRP1 89a Cell Growth, Cell Division And YPL111W CAR1 89b Metabolism, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization,
YNL189W SRP1 90a Cell Growth, Cell Division And YLR303W MET17 90b Metabolism, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization, YNL189W SRP1 91a Cell Growth, Cell Division And YDL236W PH013 91b Metabolism, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization, YNL189W SRP1 92a Cell Growth, Cell Division And YER065C ICL1 92b Metabolism, Energy, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization,
YNL154C YCK2 93a Cell Growth, Cell Division And YMR267W PPA2 93b Metabolism, Energy, Cellular DNA Synthesis, Intracellular Organization, Transport, Cell Rescue Defense, Cell Death And Aging, Cellular Organization,
YNL189W SRP1 94a Cell Growth, Cell Division And YGL221C NIF3 94b Transcription, DNA Synthesis, Intracellular Transport, Cellular Organization,
YNL189W SRP1 95a Cell Growth, Cell Division And YHL009C YAP3 95b Transcription, Cellular DNA Synthesis, Intracellular Organization, Transport, Cellular Organization,
YNL154C YCK2 96a Cell Growth, Cell Division And YCL054W 96b Transcription, Cellular DNA Synthesis, Intracellular Organization, Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YNL154C YCK2 97a Cell Growth, Cell Division And YCR011C ADP1 97b Transport Facilitation, Cellular DNA Synthesis, Intracellular Organization, Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YCR009C RVS161 98a Cell Growth, Cell Division And YBR108W 98b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cellular Organization,
YNL189W SRP1 99a Cell Growth, Cell Division And YJR133W YJR133 99b Unclassified Proteins, DNA Synthesis, Intracellular W Transport, Cellular Organization,
YNL189W SRP1 100a Cell Growth, Cell Division And YGR024C 100b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cellular Organization,
YNL154C YCK2 101a Cell Growth, Cell Division And YER079W 101b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YNL154C YCK2 102a Cell Growth, Cell Division And YKL204W 102b Unclassified Proteins, DNA Synthesis, Intracellular Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YNL154C YCK2 103a Cell Growth, Cell Division And YMR180C 103b Unclassified Proteins, DNA Synthesis, Intracellular
I Transport, Cell Rescue, Defense, Cell Death And Aging, Cellular
I-1 Organization,
YGL116W CDC20 104a Cell Growth, Cell Division And YJL030W MAD2 104b Cell Growth, Cell Division And DNA Synthesis, Protein DNA Synthesis; Destination, Cellular Organization,
YJL001W PRE3 105a Cell Growth, Cell Division And YLR386W 105b Unclassified Proteins, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YFR052W RPN12 106a Cell Growth, Cell Division And YDR273W 106b Unclassified Proteins, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YFR052W RPN12 107a Cell Growth, Cell Division And YJR133W 107b Unclassified Proteins, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YBL105C PKC1 108a Cell Growth, Cell Division And YML109W ZDS2 108b Cell Growth, Cell Division And DNA Synthesis, Signal DNA Synthesis; Transduction, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YPR054W SMK1 109a Cell Growth Cell Division And YFL029C CAK1 109b Cell Growth, Cell Division And
DNA Synthesis, Signal DNA Synthesis,
Transduction,
YLR229C CDC42 110a Cell Growth, Cell Division And YDL135C RDM 110b Cell Growth, Cell Division And
DNA Synthesis, Signal DNA Synthesis, Signal
Transduction, Cellular Transduction, Cellular
Organization, Organization,
YLR362W STE11 111a Cell Growth Cell Division And YCL032W STE50 111b Cell Growth, Cell Division And
DNA Synthesis, Signal DNA Synthesis, Signal
Transduction, Transduction,
YJR086W STE18 112a Cell Growth Cell Division And YOR212W STE4 112b Cell Growth, Cell Division And
DNA Synthesis, Signal DNA Synthesis, Signal
Transduction, Cellular Transduction, Cellular
Organization, Organization,
YLR305C STT4 113a Cell Growth Cell Division And YOR355W GDS1 113b Classification Not Yet Clear-Cut,
DNA Synthesis, Signal
Transduction,
YLR305C STT4 114a Cell Growth Cell Division And YOR047C STD1 114b Metabolism, Transcription,
DNA Synthesis, Signal
Transduction,
YMR052W FAR3 115a Cell Growth, Cell Division And YFR008W 115b Unclassified Proteins,
DNA Synthesis, Signal
Transduction,
∞ YAR003W 116a Cell Growth, Cell Division And YBR175W 116b Unclassified Proteins, I DNA Synthesis, Transcription,
YAR003W 117a Cell Growth Cell Division And YDR140W 117b Unclassified Proteins,
DNA Synthesis, Transcription,
YGL192W IME4 118a Cell Growth, Cell Division And YBR057C MUM2 118b Cell Growth, Cell Division And
DNA Synthesis, Transcription, DNA Synthesis,
Cellular Organization,
YCL055W KAR4 119a Cell Growth, Cell Division And YBR057C MUM2 119b Cell Growth, Cell Division And
DNA Synthesis, Transcription, DNA Synthesis,
Cellular Organization,
YNL210W MER1 120a Cell Growth Cell Division And YKL142W MRP8 120b Protein Synthesis, Cellular
DNA Synthesis, Transcription, Organization;
Cellular Organization,
YOR061W CKA2 121a Cell Growth, Cell Division And YOR039W CKB2 121b Transcription, Cellular
DNA Synthesis, Transcription, Organization;
Cellular Organization,
YNR010W CSE2 122a Cell Growth, Cell Division And YOR174W MED4 122b Transcription, Cellular
DNA Synthesis, Transcription, Organization,
Cellular Organization,
YHL027W RIM101 123a Cell Growth, Cell Division And YJL056C ZAP1 123b Transcription, Cellular
DNA Synthesis, Transcription, Organization,
Cellular Organization,
YOL006C TOP1 124a Cell Growth, Cell Division And YMR233W 124b Unclassified Proteins;
DNA Synthesis, Transcπption,
Cellular Organization,
YLR433C CNA1 125a Cell Growth, Cell Division And YNL047C 125b Unclassified Proteins, DNA Synthesis, Transcription, Ionic Homeostasis, Cellular Organization,
YGL058W RAD6 126a Cell Growth, Cell Division And YCR066W RAD 18 126b Cell Growth, Cell Division And DNA Synthesis, Transcription, DNA Synthesis, Protein Protein Destination, Cell Rescue, Destination, Cell Rescue, Defense, Cell Death And Aging, Defense, Cell Death And Aging, Cellular Organization, Cellular Organization,
YPR018W RLF2 127a Cell Growth, Cell Division And YBR195C MSI1 127b Cell Growth, Cell Division And DNA Synthesis, Transcription, DNA Synthesis, Transcription, Protein Destination, Cellular Protein Destination, Cellular Organization, Biogenesis, Signal Transduction,
YHR084W STE12 128a Cell Growth, Cell Division And YDR480W DIG2 128b Cell Growth, Cell Division And DNA Synthesis, Transcription, DNA Synthesis, Cellular Signal Transduction, Cellular Organization, Organization,
YBR244W 129a Cell Rescue, Defense, Cell Death YLR117C SYF3 129b Cell Growth, Cell Division And And Aging, DNA Synthesis,
YLL057C 130a Cell Rescue, Defense, Cell Death YLL057C 130b Cell Rescue, Defense, Cell And Aging, Death And Aging;
I YIL011W 131a Cell Rescue, Defense, Cell Death YMR201C RAD 14 131b Cell Rescue, Defense, Cell
H And Aging, Death And Aging, Cellular
U3 Organization,
' YHL046C 132a Cell Rescue, Defense, Cell Death YOR355W GDS1 132b Classification Not Yet Clear-Cut, And Aging;
YGR213C RTA1 133a Cell Rescue, Defense, Cell Death YHR134W 133b Unclassified Proteins, And Aging,
YDR061W 134a Cell Rescue, Defense, Cell Death YCR086W 134b Unclassified Proteins, And Aging,
YLR046C 135a Cell Rescue, Defense, Cell Death YHL006C 135b Unclassified Proteins, And Aging, )
YJL092W HPR5 136a Cell Rescue, Defense, Cell Death YOR355W GDS1 136b Classification Not Yet Clear-Cut, And Aging, Cellular Organization,
YDR077W SED1 137a Cell Rescue, Defense, Cell Death YDR044W HEM13 137b Metabolism, Cellular And Aging, Cellular Organization, Organization;
YJL092W HPR5 138a Cell Rescue, Defense, Cell Death YDR510W SMT3 138b Protein Destination, And Aging, Cellular Organization,
YJL092W HPR5 139a Cell Rescue, Defense, Cell Death YBR184W MEL1 139b Unclassified Proteins, And Aging, Cellular Organization,
YJL092W HPR5 140a Cell Rescue, Defense, Cell Death YDR078C PUN1 140b Unclassmed Proteins, And Aging, Cellular Organization,
YLR390W ECM19 141a Cellular Biogenesis, YDR145W TAF61 141b Transcription,
YHR171W 142a Cellular Biogenesis, Cellular YBR217W 142b Protein Destination, Cellular Organization, Biogenesis, Cellular Organization,
YHR171W 143a Cellular Biogenesis, Cellular YNR007C AUT1 143b Protein Destination, Intracellular Organization; Transport,
YHR171W 144a Cellular Biogenesis, Cellular YBL078C AUT7 144b Protein Destination, Intracellular
Organization, Transport, Cellular Organization,
YKR037C 145a Cellular Organization, YJR091C JSN1 145b Cell Growth, Cell Division And DNA Synthesis,
YCL059C KRR1 146a Cellular Organization, YGL201C MCM6 146b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
YDR106W ARP10 147a Cellular Organization, YHR129C ARP1 147b Cell Growth, Cell Division And DNA Synthesis, Intracellular Transport, Cellular Organization,
YMR092C AIP1 148a Cellular Organization YLR102C APC9 148b Cell Growth, Cell Division And DNA Synthesis, Protein Destination,
YDR201W 149a Cellular Organization, YIL144W TID3 149b Cellular Organization,
YER018C 150a Cellular Organization, YMR117C 150b Cellular Organization,
YKR037C 151a Cellular Organization, YDR201W 151b Cellular Organization,
YLR429W CRN1 152a Cellular Organization, YDR328C SKP1 152b Metabolism, Cell Growth, Cell Division And DNA Synthesis, Protein Destination, Cellular Organization,
YER018C 153a Cellular Organization, YHR193C EGD2 153b Metabolism, Transcription, Cellular Organization,
YDR122W KIN1 154a Cellular Organization, YOL082W 154b Unclassified Proteins, Classification Not Yet Clear-Cut,
YNL218W 155a YJL030W MAD2 155b Cell Growth, Cell Division And
DNA Synthesis,
YNL023C FAP1 156a YMR224C MRE11 156b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Biogenesis, Cell Rescue
Defense, Cell Death And Aging,
Cellular Organization,
YNL023C FAP1 157a Classification Not Yet Clear-Cut, YKL130C SHE2 157b Cell Growth) Cell Division And
DNA Synthesis, Cellular
Organization,
YCL024W 158a Classification Not Yet Clear-Cut, YKR048C NAP1 158b Cell Growth, Cell Division And
DNA Synthesis, Protein
Destination, Cellular Biogenesis,
Cellular Organization,
YFR024C-A 159a Classification Not Yet Clear-Cut, YBL007C SLA1 159b Cell Growth, Cell Division And
DNA Synthesis, Protein
Destination, Cellular
Organization,
YNL218W 160a Classification Not Yet Clear-Cut, YNL218W 160b Classification Not Yet Clear-Cut,
YLL046C RNP1 161a Classification Not Yet Clear-Cut, YFR047C 161b Metabolism,
YBR274W 162a Classification Not Yet Clear-Cut, YLR258W GSY2 162b Metabolism, Energy, Cellular
Organization;
YDL002C NHP10 163a Classification Not Yet Clear-Cut, YER092W 163b Unclassified Proteins,
YER059W PCL6 164a Classification Not Yet Clear-Cut, YJL084C 164b Unclassified Proteins,
YER059W PCL6 165a Classification Not Yet Clear-Cut, YLR190W 165b Unclassified Proteins,
YBR274W 166a Classification Not Yet Clear-Cut, YMR255W 166b Unclassified Proteins,
YDR084C 167a Classification Not Yet Clear-Cut, YGL161C 167b Unclassified Proteins,
YDR084C 168a Classification Not Yet Clear-Cut, YGL198W 168b Unclassified Proteins,
YFR024C-A 169a Classification Not Yet Clear-Cut, YGR268C 169b Unclassified Proteins,
YMR077C 170a Classification Not Yet Clear-Cut, YKL052C 170b Unclassified Proteins,
YHR039C 171a Energy, YDR480W DIG2 171b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YPR048W 172a Energy, YOR355W GDS1 172b Classification Not Yet Clear-Cut,
YPR048W 173a Energy, YDL215C GDH2 173b Metabolism, Cellular
Organization,
YPR048W 174a Energy, YNL199C GCR2 174b Metabolism, Transcription,
Cellular Organization,
YNL118C PSU1 175a Energy, YOL149W DCP1 175b Transcription,
YNL118C PSU1 176a Energy, YEL015W 176b Unclassified Proteins,
YPR048W 177a Energy, YPR070W 177b Unclassified Proteins,
YPL174C NIP100 178a Intracellular Transport, YHR129C ARP1 178b Cell Growth, Cell Division And
DNA Synthesis, Intracellular
Transport, Cellular Organization,
1 YPL174C NIP100 179a Intracellular Transport, YIL144W TID3 179b Cellular Organization,
YGR057C LST7 180a Intracellular Transport YKL015W PUT3 180b Metabolism, Transcription,
IsJ
Cellular Organization,
YPL174C NIP100 181a Intracellular Transport, YJL184W 181b Unclassified Proteins,
1 YER105C NUP157 182a Intracellular Transport, Cellular YJL030W MAD2 182b Cell Growth, Cell Division And Organization, DNA Synthesis,
YFR002W NIC96 183a Intracellular Transport. Cellular YGR120C 183b Intracellular Transport, Cellular Organization, Organization,
YHL019C APM2 184a Intracellular Transport, Cellular YKL135C APL2 184b Protein Destination, Intracellular Organization, Transport, Cellular Organization,
YGR119C NUP57 185a Intracellular Transport, Cellular YMR236W TAF17 185b Transcription, Cellular Organization, Organization,
YGR119C NUP57 186a Intracellular Transport, Cellular YJL041W NSP1 186b Transcription, Intracellular Organization, Transport, Cellular Organization,
YGR119C NUP57 187a Intracellular Transport, Cellular YGL172W NUP49 187b Transcription, Intracellular Organization, Transport, Cellular Organization,
YFR002 NIC96 188a Intracellular Transport, Cellular YMR153W 188b Unclassified Proteins, Organization,
YER105C NUP157 189a Intracellular Transport Cellular YEL015W 189b Unclassified Proteins, Organization,
YER105C NUP157 190a Intracellular Transport, Cellular YMR153W 190b Unclassified Proteins, Organization,
YMR129W POM152 191a Intracellular Transport Cellular YJL057C IKS1 191b Unclassified Proteins, Organization,
YMR129W POM 152 192a Intracellular Transport Cellular YMR153W 192b Unclassified Proteins, Organization,
YNL287W SEC21 193a Intracellular Transport, Cellular YBR281C 193b Unclassified Proteins, Organization,
Y0R115C 194a Intracellular Transport, Cellular Unclassified Proteins,
Organization,
YDR503C LPP1 195a Metabolism, YKL130C SHE2 195b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
YOR128C ADE2 196a Metabolism, YCR066W RAD 18 196b Cell Growth, Cell Division And DNA Synthesis, Protein Destination, Cell Rescue, Defense Cell Death And Aging, Cellular Organization,
YNL201C 197a Metabolism, YOR355W GDS1 197b Classification Not Yet Clear-Cut,
YOR128C ADE2 198a Metabolism, YCR067C SED4 198b Intracellular Transport, Cellular Organization,
YOR128C ADE2 199a Metabolism, YOR128C ADE2 199b Metabolism,
YIR032C DAL3 200a Metabolism, YIR032C DAL3 200b Metabolism,
YGR267C FOL2 201a Metabolism, YGR267C FOL2 201b Metabolism,
YOL061W PRS5 202a Metabolism, YER099C PRS2 202b Metabolism,
YPL214C THI6 203a Metabolism, YPL214C THI6 203b Metabolism,
YNR012W URK1 204a Metabolism, YDR020C 204b Metabolism,
YDL246C 205a Metabolism, YJR159W SOR1 205b Metabolism,
YDL246C 206a Metabolism, YDL246C 206b Metabolism,
I YFR047C 207a Metabolism, YFR047C 207b Metabolism, sJ YHL018W 208a Metabolism, YHL018W 208b Metabolism,
YHR111W 209a Metabolism, YHR111W 209b Metabolism,
I YIL074C 210a Metabolism, YER081W 210b Metabolism,
YIL074C 211a Metabolism, YIL074C 211b Metabolism,
YLR245C 212a Metabolism, YLR245C 212b Metabolism,
YLR432W 213a Metabolism, YDL215C GDH2 213b Metabolism, Cellular Organization,
YNL201C 214a Metabolism, YFL056C AAD6 214b Metabolism, Energy,
YOR226C 215a Metabolism, YPL088W 215b Metabolism, Energy,
YNL201C 216a Metabolism, YOR047C STD1 216b Metabohsmi Transcription,
YDL013W HEX3 217a Metabolism, YDR510W SMT3 217b Protein Destination,
YLR432W 218a Metabolism, YKR026C GCN3 218b Protein Synthesis, Cellular Organization,
YHR204W 219a Metabolism, YGL030W RPL30 219b Protein Synthesis, Cellular Organization,
YBR006W 220a Metabolism, YDR382W RPP2B 220b Protein Synthesis, Cellular Organization,
YDL013W HEX3 221a Metabolism, YER116C 221b Transcription,
YNL201C 222a Metabolism, YPR115W 222b Transcription,
YPL059W 223a Metabolism, YIL105C 223b Transcription,
YLR432W 224a Metabolism, YDR167W TAF25 224b Transcription, Cellular Organization,
YOR128C ADE2 225a Metabolism, YBR134W 225b Unclassified Proteins,
YGR155W CYS4 226a Metabolism, YCR086W 226b Unclassified Proteins,
YOR269W PAC1 227a Metabolism, YLR254C 227b Unclassified Proteins,
YBR006W 228a Metabolism, YKL023W 228b Unclassified Proteins,
YDL203C 229a Metabolism, YGR058W 229b Unclassified Proteins,
YDL203C 230a Metabolism, YOR372C 230b Unclassified Proteins,
YDR400W 231a Metabolism, YCR059C 231b Unclassified Proteins,
YHR204W 232a Metabolism, YER126C 232b Unclassified Proteins,
YLR432W 233a Metabolism, YDR469W 233b Unclassified Proteins,
YPL059W 234a Metabolism, YNL047C 234b Unclassified Proteins,
YDL006W PTC1 235a Metabolism, Cell Growth, Cell YDR162C NBP2 235b Protein Destination,
Division And DNA Synthesis,
Cellular Biogenesis, Signal
Transduction, Cell Rescue,
Defense, Cell Death And Aging,
YDR328C SKP1 236a Metabolism, Cell Growth, Cell YFL009W CDC4 236b Cell Growth, Cell Division And
Division And DNA Synthesis, DNA Synthesis, Cellular
Protein Destination, Cellular Organization,
Organization,
YGL155W CDC43 237a Metabolism, Cell Growth, Cell YKL019W RAM2 237b Metabolism, Protein Destination,
Division And DNA Synthesis, Cellular Organization,
Protein Destination, Cellular
Organization,
YDR328C SKP1 238a Metabolism, Cell Growth, Cell YLR352W 238b Unclassified Proteins,
Division And DNA Synthesis,
Protein Destination, Cellular
Organization,
YPL161C BEM4 239b Metabolism, Cell Growth, Cell YGL126W SCS3 239b Metabolism,
Division And DNA Synthesis,
Signal Transduction,
YPL161C BEM4 240a Metabolism, Cell Growth, Cell YIL163C 240b Unclassified Proteins,
Division And DNA Synthesis,
Signal Transduction,
YPL161C BEM4 241a Metabolism, Cell Growth, Cell YLR049C 241b Unclassified Proteins,
Division And DNA Synthesis,
Signal Transduction, I
YNL236W SIN4 242a Metabolism, Cell Growth, Cell YJL030W MAD2 242b Cell Growth, Cell Division And
Division And DNA Synthesis, DNA Synthesis,
Transcription, Cellular
Organization,
YNL236W SIN4 243a Metabolism, Cell Growth, Cell YGL238W CSE1 243b Cell Growth, Cell Division And
Division And DNA Synthesis, DNA Synthesis, Cellular
Transcription, Cellular Organization,
Organization,
YNL236W SIN4 244a Metabolism, Cell Growth, Cell YJL013C MAD3 244b Cell Growth, Cell Division And
Division And DNA Synthesis, DNA Synthesis, Cellular
Transcription, Cellular Organization,
Organization,
YNL236W SIN4 245a Metabolism, Cell Growth, Cell YOR355W GDS1 245b Classification Not Yet Clear-Cut,
Division And DNA Synthesis;
Transcription, Cellular
Organization,
YDR207C UME6 246a Metabolism, Cell Growth, Cell YOR355W GDS1 246b Classification Not Yet Clear-Cu
Division And DNA Synthesis,
Transcription, Cellular
Organization,
YNL236W SIN4 247a Metabolism, Cell Growth, Cell YFR033C QCR6 247b Energy, Cellular Organization,
Division And DNA Synthesis,
Transcription, Cellular
Organization,
YNL236W SIN4 248a Metabolism, Cell Growth, Cell YJR034W PET191 248b Energy, Protein Destination,
Division And DNA Synthesis, Cellular Organization,
Transcription, Cellular
Organization,
YNL236W SIN4 249a Metabolism, Cell Growth, Cell YDR054C CDC34 249b Metabolism, Cell Growth, Cell
Division And DNA Synthesis, Division And DNA Synthesis,
Transcription, Cellular Protein Destination, Cellular
Organization, Organization,
YNL236W SIN4 250a Metabolism, Cell Growth, Cell YKL012W PRP40 250b Transcription, Cellular
Division And DNA Synthesis, Organization,
Transcription, Cellular
Organization,
YNL236W SIN4 251a Metabolism, Cell Growth, Cell YGR046W 251b Unclassified Proteins,
Division And DNA Synthesis,
Transcription, Cellular
Organization,
YNL236W SIN4 252a Metabolism, Cell Growth, Cell YGR117C 252b Unclassified Proteins,
Division And DNA Synthesis,
Transcription, Cellular
Organization,
YDR207C UME6 253a Metabolism, Cell Growth, Cell YOL082W 253b Unclassified Proteins,
Division And DNA Synthesis,
Transcription, Cellular
Organization,
YGR144W THI43 254a Metabolism, Cell Rescue, YGR144W THI4 254b Metabolism, Cell Rescue,
Defense, Cell Death And Aging, Defense, Cell Death And Aging,
YER062C H0R2 255a Metabolism, Cell Rescue, YPL201C 255b Unclassified Proteins,
Defense, Cell Death And Aging,
YDR477W SNF1 256a Metabolism, Cell Rescue, YER027C GAL83 256b Metabolism, Transcription,
Defense, Cell Death And Aging,
Cellular Organization,
YBR176W ECM31 257a Metabolism, Cellular Biogenesis, YBR176W ECM31 257b Metabolism, Cellular Biogenesis
YDR376W ARH1 258a Metabolism, Cellular Organization; YIR024C GIF1 258b Cell Growth, Cell Division And
DNA Synthesis,
YDR408C ADE8 Metabolism, Cellular Organization, YGL127C SOH1 Cell Growth, Cell Division And DNA Synthesis, Transcription;
YDR376W ARH1 259a Metabolism, Cellular Organization, YCR093W CDC39 259b Cell Growth, Cell Division And DNA Synthesis, Transcription, Cellular Organization;
YDR408C ADE8 260a Metabolism, Cellular Organization, YCR063W 260b Classification Not Yet Clear-Cut;
YLR438W CAR2 261a Metabolism, Cellular Organization, YHL025W SNF6 261b Metabolism, Cell Growth, Cell
Division And DNA Synthesis,
Transcription, Cellular
Organization,
YOR180C EHD2 262a Metabolism, Cellular Organization, YLR284C EHD1 262b Metabolism, Cellular
Organization,
YOR202W HIS3 263a Metabolism, Cellular Organization, YOR202W HIS3 263b Metabolism, Cellular
Organization,
YER023W PR03 264a Metabolism, Cellular Organization, YER023W PR03 264b Metabolism, Cellular
Organization,
YKL067W YNK1 265a Metabolism, Cellular Organization, YKL067W YNK1 265b Metabolism, Cellular
Organization,
YGL154C LYS5 266a Metabolism, Cellular Organization, YGL254W FZF1 266b Metabolism, Transcription, Cell
Rescue Defense, Cell Death
And Aging, Cellular Organization,
YGR229C SMI1 267a Metabolism, Cellular Organization, YKR099W BAS1 267b Metabolism, Transcription,
Cellular Organization,
YBL042C FUI1 268a Metabolism, Cellular Organization, YER021W RPN3 268b Protein Destination, YHR128W FUR1 269a Metabolism, Cellular Organization, YPR185W APG13 269b Protein Destination Intracellular
Transport
YOR375C GDH1 270a Metabolism, Cellular Organization, YJL124C SPB8 270b Transcription, YDR408C ADE8 271a Metabolism, Cellular Organization, YOR174W MED4 271b Transcription, Cellular
Organization,
YOR303W CPA1 272a Metabolism Cellular Organization, YOR039W CKB2 272b Transcription, Cellular
Organization,
YGR061C ADE6 273a Metabolism, Cellular Organization, YLR386W 273b Unclassified Proteins, YLR438W CAR2 274a Metabolism, Cellular Organization, YGR010W 274b Unclassified Proteins, YLR438W CAR2 275a Metabolism, Cellular Organization, YLR328W 275b Unclassified Proteins, YOL059W GPD2 276a Metabolism, Cellular Organization, YFL017C 276b Unclassified Proteins, YNL104C LEU4 277a Metabolism, Cellular Organization, YKL183W 277b Unclassified Proteins, YLR345W 278a Metabolism, Energy YLR321C SFH1 278b Cell Growth, Cell Division And
DNA Synthesis, Transcπption,
Cellular Biogenesis, Cellular
Organization,
YJL137C GLG2 279a Metabolism, Energy, YJL137C GLG2 279b Metabolism, Energy, YGL134W PCL10 280a Metabolism, Energy, YPL031C PH085 280b Metabolism, Energy, Cell
Growth, Cell Division And DNA
Synthesis, Transcription, Cellular
Organization,
YLR345W 281a Metabolism, Energy, YGR158C MTR3 281b Transcription, Cellular
Organization,
YKR096W 282a Metabolism, Energy, YBL051C 282b Unclassified Proteins,
YER133W GLC7 283a Metabolism, Energy Cell Growth, YNL233W BNI4 283b Cell Growth, Cell Division And Cell Division And DNA Synthesis, DNA Synthesis, Protein Protein Synthesis, Cellular Destination, Cellular Organization, Organization,
YLR071C RGR1 284a Metabolism, Energy Cell Growth, YDL065C PEX19 284b Cellular Organization,
Cell Division And DNA Synthesis,
Transcription, Cellular
Organization,
YDR074W TPS2 285a Metabolism, Energy Cell Rescue, YER019C-A SBH2 285b Protein Destination, Transport
Defense, Cell Death And Aging, Facilitation, Intracellular
Cellular Organization, Transport,
YDR074W TPS2 286a Metabolism, Energy Cell Rescue, YAR066W 286b Unclassified Proteins,
Defense, Cell Death And Aging,
Cellular Organization,
YBR221C PDB1 287a Metabolism, Energy, Cellular YLR345W 287b Metabolism, Energy,
Organization,
YDR148C KGD2 288a Metabolism, Energy, Cellular YDR510W SMT3 288b Protein Destination,
Organization,
YMR267W PPA2 289a Metabolism, Energy, Cellular YKR026C GCN3 289b Protein Synthesis, Cellular
Organization, Organization,
YDR001C 290a Metabolism, Energy Cellular YLR270W 290b Unclassified Proteins,
Organization,
YCL040W GLK1 291a Metabolism, Energy, Intracellular YBR040W FIG1 291b Cell Growth, Cell Division And
Transport, Cellular Organization, DNA Synthesis, Cellular Organization,
YCL040W GLK1 292a Metabolism, Energy Intracellular YML099C ARG81 292b Metabolism, Transcription, Transport, Cellular Organization, Cellular Organization, tsj YMR079W SEC14 293a Metabolism, Intracellular YDL001W 293b Unclassified Proteins, Transport, Cellular Organization,
YDL090C RAM1 294a Metabolism, Protein Destination, YKL019W RAM2 294b Metabolism, Protein Destination, Signal Transduction Cellular Cellular Organization, Organization,
YLR150W STM1 295a Metabolism, Signal Transduction, YJR072C 295b Unclassified Proteins, YGL254W FZF1 296a Metabolism, Transcription, Cell YHR215W PH012 296b Metabolism, Cellular Rescue, Defense, Cell Death And Organization, Aging, Cellular Organization, I
YGL115W SNF4 297a Metabolism, Transcription, Cell YER027C GAL83 297b Metabolism, Transcription, Rescue, Defense, Cell Death And Aging, Cellular Organization,
YGL254W FZF1 298a Metabolism, Transcription, Cell YOR039W CKB2 298b Transcription, Cellular Rescue, Defense, Cell Death And Organization, Aging, Cellular Organization,
YGL254W FZF1 299a Metabolism, Transcription, Cell YGR047C TFC4 299b Transcription, Cellular Rescue, Defense, Cell Death And Organization, Aging, Cellular Organization,
YOL108C IN04 300a Metabolism, Transcription, YKL017C HCS1 300b Cell Growth, Cell Division And Cellular Organization, DNA Synthesis,
YOL108C IN04 301a Metabolism, Transcription, YMR317W 301b Cellular Biogenesis, Cellular Organization,
YNL314W DAL82 302a Metabolism, Transcription, YNL314W DAL82 302b Metabolism, Transcription, Cellular Organization, Cellular Organization,
YOL108C IN04 303a Metabolism, Transcription, YDR123C IN02 303b Metabolism, Transcription,
Cellular Organization, Cellular Organization,
YOL108C IN04 304a Metabolism, Transcription, YKL135C APL2 304b Protein Destination, Intracellular Cellular Organization, Transport, Cellular Organization,
YJL110C GZF3 305a Metabolism, Transcription, YNL021W HDA1 305b Transcription, Protein Cellular Organization, Destination, Cellular
Organization,
YOL108C IN04 306a Metabolism, Transcription, YNL279W 306b Unclassified Proteins,
Cellular Organization,
YOR348C PUT4 307a Metabolism, Transport Facilitation, YMR228W MTF1 307b Cell Growth, Cell Division And
Intracellular Transport, Cellular DNA Synthesis, Transcription,
Organization, Cellular Organization;
YOR348C PUT4 308a Metabolism, Transport Facilitation, YCR045C 308b Protein Destination,
Intracellular Transport, Cellular
Organization,
YOR348C PUT4 309a Metabolism, Transport Facilitation, YJL084C 309b Unclassified Proteins,
Intracellular Transport, Cellular
Organization,
YOR348C PUT4 310a Metabolism, Transport Facilitation, YLR294C 310b Unclassified Proteins,
Intracellular Transport, Cellular
Organization,
YMR091C NPL6 311a Protein Destination, YFR037C RSC8 311b Cell Growth Cell Division And
DNA Synthesis, Transcription,
Cellular Organization,
YER144C UBP5 312a Protein Destination, YBR059C 312b Classification Not Yet Clear-Cut,
YLR417W VPS36 313a Protein Destination, YPL002C SNF8 313b Metabolism,
YDL097C RPN6 314a Protein Destination, YEL009C GCN4 314b Metabolism, Transcription,
Cellular Organization,
YDR394W RPT3 315a Protein Destination, YGR232W 315b Protein Destination,
YPL003W ULA1 316a Protein Destination, YPR066W UBA3 316b Protein Destination,
YOR132W VPS 17 317a Protein Destination, YOR069W VPS5 317b Protein Destination, Cellular
Organization,
YDR098C 318a Protein Destination, YGL071W RCS1 318b Transcription, Ionic Homeostasis,
Cellular Organization,
YER174C 319a Protein Destination, YGL071W RCS1 319b Transcription, Ionic Homeostasis,
Cellular Organization,
YML094W GIM5 320a Protein Destination, YLR200W YKE2 320b Unclassified Proteins, YOL111C 321a Protein Destination, YOR007C SGT2 321b Unclassified Proteins, YHR057C CYP2 322a Protein Destination, Cell Rescue, YJR091C JSN1 322b Cell Growth', Cell Division And
Defense, Cell Death And Aging, DNA Synthesis,
Cellular Organization,
YPL149W APG5 323a Protein Destination, Cellular YBR217W 323b Protein Destination, Cellular
Biogenesis, Cellular Organization, Biogenesis, Cellular Organization,
YPL149W APG5 324a Protein Destination, Cellular YMR159C SAP18 324b Unclassified Proteins, Biogenesis, Cellular Organization, YBR217W 325a Protein Destination, Cellular YMR159C SAP 18 325b Unclassified Proteins, Biogenesis, Cellular Organization,
YMR314W PRE5 326a Protein Destination, Cellular YKL130C SHE2 326b Cell Growth, Cell Division And Organization, DNA Synthesis, Cellular Organization,
YPR051W MAK3 327a Protein Destination, Cellular YEL053C MAK10 327b Energy,
Organization,
YNL135C FPR1 328a Protein Destination, Cellular YER052C HOM3 328b Metabolism,
Organization,
YKL103C LAP4 329a Protein Destination, Cellular YKL103C LAP4 329b Protein Destination, Cellular
Organization, Organization,
YHR060W VMA22 330a Protein Destination, Cellular YLR447C VMA6 330b Protein Destination, Transport
Organization, Facilitation, Intracellular Transport Ionic Homeostasis, Cellular Organization,
YOL088C MPD2 331a Protein Destination, Cellular YHR091C MSR1 331a Protein Synthesis, Cellular
Organization, Organization,
YKL103C LAP4 332a Protein Destination, Cellular YOL082W 332b Unclassified Proteins,
Organization,
YOL088C MPD2 333a Protein Destination, Cellular YLR312C 333b Unclassified Proteins,
Organization,
YEL060C PRB1 334a Protein Destination, Cellular YML032C-A 334b Unclassified Proteins,
Organization,
YOR362C PRE10 335a Protein Destination, Cellular YFL017C 335b Unclassified Proteins,
Organization,
YDR292C SRP101 336a Protein Destination, Cellular YMR163C 336b Unclassified Proteins,
Organization,
YHR060W VMA22 337a Protein Destination, Cellular YDR469W 337b Unclassified Proteins,
Organization,
YPR185W APG 13 338a Protein Destination, Intracellu YGL180W APG1 338b Cell Growth, Cell Division And
Transport, DNA Synthesis, Protein Destination, Intracellular Transport, Cellular Organization,
YPR185W APG13 339a Protein Destination, Intracellular YGR253C PUP2 339b Cell Growthi Cell Division And Transport, DNA Synthesis, Protein Destination, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YPR185W APG13 340a Protein Destination Intracellular YGR120C 340b Intracellular Transport, Cellular
Transport, Organization,
YBR170C NPL4 341a Protein Destination, Intracellular YGR048W UFD1 341b Protein Destination,
Transport,
YPR185W APG 13 342a Protein Destination, Intracellular YNL086W 342b Unclassified Proteins,
Transport,
YNL093W YPT53 343a Protein Destination, Intracellular YNL032W SIW14 343b Unclassified Proteins,
Transport,
YPR173C VPS4 344a Protein Destination, Intracellular YLR025W SNF7 344b Metabolism, Cell Growth, Cell
Transport, Cellular Biogenesis, Division And DNA Synthesis,
Cellular Organization, Protein Destination, Cellular Organization,
YPL259C APM1 345a Protein Destination, Intracellular YKL135C APL2 345b Protein Destination, Intracellular Transport, Cellular Biogenesis, Transport, Cellular Organization, Cellular Organization
YJL154C VPS35 346a Protein Destination, Intracellular YGL166W CUP2 346b Transcription, Ionic Homeostasis, Transport, Cellular Biogenesis, Cellular Organization, Cellular Organization,
YDR142C PEX7 347a Protein Destination, Intracellular YIL160C POT1 347b Metabolism, Energy, Cellular Transport, Cellular Organization, Organization,
YNR006W VPS27 348a Protein Destination, Intracellular YHL002W 348b Signal Transduction, Transport, Cellular Organization,
YDR142C PEX7 349a Protein Destination, Intracellular YGR239C 349b Unclassified Proteins, Transport, Cellular Organization,
YDR142C PEX7 350a Protein Destination, Intracellular YHR160C 350b Unclassified Proteins, Transport, Cellular Organization,
YDL212W SHR3 351a Protein Destination, Signal YDR508C GNP1 351b Metabolism, Transport Transduction, Cellular Facilitation, Organization,
YDR115W 352a Protein Synthesis, YKL142W MRP8 352b Protein Synthesis, Cellular
Organization,
YER102W RPS8B 353a Protein Synthesis, Cellular YBR135W CKS1 353b Cell Growth, Cell Division And
Organization, DNA Synthesis,
YOR276W CAF20 354a Protein Synthesis, Cellular YOL139C CDC33 354b Cell Growth, Cell Division And
Organization, DNA Synthesis, Protein
Synthesis, Cellular Organization,
YKL142W MRP8 355a Protein Synthesis, Cellular YMR165C SMP2 355b Energy, Cell Growth, Cell Organization, Division And DNA Synthesis,
Cellular Biogenesis,
YKR026C GCN3 356a Protein Synthesis, Cellular YKR026C GCN3 356b Protein Synthesis, Cellular Organization, Organization, YKL142W MRP8 357a Protein Synthesis, Cellular YKL142W MRP8 357b Protein Synthesis, Cellular Organization, Organization, YMR309C NIP1 358a Protein Synthesis, Cellular YNL244C sun 358b Protein Synthesis, Cellular Organization, Organization, YLR264W RPS28B 359a Protein Synthesis, Cellular YOL149W DCP1 359b Transcription, Organization, YLR291C GCD7 360a Protein Synthesis, Cellular YPL070W 360b Unclassified Proteins, Organization, YMR309C NIP1 361a Protein Synthesis, Cellular YNL047C 361b Unclassified Proteins, Organization, YMR309C NIP1 362a Protein Synthesis, Cellular YOR284W 362b Unclassified Proteins, Organization, YGL189C RPS26A 363a Protein Synthesis, Cellular YLR435W 363b Unclassified Proteins, Organization, YER131W RPS26B 364a Protein Synthesis, Cellular YLR435W 364b Unclassified Proteins, Organization, YLR264W RPS28B 365a Protein Synthesis, Cellular YBR094W 365b Unclassified Proteins, Organization, YER102W RPS8B 366a Protein Synthesis, Cellular YFL017C 366b Unclassified Proteins,
Organization,
YDR429C TIF35 367a Protein Synthesis, Cellular YFL017C 367b Unclassified Proteins,
Organization,
YCR020C- MAK31 368a Retrotransposons And Plasmid YEL053C MAK10 368b Energy, A Proteins,
YHR158C KEL1 369a Signal Transduction, YOR047C STD1 369b Metabolism, Transcription,
YHR158C KEL1 370a Signal Transduction, YJR122W CAF1 370b Transcription, Cellular Organization,
YHR158C κεLi 371a Signal Transduction, YMR181C 371b Unclassified Proteins,
YCR027C 372a Signal Transduction, YOL083W 372b Unclassified Proteins,
YHL002W 373a Signal Transduction, YNR005C 373b Unclassified Proteins,
YKL166C TPK3 374a Signal Transduction, Cellular YIL033C SRA1 374b Metabolism, Cell Growth, Cell Organization, Division And DNA Synthesis, Cell Rescue, Defense, Cell Death And Aging, Cellular Organization,
YDR017C KCS1 375a Transcription, YDR099W BMH2 375b Cell Growth, Cell Division And DNA Synthesis,
YOR025W HST3 376a Transcription, YLR403W SFP1 376b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
YIL105C 377a Transcription, YER179W DMC1 377b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YDR026C 378a Transcription, YDR110W FOB1 378b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
YIL105C 379a Transcription, YKL130C SHE2 379b Cell Growth, Cell Division And DNA Synthesis, Cellular Organization,
YML015C TAF40 380a Transcription, YDR174W 380b Cellular Organization,
YGL150C INO80 381a Transcription, YOR355W GDS1 381b Classification Not Yet Clear-Cut,
YGL150C INO80 382a Transcription, YDL002C NHP10 382b Classification Not Yet Clear-Cut,
YER127W LCP5 383a Transcription, YDR299W BFR2 383b Intracellular Transport,
YPR107C YTH1 384a Transcription, YBR205W KTR3 384b Metabolism, Protein Destination,
YGL221C NIF3 385a Transcription, YGL221C NIF3 385b Transcription,
YML015C TAF40 386a Transcription, YDR167W TAF25 386b Transcription, Cellular Organization,
YPR107C YTH1 387a Transcription, YJR093C FIP1 387b Transcription, Cellular Organization,
YDR439W LRS4 388a Transcription, YCR086W 388b Unclassified Proteins,
YCR004C YCP4 389a Transcription, YDR032C 389b Unclassified Proteins,
YER116C 390a Transcription, YGR024C 390b Unclassified Proteins,
YIL105C 391a Transcription, YNL047C 391b Unclassified Proteins,
YIR005W 392a Transcription, YGL174W 392b Unclassified Proteins,
YDR311W TFB1 393a Transcription, Cell Rescue, YGR120C 393b Intracellular Transport, Cellular Defense, Cell Death And Aging, Organization, Cellular Organization,
YDR311W TFB1 394a Transcription, Cell Rescue, YKL103C LAP4 394b Protein Destination, Cellular Defense, Cell Death And Aging, Organization, Cellular Organization,
YDR311W TFB1 395a Transcription, Cell Rescue, YOL082W 395b Unclassified Proteins, Defense, Cell Death And Aging, Cellular Organization,
YDR225W HTA1 396a Transcription, Cellular YKR048C NAP1 396b Cell Growth, Cell Division And Organization, DNA Synthesis, Protein Destination, Cellular Biogenesis, Cellular Organization,
YMR112C 397a Transcription, Cellular YBR253W SRB6 397b Metabolism, Cell Growth, Cell Organization, Division And DNA Synthesis, Transcription, Cellular Organization,
YGL208W SIP2 398a Transcription, Cellular YGL115W SNF4 398b Metabolism, Transcription, Cell Organization, Rescue, Defense, Cell Death And Aging, Cellular Organization,
YGL122C NAB2 399a Transcription, Cellular YKR026C GCN3 399b Protein Synthesis, Cellular Organization, Organization,
YDL160C DHH1 400a Transcription, Cellular YOL149W DCP1 400b Transcription, Organization,
1 YGR158C MTR3 401a Transcription, Cellular YDL111C RRP42 401b Transcription,
Organization, — *
YKL028W TFA1 402a Transcription, Cellular YDR311W TFB1 402b Transcription, Cell Rescue, 1 Organization, Defense, Cell Death And Aging,
Cellular Organization,
YGL237C HAP2 403a Transcription, Cellular YBL021C HAP3 403b Transcription, Cellular Organization, Organization,
YGL237C HAP2 404a Transcription, Cellular YOR358W HAP5 404b Transcription, Cellular Organization, Organization,
YBL021C HAP3 405a Transcription, Cellular YOR358W HAP5 405b Transcription, Cellular Organization, Organization,
YOL123W HRP1 406a Transcription, Cellular YGL122C NAB2 406b Transcription, Cellular Organization, Organization,
YOL135C MED7 407a Transcription, Cellular YOR174W MED4 407b Transcription, Cellular Organization, Organization,
YPR110C RPC40 408a Transcription, Cellular YNL113W RPC19 408b Transcription, Cellular Organization, Organization,
YJL025W RRN7 409a Transcription, Cellular YBL014C RRN6 409b Transcription, Cellular Organization, Organization,
YMR270C RRN9 410a Transcription, Cellular YBL025W RRN10 410b Transcription, Cellular Organization, Organization,
YOR159C SME1 411a Transcription, Cellular YPR182W SMX3 411b Transcription, Cellular Organization, Organization,
YPR182W SMX3 412a Transcription, Cellular YLR275W SMD2 412b Transcription, Cellular Organization, Organization,
YGR104C SRB5 413a Transcription, Cellular YBR193C MED8 413b Transcription, Cellular Organization, Organization,
YDR308C SRB7 414a Transcription, Cellular YOR174W MED4 414b Transcription, Cellular
Organization, Organization,
YDR308C SRB7 415a Transcription, Cellular YOL135C MED7 415b Transcription, Cellular
Organization, Organization,
YGL112C TAF60 416a Transcription, Cellular YMR236W TAF17 416b Transcription, Cellular
Organization, Organization,
YKL028W TFA1 417a Transcription, Cellular YKR062W TFA2 417b Transcription, Cellular
Organization, Organization,
YOR210W RPB10 418a Transcription, Cellular YGL166W CUP2 418b Transcription, Ionic Homeostasis,
Organization, Cellular Organization,
YIR018W YAP5 419a Transcription, Cellular YGL071W RCS1 419b Transcription, Ionic Homeostasis,
Organization, Cellular Organization,
YDL160C DHH1 420a Transcription, Cellular YEL015W 420b Unclassified Proteins,
Organization
YPR110C RPC40 421a Transcription, Cellular YLR238W 421b Unclassified Proteins,
Organization,
YDL150W RPC53 422a Transcription, Cellular YKR025W 422b Unclassified Proteins,
Organization,
YDR088C SLU7 423a Transcription, Cellular YDL144C 423b Unclassified Proteins,
Organization,
YMR039C SUB1 424a Transcription, Cellular YMR316C- 424b Unclassified Proteins,
Organization, B
YGL112C TAF60 425a Transcription, Cellular YMR255W 425b Unclassified Proteins,
Organization,
YDR002W 426a Transcription, Intracellular YKR048C NAP1 426b Cell Growth, Cell Division And
Transport, Cellular Organization, DNA Synthesis, Protein Destination, Cellular Biogenesis, Cellular Organization,
YLR293C GSP1 427a Transcription, Intracellular YJR074W MOG1 427b Unclassified Proteins, Transport, Cellular Organization,
YOR185C GSP2 428a Transcription, Intracellular YJR074W MOG1 428b Unclassified Proteins, Transport, Cellular Organization, I
YLR216C CPR6 429a Transcription, Protein Destination, YIR037W HYR1 429b Cell Rescue, Defense, Cell Cellular Organization, Death And Aging,
YBR237W PRP5 430a Transcription, Protein Destination, YDR073W SNF11 430b Metabolism; Cell Growth, Cell Cellular Organization, Division And DNA Synthesis, Transcription, Cellular Organization,
YGR252W GCN5 431a Transcπption, Protein Destination, YDR448W ADA2 431b Transcription, Cellular
Cellular Organization, Organization,
YBR052C 432a Transport Facilitation, YDR032C 432b Unclassified Proteins;
YKR104W 433a Transport Facilitation, Cell YOL143C RIB4 433b Metabolism,
Rescue, Defense, Cell Death And
Aging,
YLL028W 434a Transport Facilitation, Cell YGL166W CUP2 434b Transcription, Ionic Homeostasis,
Rescue, Defense, Cell Death And Cellular Organization,
Aging,
YIL013C PDR11 435a Transport Facilitation, Cellular YDR174W 435b Cellular Organization,
Organization,
YOL130W ALR1 436a Transport Facilitation Intracellular YGL025C PGD1 436b Cell Growth, Cell Division And
Transport, Cell Rescue, Defense, DNA Synthesis, Transcription,
Cell Death And Aging, Ionic Cellular Organization,
Homeostasis, Cellular
Organization,
YOL130W ALR1 437a Transport Facilitation, Intracellular YLR291C GCD7 437b Protein Synthesis, Cellular
Transport, Cell Rescue, Defense, Organization;
Cell Death And Aging, Ionic
Homeostasis, Cellular
Organization,
YMR243C ZRC1 438a Transport Facilitation Intracellular YKL142W MRP8 438b Protein Synthesis, Cellular
Transport, Cell Rescue, Defense, Organization,
Cell Death And Aging, Ionic
Homeostasis, Cellular
Organization,
YOL130W ALR1 439a Transport Facilitation, Intracellular YGL024W 439b Unclassified Proteins,
Transport, Cell Rescue, Defense,
Cell Death And Aging Ionic
Homeostasis, Cellular
Organization,
I YOL130W ALR1 440a Transport Facilitation, Intracellular YNL086W 440b Unclassified Proteins, ω Transport, Cell Rescue, Defense,
Cell Death And Aging, Ionic
1 Homeostasis, Cellular Organization,
YFL060C SN03 441a Unclassified Proteins, YMR096W SNZ1 441b Cell Growth, Cell Division And
DNA Synthesis,
YDL012C 442a Unclassified Proteins, YDR151C CTH1 442b Cell Growth, Cell Division And DNA Synthesis,
YIL065C 443a Unclassified Proteins, YJR091C JSN1 443b Cell Growth, Cell Division And DNA Synthesis,
YLR392C 444a Unclassified Proteins YJR091C JSN1 444b Cell Growth, Cell Division And DNA Synthesis,
YDR214W 445a Unclassified Proteins, YJL030W MAD2 445b Cell Growth, Cell Division And DNA Synthesis,
YNL127W 446a Unclassified Proteins, YKR055W RH04 446b Cell Growth, Cell Division And DNA Synthesis,
YGR278W 447a Unclassified Proteins, YGR049W SCM4 447b Cell Growth, Cell Division And DNA Synthesis;
YMR322C 448a Unclassified Proteins YMR096W SNZ1 448b Cell Growth, Cell Division And DNA Synthesis,
YBR190W 449a Unclassified Proteins YLR117C SYF3 449b Cell Growth, Cell Division And DNA Synthesis,
YDL012C 450a Unclassified Proteins, YJL065C 450b Cell Growth, Cell Division And DNA Synthesis,
YNR029C 451a Unclassified Proteins, YJL065C 451b Cell Growth, Cell Division And DNA Synthesis,
YGL061C DU01 452a Unclassified Proteins, YER016W BIM1 452b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Biogenesis, Cellular
Organization,
YOR353C 453a Unclassified Proteins, YHR102W NRK1 453b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Biogenesis,
YBR141C 454a Unclassified Proteins, YGL091C NBP35 454b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YGR154C 455a Unclassified Proteins, YCR057C PWP2 455b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YGR017W 456a Unclassified Proteins, YLR403W SFP1 456b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YJL048C 457a Unclassified Proteins, YKL130C SHE2 457b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YPR020W 458a Unclassified Proteins, YKL130C SHE2 458b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YDL239C 459a Unclassified Proteins, YHR184W SSP1 459b Cell Growth, Cell Division And
DNA Synthesis, Cellular
Organization,
YNL078W 460a Unclassified Proteins, YKR048C NAP1 460b Cell Growth, Cell Division And
DNA Synthesis, Protein
Destination, Cellular Biogenesis,
Cellular Organization,
YDR315C 461a Unclassified Proteins, YJR117W STE24 461b Cell Growth, Cell Division And
DNA Synthesis, Protein
Destination, Cellular
Organization,
YLR200W YKε2 462a Unclassified Proteins, YMR052W FAR3 462b Cell Growth, Cell Division And
DNA Synthesis, Signal
Transduction,
YDR200C 463a Unclassified Proteins, YMR052W FAR3 463b Cell Growth, Cell Division And
DNA Synthesis, Signal
Transduction,
YDR032C 464a Unclassified Proteins, YCL032W STE50 464b Cell Growth, Cell Division And
DNA Synthesis, Signal
Transduction,
YNL127W 465a Unclassified Proteins, YAL016W TPD3 465b Cell Growth, Cell Division And
DNA Synthesis, Transcription, Y1L065C 466a Unclassified Proteins, YLR321C SFH1 466b Cell Growth, Cell Division And
DNA Synthesis, Transcription;
Cellular Biogenesis, Cellular
Organization,
YIL132C 467a Unclassified Proteins, YLR321C SFH1 467b Cell Growth, Cell Division And DNA Synthesis, Transcription, Cellular Biogenesis, Cellular Organization,
YGL230C 468a Unclassified Proteins, YKL110C KTI12 468b Cell Rescue, Defense, Cell Death And Aging,
YBL101W- 469a Unclassified Proteins, YBL043W ECM13 469b Cellular Biogenesis,
A
YGR068C 470a Unclassified Proteins, YBL102W SFT2 470b Cellular Organization,
YKL090W 471a Unclassified Proteins, YPL128C TBF1 471b Cellular Organization,
YPL260W 472a Unclassified Proteins, YIL144W TID3 472b Cellular Organization,
YKL002W 473a Unclassified Proteins, YMR117C 473b Cellular Organization,
YBR141C 474a Unclassified Proteins, YDR372C 474b Cellular Organization, Unclassified Proteins,
YMR095C SN01 475a Unclassified Proteins, YNL333W SNZ2 475b Classification Not Yet Clear-Cut,
YFL060C SN03 476a Unclassified Proteins, YNL333W SNZ2 476b Classification Not Yet Clear-Cut,
YDL012C 477a Unclassified Proteins, YOR355W GDS1 477b Classification Not Yet Clear-Cut,
YNL091W 478a Unclassified Proteins, YOR355W GDS1 478b Classification Not Yet Clear-Cut,
YMR312W 479a Unclassified Proteins, YHR187W IKI1 479b Classification Not Yet Clear-Cut,
YMR322C 480a Unclassified Proteins, YNL333W SNZ2 480b Classification Not Yet Clear-Cut,
YMR322C 481a Unclassified Proteins, YFL059W SNZ3 481b Classification Not Yet Clear-Cut,
YDR071C 482a Unclassified Proteins, YBR125C 482b Classification Not Yet Clear-Cut,
YDR482C 483a Unclassified Proteins, YGL028C 483b Classification Not Yet Clear-Cut,
YMR102C 484a Unclassified Proteins, YNL218W 484b Classification Not Yet Clear-Cut,
YJL112W 485a Unclassified Proteins, YLL001W DNM1 485b Intracellular Transport, Cellular Biogenesis,
YDR472W 486a Unclassified Proteins, YKR068C BET3 486b Intracellular Transport, Cellular Organization,
YDR128W 487a Unclassified Proteins, YLR208W SEC13 487b Intracellular Transport, Cellular Organization,
YPR105C 488a Unclassified Proteins, YGL145W TIP20 488b Intracellular Transport, Cellular Organization,
YAL034W- 489a Unclassified Proteins, YGR120C 489b Intracellular Transport, Cellular
A Organization,
YDR472W 490a Unclassified Proteins, YBR254C 490b Intracellular Transport, Cellular Organization,
YER157W 491a Unclassified Proteins, YGR120C 491b Intracellular Transport, Cellular Organization,
YNR025C 492a Unclassified Proteins, YGR120C 492b Intracellular Transport, Cellular Organization,
YOR353C 493a Unclassified Proteins, YGR120C 493b Intracellular Transport, Cellular Organization,
YPR105C 494a Unclassified Proteins YGR120C 494b Intracellular Transport, Cellular Organization,
YFL010C 495a Unclassified Proteins, YDR515W SLF1 495b Ionic Homeostasis,
YEL041W 496a Unclassified Proteins, YJR049C UTR1 496b Ionic Homeostasis,
YGR163W GTR1 497a Unclassified Proteins, YML121W GTR1 497b Metabolism,
YNL311C 498a Unclassified Proteins, YKL001C MET 14 498b Metabolism,
YOR138C 499a Unclassified Proteins, YEL062W NPR2 499b Metabolism,
YLL062C 500a Unclassified Proteins, YOL143C RIB4 500b Metabolism,
YBL101W- 501a Unclassified Proteins YNL229C URE2 501b Metabolism,
A
YDL012C 502a Unclassified Proteins, YFR047C 502b Metabolism,
YDR132C 503a Unclassified Proteins, YJL218W 503b Metabolism,
YGR294W 504a Unclassified Proteins, YHL018W 504b Metabolism,
YIL008W 505a Unclassified Proteins, YHR111W 505b Metabolism,
YNL311C 506a Unclassified Proteins, YIL074C 506b Metabolism,
YFR042W 507a Unclassified Proteins, YPR159W KRE6 507b Metabolism,
Division And DNA Synthesis,
Cellular Biogenesis, Cellular
Organization,
YML088W 508a Unclassified Proteins, YDR328C SKP1 508b Metabolism, Cell Growth, Cell
Division And DNA Synthesis,
Protein Destination, Cellular
Organization,
YGR122W 509a Unclassified Proteins, YLR025W SNF7 509b Metabolism, Cell Growth, Cell
Division And DNA Synthesis,
Protein Destination, Cellular
Organization,
YMR025W 510a Unclassified Proteins, YNR052C POP2 510b Metabolism, Cell Growth, Cell cr> Division And DNA Synthesis,
Transcription, Cellular
Organization,
YML068W 511a Unclassified Proteins, YDR073W SNF11 511b Metabolism, Cell Growth, Cell
Division And DNA Synthesis,
Transcription, Cellular
Organization,
YNL094W 512a Unclassified Proteins, YNL025C SSN8 512b Metabolism, Cell Growth, Cell
Division And DNA Synthesis,
Transcπpticri, Cellular
Organization,
YDR215C 513a Unclassified Proteins, YPL175W SPT14 513b Metabolism, Cellular Biogenesis,
Cellular Organization;
YAL032C FUN20 514a Unclassified Proteins YLR345W 514b Metabolism, Energy,
YLR465C 515a Unclassified Proteins, YML035C AMD1 515b Metabolism, Energy,
YDL012C 516a Unclassified Proteins, YIL172C 516b Metabolism, Energy,
YAR014C 517a Unclassified Proteins YER133W GLC7 517b Metabolism, Energy, Cell
Growth Cell Division And DNA
Synthesis, Protein Synthesis,
Cellular Organization,
YML053C 518a Unclassified Proteins, YJR009C TDH2 518b Metabolism, Energy, Cellular
Organization,
YGR058W 519a Unclassified Proteins, YLR113W HOG1 519b Metabolism, Signal Transduction,
Cell Rescue, Defense, Cell
Death And Aging,
YCL046W 520a Unclassified Proteins, YGL115W SNF4 520b Metabolism, Transcription, Cell
Rescue, Defense, Cell Death
And Aging, Cellular Organization,
YPL039W MET31 521a Unclassified Proteins, YEL009C GCN4 521b Metabolism, Transcription,
Cellular Organization,
YGL242C 522a Unclassified Proteins, YKR099W BAS1 522b Metabolism, Transcription,
Cellular Organization,
YDL076C 523a Unclassified Proteins, YLR098C CHA4 523b Metabolism, Transcription,
Cellular Organization,
YDL239C 524a Unclassified Proteins, YLR098C CHA4 524b Metabolism, Transcription,
Cellular Organization,
YHR145C 525a Unclassified Proteins, YEL009C GCN4 525b Metabolism, Transcription,
Cellular Organization,
YDL110C 526a Unclassified Proteins, YKL015W PUT3 526b Metabolism, Transcription,
Cellular Organization,
YGL230C 527a Unclassified Proteins, YDL210W UGA4 527b Metabolism, Transport
Facilitation, Intracellular
Transport, Cellular Organization,
YPL222W 528a Unclassified Proteins, YGR048W UFD1 528b Protein Destination,
YIL151C 529a Unclassified Proteins, YLR121C YPS4 529b Protein Destination,
YLL049W 530a Unclassified Proteins, YNR069C 530b Protein Destination,
YNR068C 531a Unclassified Proteins, YNR069C 531b Protein Destination,
YAR031W 532a Unclassified Proteins, YBR217W 532b Protein Destination, Cellular
Biogenesis, Cellular
Organization,
YAL034W- 533a Unclassified Proteins, YKL103C LAP4 533b Protein Destination, Cellular
A Organization,
YPL019C 534a Unclassified Proteins, YHR060W VMA22 534b Protein Destination, Cellular
Organization,
YPR105C 535a Unclassified Proteins, YHR060W VMA22 535b Protein Destination, Cellular
Organization,
YOL105C WSC3 536a Unclassified Proteins, YGL153W PEX14 536b Protein Destination, Intracellular
Transport, Cellular Organization,
YBR077C 537a Unclassified Proteins, YMR004W MVP1 537b Protein Destination, Intracellular
Transport, Cellular Organization,
YPL151C 538a Unclassified Proteins, YOR036W PEP12 538b Protein Destination, Intracellular
Transport, Cellular Organization,
YPR105C 539a Unclassified Proteins, YGL153W PEX14 539b Protein Destination, Intracellular
Transport, Cellular Organization,
YDR482C 540a Unclassified Proteins, YOR276W CAF20 540b Protein Synthesis, Cellular
Organization,
YBR270C 541a Unclassified Proteins YKR026C GCN3 541b Protein Synthesis, Cellular
Organization,
YER186C 542a Unclassified Proteins, YKR026C GCN3 542b Protein Synthesis, Cellular
Organization,
YMR269W 543a Unclassified Proteins, YKR026C GCN3 543b Protein Synthesis, Cellular
Organization,
YER082C 544a Unclassified Proteins YKL142W MRP8 544b Protein Synthesis Cellular
Organization,
YMR210W 545a Unclassified Proteins, YKL142W MRP8 545b Protein Synthesis, Cellular
Organization,
YDL063C 546a Unclassified Proteins, YPL131W RPL5 546b Protein Synthesis, Cellular
Organization,
YLL027W 547a Unclassified Proteins, YGL189C RPS26A 547b Protein Synthesis, Cellular
Organization,
YLL027W 548a Unclassified Proteins, YER131W RPS26B 548b Protein Synthesis, Cellular
Organization,
YDR315C 549a Unclassified Proteins, YLR264W RPS28B 549b Protein Synthesis, Cellular
Organization,
YCL020W 550a Unclassified Proteins, YFL002W-A 550b Retrotransposons And Plasmid
Proteins
YFL010C 551a Unclassified Proteins, YGR136W 551b Signal Transduction, Cellular
Organization,
YGR058W 552a Unclassified Proteins, YGR136W 552b Signal Transduction, Cellular
Organization,
YDR416W SYF1 553a Unclassified Proteins, YBR188C NTC20 553b Transcription,
YDR215C 554a Unclassified Proteins, YKR024C DBP7 554b Transcription,
YDR132C 555a Unclassified Proteins, YHR170W NMD3 555b Transcription,
YBR270C 556a Unclassified Proteins, YIL105C 556b Transcription,
YDL146W 557a Unclassified Proteins, YKL070W 557b Transcription,
YDR326C 558a Unclassified Proteins, YIL105C 558b Transcription,
YGR250C 559a Unclassified Proteins, YIR001C 559b Transcription,
YMR068W 560a Unclassified Proteins, YIL105C 560b Transcription,
YPR082C DIB1 561a Unclassified Proteins, YBR055C PRP6 561b Transcription, Cellular
Organization,
YDR313C PIB1 562a Unclassified Proteins, YPL133C YPL133C 562b Transcription, Cellular
Organization,
YGR068C 563a Unclassified Proteins, YGL019W CKB1 563b Transcription, Cellular
Organization,
YMR255W 564a Unclassified Proteins, YGL122C NAB2 564b Transcription, Cellular
Organization,
YDL098C 565a Unclassified Proteins, YGR075C PRP38 565b Transcription, Cellular
Organization,
YFL023W 566a Unclassified Proteins, YBR154C RPB5 566b Transcription, Cellular
Organization,
YDR255C 567a Unclassified Proteins, YKL144C RPC25 567b Transcription, Cellular
Organization,
YDR357C 568a Unclassified Proteins, YPR182W SMX3 568b Transcription, Cellular
Organization,
YOL106W 569a Unclassified Proteins, YPR182W SMX3 569b Transcription, Cellular
Organization,
YBR270C 570a Unclassified Proteins, YMR236W TAF17 570b Transcription, Cellular
Organization,
YML114C 571a Unclassified Proteins, YDR167W TAF25 571b Transcription, Cellular
Organization,
YDL063C 572a Unclassified Proteins, YDR381W YRA1 572b Transcription, Cellular
Organization,
YNL171C 573a Unclassified Proteins, YCR106W 573b Transcription Cellular Organization,
YAL034W- 574a Unclassified Proteins, YGL172W NUP49 574b Transcription, Intracellular
A Transport, Cellular Organization,
YKR011C 575a Unclassified Proteins, YGL166W CUP2 575b Transcription, Ionic Homeostasis, Cellular Organization,
YML006C 576a Unclassified Proteins, YGL166W CUP2 576b Transcription, Ionic Homeostasis, Cellular Organization,
YOR220W 577a Unclassified Proteins, YGL166W CUP2 577b Transcription, Ionic Homeostasis, Cellular Organization,
YHL006C 578a Unclassified Proteins, YNL021W HDA1 578b Transcription, Protein Destination, Cellular Organization,
YDL012C 579a Unclassified Proteins, YHR032W 579b Transport Facilitation, Cell Rescue, Defense, Cell Death And Aging,
YMR075C- 580a Unclassified Proteins, YCR023C 580b Transport Facilitation, Cell A Rescue Defense, Cell Death And Aging
YGR113W DAM1 581a Unclassified Proteins, YGL061C DU01 581b Unclassified Proteins,
YGL061C DU01 582a Unclassified Proteins, YDR016C 582a Unclassified Proteins,
YAL036C FUN11 583a Unclassified Proteins, YDR152W 583b Unclassified Proteins,
YAL032C FUN20 584a Unclassified Proteins, YPL151C 584b Unclassified Proteins,
YDR490C PKH1 585a Unclassified Proteins, YHR207C 585b Unclassified Proteins,
YDR490C PKH1 586a Unclassified Proteins, YIR044C 586b Unclassified Proteins,
YDR490C PKH1 587a Unclassified Proteins, YLR466W 587b Unclassified Proteins,
YLR082C SRL2 588a Unclassified Proteins, YLR082C SRL2 588b Unclassified Proteins,
YDR416W SYF1 589a Unclassified Proteins, YJR050W ISY1 589b Unclassified Proteins,
YDR416W SYF1 590a Unclassified Proteins, YGR129W SYF2 590b Unclassified Proteins,
YHR016C YSC84 591a Unclassified Proteins, YLR243W 591b Unclassified Proteins,
YHR016C YSC84 592a Unclassified Proteins YMR255W 592b Unclassified Proteins,
YHL006C 593a Unclassified Proteins, YDR078C PUN1 593b Unclassified Proteins,
YNL056W 594a Unclassified Proteins, YNL032W SIW14 594b Unclassified Proteins,
YFL023W 595a Unclassified Proteins, YLR200W YKE2 595b Unclassified Proteins,
YAR031W 596a Unclassified Proteins, YCR030C 596b Unclassified Proteins,
YBL101W- 597a Unclassified Proteins, YFL002W-A 597b Unclassified Proteins,
A
YBL101W- 598a Unclassified Proteins, YJL162C 598b Unclassified Proteins,
A
YBR103W 599a Unclassified Proteins, YIL112W 599b Unclassified Proteins,
YBR228W 600a Unclassified Proteins, YLR135W 600b Unclassified Proteins,
YDL012C 601a Unclassified Proteins, YHR140W 601b Unclassified Proteins,
YDL071C 602a Unclassified Proteins, YDR183W 602b Unclassified Proteins,
YDL071C 603a Unclassified Proteins, YEL068C 603b Unclassified Proteins,
YDL071C 604a Unclassified Proteins, YFL017C 604b Unclassified Proteins,
YDL071C 605a Unclassified Proteins, YGR269W 605b Unclassified Proteins,
YDL071C 606a Unclassified Proteins, YNL155W 606b Unclassified Proteins,
YDL089W 607a Unclassified Proteins, YDL089W 607b Unclassified Proteins,
YDL089W 608a Unclassified Proteins, YLR324W 608b Unclassified Proteins,
YDL089W 609a Unclassified Proteins, YMR316C-B 609b Unclassified Proteins,
YDL110C 610a Unclassified Proteins, YOR078W 610b Unclassified Proteins,
YDL113C 611a Unclassified Proteins, YJL036W 611b Unclassified Proteins,
YDL133W 612a Unclassified Proteins, YDL001W 612b Unclassified Proteins,
YDL216C 613a Unclassified Proteins, YMR025W 613b Unclassified Proteins,
YDL239C 614a Unclassified Proteins, YOL091W 614b Unclassified Proteins,
YDR013W 615a Unclassified Proteins, YDR489W 615b Unclassified Proteins,
YDR032C 616a Unclassified Proteins, YDR032C 616b Unclassified Proteins,
YDR051C 617a Unclassified Proteins, YDR051C 617b Unclassified Proteins,
YDR070C 618a Unclassified Proteins, YFL017C 618b Unclassified Proteins,
YDR179C 619a Unclassified Proteins, YMR025W 619b Unclassified Proteins,
YDR200C 620a Unclassified Proteins, YNL127W 620b Unclassified Proteins,
YDR236C 621a Unclassified Proteins, YDR398W 621b Unclassified Proteins,
YDR267C 622a Unclassified Proteins, YHR122W 622b Unclassified Proteins,
YDR279W 623a Unclassified Proteins, YLR154C 623b Unclassified Proteins,
YDR315C 624a Unclassified Proteins, YLR323C 624b Unclassified Proteins,
YDR315C 625a Unclassified Proteins, YOR078W 625b Unclassified Proteins,
YDR326C 626a Unclassified Proteins, YER007C-A 626b Unclassified Proteins,
YDR348C 627a Unclassified Proteins, YMR295C 627b Unclassified Proteins,
1 YEL023C 628a Unclassified Proteins, YDL011C 628b Unclassified Proteins,
J YER010C 629a Unclassified Proteins, YER010C 629b Unclassified Proteins, o YER046W 630a Unclassified Proteins, YFL017C 630b Unclassified Proteins,
1 YER063W 631a Unclassified Proteins, YAL049C 631b Unclassified Proteins,
YER106W 632a Unclassified Proteins, YCR086W 632b Unclassified Proteins,
YFL010C 633a Unclassified Proteins, YOR197W 633b Unclassified Proteins,
YFR043C 634a Unclassified Proteins, YDR489W 634b Unclassified Proteins,
YGL051W 635a Unclassified Proteins, YAR033W 635b Unclassified Proteins,
YGL198W 636a Unclassified Proteins, YGL161C 636b Unclassified Proteins,
YGL214W 637a Unclassified Proteins, YLR435W 637b Unclassified Proteins,
YGL230C 638a Unclassified Proteins, YOR161C 638b Unclassified Proteins,
YGR010W 639a Unclassified Proteins, YGR010W 639b Unclassified Proteins,
YGR017W 640a Unclassified Proteins, YLR072W 640b Unclassified Proteins,
YGR024C 641a Unclassified Proteins, YGR024C 641b Unclassified Proteins,
YGR058W 642a Unclassified Proteins, YGR058W 642b Unclassified Proteins,
YGR058W 643a Unclassified Proteins, YNL047C 643b Unclassified Proteins,
YGR173W 644a Unclassified Proteins, YDR152W 644b Unclassified Proteins,
YIL007C 645a Unclassified Proteins, YHR185C 645b Unclassified Proteins,
YIL082W 646a Unclassified Proteins, YGR024C 646b Unclassified Proteins,
YIL132C 647a Unclassified Proteins, YLR322W 647b Unclassified Proteins,
YIL132C 648a Unclassified Proteins, YLR376C 648b Unclassified Proteins,
YIL151C 649a Unclassified Proteins, YBL051C 649b Unclassified Proteins,
YIL151C 650a Unclassified Proteins, YDR140W 650b Unclassified Proteins,
YJR024C 651a Unclassified Proteins, YJR024C 651b Unclassified Proteins,
YJR072C 652a Unclassified Proteins, YLR243W 652b Unclassified Proteins,
YJR072C 653a Unclassified Proteins, YOR262W 653b Unclassified Proteins,
YJR125C 654a Unclassified Proteins, YOR111W 654b Unclassified Proteins,
YJR136C 655a Unclassified Proteins YKL033W 655b Unclassified Proteins
YKL090W 656a Unclassified Proteins YGR024C 656b Unclassified Proteins
YKR007W 657a Unclassified Proteins YBR077C 657b Unclassified Proteins
YKR022C 658a Unclassified Proteins YBL010C 658b Unclassified Proteins
YKR060W 659a Unclassified Proteins YDR179C 659b Unclassified Proteins
YKR083C 660a Unclassified Proteins YKL052C 660b Unclassified Proteins
YLR015W 661a Unclassified Proteins YDR469W 661b Unclassified Proteins
YLR065C 662a Unclassified Proteins YDL149W 662b Unclassified Proteins
YLR315W 663a Unclassified Proteins YDR383C 663b Unclassified Proteins
YLR328 664a Unclassified Proteins YGR010 664b Unclassified Proteins
YLR328W 665a Unclassified Proteins YLR328W 665b Unclassified Proteins
YLR424W 666a Unclassified Proteins YKR022C 666b Unclassified Proteins
YML119W 667a Unclassified Proteins YLL032C 667b Unclassified Proteins
YMR093W 668a Unclassified Proteins YDR398W 668b Unclassified Proteins
YNL056W 669a Unclassified Proteins YNL099C 669b Unclassified Proteins
YNL086W 670a Unclassified Proteins YKL061W 670b Unclassified Proteins
YNL091W 671a Unclassified Proteins YKL075C 671b Unclassified Proteins
YNL091W 672a Unclassified Proteins YNL164C 672b Unclassified Proteins
YNL091W 673a Unclassified Proteins YNL288W 673b Unclassified Proteins
YNL091W 674a Unclassified Proteins YPL229W 674b Unclassified Proteins
YNL094W 675a Unclassified Proteins YAL049C 675b Unclassified Proteins
1 YNL122C 676a Unclassified Proteins YKL061W 676b Unclassified Proteins
■c YNR004W 677a Unclassified Proteins YPL157W 677b Unclassified Proteins
YNR029C 678a Unclassified Proteins YJL064W 678b Unclassified Proteins
1 YOL070C 679a Unclassified Proteins YNL078W 679b Unclassified Proteins
YOR023C 680a Unclassified Proteins YCR082W 680b Unclassified Proteins
YOR138C 681a Unclassified Proteins YGR268C 681b Unclassified Proteins
YOR215C 682a Unclassified Proteins YHR115C 682b Unclassified Proteins
YOR264W 683a Unclassified Proteins YCR086W 683b Unclassified Proteins
YOR264W 684a Unclassified Proteins YGR058W 684b Unclassified Proteins
YOR353C 685a Unclassified Proteins YOL082W 685b Unclassified Proteins
YPL110C 686a Unclassified Proteins YGR024C 686b Unclassified Proteins
YPL192C 687a Unclassified Proteins YPL192C 687b Unclassified Proteins
YPR105C 688a Unclassified Proteins YLR315W 688b Unclassified Proteins
YPR105C 689a Unclassified Proteins YMR181C 689b Unclassified Proteins
YPR105C 690a Unclassified Proteins YOR164C 690b Unclassified Proteins
YPR105C 691a Unclassified Proteins YOR331C 691b UnclassifieαJ Proteins
YPR152C 692a Unclassified Proteins YBR194W 692b Unclassified Proteins
In certain embodiments, the first polypeptide is labeled. In other embodiments, the second polypeptide is labeled, while in some embodiments, both the first and second polypeptides are labeled. Labeling can be performed using any art recognized method for labeling polypeptides. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin. and examples of suitable radioactive material include I25I, 131I, 35S or 3H.
The invention also includes complexes of two or more polypeptides in which at least one of the polypeptides is present as a fragment of a complex-forming polypeptide according to the invention. For example, one or more polypeptides may include an amino acid sequence sufficient to bind to its corresponding polypeptde. A binding domain of a given first polypeptide can be any number of amino acids sufficient to specifically bind to, and complex with, the corresponding second polypeptide under conditions suitable for complex formation. The binding domain can be the minimal number of amino acids required to retain binding affinity, or may be a larger fragment or derivative of the polypeptides listed in Table 3, columns 1 and 4. Procedures for identifying binding domains can be readily identified by one of ordinary skill in the art and the procedures described herein. For example, nucleic acid sequences containing various portions of a "bait" protein can be tested in a yeast two hybrid screening assay in combination with a nucleic acid encoding the corresponding "prey" protein.
In certain embodiments, the "bait" polypeptides of the complex are polypeptides categorized, for example, as a "Metabolism" protein in the MIPS database. In some embodiments, the "prey" protein of the complex is also a "Metabolism" protein, while in other embodiments the "prey" protein is, for example, an "Unclassified" protein (see Table 3; e.g., ProPair 195a-310a and ProPair 195b-310b). Other MIPS categories include, e.g., "Cell Growth/Cell Division/DNA Synthesis" proteins (see Table 2).
In other embodiments, the complexes are human ortholog complexes, chimeric complexes, or specific complexes implicated in fungal pathways, as discussed in detail below. Polypeptides forming the complexes according to the invention can be made using techniques known in the art. For example, one or more of the polypeptides in the complex can be chemically synthesized using art-recognized methods for polypeptide synthesis. These methods are common in the art, including synthesis using a peptide synthesizer. See, e.g., Peptide Chemistry, A Practical Textbook, Bodasnsky, Ed. Springer- Verlag, 1988; Merrifield, Science 232: 241-247 (1986); Barany, et al, Intl. J. Peptide Protein Res. 30: 705-739 (1987); Kent, Ann. Rev. Biochem. 57:957-989 (1988), and Kaiser, et al, Science 243: 187-198 (1989).
Alternatively, polypeptides can be made by expressing one or both polypeptides from a nucleic acid and allowing the complex to form from the expressed polypeptides. Any known nucleic acids that express the polypeptides, whether yeast or human (or chimerics of these polypeptides) can be used, as can vectors and cells expressing these polypeptides. Sequences of yeast ORFs and human polypeptides as referenced in Tables 3 and 7 are publicly available, e.g. at the Saccharomyces Genome Database (SGD) and GenBank (see, e.g. Hudson et al, Genome Res. 7: 1169-1173 (1997). If desired, the complexes can then be recovered and isolated.
Recombinant cells expressing the polypeptide, or a fragment or derivative thereof, may be obtained using methods known in the art, and individual gene product or complex may be isolated and analyzed (See, e.g., e.g., as described in Sambrook et al., eds., MOLECULAR CLONING: A LABORATORY MANUAL, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989; and Ausubel, et al., eds., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993). This is achieved by assays that are based upon the physical and/or functional properties of the protein or complex. The assays can include, e.g., radioactive labeling of one or more of the polypeptide complex components, followed by analysis by gel electrophoresis, immunoassay, cross-linking to marker-labeled products. Polypeptide complex may be isolated and purified by standard methods known in the art (either from natural sources or recombinant host cells expressing the proteins/protein complex). These methods can include, e.g., column chromatography (e.g., ion exchange, affinity, gel exclusion, reverse-phase, high pressure, fast protein liquid, etc), differential centrifugation, differential solubility, or similar methods used for the purification of proteins.
Complexes Useful for Identifying Anti-Fungal Agents
The invention further provides complexes of polypeptides useful, /«ter alia, in identifying agents that inhibit the growth of microorganisms such as fungi. Human fungal infections have increased dramatically in incidence and severity in recent years. Advances in surgery and cancer treatments as well as the increasing use of broad-spectrum antimicrobials and the spread of HIV have increased the number of patients at risk for fungal infections. Most fungi are completely resistant to conventional antibacterial drugs.
The antifungal drugs presently available fall into several categories depending on their mode of action, as discussed below. Because several complexes according to the invention include proteins associated with these modes of action, the complexes can be used to identify anti-fungal agents.
Protein interactions which are useful for identifying anti-fungal agents are considered below.
(i) Interference In Nuclear Division
Griseofulvin interferes with nuclear division in fungal mitosis by disrupting the mitotic spindle and inhibiting cytoplasmic microtubule aggregation by interacting with polymerized microtubules. There is evidence that gπseofulvin binds to a microtubule-associated protein in addition to binding to tubulin.
In accordance with the present invention, several interactions have presently been identified where one of the interacting partners is a microtubule or a microtubule-associated protein. Inhibiting any of these interactions could lead to the disruption of microtubules and interference in mitotic division, similar to the mode of action of griseofulvin, thereby providing a new means of inhibiting fungal activity. Accordingly, in some embodiments, the invention provides purified complexes of the proteins detailed in Table 4, below (interacting protein pairs are in bold, by row; a description of each protein follows).
Table 4: Microtubule-related interactions identified
Figure imgf000046_0001
Figure imgf000047_0001
secreted isoform, plays a role in the stress that when overexpressed can suppress the response hyperstable microtubule phenotype of tub2- 150
SPC34 JSN1
Protein component of the spmdle pole body Benomyl dependent tubulin mutant, Protein that when overexpressed can suppress the hyperstable microtubule phenotype of tub2-150
YIL065C JSN1
Protein of unknown function Benomyl dependent tubulin mutant. Protein that when overexpressed can suppress the hyperstable microtubule phenotype of tub2- 150
YLR392C JSN1
Protein of unknown function Benomyl dependent tubulin mutant, Protein that when overexpressed can suppress the hyperstable microtubule phenotype of tub2- 150
As described above, in certain embodiments of these complexes contain the binding domains, of the polypeptides recited in Table 4, while other embodiments contain conservative variants of these polypeptides, or polypeptides which contain the polypeptides recited in Table 4.
(ii) Disruption of Ergosterol Biosynthesis
Azoles are synthetic compounds that can be classified as imidazoles (ketoconazole, clotrimazole and miconazole) or triazoles (itraconizole and fluconazole). The antifungal activity of azole drugs result from their reduction in the biosynthesis of ergosterol, the main sterol in the cell membranes of fungi. Reduction of ergosterol alters the structure of the cytoplasmic membrane as well as the function of several membrane-bound enzymes (such as those involved in nutrient transport and chitin synthesis). The azole drugs reduce ergosterol synthesis by inhibiting the fungal cytochrome p450 enzymes, specifically they inhibit the sterol 14-alpha-demethylase, a microsomal cytochrome P450-dependent enzyme system, leading to a decrease in ergosterol and an accumulation of 14-alpha-methylsterols. There is some evidence that the primary target of the azoles is the heme protein, which cocatalyzes cytochrome P-450-dependent 14-alpha-dependent 14-alpha-demethylation of lanosterol. One interaction containing a heme biosynthesis protein has been presently been identified (Table 5). Disruption of this interaction could also lead to depletion of ergosterol and accumulation of sterol precursors, including 14-alpha-methylated sterols, forming a membrane with altered structure and function. Accordingly, in some embodiments, the invention provides a purified complex of the proteins recited in Table 5, below. Table 5: Heme biosynthesis protein interaction identified
Figure imgf000049_0001
Complexes containing one or more variants of these polypeptides are within the scope of the present invention, as are polypeptides having amino acid sequences which include the polypeptides recited in Table 5.
(iii) Cell Wall Synthesis Inhibition
Fungi share many biochemical targets with other eukaryotic cells. However, the fungal cell wall is a unique organelle and contains compoundsTsuch as mannan, chitin and glucans, that are unique to fungi. The cell wall is dynamic and essential to the viability of the fungi due to its roles in osmotic protection, transport of macromolecules, growth, conjugation and spore formation. Major disruption of the composition or organization of the cell wall deleteπously affects cell growth. A number of compounds have been discovered that inhibit the development of fungal cell walls. Two class of these antifungal drugs are echinocandins, which inhibit glucan synthesis, and nikkomycins, which inhibit chitin synthesis. Several interactions between proteins localized to the cell wall or enzymes responsible for production of cell wall components have presently been identified. Inhibiting any of these interactions could lead to a disruption of the cell wall, hence providing new means for inhibiting fungal viability. Accordingly, in certain embodiments, the present invention provides purified complexes of the proteins detailed in Table 6, below.
Table 6. Cell wall-related protein interactions identified
Figure imgf000049_0002
WSC3 PEX14
Protein required for maintenance of cell wall Peroxisomal peripheral membrane protein integrity and for the stress response (peroxin) involved in impoπ of peroxisomal matrix proteins
Embodiments of these complexes containing the binding domains or conservative variants of these polypeptides are within the scope of the present invention, as are polypeptides which contain the polypeptides recited in Table 6.
Complexes Containing One or More Human Polypeptides
The invention also provides purified complexes of two or more human polypeptides. In some embodiments, the interacting polypeptides are human orthologs of the interacting yeast polypeptides. Human orthologs according to the invention are set out in Table 7, below.
Complexes of human ortholog binding domains, conservative variants, and polypeptides including the human orthologs recited in Table 7, are within the scope of the invention, as are labeled ortholog complexes and/or polypeptides.
Table 7: Human ortholog protein interactions
Yeast Human Human Human ortholog description Yeast Human Human Human ortholog description accno ortholog ortholog accno ortholog ortholog
(bait) accno name (prey) accno name yal032c Q13573 SKIP Nuclear protein Skip ylr345 p16118 PFKFB1 6-phosphofructo-2-kιnase/ fructose-2,6- bιsphosphatase/6PF-2-K FRU-2,6-P2ase liver isozyme yal032c Q13573 SKIP Nuclear protein Skip ylr423c q02224 CENPE Centromeπc protein E/CENP-E protein yal032c Q13573 SKIP Nuclear protein Skip ypl151c p35606 COPP Beta subunit of coatomer complex yal034w-a P06468 TPM2 Fibroblast muscle-type tropomyosm ygl172w p49790 NUP153 Nuclear pore complex protein NUP153 yal034w-a P07951 TPM2 Skeletal beta-tropomyosin ygl172w p35658 NUP214 Nuclear pore complex protein NUP214/CAN protein yal034w-a P35749 MYH11 Myosin heavy chain, smooth muscle isoform/SMMHC ygl172w P52948 NUP98 Nuclear pore complex protein NUP98/Nucleopoπn NUP
[FRAGMENT] 98 yal034w-a P49454 CENPF CENP-F kinetochore protein ygl172w p23490 LOR Loricπn yal034w-a Q15545 TAF2F Transcription initiation factor TFIID 55 kD subunit ygl1 2w p09651 HNRPA1 Heterogenous nuclear πbonucleoprotein A1/helιx- destabi zing protein/single-strand binding protein/HNRNP core protein A1 yal034w-a P06468 TPM2 Fibroblast muscle-type tropomyosm ygr120c p49454 CENPF CENP-F kinetochore protein yal034w-a P07951 TPM2 Skeletal beta-tropomyosin ygr120c p30622 RSN Restm yal034w-a P49454 CENPF CENP-F kinetochore protein ygr120c p04114 APOB Apolipoprotein B yar003w P78406 MRNP41 mRNA-associated protein mRNP 41 ybr175w 014727 APAF1 Apoptotic protease activating factor 1/APAF-1 sD yar003w Q05048 CSTF1 Cleavage stimulation factor, 50 kDa subunit ybr175w p35606 COPP Beta subunit of coatomer complex yar003w Q09028 RBAP48 Chromatin assembly factor 1 P48 ybrl 75w q 15542 TAF2D Transcription initiation factor TFIID 100 Kd subunit/retinoblastoma binding protein P48 subunιt/TAFII-100/TAFIHOO yar003w Q15542 TAF2D Transcription initiation factor TFIID 100 Kd ybr175w p04901 GNB1 Guanine nucleotide-binding protein G(I)/G(S) G(T) beta subunιt/TAFII-100/TAFII100 subunit 1 yar003w Q16576 RBBP7 Histone acetyl transferase type B subunit ybrl 75w p43034 PAFAH1 B1 Platelet-activating factor acetylhydrolase IB alpha 2/retιnoblastoma-bιndιng protein subunit yar014c P19338 NCL Nucleolin/protein C23 yer133w p37140 PPP1CB Seπne/threonine-protein phosphatase PP1-beta catalytic subunit yar014c P23327 HRC Sarcoplasmic reticulum histidine-πch calcium binding yyeerr113333ww p08129 PPP1CA Seπne/threonine protein phosphatase PP1-alpha 1 protein catalytic subunit yar014c P35663 CYLC1 Cyclin I yer133w p05323 PPP2CA Seπne/threonine protein phosphatase PP2A-alpha, catalytic subunit yar014c P46100 ATRX Transcriptional regulator ATRX/X- nked helicase ll/X- yer133w p11082 PPP2CB Seπne/threonine protein phosphatase PP2A-beta, hnked nuclear protein catalytic subunit ybl101w-a 015016 KIAA0298 Hypothetical protein KIAA0298 ybl043w q06481 APLP2 Amyloid-like protein 2/APPH/amyloιd protein homolog ybl101w-a 015016 KIAA0298 Hypothetical protein KIAA0298 yfl002w-a q01484 ANK2 Ankyπn, brain variant 1/ankyπn B ybl101w-a 015016 KIAA0298 Hypothetical protein KIAA0298 yjl162c p31689 HSJ2 DNAJ protein homolog 2/HSJ-2 ybl105c P05127 PRKCB Protein kinase C-beta-2/PKC-beta-2 yml109w p46821 MAP1 B Microtubule-associated protein 1B ybl105c P 17252 PRKCA Protein kinase C alpha yml109 q14669 TRIP12 Thyroid receptor interacting protein 12 KIAA0045 ybrOOδw P30837 ALDH5 Mitochondπal aldehyde dehydrogenase X ydr382 p05387 RPLP2 60S acidic nbosomal protein P2
ybrOOΘw P00352 ALDH1 Aldehyde dehydrogenase, cytosolic ALDH class ykl023w p35579 MYH9 Myosin heavy chain, nonmuscle type A/cellular myosin
1/ALDHII/ALDH-E1 heavy chain, type A/NMMHC-A ybrOOβw P05091 ALDH2 Aldehyde dehydrogenase, mitochondπal/class ykl023w q08170 SFRS4 Pre-mRNA splicing factor SRp75
2/ALDHI/ALDH-E2 ybrOOβw P30837 ALDH5 Mitochondπal aldehyde dehydrogenase X ykl023w p35663 CYLC1 Cyclin I ybr006w P47895 ALDH6 Aldehyde dehydrogenase 6 ykl023w q14093 CYLC2 Cyhcin II ybrOOδw P49189 ALDH9 Aldehyde dehydrogenase, E3 isozyme/gamma- ykl023w q14203 DCTN1 Dynactin, 150 kD isoform [fragment] aminobutyraldehyde dehydrogenase ybrOOδw P51649 SSADH Succinate sumialdehyde dehydrogenase/NAD+- ykl023w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin dependent succinate-semialdehyde dehydrogenase heavy chain, type B/NMMHC-B ybr103w 014727 APAF1 Apoptotic protease activating factor 1/APAF-1 yιl112w P55273 CDKN2D Cyc n-dependent kinase 4 inhibitor D/P19INK4D ybr103w P43034 PAFAH1B1 Platelet-activating factor acetylhydrolase IB alpha yιl112w q01484 ANK2 Ankyπn, brain variant 1/ankyπn B subunit ybr103w Q 15269 PWP2H Periodic tryptophan protein 2 homolog yιl112w q01485 ANK2 Brain ankyπn variant 2 ybr103w Q 15542 TAF2D Transcription initiation factor TFIID 100 Kd yιl112w p20749 BCL3 B-cell lymphoma 3-encoded protein subunιt/TAFII-100/TAFII100 ybr221c P11177 PDHB Pyruvate dehydrogenase E1-beta subunit ylr345w q 16875 F26P 6PF-2-K/FRU-2,6-P2ase braιn/placenta-type ιsozyme/6-phosphofructo-2-kιnase/fructose-2,6- bisphosphatase ybr221c P21953 BCKDHB 2-oxoιsovalerate dehydrogenase beta subunit ylr345 p16118 PFKFB1 6-phosphofructo-2-kιnase/ fructose-2,6- bιsphosphatase/6PF-2-K/FRU-2,6-P2ase liver isozyme
' ybr221c P51854 TKT2 Transketolase 2 ylr345w q 16877 F263 6PF-2-K FRU-2,6-P2ase testis-type ιsozyme/6- n phosphofructo-2-kιnase/fructose-2,6-bιsphosphatasede
° ybr244w P07203 GPX1 Glutathione peroxidase ylr117c q 14690 KIAA0185 RRP5 protein homolog/KIAA0185 [fragment]
1 ybr244w P18283 GPX2 Glutathione peroxidase-GI ylr117c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ybr270c P30414 NKTR NK-tumor recognition protein/Natural-killer cells yιl105c p20226 TBP TATA-binding protein/transcription initiation factor TFIID cyclophilin-related protein ybr270c P30414 NKTR NK-tumor recognition protein/Natural-killer cells ykr026c q 14232 ELF2B1 Translation initiation factor elF-2B alpha subunit cyclophilin-related protein ybr270c P30414 NKTR NK-tumor recognition protein/Natural-killer cells ylr423c q02224 CENPE Centromeπc protein E/CENP-E protein cyclophilin-related protein ybr270c P30414 NKTR NK-tumor recognition protein/Natural-killer cells Ymr236w q 16594 TAF2G Transcription initiation factorTFIID 31 kD subunit cyclophilin-related protein ybr274w P53355 DAPK1 Death-associated protein kinase 1/DAP-kιnase 1 ylr258w p54840 GYS2 Glycogen synthase, liver ybr274w P54646 PRKAA2 5'-AMP-actιvated protein kinase, catalytic alpha-2 ylr258w p13807 GYS1 Muscle glycogen synthase chain ybr274w P27448 P78 Putative seπnd/threonine-protein kinase P78 Ymr255w p46821 MAP1B Microtubule-associated protein 1 B ybr274w P51812 RPS6KA3 Ribosomal protein S6 kinase II alpha 3/ιnsulιn- Ymr255w p29375 RBBP2 RBBP-2/retιnoblastoma binding protein 2 stimulated protein kinase 1 ybr274w p53355 DAPK1 Death-associated protein kinase 1/DAP-kιnase 1 Ymr255 q03111 ENL ENL protein ybr274w p54646 PRKAA2 5'-AMP-actιvated protein kinase, catalytic alpha-2 Ymr255w p51825 MLLT2 AF-4 protein chain ybr274w q14012 CAMK1 Calcium/calmodulin-dependent protein kinase type I Ymr255w p11387 TOP1 Topoisomerase I ybr274w q15831 STK11 Seπne/threonine-protein kinase 11 Ymr255 p46939 UTRN Utrophin
ycl020w O15016 KIAA0298 Hypothetical protein KIAA0298 yfl002w-a q01484 ANK2 Ankyπn, brain variant 1/ankyrιn B ycl024w p15735 PHKG2 Phosphorylase kinase, testis/liver, gamma-2 ykr048c q01105 SET Set protein/ HLA-DR associated protein ll/PHAPII ycl024w p27448 P78 Putative seπnd/threonine-protein kinase P78 ykr048c p46060 RANGAP1 RanGTPase activating protein 1 ycl024w P53355 DAPK1 Death-associated protein kinase 1/DAP-kιnase 1 ykr048c q99457 NAP1L3 Nucleosome assembly protein 1-lιke3 ycl024w p54646 PRKAA2 5'-AMP-actιvated protein kinase catalytic alpha-2 ykr048c p55209 NAP1L1 NAP-1/nucleosome assembly protein 1-lιke 1 chain ycl024w q13131 PRKAA1 5'-AMP-actιvated protein kinase, catalytic alpha-1 ykr048c 015355 PPM1C Protein phosphatase 2C gamma ιsoform/PP2C- chain GAMMA ycl024w q14012 CAMK1 Calcium/calmodu n-dependent protein kinase type I ykr048c q01534 TSPY Homo sapiens testicular protein (TSPY) mRNA, complete eds ycl024w q15831 STK11 Seπne/threonine-protein kinase 11 ykr048c p19338 NCL Nucleolin/protem C23 ycl024w q 16566 CAMK4 calcium/calmodulin-dependent protein kinase IV ykr048c q99733 NAP1L4 Nucleosome assembly protein 2/nucleosome assembly protein 1 -like 4 ycl024w q16816 PHKG1 Phosphorylase B kinase gamma catalytic chain, ykr048c p21817 RYR1 Ryanodine receptor 1 skeletal muscle isoform ycl059c P46821 MAP1B Microtubule-associated protein 1B ygl201c P49736 MCM2 DNA replication licensing factor MCM2/KIAA0030 ycl063w q05682 CALD1 Caldesmon/CDM ylr423c q02224 CENPE Centromeπc protein E/CENP-E protein ycrOOΘc p15924 DSP Desmoplakin I and II ybr108w p04280 PRB1 Salivary proline-nch protein/clone CP3, CP4, and CP5 ycr009c p49418 AMPH Amphiphysin ybr108w p54259 DRPLA Atrophιn-1/dentatorubral-pallιdoluysιan atrophy protein ydl006w 015355 PPM1C Protein phosphatase 2C gamma ιsoform/PP2C- ydr162c p46108 CRK Proto-oncogene C-CRK
GAMMA
1 ydlOOΘw p35813 PPM1A Protein phosphatase 2C alpha ydr162c p00519 ABL1 Proto-oncogene tyrosine-protein kinase ABL/c-abl υi ydlOOΘw p49593 KIAA0015 Putative protein phosphatase 2C/PP2C/KIAA0015 ydr162c P51451 BLK Tyrosine-protem kinase BLK H ydl012c p20226 TBP TATA-binding protein/transcription initiation factor ydr151c 015541 ZNF183 zinc finger protein 183
TFIID ydl012c p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM ydr151c p26651 ZFP36 Trιstetraprolιne/TTP/ZFP-36 ydl012c q10571 MN1 Probable tumor suppressor protein MN1 ydr151c p47974 BRF2 TIS11D protein/butyrate response factor 2/EGF- response factor 2 ydl012c q93074 KIAA0192 Hypothetical protein KIAA0192 ydr151c q07352 BRF1 Tιs11B protein/butyrate response factor 1/EGF- respoπse factor 1 ydl012c p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM yfr047c q15274 NADC Nicctmate-nucleotide pyrophosphorylase
[carboxylatingj/quino nate phosphoπbosyl transferase ydl012c p20226 TBP TATA-binding protein/transcription initiation factor yor355w q 14669 TRIP12 Thyroid receptor interacting protein 12/KIAA0045
TFIID ydl012c P51531 SMARCA2 Possible global transcription activator SNF2L2/BRM yor355w p42568 MLLT3 AF-9 protein ydl013w q07283 THH Tπchohyalin ydr510w p55854 SMT3H1 Ubiquitin-hke protein SMT3A ydl013w q07283 THH Tπchohyalin yer116c p38398 BRCA1 BREAST CANCER, TYPE 1 ydl017w p24941 CDK2 Cell division protein kinase 2 ycr050c p49368 CCT3 T-complex protein 1 , gamma subunit ydl017w p19784 CSNK2A2 Casein kinase II alpha' ydl160c p38919 NUK-34 Nuk_34 mRNA for translation initiation factor. ydl017w P24941 CDK2 Cell division protein kinase 2 ydl160c q 13838 BAT1 Probably ATP-dependent RNA helicase P47 ydl017w q00526 CDK3 Cell division protein kinase 3 ydl160c p04765 EIF4A1 Eukaryotic initiation factor 4AI ydl017w q00534 CDK6 Cell division protein kinase 6/PLSTIRE for ydl160c q 14240 EIF4A2 Eukaryotic initiation factor 4AII senπe/threonine protein kinase ydl017w q00536 PCTK1 Seπne/threonine protein kinase PCTAIRE-1 ydl160c P26196 DDX6 Probable ATP-dependent RNA helicase P54
ydl017w p24941 CDK2 Cell division protein kinase 2 yjl088w p00480 OTC Ornithine carbamoyltransferase [precursor]/OTCase/ornιthιne transcarbamylase ydl074c p11055 MYH3 Embryonic myosin heavy chain ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ydl074c p12883 MYH7 Myosin heavy chain cardiac muscle beta isoform ylr423c p12270 TPR Nucleoprotein TPR ydl074c p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform ylr423c p30622 RSN Restin ydl074c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ylr423c p05787 KRT8 Keratin, type II cytoskeletal 8/cytokeratιn 8/K8/CK8 ydl074c p15924 DSP Desmoplakin I and II ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ydl074c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ylr423c p11047 LAMC1 Laminin gamma-1 chain [precursor]/lamιnιn B2 chain myosin heavy chain, type B/NMMHC-B ydl074c p49454 CENPF CENP-F kinetochore protein ylr423c p 15924 DSP Desmoplakin I and II ydl074c q02224 CENPE Centromeπc protein E/CENP-E protein ylr423c p49454 CENPF CENP-F kinetochore protein ydl074c q03001 BPAG1 Bullous 230 kDa pemphigoid antigen 1 ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ydl090c p49356 FNTB farnesyl-protein transferase beta-subunit ykl019w p49354 FNTA Protein farnesyltransferase alpha-subunit ydl090c p53609 PGGT1B Geranylgeranyltransferase type I beta-subunit ykl019w q92696 RABGGTA RAB geranylgeranyl transferase alpha subunit ydl097c q 13098 GPS1 G protein pathway suppressor 1 yel009c p05412 JUN Transcription factor AP-1/c-jun proto oncogene ydl113c p 15924 DSP Desmoplakin I and II yjl036w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin heavy chain, type B/NMMHC-B ydl113c q02224 CENPE Centromeπc protein E/CENP-E protein yjl036w p49454 CENPF CENP-F kinetochore protein ydl113c p 15924 DSP Desmoplakin I and II ylr423c p49454 CENPF CENP-F kinetochore protein ydl113c q02224 CENPE Centromeπc protein E/CENP-E protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein
, ydl150w p05423 BN51T BN51 protein ykr025w p39687 PHAP1 HLA-DR associated protein I ydl150w p06748 NPM1 Nucleophosmin ykr025w 015355 PPM1C Protein phosphatase 2C gamma ιsoform/PP2C-
M GAMMA ydl150w p35663 CYLC1 Cyclin I ykr025w p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- nked nuclear protein ydl150w p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll X- ykr025w p21815 IBSP Bone sialoprotein II [precursor]/BSPII/Cell-bιndιng linked nuclear protein sialoprotein ydl150w p55081 MFAP1 Microfibπllar protein 1 ykr025w p19338 NCL Nucleolin/protein C23 ydl150w q 14093 CYLC2 Cylicin II ykr025w p17480 UBTF Nucleolar transcription factor 1 /upstream binding factor
1/UBF-1 ydl154w p20585 MSH3 DNA mismatch repair protein MSH3 ygl025c q02817 MUC2 Intestinal mucin 2/mucιn 2 ydl154 p43246 MSH2 DNA mismatch repair protein MSH2 ygl025c q02078 MEF2A Myocyte-specific enhancer factor 2A ydl154w p20585 MSH3 DNA mismatch repair protein MSH3 yιl144w p49454 CENPF CENP-F kinetochore protein ydl154w p43246 MSH2 DNA mismatch repair protein MSH2 yιl144w q02224 CENPE Centromenc protein E/CENP-E protein ydl154w p52701 MSH6 DNA mismatch repair protein MSH6/G/T mismatch yιl144w p15924 DSP Desmoplakin I and II binding protein ydl154w p43246 MSH2 DNA mismatch repair protein MSH2 Ymr224c p49959 MRE11A Double-strand break repair protein MRE11 A/MRE11 homolog ydl155w p14635 CCNB1 G2/mιtotιc-specιfic cyclin B1 ybr135w p10275 AR Androgen receptor ydl203c q14154 KIAA0141 Hypothetical protein KIAA0141 ygr058w p28676 GCA Grancalcin ydl203c q14154 KIAA0141 Hypothetical protein KIAA0141 yor372c p54259 DRPLA Atrophιn-1/dentatorubral-pallιdoluysιan atrophy protein ydl239c p12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ydl239c p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform ylr423c p12270 TPR Nucleoproteip TPR
ydl239c p 15924 DSP Desmoplakin I and II ylr423c p13535 MYH8 Myosin heavy chain perinatal skeletal muscle ydl239c P30622 RSN Restin ylr423c P05787 KRT8 Keratin, type II cytoskeletal 8/cytokeratιn 8 K8/CK8 ydl239c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ylr423c p11047 LAMC1 Laminm gamma-1 chain [precursor]/lamιnιn B2 chain myosin heavy chain, type B/NMMHC-B ydl239c P49454 CENPF CENP-F kinetochore protein ylr423c P15924 DSP Desmoplakin I and II ydl239c q02224 CENPE Centromeπc protein E/CENP-E protein ylr423c P49454 CENPF CENP-F kinetochore protein ydl239c q03001 BPAG1 Bullous 230 kDa pemphigoid antigen 1 ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ydl239c q08378 GOLGA3 Golgιn-160 ylr423c P30622 RSN Restin ydl239c P13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform yol091w q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ydl239c p 15924 DSP Desmoplakin I and II yol091w P12270 TPR Nucleoprotein TPR ydl239c p49454 CENPF CENP-F kinetochore protein yol091w P42566 EPS15 Epidermal growth factor receptor substrate 15 ydl239c q02224 CENPE Centromeπc protein E/CENP-E protein yol091w P49454 CENPF CENP-F kinetochore protein ydl239c q03001 BPAG1 Bullous 230 kDa pemphigoid antigen 1 yol091w q02224 CENPE Centromenc protein E/CENP-E protein ydl239c q08378 GOLGA3 Golgιn-160 yol091w P35579 MYH9 Myosin heavy chain nonmuscle type A/cellular myosin heavy chain, type A/NMMHC-A ydl246c p11766 ADH5 Class III alcohol dehydrogenase chi subunit ydl246c P11766 ADH5 Class III alcohol dehydrogenase chi subunit ydl246c q00796 SORD Sorbitol dehydrogenase/L-ιdιtol-2 dehydrogenase ydl246c q00796 SORD Sorbitol dehydrogenase/L-ιdιtol-2 dehydrogenase ydl246c p11766 ADH5 Class III alcohol dehydrogenase chi subunit yjr159w P11766 ADH5 Class III alcohol dehydrogenase chi subunit ydl246c q00796 SORD Sorbitol dehydrogenase/L-ιdιtol-2 dehydrogenase yjr159w q00796 SORD Sorbitol dehydrogenase/L-ιdιtol-2 dehydrogenase ydr002w p07197 NEFM Neurofilament triplet M proteιn/160 Kd neurofilament ykr048c p21817 RYR1 Ryanodine receptor 1 protein/NF-M ydr002w p12036 NEFH Neurofilament triplet H proteιn/200 Kd neurofilament
Figure imgf000055_0002
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Figure imgf000055_0001
Set protein/ HLA-DR associated protein ll/PHAPII protein ydr002w P35663 CYLC1 Cyclin I ykr048c P55209 NAP1 L1 NAP-1/nucleosome assembly protein 1-lιke 1 ydrf)02w p43487 RANBP1 RAN specific GTPase-activating proteιn/RanBP1 ykrt)48c p46060 RANGAP1 RanGTPase activating protein 1 ydrf)02w p46821 MAP1 B Microtubule-associated protein 1 B ykr048c q99457 NAP1L3 Nucleosome assembly protein 1-lιke3 ydr002w P49792 RANBP2 Nuclear pore complex protein NUP358/nucleopoπn ykr048c q99733 NAP1 L4 Nucleosome assembly protein 2/nucleosome assembly
NUP358 protein 1 -like 4 ydr002w q92794 MOZ Monocytic leukemia zinc finger protein ykr048c q01534 TSPY Homo sapiens testicular protein (TSPY) mRNA, complete eds ydr061w P21439 MDR3 Membrane glycoprotein P ycr086w P39880 CUTL1 CCAAT displacement protein/CDP ydr077w q02817 MUC2 Intestinal mucin 2/mucιn 2 ydr044w p36551 CPO Coproporphytinogen III oxidase/coprogen oxidase ydr099w P42655 YWHAE 14-3-3 protein epsilon ybl043w q06481 APLP2 Amyloid-like protein 2/APPH/amyloιd protein homolog ydr099w P42655 YWHAE 14-3-3 protein epsilon ynl042w P54259 DRPLA Atrophιn-1/dentatorubral-pallιdoluysιan atrophy protein ydr128w O00628 PTS2R Peroxisomal targeting signal 2 receptor ylr208w q09028 RBAP48 Chromatin assembly factor 1 P48 subunit/retinoblastoma binding protein P48 ydr128w P35606 COPP Beta subunit of coatomer complex ylr208w P25388 GNB2-RS1 Guanine nucleotide-binding protein beta subumt-like protein 12 3 ydr128w q09028 RBAP48 Chromatin assembly factor 1 P48 ylr208w q 16576 RBBP7 Histone acetyl transferase type B subunit subunit/retinoblastoma binding protein P48 2/retιnoblastoma-bιndιng protein ydr128w q16576 RBBP7 Histone acetyl transferase type B subunit ylr208w P43034 PAFAH1B1 Platelet-activating factor acetylhydrolase IB alpha 2/reιιnoblastoma-bιndιng protein subunit
ydr142c pp2255338888 GGNNBB22--RRSS1 Guanine nucleotide-binding protein beta subunit-like yyιιll116600cc p55084 HADHB Tπfunctional enzyme beta subunit, mitochondnal protein 12 3 [precursor] ydr142c q09028 RBAP48 Chromatin assembly factor 1 P48 yιl160c p24752 AMLAD ALPHA-METHYLACETOACETICACIDURIA subunit retinoblastoma binding protein P48 ydr142c q13216 CKN1 Cockayne syndrome WD-repeat protein CSA yιl160c p42765 THIM 3-ketoacyl-CoA thiolase mitochondπal/mitochondrial 3- oxoacyl-CoA thiolase ydr142c q13610 PWP1 Periodic tryptophan protein 1 homolog/keratinocyte yιl160c p22307 SCP2 Nonspecific pid-transfer protein/sterol carrier protein protein IEF SSP 9502 X/sterol carrier protein 2 ydr142c q 16576 RBBP7 Histone acetyl transferase type B subunit yιl160c p09110 ACAA 3-ketoacyl-CoA thiolase, peroxιsomal/3-oxoacyl-CoA 2/retιnoblastoma-bιndιng protein peroxisomal thiolase ydr148c p10515 DLAT Dihydrolipoamide acetyltransferase component of ydr510w q93068 SMT3H3 Ubiquitin-like protein SMT3C pyruvate dehydrogenase complex/PDC-E2 ydr148c p11182 DBT Lipoamide acyl transferase component of branched- ydr510w p55855 SMT3H2 Ubiquitin-like protein SMT3B chain alpha-keto acid dehydrogenase complex ydr148c p17677 GAP43 Neuromoduhn/axonal membrane protein GAP-43 ydr510w p55854 SMT3H1 Ubiquitin-like protein SMT3A ydr200c p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform Ymr052w p30622 RSN Restin ydr200c p49454 CENPF CENP-F kinetochore protein Ymr052w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin heavy chain, type B/NMMHC-B ydr200c p49454 CENPF CENP-F kinetochore protein ynl127w p20309 CHRM3 Muscaπnic acetylcholine receptor M3 ydr201w p12270 TPR Nucleoprotein TPR yιl144w p49454 CENPF CENP-F kinetochore protein
, ydr201w p30622 RSN Restin yιl144w q02224 CENPE Centromenc protein E/CENP-E protein ydr218c 043236 PNUTL2 Peanut-like protein 2/Braιn protein H5 yjr076c q14141 KIAA0128 Septin 2 homolog [fragment]
S ydr218c q14141 KIAA0128 Septin 2 homolog [fragment] yjr076c q15019 NEDD5 NEDD5 protein homolog/KIAA0158
, ydr218c q15019 NEDD5 NEDD5 protein homolog/KIAA0158 yjr076c q 16643 DBN1 Drebin E ydr218c q16181 CDC10 CDC10 protein homolog yjr076c q16181 CDC10 CDC10 protein homolog ydr225w p02261 H2AFA Histone H2A 1 ykr048c p46060 RANGAP1 RanGTPase activating protein 1 ydr225w p04908 none Histone H2A 5 ykr048c q99457 NAP1L3 Nucleosome assembly protein 1-lιke3 ydr225w p16104 H2AX Histone H2A X ykr048c q99733 NAP1L4 Nucleosome assembly protein 2 nucleosome assembly protein 1 -like 4 ydr225w p28001 H2AFO Histone H2A 2/H2A/0 ykr048c p55209 NAP1L1 NAPj 1 /nucleosome assembly protein 1-lιke 1 ydr228c p20226 TBP TATA-binding protein/transcription initiation factor ylr423c p49454 CENPF CENP-F kinetochore protein
TFIID ydr228c p54252 MJD1 Machado-joseph disease protein 1 ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ydr228c q10571 MN1 Probable tumor suppressor protein MN1 ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ydr228c q93074 KIAA0192 Hypothetical protein KIAA0192 ylr423c p 15924 DSP Desmoplakin I and II ydr259c p11055 MYH3 Embryonic myosin heavy chain ylr423c p 15924 DSP Desmoplakin I and II ydr259c p15924 DSP Desmoplakin I and II ylr423c p49454 CENPF CENP-F kinetochore protein ydr259c p49454 CENPF CENP-F kinetochore protein ylr423c q02224 CENPE Centromeπc protein E/CENP-E protein ydr308c p24928 POLR2A DNA-directed RNA polymerase II largest subunit yor174w p49321 NASP Nuclear autoantigenic sperm protein ydr308c q03001 BPAG1 Bullous 230 kDa pemphigoid antigen 1 yor174w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin heavy chain, type B/NMMHC-B ydr311w p32780 BTF2 Basic transcription factor 62kD subunit ygr120c p04114 APOB Apolipoprotein B ydr311w p32780 BTF2 Basic transcription factor 62kD subunit ylr423c q02224 CENPE Centromenc protein E/CENP-E protein
ydr328c p07199 CENP-B Major centromere autoantigen B/centromere protein B yflOOΘw p35606 COPP Beta subunit of coatomer complex ydr328c p17480 UBTF Nucleolar transcription factor 1 /upstream binding yfl009w q15542 TAF2D Transcription initiation factor TFIID 100 Kd factor 1/UBF-1 subunιt TAFII-100/TAFI1100 ydr328c p19338 NCL Nucleolin/protein C23 yfl009w p04901 GNB1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1 ydr328c p34991 TCEB1L Cyclin A CDK2-assocιated p19 yfl009w p43034 PAFAH1 B1 Platelet-activating factor acetylhydrolase IB alpha subunit ydr376w p22570 FDXR NADPH adrenodoxin oxidoreductase ycr093w p54252 MJD1 Machado-joseph disease protein 1
[precursor]/adrenodoxιn reductase/ferredosιn-NADP+ reductase ydr376w p22570 FDXR NADPH adrenodoxin oxidoreductase yιr024c p49321 NASP Nuclear autoantigenic sperm protein
[precursor]/adrenodoxιn reductase/ferredosιn-NADP+ reductase ydr388w p14317 HCLS1 Hematopoietic lineage cell specific protein ycr009c p15924 DSP Desmoplakin I and II ydr388w p49418 AMPH Amphiphysin ycr009c p49418 AMPH Amphiphysin ydr394w p17980 PSMC3 26S protease regulatory subunit 6A TAT-bιndιng ygr232w q06547 E4TF1 B GA binding protein beta-1 chain protein 1 TBP-1 ydr394w p35998 PSMC2 26S protease regulatory subunit 7/MSS1 protein ygr232w q01485 ANK2 Brain ankyπn variant 2 ydr394w p43686 PSMC4 26S protease regulatory subunit 6B/TAT-bιndιng ygr232w p53355 DAPK1 Death-associated protein kinase 1/DAP-kιnase 1 proteιn-7/TBP-7 ydr394w p47210 PSMC5 26S proteasome regulatory subunit 8/proteasome ygr232w p20749 BCL3 B-cell lymphoma 3-encoded protein subunit p45
1 ydr394w q03527 PSMC1 26S protease (S4) regulatory subunit ygr232w q01484 ANK2 Ankynn, brain variant 1/ankyrιn B LΠ ydr394w q92524 PSMC6 26S protease regulatory subunit S10B/proteasome ygr232w p42773 CDN2C Cyclin dependent kinase 6 inhibitor subunit P42
I ydr408c p22102 GART Tπfunctional puπne biosynthetic protein adenosιne-3 ycr063w p41223 EDG2 G10 protein homolog ydr408c p22102 GART Tnfunctional puπne biosynthetic protein adenosιne-3 yorl 74w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin heavy chain, type B/NMMHC-B ydr416w q14690 KIAA0185 RRP5 protein homolog/KIAA0185 [fragment] ygr129w q02224 CENPE Centromenc protein E/CENP-E protein ydr429c p33240 CSTF2 Cleavage stimulation factor, 64 kD subunit yfl017c p08578 SNRPE Small nuclear nbonucleoprotein E/snRNP-E ydr439w p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ycr086w p39880 CUTL1 CCAAT displacement protein/CDP ydr477w p54646 PRKAA2 5'-AMP-actιvated protein kinase, catalytic alpha-2 yer027c p10451 SPP1 Ostdopontin [precursor] chain ydr482c p42566 EPS15 Epidermal growth factor receptor substrate 15 ygl028c q02505 MUC3 Mucm 3 [fragments]/ιntestιnal mucm 3 ydr482c q02224 CENPE Centromenc protein E/CENP-E protein ygl028c q02817 MUC2 Intestinal mucm 2/mucιn 2 ydr490c p17612 PRKACA cAMP-dependent protein kinase catalytic subunit type ylr466w q02505 MUC3 Mucm 3 [fragments]/ιntestιnal mucm 3 alpha I yer018c P02546 LMN1 Lamm C yhr193c p50502 HIP Progesterone receptor-associated p48 protein yer018c p02545 LMN1 Lamm A/70 KD Lamm Ymr117c p30622 RSN Restin yer018c p02546 LMN1 Lamm C Ymr117c p49454 CENPF CENP-F kinetochore protein yer018c p35749 MYH11 Myosin heavy chain smooth muscle isoform/SMMHC Ymr117c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin
[FRAGMENT] heavy chain, type B/NMMHC-B yer018c q07283 THH Tπchohyalin Ymr117c p11055 MYH3 Embryonic myosin heavy chain yer018c q93074 KIAA0192 Hypothetical protein KIAA0192 Ymr117c p42566 EPS15 Epidermal growth factor receptor substrate 15 yer023w P32322 PYCR1 Pyrrolme 5-carboxylate reductase yer023w p32322 PYCR1 Pyrrolme 5-carboxylate reductase
yer082c p11016 GNB2 Guanine nucleotide-binding protein beta subunit 2 ykl142w p07942 LAMB1 Laminin beta-1 chain/Lamimn B1 chain yer102w p09058 RPS8 40S πbosomal protein S8 ybr135w p10275 AR Androgen receptor yer102w p09058 RPS8 40S πbosomal protein S8 yfl017c p08578 SNRPE Small nuclear πbonucleoprotem E/snRNP-E yer106w q13416 0RC2L Origin recognition complex subunit 2 ycr086w p39880 CUTL1 CCAAT displacement protem/CDP yer127w p30622 RSN Restin ydr299w p19338 NCL Nucleolin/protem C23 yer127w p35663 CYLC1 Cyclin I ydr299w p46060 RANGAP1 RanGTPase activating protein 1 yerl 27w p35749 MYH11 Myosin heavy chain, smooth muscle isoform/SMMHC ydr299w p07197 NEFM Neurofilament triplet M proteιn/160 Kd neurofilament
[FRAGMENT] protem/NF-M yer127w p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- ydr299w p21817 RYR1 Ryanodine receptor 1 linked nuclear protein yer127w q01484 ANK2 Ankyπn, brain variant 1/ankyπn B ydr299w p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- linked nuclear protein yer131w q06722 RPS26 Ribosomal protein S26 ylr435w p27797 CALR Calretιculιn/52kD πbonucleoprotein autoantigen RO/SS- yer133w p05323 PPP2CA Seπne/threonine protein phosphatase PP2A-alpha, ynl233w p35251 RFC1 Replication factor C large subunit/activator 1140 Kd catalytic subunit subunit yer133w p08129 PPP1CA Seπne/threonine protein phosphatase PP1-alpha 1 ynl233w p35663 CYLC1 Cyclin I catalytic subunit yer133w P11082 PPP2CB Seπne/threonine protein phosphatase PP2A-beta, ynl233w p51825 MLLT2 AF-4 protein catalytic subunit yer133w p36873 PPP1CC Seπne/threonine-protein phosphatase PP1-gamma ynl233w p46821 MAP1B Microtubule-associated protein 1B catalytic subunit i yer133w p37140 PPP1CB Seπne/threonine-protein phosphatase PP1-beta ynl233w p35659 DEK Dek protein catalytic subunit
I yer144c O00507 FAF-Y Probable ubiquitm carboxyl-terminal hydrolase FAF-Y ybr059c q16816 PHKG1 Phosphorylase B kinase gamma catalytic chain, skeletal muscle isoform yer144c p45974 USP5 Ubiquitin carboxyl-terminal hydrolase 5/ιsopeptιdase T ybr059c P51956 NEK3 Seπne/threonine-protein kinase NEK3 [fragment] yer144c p51784 USP11 Ubiquitm C-terminal hydrolase 11 ybrf)59c p49137 MAPKAPK-2 : Map kmase-activated protein kinase 2 yer144c P54578 USP14 Queuine tRNA-πbosyl transferase/tRNA-guanme ybr059c p51955 NEK2 Seπne/threonine-protein kinase NEK2 transglycosylase yer144c q02817 MUC2 Intestinal mucm 2/mucιn 2 ybr059c p15735 PHKG2 Phosphorylase kinase, testis/hver, gamma-2 yer144c q92995 USP13 Ubiquitm carboxyl-terminal hydrolase 13/ιsopeptιdase ybr059c q13177 PAK2 Seπne/threonine-protein kinase PAK-gamma
T-3 yer144c q93008 USP9X Probable ubiquitm carboxyl-terminal hydrolase FAF-X ybr059c p27448 P78 Putative sennd/threonine-protein kinase P78 yer144c q93009 USP7 Ubiquitm carboxyl-terminal hydrolase 7/herpesvιrus ybr059c p51957 STK2 Serine/threonme-protein kinase NRK2 associated ubiquitin-specific protease yer179w q06609 RAD51 DNA repair protein RAD51 yer179w q06609 RAD51 DNA repair protein RAD51 yer179w q14565 DMC1 Meiotic recombination protein DMC1/LIM15 homolog yer179w q14565 DMC1 Meiotic recombination protein DMC1/LIM15 homolog yflOIOc p02812 PRB2 Salivary proline-πch protein/Clone CP7 ygr136w p29354 GRB2 Growth factor receptor-bound protein 2 yflOIOc p04280 PRB1 Salivary prolme-πch protein/clone CP3 CP4, and CP5 ygr136w p06241 FYN Proto-oncogene tyrosine-protem kinase FYN/SYN yflOIOc p10161 PRB4 Salivary proline-πch protein PO [fragment]/allele M ygr136w p14317 HCLS1 Hematopoietic lineage cell specific protein yflOIOc p10162 PRB4 Salivary proline-πch protein PO [fragmenfj/allele K ygr136w p19878 NCF2 Neutrophil cytosol factor 2 NCF-2/ neutrophil NADPH oxidase factorde 2/P67-PHOX yflOIOc p17600 SYN1 Synapsm l/braιn protein 4 1 ygr136w q92794 MOZ Monocytic leukemia zinc finger protein
yflOIOc p22670 RFX1 MHC class II regulatory factor RFX1 ygr136w q15811 ITSN lntersectιn/SH3 domain-containing protein SH3P17 yflOIOc p23246 PSF PTB-associated splicing factor ygr136w p16333 NCK Cytoplasmic protein NCK yflOIOc P35637 FUS RNA-bindmg protein FUS/TLS ygr136w p46108 CRK Proto-oncogene C-CRK yflOIOc q92793 CREBBP CREB-BINDING PROTEIN ygr136w p07947 YES1 Proto-oncogene tyrosine-prote kinase YES/C-YES yflOIOc q92794 MOZ Monocytic leukemia zinc finger protein ygr136w p 15498 VAV Vav proto-oncogene yflOIOc q99217 AIH1 AMELOGENESIS IMPERFECTA 1 , HYPOPLASTIC ygrl 36w p46109 CRKL Crk-like protein
TYPE yflOIOc p02812 PRB2 Salivary proline-πch protein/Clone CP7 yor197w p02812 PRB2 Salivary proline-nch protein/Clone CP7 yflOIOc p04280 PRB1 Salivary proline-πch protein/clone CP3, CP4, and CP5 yorl 97w p04280 PRB1 Salivary proline-nch protein/clone CP3, CP4, and CP5 yflOIOc p10161 PRB4 Salivary proline-nch protein PO [fragment]/allele M yorl 97w p54253 SCA1 Ataxιn-1/Spιnocerebellar ataxia type 1 protein yflOIOc p22670 RFX1 MHC class II regulatory factor RFX1 yor197w q09472 EP300 E1A-assocιated protein P300 yflOIOc p23246 PSF PTB-associated splicing factor yor197w q93074 KIAA0192 Hypothetical protein KIAA0192 yflOIOc p35637 FUS RNA-bindmg protein FUS TLS yor197w p42858 HD Huntingtin/huntington's disease protein yflOIOc q99217 AIH1 AMELOGENESIS IMPERFECTA 1 HYPOPLASTIC yor197w q01844 EWSR1 RNA-bindmg protein EWS
TYPE yfl023w q02224 CENPE Centromenc protein E/CENP-E protein ybr154c p19388 POLR2E DNA-directed RNA polymerase II 23 kD polypeptιde/RPB25/XAP4 yfl023w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ylr200w p49454 CENPF CENP-F kinetochore protein myosin heavy chain, type B/NMMHC-B yfl023w p46100 ATRX Transcriptional regulator ATRX/X linked helicase ll/X- ylr200w q08379 G0LGA2 Golgιn-95 linked nuclear protein
I yfl023w p48681 NES Nestm ylr200w p42566 EPS15 Epidermal growth factor receptor substrate 15 υ, y !023w q02224 CENPE Centromenc protein E/CENP-E protein ylr200w q02224 CENPE Centromenc protein E/CENP-E protein
^ yfr024c-a p14317 HCLS1 Hematopoietic lineage cell specific protein ybi007c q99102 MUC4 Tracheo-bronchial mucm 4/mucιn 4 [fragment]
I yfr024c-a p16333 NCK Cytoplasmic protein NCK ybl007c p16333 NCK Cytoplasmic protein NCK yfr024c-a p29354 GRB2 Growth factor receptor-bound protein 2 ybl007c p29354 GRB2 Growth factor receptor-bound protein 2 yfr024c-a p41240 CSK Tryrosine-protein kinase CSK ybl007c p06241 FYN Proto-oncogene tyrosine-protem kinase FYN/SYN yfr024c-a p46109 CRKL Crk-like protein ybl007c p09769 M 19722 Human fgr proto-oncogene encoded p55-c-fgr protein, complete eds yfr024c-a p98171 RGC1 RHO-GAP hematopoietic protein C1 ybl007c q15811 ITSN lntersectιn/SH3 domain-containing protein SH3P17 yfr024c-a q13813 SPTA2 Spectπn alpha chain, bram/nonerythroid alpha- ybl007c p07947 YES1 Proto-oncogene tyrosine-protem kinase YES/C-YES spectπn yfr024c-a q15811 ITSN lntersectιn/SH3 domain-containing protein SH3P17 ybl007c q 14687 KIAA0182 Hypothetical protein KIAA0182 yfr024c-a p46109 CRKL Crk-like protein ygr268c q92794 MOZ Monocytic leukemia zinc finger protein yfr047c q 15274 NADC Nicotinate-nucleotide pyrophosphorylase yfr047c q 15274 NADC Nicotinate nucleotide pyrophosphorylase
[carboxylatingj/quinolinate phosphoπbosyl transferase [carboxylatιng]/quιnolιnate phosphoπbosyl transferase ygl058w p23567 UBE2B Ubiquitin-conjugating enzyme E2 17 kD ycr066w q00755 PML Probable transcription factor PML ygl058w p47986 UBE2D3 Ubiquitin-conjugatmg enzyme E2 17 kD 3 ycr066w p35227 MEL18 DNA-bindmg protein MEL-18/Zιnc finger protein 144 ygl058w p49459 UBE2A Ubiquitin-conjugating enzyme E2 17 kD/HR6A ycr066w p15918 RAG1 V(D)J recombination activating protein 1 ygl058w p50550 UBE2I Ubiquitm conjugating enzyme E2 18 kD ycr066w 015541 ZNF183 zinc finger protein 183 ygl058w p51668 UBE2D1 Ubiquitm conjugating enzyme E2 17 kD ycr066w p35226 BMI1 DNA-bindmg protein BMI1 ygl058w p51669 UBE2D2 Ubiquitm conjugating enzyme E2 17 kD 2 ycr066w p38398 BRCA1 BREAST CANCER, TYPE 1 ygl058w p51965 UBE2E1 Ubiquitm conjugating enzyme E2 21 kD UBCH6 ycr066w p29591 PML Probable transcription factor PML
ygl058w p56554 UBE2G2 Ubiquitin-conjugating enzyme E2 G2 ycr066w p29592 PML Probable transcription factor PML ygl058w q 16781 UBE2N Ubiquitin-conjugating enzyme E2-17 kD ycr066w p29590 PML Probable transcription factor PML ygl058w q99462 UBE2G1 Ubiquitin-conjugating enzyme E2 G1 ycr066w p29593 PML Probable transcription factor PML yg!112c p49848 TAF2E Transcription initiation factor TFIID 70 kD Ymr236w q 16594 TAF2G Transcription initiation factorTFIID 31 kD subunit subunιt/TAFII-70 ygl112c p49848 TAF2E Transcription initiation factor TFIID 70 kD Ymr255w p51825 MLLT2 AF-4 protein subunιt/TAFII-70 ygl115w P54619 PRKAG1 5'-AMP-actιvated protein kinase, gamma-1 subunit yer027c p10451 SPP1 Osteopontm [precursor] ygl122c p42858 HD Huntingtm/huntington's disease protein ykr026c q14232 ELF2B1 Translation initiation factor el F-2B alpha subunit ygl122c q14814 MEF2D Myocyte-specific enhancer factor 2D ykr026c p49770 EIF2B2 Translation initiation factor EIF-2B beta subunιt S20ιιι15 ygl150c 014647 CHD2 Chromodomain-helicase-DNA-binding protein 2/CHD- ydl002c p17480 UBTF Nucleolar transcription factor 1/upstream binding factor
2 1/UBF-1 ygl150c p19338 NCL Nucleolm/protein C23 ydl002c p36402 TCF7 T-cell-specific transcription factor 1 TCF-1 ygl150c p28370 SMARCA1 Possible global transcription activator SNF2L1 ydl002c q00059 TCF6L1 Mitochondπal transcπption factor 1 ygl150c p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- ydl002c p26583 HMG2 High mobility group protein HMG2/HMG-2 hnked nuclear protein ygl150c p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM ydl002c q06945 SOX4 Transcription factor SOX-4 ygl150c p51532 SMARCA4 Possible global transcription activator SNF2L4/BRG-1 ydl002c q08945 SSRP1 Structure-specific recognition protein 1 protein ygl150c q03468 CSB Excision repair protein ERCC-6/cockayne syndrome ydl002c p09429 HMG1 High mobility group-1 protein protein CSB
I ygl150c p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- yor355w q14669 TRIP12 Thyroid receptor interacting protein 12/KIAA0045 on linked nuclear protein
∞ ygl150c q03468 CSB Excision repair protein ERCC-6/cockayne syndrome yor355w p42568 MLLT3 AF-9 protein
I protein CSB ygl155w p49356 FNTB famesyl-protein transferase beta subunit ykl019w p49354 FNTA Protein farnesyltransferase alpha-subumt ygl155w p53609 PGGT1B Geranylgeranyltransferase type I beta-subunit ykl019w q92696 RABGGTA RAB geranylgeranyl transferase alpha subunit ygl158w p15735 PHKG2 Phosphorylase kinase, testis/liver, gamma-2 ylr113w p53779 MAPK10 Mitogen-activated protein kinase 10 ygl158w p27448 P78 Putative seπnd/threonine-protein kinase P78 ylr113w p53778 MAPK12 Mitogen-activated protein kinase 12/ERK6/extracellular signal-regulated kinase 6 yg!158w p49137 MAPKAPK-2 Map kmase-activated protein kinase 2 ylr113w p27361 MAPK3 Mitorjen-activated protein kinase 3/extracellular signal- regulated kinase 1 ygl158w p51812 RPS6KA3 Ribosomal protein S6 kinase II alpha 3/ιnsulιn- ylr113w q15759 MAPK11 Mitogen-activated protein kinase 11 stimulated protein kinase 1 ygl158w p53355 DAPK1 Death-associated protein kinase 1/DAP-kιnase 1 ylr113w p28482 MAPK1 Mitogen-activated protein kinase 1 /extracellular signal- regulated kinase 2 ygl158w q14012 CAMK1 Calcium/calmodulin-dependent protein kinase type I ylr113w q16539 MAPK14 Mitogen-activated protein kinase 14/CSBP ygl158w q16566 CAMK4 calcium/calmodulin-dependent protein kinase IV ylr113w q13164 MAPK7 Mitogen-activated protein kinase 7/ERK5 ygl158w q16816 PHKG1 Phosphorylase B kinase gamma catalytic chain, ylr113w p45984 MAPK9 Mitogen activated protein kinase 9 skeletal muscle isoform ygl189c q06722 RPS26 Ribosomal protein S26 ylr435w p27797 CALR Calretιculιn/52kD πbonucleoprotein autoantigen RO/SS-
A ygl192w p04062 GBA Glucosylceramidase ybr057c p49454 CENPF CENP-F kinetochore protein
ygl237c p23511 NFYA CAAT-box DNA binding protein subunit B ybl021c p25208 NFYB CCAAT-bmdmg Transcription factor subunit A/CAAT- box DNA binding protein subunit B ygl237c P54259 DRPLA Atrophιn-1/dentatorubral-pallιdoluysιan atrophy protein ybl021c q01658 DR1 TATA binding protein-associated phosphoprotein ygl242c P20749 BCL3 B-cell lymphoma 3-encoded protein ykr099w p 10244 MYBL2 Myb-related protein B/B-myb ygl242c P53355 DAPK1 Death-associated protein kinase 1/DAP-kιnase 1 ykr099w p 10242 MYB MYB proto-oncogene protein ygl242c q01484 ANK2 Ankyπn, brain variant 1/ankynn B ykr099w p25054 APC Adenomatous polyposis coli protein ygl242c q01485 ANK2 Brain ankyπn variant 2 ykr099w p10243 MYBL1 Myb-related protein A A-myb ygl254w P08151 GLI1 GLI protein/zinc finger protein GLI1 ygr047c p19338 NCL Nucleolin/protem C23 ygl254w p41182 BCL6 B-cell lymphoma 6 protein/zinc finger protein 51 ygr047c p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM ygl254w P41182 BCL6 B-cell lymphoma 6 protein/zinc finger protein 51 yor039w p13862 CSNK2B Casein kinase II beta subunit ygrOIOw q92764 KRTHA5 Keratin, type I cuticular HA5/haιr keratin, type I HA5 ygrOIOw q92764 KRTHA5 Keratin, type I cuticular HA5/haιr keratin, type I HA5 ygr014w P35658 NUP214 Nuclear pore complex protein NUP214/CAN protein yιl144w p15924 DSP Desmoplakin I and II ygr014w q02817 MUC2 Intestinal mucm 2/mucιn 2 yιl144w q02224 CENPE Centromenc protein E/CENP-E protein ygr014w q14157 KIAA0144 Hypothetical protein KIAA0144 yιl144w p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform ygr014w q99102 MUC4 Tracheo-bronchial mucm 4/mucιn 4 [fragment] yιl144w p49454 CENPF CENP-F kinetochore protein ygr017w p 17480 UBTF Nucleolar transcπption factor 1/upstream binding ylr403w q92785 REQ Zinc-finger protein UBI-D4/apoptosιs response zinc factor 1/UBF-1 finger protein requiem ygr058w P07384 CAPN1 Calpain 1 , large [catalytic] subunit/calcium activated ygr058w p07384 CAPN1 Calpain 1 , large [catalytic] subunit calcium activated neutral prote ase neutral protemase ygr058w p 17655 CAPN2 Ca2-actιvated neutral proteinase/calpam 2, Large ygr058w p17655 CAPN2 Ca2-actιvated neutral proteinase/calpam 2, Large
[catalytic] subunit [catalytic] subunit
1 ygr058w p20807 CAPN3 Calpain P94, large [catalytic] subunit/CANP ygr058w p20807 CAPN3 Calpain P94, large [catalytic] subunit/CANP
£ ygr058w P28676 GCA Grancalcin ygr058w p28676 GCA Grancalcin ygr058w P30626 SRI Sorcm ygr058w p30626 SRI Sorcm ygr058w P07384 CAPN1 Calpain 1 , large [catalytic] subunit/calcium activated ygr136w p46108 CRK Proto-oncogene C-CRK neutral protemase ygr058w P17655 CAPN2 Ca2-actιvated neutral proteinase/calpam 2, Large ygrl 36w p06241 FYN Proto-oncogene tyrosine-protem kinase FYN/SYN
[catalytic] subunit ygr058w P20807 CAPN3 Calpain P94, large [catalytic] subunit/CANP ygr136w p29354 GRB2 Growth factor receptor-bound protein 2 ygr058w P28676 GCA Grancalcin ygr136w p46109 CRKL Crk-|ιke protein ygr058w P30626 SRI Sorcm ygrl 36w p14317 HCLS1 Hematopoietic lineage cell specific protein ygr058w P07384 CAPN1 Calpain 1 , large [catalytic] subunit/calcium activated ylr113w q13164 MAPK7 Mitogen-activated protein kinase 7/ERK5 neutral protemase ygr058w p 17655 CAPN2 Ca2-actιvated neutral proteinase/calpam 2, Large ylr113w p53778 MAPK12 Mitogen-activated protein kinase 12/ERK6/extracellular
[catalytic] subunit signal-regulated kinase 6 ygr058w P20807 CAPN3 Calpain P94, large [catalytic] subunit/CANP ylr113w p45984 MAPK9 Mitogen activated protein kinase 9 ygr058w P28676 GCA Grancalcin ylr113w p28482 MAPK1 Mitogen-activated protein kinase 1 /extracellular signal- regulated kinase 2 ygr058w p30626 SRI Sorcm ylr113w p53779 MAPK10 Mitogen-activated protein kinase 10 ygr058w P07384 CAPN1 Calpain 1, large [catalytic] subunit calcium activated ynl047c q92636 NSMAF Protein fan/factor asociated with n-smase activation neutral protemase ygr058w p28676 GCA Grancalcin ynl047c q99418 ARNO ARF nucleotide-binding site opener/ARNO protem/ARF exchange factor
ygr108w p14635 CCNB1 G2/mιtotιc-specιfιc cyclin B1 ybr135w p10275 AR Androgen receptor ygr119c p23490 LOR Loπcrin ygl172w p35658 NUP214 Nuclear pore complex protein NUP214/CAN protein ygr119c p35637 FUS RNA-bindmg protein FUS/TLS ygl172w p49790 NUP153 Nuclear pore complex protein NUP153 ygr119c p35658 NUP214 Nuclear pore complex protein NUP214/CAN protein ygl172w p09651 HNRPA1 Heterogenous nuclear πbonucleoprotein A1/helιx- destabilizmg protein/smgle-strand binding protem/HNRNP core protein A1 ygr119c p37198 NUP62 Nuclear pore glycoprotein P62 ygl172w p23490 LOR Loπcrin ygr119c p49790 NUP153 Nuclear pore complex protein NUP153 ygl172w p52948 NUP98 Nuclear pore complex protein NUP98/Nucleoporιn NUP
98 ygr119c p52948 NUP98 Nuclear pore complex protein NUP98/Nucleopoπn ygl172w p13645 KRT10 Keratin, type I cytoskeletal 10
NUP 98 ygr119c p23490 LOR Loricπn yjl041w q14093 CYLC2 Cy cin II ygr119c p35637 FUS RNA-bindmg protein FUS/TLS yjl041w p35663 CYLC1 Cyclin I ygr119c p35658 NUP214 Nuclear pore complex protein NUP214/CAN protein yjl041w p35658 NUP214 Nuclear pore complex protein NUP214/CAN protein ygr119c p37198 NUP62 Nuclear pore glycoprotein P62 yjl041w p37198 NUP62 Nuclear pore glycoprotein P62 ygr119c p49790 NUP153 Nuclear pore complex protein NUP153 yjl041w p49790 NUP153 Nuclear pore complex protein NUP153 ygr119c p52948 NUP98 Nuclear pore complex protein NUP98/Nucleoporιn yjl041w P52948 NUP98 Nuclear pore complex protein NUP98/Nucleoporιn NUP
NUP 98 98 ygr119c p23490 LOR Loπcrin ylr423c p 15924 DSP Desmoplakin I and II ygr119c p35637 FUS RNA-bindmg protein FUS/TLS ylr423c p49454 CENPF CENP-F kinetochore protein ygr119c p35658 NUP214 Nuclear pore complex protein NUP214/CAN protein ylr423c p30622 RSN Restin ygr119c p37198 NUP62 Nuclear pore glycoprotein P62 ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ygr119c p49790 NUP153 Nuclear pore complex protein NUP153 ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ygr119c p52948 NUP98 Nuclear pore complex protein NUP98/Nucleoporιn ylr423c p12270 TPR Nucleoprotein TPR
NUP 98 ygr119c p37198 NUP62 Nuclear pore glycoprotein P62 Ymr236w q 16594 TAF2G Transcription initiation factorTFIID 31 kD subunit ygr144w q16134 ETFDH Electron transfer flavoprotem-ubiquinone ygr144w q16134 ETFDH Electron transfer flavoprotein-ubtqumoπe oxidereductase oxidereductase ygrl 55w p35520 CBS Cystathionine beta-synthase ycr086w p39880 CUTL1 CCAAT displacement protem/CDP ygr229c p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- ykrt)99w p10243 MYBL1 Myb-related protein A/A-myb hnked nuclear protein I ygr229c p46821 MAP1B Microtubule-associated protein 1 B ykr099w p25054 APC Adenomatous polyposis coli protein ygr229c q05682 CALD1 Caldesmon/CDM ykr099w p10242 MYB MYB proto-oncogene protein ygr229c q07283 THH Tπchohyalin ykr099w p 10244 MYBL2 Myb-related protein B/B-myb ygr250c p11940 PABPL1 PolyA binding protein 1 yιr001c p26378 ELAVL4 Paraneoplastic encephalomyelitis antigen 3 ygr250c p26378 ELAVL4 Paraneoplastic encephalomyelitis antigen 3 yιr001c q01844 EWSR1 RNA-bindmg protein EWS ygr250c p29558 RBMS1 Single-stranded DNA binding protein MSSP-1 yιr001c p35637 FUS RNA-bindmg protein FUS/TLS ygr250c p33240 CSTF2 Cleavage stimulation factor, 64 kD subunit yirOOIc p33240 CSTF2 Cleavage stimulation factor, 64 kD subunit ygr250c p38159 HNRPG Heterogeneous nuclear πbonucleoprotein G/HNRNP yιr001c q01085 TIAL1 Nucleolysm TIAR
G/glycoprotem P43 ygr250c p98179 RBM3 Putative RNA binding protein 3 yirOOIc p11940 PABPL1 PolyA binding protein 1 ygr250c q01085 TIAL1 Nucleolysm TIAR yirOOIc p08621 SNRP70 U1 small nuclear πbonucleoprotein 70kD ygr250c q15427 SAP49 Spliceosome associated protein 49/SAP49 yirOOIc p98179 RBM3 Putative RNA binding protein 3
ygr267c p30793 GCH1 GTP cyclohydrolase I ygr267c p30793 GCH1 GTP cyclohydrolase I yhl004w p08865 LAMR1 Colon carcinoma laminin-binding protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein yhl018w p80095 PCBD Pteπn-4-alpha-carbιnolamιne dehydratase yhl018w p80095 PCBD PTERIN-4-ALPHA-CARBINOLAMINE DEHYDRATASE yhl019c p20172 CLAPM1 Clathπn coat assembly protein AP50/KIAA0109 gene ykl135c p21851 CLAPB1 Beta adaptin yhl019c p53677 P47B Clathπn coat assembly protein AP47 homolog 2 ykl135c q 10567 ADTB1 Beta-adapt 1 yhl027w p08047 SP1 Transcription factor SP1 [fragment] yjl056c p52745 ZNF36 Zinc finger protein 36/zιnc finger protein KOX18 yhl027w p08151 GLI1 GLI protein/zinc finger protein GLI1 yjl056c p52740 ZNF132 Zinc finger protein 132 yhl027w p 10070 GLI2 Tax helper protein 2/zιnc finger protein GLI2 yjl056c p52736 ZNF133 Zinc finger protein 133 yhl027w p10071 GLI3 Zinc finger protein GLI3 yjl056c p52742 ZNF135 Zinc finger protein 135 yhl027w p11161 EGR2 Early growth response protein 2/EGR-2 yjl056c q15072 ZNF146 Zinc finger protein OZF yhl027w p18146 EGR1 Early growth response protein 1 yjl056c q 16600 ZNF239 Zinc finger protein 239/HOK-2 yhl027w p19544 WT1 Wilms' tumor protwιn/WT33 yjl056c p17032 ZNF37A Zinc finger protein 37A [fragment] yhl027w p28160 ZNF43 Zinc finger protein 43/Zιnnc protein HTF6 yjl056c q13360 ZNF177 Zinc finger protein 177 yhl027w q02446 SP4 Transcription factor SP4/SPR-1 yjl056c p51786 ZNF157 Zinc finger protein 157 yhl027w q05215 EGR4 Early growth response protein 4 yjl056c q06730 ZNF33A Zinc finger protein 33A KIAA0065 yhl027w q06889 EGR3 Early growth response protein 3 yjl056c q05516 ZNF145 Zinc finger protein PLZF/zmc finger protein 145 yhr016c p06241 FYN Proto-oncogene tyrosine-protem kinase FYN/SYN Ymr255w q03111 ENL ENL protein yhr016c p14317 HCLS1 Hematopoietic lineage cell specific protein Ymr255w p29375 RBBP2 RBBP-2/retιnoblastoma binding protein 2 yhr016c p16333 NCK Cytoplasmic protein NCK Ymr255w p11387 TOP1 Topoisomerase I yhr016c p29354 GRB2 Growth factor receptor-bound protein 2 Ymr255w p46821 MAP1 B Microtubule-associated protein 1B
I yhr016c p41240 CSK Tryrosine-protein kinase CSK Ymr255w p51825 MLLT2 AF-4 protein yhr016c q13813 SPTA2 Spectπn alpha chain bram/nonerythroid alpha- Ymr255w 014647 CHD2 Chromodomain-helicase-DNA-binding protein 2/CHD-2 spectπn
1 yhr016c q15811 ITSN lntersectιn/SH3 domain-containing protein SH3P17 Ymr255w p46939 UTRN Utrophm yhr039c p30837 ALDH5 Mitochondπal aldehyde dehydrogenase X ydr480w p17931 LGALS3 Galectιn-3/lgE-bιndιng protein yhr060w p25789 PSMA4 Proteasome subunit C9 ylr447c q02547 ATP6E Vacuolar ATP synthase subunit AC39 yhr084w p24928 POLR2A DNA-directed RNA polymerase II largest subunit ydr480w p17931 LGALS3 Galectιn-3/lgE-bιndιng protein yhr108w q03001 BPAG1 Bullous 230 kDa pemphigoid antigen 1 ylr423c q02224 CENPE Centromenc protein E/CENP-E protein yhr111w p22314 UBE1 Ubiquitm activating enzyme E1 yhr111w p22314 UBE1 Ubiquitm activating enzyme E1 yhr111w p41226 UBE1 L Ubiquit -activating enzyme E1 homolog yhr111w p41226 UBE1 L Ubiquitm-activating enzyme E1 homolog yhr114w p07332 FES C-FES/ proto-oncogene tyrosine-protem kinase ylr423c p49454 CENPF CENP-F kinetochore protein
FES/FPS yhr114w p12270 TPR Nucleoprote TPR ylr423c p05787 KRT8 Keratin, type II cytoskeletal 8/cytokeratιn 8/K8 CK8 yhr114w p12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle yhr114w p14317 HCLS1 Hematopoietic lineage cell specific protein ylr423c p 15924 DSP Desmoplakin I and II yhr114w p16333 NCK Cytoplasmic protein NCK ylr423c p30622 RSN Restin yhr114w p16591 FER Tyrosme kinase FER ylr423c q02224 CENPE Centromenc protein E/CENP-E protein yhr114w p98171 RGC1 RHO-GAP hematopoietic protein C1 ylr423c p12270 TPR Nucleoprotem TPR yhr114w q14247 CTTN SRC substrate cortactin/amplaxin ylr423c p11047 LAMC1 Laminin gamma-1 chain [precursor]/lamιnιn B2 chain yhr114w q15811 ITSN lntersectιn/SH3 domain-containing protein SH3P17 ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein yhr143w-a p53803 POLR2K DNA-directed RNA polymerases I, II, and III 7 0 kD ylr423c q02224 CENPE Centromenc protein E/CENP-E protein polypeptide yhr171w p22314 UBE1 Ubiquitm activating enzyme E1 ynr007c p 19338 NCL Nucleolin/protem C23
yhr204w P33908 MA12 Mannosyl-oligosacchaπde alpha-1 ,2-mannosιdase ygl030w P04645 RPL30 Ribosomal protein L30 yιl013c p45844 ABCG1 White protein homolog ydr174w P09429 HMG1 High mobility group-1 protein yιl074c P56545 CTBP2 C-terminal binding protein 2 yer081w P56545 CTBP2 C-terminal binding protein 2 yιt074c q13363 CTBP1 C-terminal binding protein 1 yer081w q 13363 CTBP1 C-terminal binding protein 1 yιl074c P56545 CTBP2 C-termmal binding protein 2 yιl074c P56545 CTBP2 C-terminal binding protein 2 yιl074c q 13363 CTBP1 C-terminal binding protein 1 yιl074c q13363 CTBP1 C-terminal binding protein 1 yιl105c P20226 TBP TATA-binding protein/transcription initiation factor yer179w q 14565 DMC1 Meiotic recombination protein DMC1/LIM15 homolog
TFIID yιl105c q93074 KIAA0192 Hypothetical protein KIAA0192 yer179w q06609 RAD51 DNA repair protein RAD51 yιl105c P20226 TBP TATA-binding protein/transcription initiation factor ynl047c q99418 ARNO ARF nucleotide-binding site opener/ARNO protein/ARF
TFIID exchange factor yιl105c q93074 KIAA0192 Hypothetical protein KIAA0192 ynl047c q92636 NSMAF Protein fan/factor asociated with n-smase activation yιr005w P33240 CSTF2 Cleavage stimulation factor, 64 kD subunit ygl174w P35663 CYLC1 Cyclin I yjl036w P08670 VIM Vimentin ylr423c P30622 RSN Restin yjl036w p 12882 MYSS Myosin heavy chain skeletal muscle, light ylr423c P15924 DSP Desmoplakin I and II meromyosin region yjl036w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ylr423c P49454 CENPF CENP-F kinetochore protein myosin heavy chain, type B/NMMHC-B yjl036w P35749 MYH11 Myosin heavy chain, smooth muscle isoform/SMMHC ylr423c P12270 TPR Nucleoprotem TPR
[FRAGMENT] yjl036w p48681 NES Nestm ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle
1 yjl036w p49454 CENPF CENP-F kinetochore protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein cn yjl036w q 15036 KIAA0064 Hypothetical protein KIAA0064 ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein
M yjl092w P35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ydr510w P55854 SMT3H1 Ubiquitin-like protein SMT3A
1 myosin heavy chain, type B/NMMHC-B yjl092w P35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular yor355w P42568 MLLT3 AF-9 protein myosin heavy chain, type B/NMMHC-B yjl110c P23769 GATA2 Endothelial transcription factor GATA-2 ynl021w q 13547 HDAC1 Histone deacetylase 1/HD1 yjl110c P23771 GATA3 Trans-acting T-cell specific transcription factor GATA- ynl021w q92769 HDAC2 Histone deacetylase 2/HD2
3 yjl110c P43694 GATA4 Transcription factor GATA-4 ynl021w 015379 DHAC3 Histone deacetylase 3 yjl110c q92908 GATA6 Transcription factor GATA-6 ynl021w P56524 KIAA0288 Hypothetical protein KIAA0288 yjl 112w P11016 GNB2 Guanine nucleotide-binding protein beta subunit 2 yllOOIw q05193 DNM1 Dynamιn-1 yjl112w P43034 PAFAH1B1 Platelet-activating factor acetylhydrolase IB alpha yllOOIw P20591 MX1 Interferon-regulated resistance GTP-bmding protein subunit MXA/interferon-mduced protein P78 yjl 112w q 12788 SAZD WD-repeat protein SAZD yllOOIw P50570 DNM2 Dynamιn-2 yjl112w q 15542 TAF2D Transcription initiation factor TFIID 100 Kd yllOOIw P20592 MX2 Interferon-regulated resistance GTP-bmding protein subunιt/TAFII-100 TAFII100 MXB yjl 137c P46976 GYG Glycogenιn-1 yjl137c P46976 GYG Glycogenιn-1 ykl028w P07199 CENP-B Major centromere autoantigen B/centromere protein B ydr311w P32780 BTF2 Basic transcription factor 62kD subunit ykl028w P07199 CENP-B Major centromere autoantigen B/centromere protein B ykr062w P29084 GTF2E2 Transcription factor HE beta subunit ykl067w O00746 NME4 Nucieoside-diphosphate kinase ykl067w O00746 NME4 Nucleoside diphosphate kinase, mitochondrial ykl067w p15531 NME1 Nucleoside-diphosphate kinase A ykl067w P15531 NME1 Nucleoside-diphosphate kinase A
ykl067w p22392 NME2 Nucleoside diphosphate kinase B/NDP kinase ykl067w p22392 NME2 Nucleoside diphosphate kinase B/NDP kinase B/nm23- B/nm23-H2 H2 ykl142w p07942 LAMB1 Lammin beta-1 chain/Laminin B1 chain yk!142w p07942 LAMB1 Laminm beta-1 chain/Laminin B1 chain ykl142w P07942 LAMB1 Laminm beta-1 chain/Laminin B1 chain Ymr165c p51825 MLLT2 AF-4 protein ykl166c p14619 PRKG1 Type I beta cGMP-dependent protein kinase yιl033c P10644 PRKAR1A cAMP-dependent protein kinase regulatory subunit type l-alpha ykl166c p17612 PRKACA cAMP-dependent protein kinase catalytic subunit type i yιl033c q16281 CNCG3 CNG3/cyclιc nucleotide-gated cation channel 3 alpha [fragment] ykl166c p22694 PRKACB Testis-specific cAMP-dependent protein kinase yιl033c q 14028 CNG4 Cyc c-nucleotide-gated cation channel 4 catalytic subunit C-beta isoform ykl166c p23443 RPS6KB1 P70 ribosomal S6 kinase alpha-ll yιl033c p29973 CNCG1 CGMP-gated cation channel protein/cyclic nucleotide gated channel, photoreceptor/cyclic-nucleotide-gated cation channel1/CNG channel 1/CNG1/CNG-1 ykl166c p24723 PRKCH Protein kinase C, ETA type/protein kinase C-L yιl033c p31321 PRKAR1B cAMP-dependent protein kinase regulatory subunit Rl- beta ykl166c p31749 AKT1 RAC-alpha seπne/threonine kinase yιl033c P13861 PRKAR2A cAMP-dependent protein kinase type ll-alpha regulatory chain ykl166c p31751 AKT2 RAC-beta seπne/threonine kinase yιl033c p31323 PRKAR2B cAMP-dependent protein kinase subunit Rll-beta ykl166c p51812 RPS6KA3 Ribosomal protein S6 kinase II alpha 3/ιnsulιn- yιl033c p14619 PRKG1 Type I beta cGMP-dependent protein kinase stimulated protein kinase 1
I ykr026c p49770 EIF2B2 Translation initiation factor EIF-2B beta ykr026c p49770 EIF2B2 Translation initiation factor EIF-2B beta subunιt S20ιιι15
0^ subunιt/S20ιιι15 ω ykr026c q14232 ELF2B1 Translation initiation factor elF-2B alpha subunit ykr026c q14232 ELF2B1 Translation initiation factor elF-2B alpha subunit
I ykr037c p42566 EPS15 Epidermal growth factor receptor substrate 15 ydr201w p30622 RSN Restin ykr083c p09429 HMG1 High mobility group-1 protein ykl052c p19338 NCL Nucleolin/protein C23 ykr083c p17480 UBTF Nucleolar transcription factor 1 /upstream binding ykl052c q92794 MOZ Monocytic leukemia zinc finger protein factor 1/UBF-1 yll046c p33240 CSTF2 Cleavage stimulation factor, 64 kD subunit yfr047c q 15274 NADC Nicotmate-nucleo tide pyrophosphorylase
[carboxylatιng]/quιnolιnate phosphoπbosyl transferase ylr200w p49454 CENPF CENP-F kinetochore protein Ymr052w p30622 RSN Restin ylr200w q02224 CENPE Centromeπc protein E/CENP-E protein Ymr052w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin heavy chain, type B/NMMHC-B ylr216c p05092 CYPA Peptidyl-prolyl cis-trans isomerase A cyclophilin A yιr037w p36969 GPX4 Phospholipid hydroperoxide glutathione peroxidase/PHGPX ylr216c p23284 PPIB Peptidyl-prolyl CIS-trans isomerase B yιr037w p18283 GPX2 Glutathione peroxidase-GI [precursorj/cyclophilin B ylr216c p30405 CYP3 Peptidyl-prolyl CIS-Trans isomerase/cyclophilin yιr037w p12079 GPRP Glutathione peroxidase-related protein 1 ylr216c p45877 PPIC Peptidyl-prolyl cis-trans isomerase C/cyclophilm C yιr037w p22352 GPX3 Plasma glutathione peroxidase ylr216c q08752 PPID 40 kD peptidyl-prolyl CIS-TRANS yιr037w p07203 GPX1 Glutathione peroxidase ιsomerase/cyclophιlιn-40 mRNA, complete eds ylr229c p21181 CDC42 G25K GTP-bmding protein ydl135c p52565 ARHGDIA Rho GDP-dissociation Inhibitor 1 ylr229c p25763 CDC42 GTP-bmding protein G25K, placental isoform ydl135c p52566 ARHGDIB Rho GDP-dissociation inhibitor 2 ylr245c p32320 CDA Cytidine deammase ylr245c p32320 CDA Cytidine deammase ylr305c p42336 PIK3CA Phosphatidylmositol 3-kιnase catalytic subunit, alpha yor355w q 14669 TRIP12 Thyroid receptor interacting protein 12/KIAA0045
isoform ylr305c p42345 FRAP FKBP-rapamycm associated protein yor355w p42568 MLLT3 AF-9 protein ylr423c p 15924 DSP Desmoplakin I and II ygr120c p30622 RSN Restin ylr423c p49454 CENPF CENP-F kinetochore protein ygr 20c p49454 CENPF CENP-F kinetochore protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ygr120c p04114 APOB Apolipoprote B ylr423c p05787 KRT8 Keratin, type II cytoskeletal 8/cytokeratιn 8/K8/CK8 ylr423c p05787 KRT8 Keratin, type II cytoskeletal 8/cytokeratιn 8/K8/CK8 ylr423c p11047 LAMC1 Laminm gamma-1 chain [precursor]/lamιnιn B2 chain ylr423c p11047 LAMC1 Laminm gamma-1 chain [precursor]/lamιnιn B2 chain ylr423c p12270 TPR Nucleoprotem TPR ylr423c p12270 TPR Nucleoprotem TPR ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ylr423c p 15924 DSP Desmoplakin I and II ylr423c p15924 DSP Desmoplakin I and II ylr423c p30622 RSN Restin ylr423c P30622 RSN Restin ylr423c p49454 CENPF CENP-F kinetochore protein ylr423c p49454 CENPF CENP-F kinetochore protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ylr424w P49454 CENPF CENP-F kinetochore protein ykr022c p49454 CENPF CENP-F kinetochore protein ylr424w p52756 LUCA15 Putative tumor suppressor LUCA15 ykr022c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ylr424w P98175 DXS8237E DXS8237E protein ykr022c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin heavy chain, type B/NMMHC-B ylr429w p31146 C0R01 Coronin-like Protein p57 ydr328c p07199 CENP-B Major centromere autoantigen B/centromere protein B ylr429w p43034 PAFAH1B1 Platelet-activating factor acetylhydrolase IB alpha ydr328c p34991 TCEB1L Cyclin A/CDK2-assocιated p19 subunit
I ylr429w p46821 MAP1B Microtubule-associated protein 1 B ydr328c p17480 UBTF Nucleolar transcription factor 1/upstream binding factor
1/UBF-1
*" ylr429w q16576 RBBP7 Histone acetyl transferase type B subunit ydr328c p19338 NCL Nucleolin/protem C23 1 2/retιnoblastoma-bιndιng protein ylr432w P12268 IMPDH2 Inosine monophosphate dehydrogenase 2 ydr167w q12962 TAF2H Transcription initiation factor TFIID 30 Kd subunit TAFII-
30 TAFII30 ylr432w P12268 IMPDH2 Inosine monophosphate dehydrogenase 2 ykr026c q14232 ELF2B1 Translation initiation factor elF-2B alpha subunit ylr432w p20839 IMPDH1 lnosιne-5'-monophosphate dehydrogenase 1/IMP ykr026c p49770 EIF2B2 Translation initiation factor EIF-2B beta subunιt S20ιιι15 dehydrogenase 1/IMPDH-l/IMPD I ylr433c p05323 PPP2CA Seπne/threonine protein phosphatase PP2A-alpha, ynl047c q99418 ARNO ARF nucleotide-binding site opener/ARNO protem/ARF catalytic subunit exchange factor ylr433c q08209 PPP3CA Seπne/threonine protein phosphatase 2B catalytic ynl047c q92636 NSMAF Protein fan/factor aso ated with n-smase activation subunit Alpha isoform/calmodulin-dependent calcineuπn A subunit, alpha subunit ylr438w p04181 OAT Ornithine ammotransferase ygrOIOw q92764 KRTHA5 Keratin, type I cuticular HA5/haιr keratin, type I HA5 ylr438w p04181 OAT Ornithme ammotransferase yhl025w p20226 TBP TATA-binding protein/transcription initiation factor TFIID yml015c p52655 GTF2A1 Transcription initiation factor MA alpha and beta ydr167w q12962 TAF2H Transcription initiation factor TFIID 30 Kd subunit TAFII- chaιns/TFIIA-42 30/TAFII30 yml015c P52655 GTF2A1 Transcription initiation factor HA alpha and beta ydr174w p09429 HMG1 High mobility group-1 protein chaιns/TFIIA-42 yml015c q 15544 TAF2I Transcription initiation factor TFIID 28 kD subunit ydr174w p26583 HMG2 High mobility group protein HMG2/HMG-2
yml088w p46100 ATRX Transcriptional regulator ATRX X-linked helicase ll/X- ydr328c p07199 CENP-B Major centromere autoantigen B/centromere protein B linked nuclear protein yml094w p49454 CENPF CENP-F kinetochore protein ylr200w q02224 CENPE Centromenc protein E/CENP-E protein yml094w q99471 MM-1 C-myc binding protein MM-1 ylr200w p49454 CENPF CENP-F kinetochore protein yml114c q02832 BLSA B-lymphocyte antigen/B-lymphocyte surface antigen ydr167w q 12962 TAF2H Transcription initiation factor TFIID 30 Kd subunit/TAFII-
30/TAFII30 ymr032w p02533 KRT14 Keratin, type I cytoskeletal 14 ylr423c p49454 CENPF CENP-F kinetochore protein ymr032w p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ymr052w p30622 RSN Restin yfrOOδw p12270 TPR Nucleoprotem TPR ymr052w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular yfrOOδw q02224 CENPE Centromenc protein E/CENP-E protein myosin heavy chain, type B/NMMHC-B ymr068w p20749 BCL3 B-cell lymphoma 3-encoded protein yιl105c q10571 MN1 Probable tumor suppressor protein MN1 ymr068w q01484 ANK2 Ankyπn, brain variant 1/ankyπn B yιl105c p20226 TBP TATA-binding protein/transcription initiation factor TFIID ymr068w q01485 ANK2 Brain ankyπn variant 2 yιl105c q93074 KIAA0192 Hypothetical protein KIAA0192 ymr077c p12270 TPR Nucleoprotem TPR ykl052c P19338 NCL Nucleolin/protem C23 ymr077c p35579 MYH9 Myosin heavy chain, nonmuscle type A/cellular ykl052c q92794 MOZ Monocytic leukemia zinc finger protein myosin heavy chain, type A/NMMHC-A ymr091c p07199 CENP-B Major centromere autoantigen B/centromere protein B yfr037c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ymr093w 014727 APAF1 Apoptotic protease activating factor 1/APAF-1 ydr398w p 17480 UBTF Nucleolar transcription factor 1/upstream binding factor 1/UBF-1 ymr093w p25388 GNB2-RS1 Guanine nucleotide-binding protein beta subunit-like ydr398w p07199 CENP-B Major centromere autoantigen B/centromere protein B protein 12 3
< ymr093w p35606 COPP Beta subunit of coatomer complex ydr398w p27824 CANX Calnexιn/IP90 ymr093w q13610 PWP1 Periodic tryptophan protein 1 homolog/keratinocyte ydr398w P39687 PHAP1 HLA-DR associated protein I protein IEF SSP 9502 ymr093w q 15542 TAF2D Transcription initiation factor TFIID 100 kD ydr398w q01105 SET Set protein/ HLA-DR associated protein ll/PHAPII subunιt/TAFII-100/TAFII100 ymr102c p25388 GNB2-RS1 Guanine nucleotide-binding protein beta subunit-like ynl218w p35249 RFC4 Activator 1 37 kD subunit/rephcation factor C, 37-kDa protein 12 3 subunit ymr102c p43034 PAFAH1B1 Platelet-activating factor acetylhydrolase IB alpha ynl218w p35250 RFC2 Actwator 1 40 kD subunit/rephcation factor C, 40 kDa subunit subunit ymr102c p53621 COPA Coatomer alpha subunit ynl218w p40937 RFC5 Activator 1 36 kD subunit/rephcation factor C, 36-kDa subunit ymr102c q13610 PWP1 Periodic tryptophan protein 1 homolog/keratinocyte ynl218w p35251 RFC1 Replication factor C large subunit/activator 1140 Kd protein IEF SSP 9502 subunit ymr210w p08910 PHS1-2 PHS1-2 with ORF homologous to membrane receptor ykl142w p07942 LAMB1 Laminm beta-1 chain/Laminin B1 chain proteins ymr212c q14156 KIAA0143 Hypothetical protein KIAA0143 ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ymr255w 014647 CHD2 Chromodomain-helicase-DNA-binding protein 2/CHD- ygl122c q92794 MOZ Monocytic leukemia zinc finger protein
2 ymr255w p11387 TOP1 Topoisomerase I ygl122c q93074 KIAA0192 Hypothetical protein KIAA0192 ymr255w p29375 RBBP2 RBBP-2/retιnoblastoma binding protein 2 ygl122c p20226 TBP TATA-binding protein/transcription initiation factor TFIID ymr255w p46821 MAP1B Microtubule-associated protein 1B ygl122c p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM
ymr255w p46939 UTRN Utrophin ygl122c q10571 MN1 Probable tumor suppressor protein MN1 ymr255w P51825 MLLT2 AF-4 protein ygl122c p42858 HD Huntingtm/huntingtoπ's disease protein ymr255w q03111 ENL ENL protein ygl122c q14814 MEF2D Myocyte-specific enhancer factor 2D ymr267w q15181 P Inorganic pyrophosphatase [fragment]/Ppase ykr026c q 14232 ELF2B1 Translation initiation factor elF-2B alpha subunit ymr269w p35663 CYLC1 Cyclin I ykr026c q14232 ELF2B1 Translation initiation factor elF-2B alpha subunit ymr269w q 14093 CYLC2 Cylicm II ykr026c p49770 EIF2B2 Translation initiation factor EIF-2B beta subunιt/S20ιιι15 ymr309c p 17480 UBTF Nucleolar transcription factor 1/upstream binding ynl047c q92636 NSMAF Protein fan/factor asociated with n-smase activation factor 1/UBF-1 ymr309c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ynl047c q99418 ARNO ARF nucleotide-binding site opener/ARNO protem/ARF myosin heavy chain, type B/NMMHC-B exchange factor ymr309c P35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ynl244c p41567 sun Protein translation factor SUI1 homolog/suι1ιso1 myosin heavy chain, type B/NMMHC-B ynl023c P35555 FBN1 Fibπllin 1 [precursor] Ymr224c p49959 MRE11A Double-strand break repair protein MRE11A/MRE11 homolog ynl078w p18583 SON Son proteιn/son3 ykr048c p55209 NAP1L1 NAP-1/nucleosome assembly protein 1-lιke 1 ynl091w q02832 BLSA B-lymphocyte antigen/B-lymphocyte surface antigen ynl164c q13190 STX5A Syntaxm 5 ynl091w p46821 MAP1B Microtubule-associated protein 1B yor355w q14669 TRIP12 Thyroid receptor interacting protein 12/KIAA0045 ynl091w q02832 BLSA B-lymphocyte antigen/B-lymphocyte surface antigen yor355w p42568 MLLT3 AF-9 protein ynl091w p23327 HRC Sarcoplasmic reticulum histidine-nch calcium binding ypl229w p20265 POU3F2 Nervous-system specific octamer-bindmg transcription protein factor N-Oct 3/N-Oct 5a/N-Oct 5b ynl091w p35579 MYH9 Myosin heavy chain, nonmuscle type A/cellular ypl229w p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM myosin heavy chain, type A/NMMHC-A
C ynl091w p35749 MYH11 Myosin heavy chain, smooth muscle tsoform/SMMHC ypl229w q93074 KIAA0192 Hypothetical protein KIAA0192 n [FRAGMENT]
I ynl091w p45379 TNNT2 Troponm T, cardiac muscle isoforms ypl229w q01826 SATB1 DNA binding protein SATB1 ynl091w p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- yp!229w p54252 MJD1 Machado-joseph disease protein 1 linked nuclear protein ynl091w p46821 MAP1 B Microtubule-associated protein 1B ypl229w p42858 HD Huntingtin/huntmgton's disease protein ynl091w q02832 BLSA B-lymphocyte antigen/B-lymphocyte surface antigen ypl229w p10275 AR Androgen receptor ynl091w q05682 CALD1 Caldesmon/CDM ypl229w q10571 MN1 Probable tumor suppressor protein MN1 ynl091w q07283 THH Tπchohyalin ypl229w p20226 TBP TATA-binding protein/transcription initiation factor TFIID ynl091w q 15696 U2AF1-RS2 U2 small nuclear πbonucleoprotein auxiliary factor 35 ypl229w p54253 SCA1 Ataxιn-1/Spιnocerebellar ataxia type 1 protein kD subunit related-protein 2 ynl127w p20309 CHRM3 Muscaπnic acetylcholme receptor M3 yal016w p30153 PPP2R1A Protein phosphatase PP2A, 65Kd regulatory subunit alpha-isotype ynl127w p20309 CHRM3 Muscaπnic acetylcholme receptor M3 ykr055w p21181 CDC42 G25K GTP-bmding protein ynl154c p48729 CSNK1A1 Casein kinase I, alpha ιsoform/CKI-alpha/CK1 ycl054w q05682 CALD1 Caldesmon/CDM ynl154c p48730 CSNK1D Casein kinase I delta isoform ycl054w P35663 CYLC1 Cyclin I ynl154c p49674 CSNK1E Casein kinase I epsilon ycl054w p12883 MYH7 MYOSIN, CARDIAC, HEAVY CHAIN, BETA ynl154c p51812 RPS6KA3 Ribosomal protein S6 kinase II alpha 3/ιnsulιn- ycl054w p19338 NCL Nucleolin/protem C23 stimulated protein kinase 1 yn!154c p78368 CSNK1G2 Casein kinase I, gamma 2 isoform ycl054w p35579 MYH9 Myosin heavy chain, nonmuscle type A/cellular myosin heavy chain, type A/NMMHC-A
ynl154c p48730 CSNK1 D Casein kinase I delta isoform ycr011c p45844 ABCG1 White protein homolog ynl154c p48729 CSNK1A1 Casein kinase I, alpha ιsoform/CKI-alpha/CK1 ykl204w p10163 PRB4 PROLINE-RICH PROTEIN BstNI SUBFAMILY 4 ynl154c p48730 CSNK1 D Casein kinase I delta isoform ykl204w p48634 BAT2 Large proline-nch protein BAT2/HLA-B-assocιated transcript 2 ynl154c p49674 CSNK1 E Casein kinase I epsilon ykl204w p54259 DRPLA Atrophιn-1/dentatorubral-pallιdoluysιan atrophy protein ynl154c p51812 RPS6KA3 Ribosomal protein S6 kinase II alpha 3/ιnsulιn- ykl204w p04280 PRB1 Salivary proline-nch protein/clone CP3, CP4, and CP5 stimυlated protein kinase 1 ynl154c p78368 CSNK1 G2 Casein kinase I, gamma 2 isoform ykl204w p02812 PRB2 Salivary proline-nch protein/Clone CP7 ynl154c p48730 CSNK1 D Casein kinase I delta isoform Ymr267w q15181 PP Inorganic pyrophosphatase [fragmeπt]/Ppase ynl154c p48730 CSNK1 D Casein kinase I delta isoform yor355w p42568 MLLT3 AF-9 protein ynl154c p49674 CSNK1 E Casein kinase I epsilon yor355w q14669 TRIP12 Thyroid receptor interacting protein 12/KIAA0045 ynl189w p35222 CTNNB1 Beta-catenin ybr252w p33316 DUT Deoxyuπdine tπphosphatase nucleotidohydrolase ynl189w p52294 KPNA1 Importin alpha-1 subunιt/SRP1-beta/nucleoproteιn ybr252w p10265 PRT Retrovirus-related protease mteractor 1 ynl189w O00505 KPNA3 Karyopheπn alpha 3 yhl009c p17861 XBP1 X box binding proteιn-1/XBP-1 ynl189w O00629 QIP1 Karyopheπn alpha 4/Qιp1 yhl009c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein ynl189w p35222 CTNNB1 Beta-catenin yhl009c p25054 APC Adenomatous polyposis coli protein ynl189w p52292 KPNA2 Importin alpha-2 subunιt/SRP1-alpha yhl009c p12270 TPR Nucleoprotem TPR ynl189w P52294 KPNA1 Importin alpha-1 subunιt/SRP1-beta/nucleoproteιn yhl009c q02224 CENPE Centromenc protein E/CENP-E protein mteractor 1 ynl189w p35222 CTNNB1 Beta-catenin yjrl 59w p11766 ADH5 Class III alcohol dehydrogenase chi subunit
I ynl189w P52294 KPNA1 Importin alpha-1 subunιt/SRP1-beta/nucleoproteιn yjrl 59w q00796 SORD Sorbitol dehydrogenase/L-ιdιtol-2 dehydrogenase
OΛ mteractor 1
-J ynl189w p35222 CTNNB1 Beta-catenin ylr303w p32929 CTH Cystathiomne gamma-lyase
I ynl189w O00505 KPNA3 Karyopheπn alpha 3 yml028w p32119 TDPX1 Thioredoxin peroxidase 1/thιoredoxιn-dependent peroxide reductase 1/thιol-specιfic antioxidant protein/TSA/PRP/natural killer cell enhancing factor
B/NKEF-B ynl189w O00629 QIP1 Karyopheπn alpha 4/Qιp1 yml028w q13162 AOE372 Thioredoxin peroxidase A0372/antιoxιdant enzyme
AOE372 ynl189w p35222 CTNNB1 Beta-catenin yml028w q06830 TDPX2 Thioredoxin peroxidase 2/prolιferatιon-assocιated gene
(pag) ynl189w p52292 KPNA2 Importin alpha-2 subunιt/SRP1-alpha yml028w p30041 AOP2 Antioxidant protein 2 ynl189w p52294 KPNA1 Importin alpha-1 subunιt/SRP1-beta/nucleoproteιn yml028w p30048 AOP1 Mitochondπal thioredoxin-dependent peroxide mteractor 1 reductase/antioxidant protein 1 ynl189w O00505 KPNA3 Karyophenn alpha 3 Ymr226c p15428 PGDH1 15-Hydroxyprostaglandιn dehydrogenase
[NAD(+)]/PGDH ynl189w p35222 CTNNB1 Beta-catenin Ymr226c q02338 BDH D-beta-hydroxybutyrate dehydrogenase/3- hydroxybutyrate dehydrogenase yn!189w P52292 KPNA2 Importin alpha-2 subunιt/SRP1-alpha Ymr226c q92781 RDH1 11 -as retmol dehydrogenase ynl189w P52294 KPNA1 Importin alpha-1 subunιt/SRP1-beta/nucleoproteιn Ymr226c p14061 E2DH Estradiol 17 beta-dehydrogenase 1/17-beta-HSD 1 mteractor 1 ynl189w p35222 CTNNB1 Beta-catenin yol058w p00966 ASS Arginmosuccinate synthase/citrulline-aspartate ligase ynl189w p35222 CTNNB1 Beta-catenin ypl111w p78540 ARG2 Argmase ll/non-hepatic arginase
ynl189w p52294 KPNA1 Importin alpha-1 subunιt SRP1-beta/nucleoproteιn ypl111w p05089 ARG1 Arginase 1 mteractor 1 ynl210w q00341 HBP High density lipoprotem binding protein ykl142w p07942 LAMB1 Laminm beta-1 chain/Laminin B1 chain ynl218w p35249 RFC4 Activator 1 37 kD subunit/rephcation factor C, 37-kDa ylr423c p49454 CENPF CENP-F kinetochore protein subunit ynl218w p35250 RFC2 Activator 1 40 kD subunit rephcation factor C, 40 kDa ylr423c p15924 DSP Desmoplakin I and II subunit ynl218w p35251 RFC1 Replication factor C large subunit/activator 1140 Kd ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle subunit ynl218w p40937 RFC5 Activator 1 36 kD subunit rephcation factor C, 36-kDa ylr423c q02224 CENPE Centromenc protein E/CENP-E protein subunit ynl218w p35249 RFC4 Activator 1 37 kD subunit rephcation factor C, 37-kDa ynl218w p35249 RFC4 Activator 1 37 kD subunit/rephcation factor C, 37-kDa subunit subunit ynl218w p35250 RFC2 Activator 1 40 kD subunit/replication factor C, 40 kDa ynl218w p35250 RFC2 Activator 1 40 kD subunit rephcation factor C, 40 kDa subunit subunit ynl218w p35251 RFC1 Replication factor C large subunit/activator 1140 Kd ynl218w p35251 RFC1 Replication factor C large subunit/activator 1140 Kd subunit subunit ynl218w p40937 RFC5 Activator 1 36 kD subunit/rephcation factor C, 36-kDa ynl218w p40937 RFC5 Activator 1 36 kD subunit/rephcation factor C, 36-kDa subunit subunit ynl287w p21851 CLAPB1 Beta adaptin ybr281c p31146 COR01 Coronm-like Protein P57 ynl287w q 10567 ADTB1 Beta-adaptm 1 ybr281c p35606 COPP Beta subunit of coatomer complex ynr006w p12036 NEFH Neurofilament triplet H proteιn/200 Kd neurofilament yhl002w q15811 ITSN lntersectιn/SH3 domain-containing protein SH3P17
1 protein ynrOOδw p26358 DNMT DNA/cytosιne-5)0methyl transferase/DNA yhl002w q 14247 CTTN SRC substrate cortactin/amplaxin methyltransferase/DNA metase/MCMT/M HSAI
I ynr006w p46100 ATRX Transcriptional regulator ATRX/X-linked helicase ll/X- yhl002w p19174 PLCG1 1-phosphatιdylιnosιtol-4,5-bιsphosphate linked nuclear protein phosphodiesterase gamma 1/phospholιpase C-gamma
1 ynr006w p80303 NEFA DNA binding protein NEFA yhl002w p16333 NCK Cytoplasmic protein NCK ynr006w p98174 FGD1 Putative RHO/RAC guanine nucleotide exchange yhl002w p14317 HCLS1 Hematopoietic lineage cell specific protein factor/faciogenital dysplasia protein ynr006w q02224 CENPE Centromenc protein E/CENP-E protein yhl002w p29354 GRB2 Growth factor receptor-bound protein 2 ynr006w q07283 THH Tπchohyalin yhl002w p98171 RGC1 RHO-GAP hematopoietic protein C1 ynr006w q 13438 0S9 Protein OS-9 precurosor yhl002w p46109 CRKL Crk-like protein ynrOOΘw q92794 MOZ Monocytic leukemia zinc finger protein yhl002w q13813 SPTA2 Spectπn alpha chain, bram/nonerythroid alpha-spectπn yoi034w p11055 MYH3 Embryonic myosin heavy chain Ymr117c p04264 KRT1 Keratin, type II cytoskeletal 1/cytokeratιn
1/Kl/CK1/67Kd cytokeratin/hair alpha protein yol034w p12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform Ymr117c p30622 RSN Restin yol034w p 13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform Ymr117c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin heavy chain, type B/NMMHC-B yol034w p 15924 DSP Desmoplakin I and II Ymr11 c p11055 MYH3 Embryonic myosin heavy chain yol034w p49454 CENPF CENP-F kinetochore protein Ymr117c p42566 EPS 15 Epidermal growth factor receptor substrate 15 yol034w q02224 CENPE Centromenc protein E/CENP-E protein Ymr117c p49454 CENPF CENP-F kinetochore protein yol059w p21695 GPD1 L-glycerol-3-phosphate dehydrogenase [NAD+] yfl017c p08578 SNRPE Small nuclear πbonucleoprotein E/snRNP-E
yol061w p09329 PRPS1 Phosphoπbosyl pyrophosphate synthetase l/πbose- yer099c p09329 PRPS1 Phosphonbosyl pyrophosphate synthetase l/πbose- phosphate pyrophosphokmase I phosphate pyrophosphokmase I yol061w p11908 PRPS2 Phosphoπobosyl pyrophosphate synthetase subunit II yer099c p11908 PRPS2 Phosphoπobosyl pyrophosphate synthetase subunit II yol061w p21108 PRPS3 Phosphoπbosyl pyrophosphate synthetase subunit III yerf)99c p21108 PRPS3 Phosphonbosyl pyrophosphate synthetase subunit III yol069w p 15924 DSP Desmoplakin I and II yer099c p21108 PRPS3 Phosphonbosyl pyrophosphate synthetase subunit III yol069w p49454 CENPF CENP-F kinetochore protein yer099c p11908 PRPS2 Phosphoπobosyl pyrophosphate synthetase subunit II yol069w q02224 CENPE Centromeπc protein E/CENP-E protein yer099c p09329 PRPS1 PHOSPHORIBOSYLPYROPHOSPHATE
SYNTHETASE I yol069w p12270 TPR Nucleoprotem TPR ylr423c p05787 KRT8 Keratin, type II cytoskeletal 8/cytokeratιn 8/K8/CK8 yol069w p12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform ylr423c p30622 RSN Restin yol069w p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform ylr423c p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle yol069w p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein yol069w p15924 DSP Desmoplakin I and II ylr423c p15924 DSP Desmoplakin I and II yol069w p30622 RSN Restin ylr423c p11047 LAMC1 Laminm gamma-1 chain [precursor]/lamιnιn B2 chain yol069w p35580 MYH10 Myosin heavy chain nonmuscle type B/cellular ylr423c p12270 TPR Nucleoprotem TPR myosin heavy chain, type B/NMMHC-B yol069w p49454 CENPF CENP-F kinetochore protein ylr423c p49454 CENPF CENP-F kinetochore protein yol069w q02224 CENPE Centromenc protein E/CENP-E protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein yol088c p 13667 ERP72 Protein disulfide isomerase related proteιn/ERP72 yhr091c p54136 RARS ArgRS/argmyl-tRNA synthetase yol105c q02505 MUC3 Mucm 3 [fragments]/ιntestιnal mucm 3 ygl153w q02224 CENPE Centromenc protein E/CENP-E protein
, yol105c q99102 MUC4 Tracheo-bronchial mucm 4/mucιn 4 [fragment] ygl153w q03001 BPAG1 Bullous 230 kDa pemphigoid antigen 1 φ yollOβc p98171 RGC1 RHO-GAP hematopoietic protein C1 ykl017c p38935 IGHMBP2 DNA-bindmg protein SMBP2 so yoMOδc p98171 RGC1 RHO-GAP hematopoietic protein C1 ykl135c q 10567 ADTB1 Beta-adaptm 1 i yol108c p98171 RGC1 RHO-GAP hematopoietic protein C1 Ymr317w q02817 MUC2 Intestinal mucm 2/mucιn 2 yol111c p11441 GDX Ubiquitin-like protein GDX yor007c p50502 HIP Progesterone receptor-associated p48 protein yol111c p54725 RAD23A UV excision repair protein protein RAD23 homolog yor007c p30260 CDC27 Protein CDC27HS/cell division cycle protein 27
A/HHR23A homolog yol111c p54727 D21090 UV excision repair protein protein RAD23 homolog yor007c q08752 PPID 40 kD peptidyl-prolyl CIS-TRANS
B/XP-C repair complementing protein (p58/HHR23B), ιsomerase/cyclophιlιn-40 mRNA, complete eds complete eds yol123w p07029 UP2 Heterogeneous nuclear πbonucleoprotein UP2 ygl122c p20226 TBP TATλ-binding protein/transcription initiation factor TFIID yol123w p09651 HNRPA1 Heterogenous nuclear πbonucleoprotein A1/helιx- ygl122c q10571 MN1 Probable tumor suppressor protein MN1 destabilizmg protein/smgle-straπd binding protem/HNRNP core protein A1 yol123w p11940 PABPL1 PolyA binding protein 1 ygl122c q14814 MEF2D Myocyte-specific enhancer factor 2D yol123w p22626 HNRPA2B1 Heterogeneous nuclear πbonucleoproteins A2/B1 ygl122c p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM yol123w p26378 ELAVL4 Paraneoplastic encephalomyelitis antigen 3 ygl122c p42858 HD Huntingtm/huntington's disease protein yol123w p38159 HNRPG Heterogeneous nuclear πbonucleoprotein G/HNRNP ygl122c q92794 MOZ Monocytic leukemia zinc finger protein
G/glycoprotein P43 yol123w q 15427 SAP49 Spliceosome associated protein 49/SAP49 ygl122c q93074 KIAA0192 Hypothetical protein KIAA0192 yol130w p46821 MAP1B Microtubule-associated protein 1 B ygl025c q02078 MEF2A Myocyte-specific enhancer factor 2A yol130w q04724 TLE1 Transducin-like enhancer protein ygl025c q02817 MUC2 Intestinal mucm 2/mucιn 2 yol130w p46821 MAP1B Microtubule-associated protein 1 B ylr291c q14232 ELF2B1 Translation initiation factor elF-2B alpha subunit yol130w q04724 TLE1 Transducin-like enhancer protein ylr291c p49770 EIF2B2 Translation initiation factor EIF-2B beta subunιt/S20ιιι15
yor061w p24941 CDK2 Cell division protein kinase 2 yor039w p 13862 CSNK2B Casein kinase II beta subunit yor128c p22234 PAICS ADE2 showing homologies to SAICAR synthetase and ycr066w p35226 BMI1 DNA-bindmg protein BMI1
AIR carboxylase of the puπne pathway yor128c p22234 PAICS ADE2 showing homologies to SAICAR synthetase and ycr067c p42568 MLLT3 AF-9 protein
AIR carboxylase of the puπne pathway yor128c p22234 PAICS ADE2 showing homologies to SAICAR synthetase and yor128c p22234 PAICS ADE2 showing homologies to SAICAR synthetase and
AIR carboxylase of the puπne pathway AIR carboxylase of the puπne pathway yor132w q00839 HNRNPU Heterogenous nuclear πbonucleoprotein U/scaffold yor069w q 12840 KIF5C Neuronal kinesm heavy chain attachment factor A yor269w p25388 GNB2-RS1 Guanine nucleotide-binding protein beta subunit-like ylr254c p49454 CENPF CENP-F kinetochore protein protein 12 3 yor269w p35606 COPP Beta subunit of coatomer complex ylr254c q02224 CENPE Centromenc protein E/CENP-E protein yor269w p43034 PAFAH1B1 Platelet-activating factor acetylhydrolase IB alpha ylr254c p 13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform subunit yor303w p31327 CPS1 Carbamoyl-phosphate synthase [ammonia], yor039w p13862 CSNK2B Casein kinase II beta subunit mitochondπal [precursor] yor348c p52569 SLC7A2 Low-affinity cationic ammo acid transporter-2/CAT-2 ycr045c p29144 TTP2 Tπpeptidyl-peptidase II yor348c p52569 SLC7A2 Low-affinity cationic ammo acid transporter-2/CAT-2 yjl084c q03164 MLL Zinc finger protein HRX yor348c p52569 SLC7A2 Low-affinity cationic ammo acid transporter-2/CAT-2 Ymr228w q01082 SPTB2 Beta-spectπn chain, brain yor353c p22792 CPN2 Carboxypeptidase N ygr120c p49454 CENPF CENP-F kinetochore protein yor353c p35858 IGFALS IGF binding protein complex acid-labile ygr120c p04114 APOB Apolipoprotem B yor353c q06828 FMOD Fibromodu n ygr120c P30622 RSN Restin o yor353c p07585 DCN Bone proteoglycan II [precursor]/PG40 yhr102w q13177 PAK2 Seπne/threonine-protein kinase PAK-gamma yor353c p22792 CPN2 Carboxypeptidase N yhr102w q02750 PRKMK1 Dual specificity mitogen-activated protein kinase kinase
1 yor353c p23515 OMG Oligodendrocyte-myelin glycoprotein yhr102w q13153 PAK1 Seπne/threonine-protein kinase PAK-alpha yor353c p35858 IGFALS IGF binding protein complex acid-labile yhr102w q99759 MAP3K3 Mitogen-activated protein kinase kinase kinase 3/MEK kinase 3 yor353c q06828 FMOD Fibromoduhn yhr102w p45985 MAP2K4 Dual specificity mitogen-activated protein kinase kinase
4 yor353c q 14392 GARP Garp protein/Garpm yhr102w q13163 MAP2K5 Dual specificity mitogen-activated protein kinase kinase
5 yor353c q99102 MUC4 Tracheo-bronchial mucm 4/mucιn 4 [fragment] yhr102w p51955 NEK2 Seπne/threonine-protein kinase NEK2 yor362c p25786 PSMA1 Proteasome subunit C2 yfl017c p08578 SNRPE Small nuclear nbonucleoprote E/snRNP-E yor375c p00367 GLUD1 Glutamate dehydrogenase 1 yjl124c p14678 SNRPB Small nuclear nbonucleoprotem associated proteins B and B' yor375c p49448 GLUD2 Glutamate dehydrogenase 2 yjl 124c p14648 SNRPN Small nuclear nbonucleoprotem associated protein N ypl049c p51825 MLLT2 AF-4 protein ydr480w p17931 LGALS3 Galectιn-3/lgE-bιndιng protein ypl059w p35754 GLRX Glutaredoxm yιl105c p20226 TBP 1 ATA-binding protein/transcription initiation factor TFIID ypl059w p35754 GLRX Glutaredoxm ynl047c q99418 ARNO ARF nucleotide-binding site opener/ARNO protem/ARF exchange factor ypl140c p45985 MAP2K4 Dual specificity mitogen-activated protein kinase yhr030c q15759 MAPK11 Mitogen-activated protein kinase 11 kinase 4
ypl140c p46734 MAP2K3 Dual specificity mitogen-activated protein kinase yhr030c p53778 MAPK12 Mitogen-activated protein kinase 12/ERK6/extracellular kinase 3/MAP kinase kinase 3 signal-regulated kinase 6 yplHOc p52564 MAP2K6 Dual specificity mitogen-activated protein kinas kinase yhr030c p27361 MAPK3 Mitogen-activated protein kinase 3/extracellular signal- 6 regulated kinase 1 ypl140c q02750 PRKMK1 Dual specificity mitogen-activated protein kinase yhr030c q13164 MAPK7 Mitogen-activated protein kinase 7/ERK5 kinase 1 ypl140c q13163 MAP2K5 Dual specificity mitogen-activated protein kinase yhr030c q16539 MAPK14 Mitogen-activated protein kinase 14/CSBP kinase 5 yplHOc q99759 MAP3K3 Mitogen-activated protein kinase kinase kinase 3/MEK yhr030c P28482 MAPK1 Mitogen-activated protein kinase 1 /extracellular signal- kinase 3 regulated kinase 2 ypl151c p35606 COPP Beta subunit of coatomer complex yor036w q02224 CENPE Centromenc protein E/CENP-E protein ypl151c p43034 PAFAH1B1 Platelet-activating factor acetylhydrolase IB alpha yor036w P49454 CENPF CENP-F kinetochore protein subunit ypl151c q 15542 TAF2D Transcription initiation factor TFIID 100 Kd yor036w p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular myosin subunιt/TAFII-100/TAFII100 heavy chain, type B/NMMHC-B ypl174c p49454 CENPF CENP-F kinetochore protein yhr129c P42024 ACTR1A Alpha-centract y pi 174c q02224 CENPE Centromenc protein E/CENP-E protein yhr129c P42025 ACTR1B Beta-centractm ypl174c p11055 MYH3 Embryonic myosin heavy chain yιl144w P11055 MYH3 Embryonic myosin heavy chain ypl174c p12882 MYSS Myosin heavy chain skeletal muscle light yιl144w P30622 RSN Restin meromyosin region ypl174c p12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform yιl144w P12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform I ypl174c p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform yιl144w P13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform -j ypH74c P30622 RSN Restin yιl144w p35579 MYH9 Myosin heavy chain, nonmuscle type A/cellular myosin heavy chain, type A/NMMHC-A
1 yph74c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular yιl144w p13535 MYH8 Myosin heavy chain, perinatal skeletal muscle myosin heavy chain, type B/NMMHC-B ypl174c p49454 CENPF CENP-F kinetochore protein yιl144w p49454 CENPF CENP-F kinetochore protein ypl174c q02224 CENPE Centromenc protein E/CENP-E protein yιl144w q02224 CENPE Centromenc protein E/CENP-E protein ypl174c q14203 DCTN1 Dynactm, 150 kD isoform [fragment] yιl144w P15924 DSP Desmoplakin I and II ypl174c p11055 MYH3 Embryonic myosin heavy chain ylr423c P12270 TPR Nucleoprotem TPR ypl174c p12882 MYSS Myosin heavy chain skeletal muscle, light ylr423c P11047 LAMC1 Laminm gamma-1 chain [precursor]/lamιnιn B2 chain meromyosin region y pi 174c p 12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform ylr423c P30622 RSN Restin ypl174c p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform ylr423c P13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ypl174c p30622 RSN Restin ylr423c P05787 KRT8 Keratin, type II cytoskeletal 8/cytokeratιn 8 K8 CK8 ypl174c p35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ylr423c q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein myosin heavy chain, type B/NMMHC-B ypl174c p49454 CENPF CENP-F kinetochore protein ylr423c P49454 CENPF CENP-F kinetochore protein ypl174c q02224 CENPE Centromenc protein E/CENP-E protein ylr423c q02224 CENPE Centromenc protein E/CENP-E protein ypl174c q14203 DCTN1 Dynactm, 150 kD isoform [fragment] ylr423c p 15924 DSP Desmoplakin I and II ypl259c p53677 P47B Clathπn coat assembly protein AP47 homolog 2 ykl135c q 10567 ADTB1 Beta-adaptm 1 ypl259c p53680 CLAPS2 Clathπn coat assembly protein AP17/clathnn coat ykl135c p21851 CLAPB1 Beta adaptm associated protein AP17 ypl260w p 12270 TPR Nucleoprotem TPR yιl144w p12883 MYH7 Myosin heavy chain, cardiac muscle beta isoform
ypl260w p17661 DES Desmin yιl144w p30622 RSN Restin ypl260w p33176 KNS1 Kinesin heavy chain yιl144w P15924 DSP Desmoplakin I and II ypl260w p49454 CENPF CENP-F kinetochore protein yιl144w p49454 CENPF CENP-F kinetochore protein ypl260w q02224 CENPE Centromenc protein E/CENP-E protein yιl144w q02224 CENPE Centromenc protein E/CENP-E protein ypl260w q 15032 KIAA0029 Hypothetical protein KIAA0029 yιl144w P13535 MYH8 Myosin heavy chain, perinatal skeletal muscle ypl260w q15431 SYCP1 Synaptonemal complex protein 1/SCP-1 protein yιl144w P11055 MYH3 Embryonic myosin heavy chain ypl260w q 16787 LAMA3 Laminm alpha-3 chain yιl144w p13533 MYH6 Myosin heavy chain, cardiac muscle alpha isoform ypr018w p35241 RDX Radixin ybr195c O00628 PTS2R Peroxisomal targeting signal 2 receptor ypr018w P35580 MYH10 Myosin heavy chain, nonmuscle type B/cellular ybr195c P04901 GNB1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) beta myosin heavy chain, type B/NMMHC-B subunit 1 ypr018w p46821 MAP1B Microtubule-associated protein 1 B yybbrr119955cc qq0099002288 R RBBAAPP448£ Chromatin assembly factor 1 P48 subunit retinoblastoma binding protein P48 ypr018w q02832 BLSA B-lymphocyte antigen/B-lymphocyte surface antigen ybr195c pp1111001166 G GNNBB22 Guanine nucleotide-binding protein beta subunit 2 ypr018w q14203 DCTN1 Dynactm, 150 kD isoform [fragment] ybr195c qq1166557766 R RBBBBPP77 Histone acetyl transferase type B subunit
2/retιnoblastoma-bιndιng protein ypr018w q16643 DBN1 Drebin E yybbrr119955cc p P1166552200 G GNNBB33 Guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 3 ypr048w p29475 N0S1 Nitric oxide synthase/neuronal NOS yor355w p42568 MLLT3 AF-9 protein ypr048w p35228 N0S2 Inducible nitric oxide synthase yor355w q14669 TRIP12 Thyroid receptor interacting protein 12/KIAA0045 ypr054w p28482 MAPK1 Mitogen-activated protein kinase 1 /extracellular signal - yfl029c P24941 CDK2 Cell division protein kinase 2 regulated kinase 2 ypr054w p53778 MAPK12 Mitogen-activated protein kinase yyffll002299cc Pp5500661133 CCDDKK77 Cell division protein kinase 7/CAK/CDK-actιvatιng
12/ERK6/extracellular signal-regulated kinase 6 kinase ypr054w p53779 MAPK10 Mitogen-activated protein kinase 10 yfl029c P49840 GSK3A Glycogen synthase kιnase-3 alpha ypr054w q13164 MAPK7 Mitogen-activated protein kinase 7/ERK5 yfl029c q00526 CDK3 Cell division protein kinase 3 ypr054w q15759 MAPK11 Mitogen-activated protein kinase 11 yfl029c p49841 GSK3B Glycogen synthase kιnase-3 beta ypr054w q16539 MAPK14 Mitogen-activated protein kinase 14/CSBP yfl029c q00535 CDK5 Cell division protein kinase 5/TAU protein kinase II catalytic subunit/TPKII catalytic subunit ypr105c p07197 NEFM Neurofilament triplet M proteιn/160 Kd neurofilament ygl145w p35749 MYH11 Myosin heavy chain, smooth muscle isoform/SMMHC protein/NF-M [FRAGMENT] ypr105c p07197 NEFM Neurofilament triplet M proteιn/160 Kd neurofilament ygl153w q03001 BPAG1 Bullous 230 kDa pemphigoid antigen 1 protem/NF-M ypr105c p07197 NEFM Neurofilament triplet M proteιn/160 Kd neurofilament ygr120c P04114 APOB Apolipoprote B protem/NF-M ypr105c p07197 NEFM Neurofilament triplet M proteιn/160 Kd neurofilament yhr060w P25789 PSMA4 Proteasome subunit C9 protem/NF-M ypr110c p19387 P0LR2C DNA-directed RNA polymerase II 33Kd ylr238w p49454 CENPF CENP-F kinetochore protein
Figure imgf000074_0001
ypr110c p19387 P0LR2C DNA-directed RNA polymerase II 33Kd ynl113w q06481 APLP2 Amyloid-like protein 2/APPH/amyloιd protein homolog subunιt/RPB33 ypr119w p14635 CCNB1 G2/mιtotιc-specιfιc cyclin B1 ybr135w P33551 CKS1 Cyclm-dependent kinases regulatory subunit 1 ypr119w p20248 CCNA G2/mιtotιc-specιfic cyclin A ybrl 35w P10275 AR Androgen receptor ypr119w p14635 CCNB1 G2/mιtotιc-specιfic cyclin B1 ydr412w p36777 LONN Lon protease-like protein ypr119w p20248 CCNA G2/mιtotιc-specιfic cyclin A ydr412w P36776 LONM Mitochondπal LON protease homolog [precursor]
ypr119w p14635 CCNB1 G2/mιtotιc-specιfic cyclin B1 yhr035w q15437 SEC23B Protein transprot protein Sec23 B isoform ypr119w p20248 CCNA G2/mιtotιc-specιfic cyclin A yhr035w q15436 SEC23A Protein transprot protein Sec23 A isoform ypr119w p14635 CCNB1 G2/mιtotιc-specιfic cyclin B1 ynl135c q00688 FKBP3 Rapamycin-selective 25 Kd immunophilin ypr119w p20248 CCNA G2/mιtotιc-specιfic cyclin A ynl135c p26885 FKBP2 FK506-bιndιng proteιn/FKBp-13 ypr173c q03527 PSMC1 26S protease (S4) regulatory subunit ylr025w p14314 PRKCSH Protein kinase C substrate, 80 kD protein, heavy chaιn/80K-H protein ypr173c q 13608 PEX6 Peroxisome assembly factor-2/peroxιsomal-type ylr025w q14203 DCTN1 Dynactm, 150 kD isoform [fragment]
ATPase 1 ypr185w p20226 TBP TATA-binding protein/transcription initiation factor ygl180w p22694 PRKACB Testis-specific cAMP-dependent protein kinase catalytic
TFIID subunit C-beta isoform ypr185w p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM ygl180w p17612 PRKACA CAMP-dependent protein kinase catalytic subunit type alpha ypr185w p54252 MJD1 Machado-joseph disease protein 1 ygl180w p54646 PRKAA2 5'-AMP-actιvated protein kinase, catalytic alpha-2 chain ypr185w q10571 MN1 Probable tumor suppressor protein MN1 ygl180w q04759 PRKCQ Protein kinase C-theta type ypr185w q93074 KIAA0192 Hypothetical protein KIAA0192 ygl180w p27448 P78 Putative seπnd/threonine-protein kinase P78 ypr185w p20226 TBP TATA-binding protem/transcπption initiation factor ygr120c p30622 RSN Restin
TFIID ypr185w p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM ygr120c p49454 CENPF CENP-F kinetochore protein ypr185w p54252 MJD1 Machado-joseph disease protein 1 ygr120c p04114 APOB Apolipoprotem B ypr185w p20226 TBP TATA-binding protein/transcription initiation factor ygr253c p25788 PSMA3 Proteasome subunit C8
TFIID
I ypr185w p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM ygr253c p25787 PSMA2 Proteasome subunit C3
^ ypr185w p54252 MJD1 Machado-joseph disease protein 1 ygr253c p25786 PSMA1 Proteasome subunit C2 w ypr185w q10571 MN1 Probable tumor suppressor protein MN1 ygr253c p34062 PSMA6 Proteasome iota chaιn/PROS-27
I ypr185w q93074 KIAA0192 Hypothetical protein KIAA0192 ygr253c p25789 PSMA4 Proteasome subunit C9 ypr185w p20226 TBP TATA-binding protein/transcription initiation factor ylr423c p 15924 DSP Desmoplakin I and II
TFIID ypr185w p51531 SMARCA2 Possible global transcription activator SNF2L2/BRM ylr423c p49454 CENPF CENP-F kinetochore protein ypr185w p54252 MJD1 Machado-joseph disease protein 1 ylr423c q02224 CENPE Centromeπc protein E/CENP-E protein ypr185w q10571 MN1 Probable tumor suppressor protein MN1 ylr423c p30622 RSN Restin ypr185w q93074 KIAA0192 Hypothetical protein KIAA0192 ylr423c p13535 MYH8 Myo'sm heavy chain, perinatal skeletal muscle
The human polypeptides disclosed in Table 7 are related as orthologs to yeast polypeptides that interact to form complexes according to the invention. Table 7 reflects this relationship and specifies a yeast accession number for a given human ortholog. In particular, Table 7 includes in column 1 the yeast accession number for the yeast "bait" sequence corresponding to the indicated human ortholog. Columns 2-4 provide the accession number of the human ortholog, the name of the human ortholog, and a description of the human ortholog, respectively, of the yeast "bait sequence". Column 5 of Table 7 provides the yeast accession number of the yeast "prey" sequence. Columns 6-8 provide the accession number of the human ortholog, the name of the human otholog, and a description of the human ortholog, respectively, of the yeast "prey sequence".
In certain embodiments, one of the ortholog polypeptides includes a "bait" polypeptide selected from the polypeptides recited in Table 7, column 2, and the other ortholog polypeptide includes a "prey" protein selected from the polypeptides recited in Table 7, column 6. The yeast orthologs of these proteins are set out in columns 1 and 4 of Table 7, respectively. In some embodiments the first and second polypeptides of the complex are the polypeptides enumerated in Table 7. In some embodiments a first polypeptide is a "bait" polypeptide and a second polypeptide is "target" polypeptide, while in other embodiments the first polypeptide is a "target" polypeptide and the second is a "bait" polypeptide. Conservative variants of either polypeptide which retain binding specificity are within the scope of the invention, as are labeled forms of the complexes, as described above.
In other embodiments, the polypeptides are the binding domains of the "bait" and "prey" polypeptides listed in Table 7. A binding domain of a given first polypeptide may be any number of amino acids sufficient to specifically bind to, and complex with, the corresponding second polypeptide under conditions suitable for complex formation. A binding domain may be the minimal number of amino acids required to retain binding affinity, or may be a larger fragment or derivative of the polypeptides listed in Table 7, columns 2 and 6.
In certain embodiments, the "bait" polypeptides of the ortholog complex are polypeptides categorized, for example, as a "Metabolism" protein in the MIPS database. In some embodiments, the "prey" protein of the complex is also a "Metabolism" protein, while in other embodiments the "prey" protein is, for example, an "Unclassified" protein (see Table 7). Other exemplary MIPS categories include, e.g., "Cell Growth/Cell Division/DNA Synthesis" proteins (see Table 2). In a further aspect, the invention provides chimeric polypeptide complex that includes at least one yeast polypeptide and at least one human ortholog of the corresponding interacting yeast polypeptide. In one embodiment, there is provided a purified chimeric complex including a yeast "bait" polypeptide selected from the polypeptides recited in Table 7, column 1 and a human ortholog of the corresponding yeast "prey" polypeptide; the human ortholog is selected from the polypeptides recited in Table 7, column 6 (while the corresponding yeast "prey" proteins are recited in column 5). For example, with reference to Table 7, first row, in one embodiment, a chimeric protein containing YAL032C and PI 6118 is provided (PI 6118 is the human ortholog of corresponding yeast "prey" protein YLR345W).
In other embodiments, the complex contains a human ortholog of a yeast "bait" protein and a yeast "prey" protein. The yeast "prey" protein is selected from the polypeptides recited in Table 7, column 5, and the human ortholog of the corresponding yeast "bait" protein is selected from the polypeptides recited in Table 7, column 2 (while the corresponding yeast "bait" proteins themselves are recited in column 1). For example, with reference to Table 7, first row, in one embodiment, a chimeric protein containing Q 13573 and YLR345W is provided (Q13573 is the human ortholog of corresponding yeast "bait" protein YAL032C).
In certain embodiments the first and second polypeptides of the chimeric complex are the polypeptides recited in Table 7, columns 1 and 6, or columns 2 and 5, respectively, while in other embodiments, the polypeptides of the chimeric complex contain the polypeptides recited in Table 7. Conservative variants of either polypeptide which retain binding specificity are within the scope of the invention, as are labeled forms of the chimeric complexes, and chimeric complexes of binding domains, as described above.
Chimeric Polypeptides, DNA, Vectors and Recombinant Cells
In a further aspect, the invention provides a chimeric polypeptide that includes sequences of two interacting proteins according to the invention. The interacting proteins can be, e.g., the interacting protein pairs disclosed in Tables 3-7, herein. Also included are chimeric polypeptides including multimers, i.e., sequences from two or more pairs of interacting proteins. An example of such a chimeric polypeptide is a polypeptide that includes amino acid sequences from ProPair la and lb, and from ProPair 2a and 2b. The chimeric polypeptide includes a region of a first protein covalently linked, e.g. via peptide bond, to a region of a second protein. In certain embodiments, the second protein is a species ortholog of the first protein. In some embodiments, the chimeric polypeptide contains regions of first and second proteins from yeast, where the proteins are selected from the "bait" and corresponding "prey" proteins recited in Table 3, columns 1 and 4, respectively. In other embodiments, the chimeric polypeptide contains regions of first and second human ortholog proteins, where the proteins are selected from the "bait" and corresponding "prey" proteins recited in Table 7, columns 2 and 6, respectively (the yeast orthologs of these proteins are recited in columns 1 and 5, respectively). In still other embodiments, the chimeric polypeptide contains regions of a first protein from yeast, and a second human ortholog protein, where the yeast proteins are selected from the "bait" and corresponding "prey" proteins recited in Table 7, columns 1 and 5, respectively, while the human ortholog proteins are selected from the "bait" and corresponding "prey" proteins recited in Table 7, columns 2 and 6, respectively. In some embodiments, the chimeric polypeptide(s) of the complex include(s) six or more amino acids of a first protein covalently linked to six or more amino acids of a second protein. In other embodiments, the chimeric polypeptide includes at least one binding domain of a first or second protein.
Preferably, the chimeric polypeptide includes a region of amino acids of the first polypeptide able to bind to a second polypeptide. Alternatively, or in addition, the chimeric polypeptide includes a region of amino acids of the second polypeptide able to bind to the first polypeptide.
Nucleic acid encoding the chimeric polypeptide, as well as vectors and cells containing these nucleic acids, are within the scope of the present invention. The chimeric polypeptides can be constructed by expressing nucleic acids encoding chimeric polypeptides using recombinant methods, described above, then recovering the chimeric polypeptides, or by chemically synthesizing the chimeric polypeptides. Host-vector systems that can be used to express chimeric polypeptides include, e.g. : (i) mammalian cell systems which are infected with vaccinia virus, adenovirus; (ii) insect cell systems infected with baculovirus; (Hi) yeast containing yeast vectors or (iv) bacteria transformed with bacteriophage, DNA, plasmid DNA, or cosmid DNA. Depending upon the host-vector system utilized, any one of a number of suitable transcription and translation elements may be used. The expression of the specific proteins may be controlled by any promoter/enhancer known in the art including, e.g. : (i) the SV40 early promoter (see e.g., Bernoist & Chambon, Nature 290: 304-310 (1981)); (ii) the promoter contained within the 3'-terminus long terminal repeat of Rous Sarcoma Virus (see e.g., Yamamoto, et al, Cell 22: 787-797 (1980)); (Hi) the Herpesvirus thymidine kinase promoter (see e.g., Wagner, et al, Proc. Natl. Acad. Sci. USA 78: 1441-1445 (1981)); (iv) the regulatory sequences of the metallothionein gene (see e.g., Brinster, et al, Nature 296: 39-42 (1982)); (v) prokaryotic expression vectors such as the β- lactamase promoter (see e.g., Villa-Kamaroff, et al, Proc. Natl. Acad. Sci. USA 75: 3727- 3731 (1978)); (vi) the tac promoter (see e.g., DeBoer, et al, Proc. Natl. Acad. Sci. USA 80: 21-25 (1983)).
Plant promoter/enhancer sequences within plant expression vectors may also be utilized including, e.g.,: (i) the nopaline synthetase promoter (see e.g., Herrar-Estrella, et al, Nature 303: 209-213 (1984)); (/'/) the cauliflower mosaic virus 35S RNA promoter (see e.g., Garder, et al, Nuc. Acids Res. 9: 2871 (1981)) and (Hi) the promoter of the photosynthetic enzyme ribulose bisphosphate carboxylase (see e.g., Herrera-Estrella, et al, Nature 310: 115- 120 (1984)).
Promoter/enhancer elements from yeast and other fungi (e.g., the Gal4 promoter, the alcohol dehydrogenase promoter, the phosphoglycerol kinase promoter, the alkaline phosphatase promoter), as well as the following animal transcriptional control regions, which possess tissue specificity and have been used in transgenic animals, may be utilized in the production of proteins of the present invention.
Other animal transcriptional control sequences derived from animals include, e.g.,: (i) the insulin gene control region active within pancreatic β-cells (see e.g., Hanahan, et al, Nature 315: 115-122 (1985)); (ii) the immunoglobulin gene control region active within lymphoid cells (see e.g., Grosschedl, et al, Cell 38: 647-658 (1984)); ( / ) the albumin gene control region active within liver (see e.g., Pinckert, et al, Genes and Devel 1: 268-276 (1987)); (iv) the myelin basic protein gene control region active within brain oligodendrocyte cells (see e.g., Readhead, et al, Cell 48: 703-712 (1987)); and (v) the gonadotrophin-releasing hormone gene control region active within the hypothalamus (see e.g., Mason, et al, Science 234: 1372-1378 (1986)).
The vector may include a promoter operably-linked to nucleic acid sequences which encode a chimeric polypeptide, one or more origins of replication, and optionally, one or more selectable markers (e.g., an antibiotic resistance gene). A host cell strain may be selected which modulates the expression of chimeric sequences, or modifies/processes the expressed proteins in a desired manner. Moreover, different host cells possess characteristic and specific mechanisms for the translational and post-translational processing and modification (e.g., glycosylation, phosphorylation, and the like) of expressed proteins. Appropriate cell lines or host systems may thus be chosen to ensure the desired modification and processing of the foreign protein is achieved. For example, protein expression within a bacterial system can be used to produce an unglycosylated core protein; whereas expression within mammalian cells ensures "native" glycosylation of a heterologous protein.
Antibodies Specific for Polypeptide Complexes The invention further provides antibodies and antibody fragments (such as Fab or
(Fab)2 fragments) that bind specifically to the complexes described herein. By "specifically binds" is meant an antibody that recognizes and binds to a particular polypeptide complex of the invention, but which does not substantially recognize or bind to other molecules in a sample, or to any of the polypeptides of the complex when those polypeptides are not complexed.
For example, a purified complex, or a portion, variant, or fragment thereof, can be used as an immunogen to generate antibodies that specifically bind the complex using standard techniques for polyclonal and monoclonal antibody preparation.
A full-length polypeptide complex can be used, if desired. Alternatively, the invention provides antigenic fragments of polypeptide complexes for use as immunogens. In some embodiments, the antigenic complex fragment includes at least 6, 8, 10, 15, 20, or 30 or more amino acid residues of a polypeptide. In one embodiment, epitopes encompassed by the antigenic peptide include the binding domains of the polypeptides, or are located on the surface of the protein, e.g., hydrophilic regions. If desired, peptides containing antigenic regions can be selected using hydropathy plots showing regions of hydrophilicity and hydrophobicity. These plots may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, Proc. Nat. Acad. Sci. USA 75:3824-3828 (1981); Kyte and Doolittle, J. Mol. Biol. 157:105-142 (1982). The term "antibody" as used herein refers to immunoglobulin molecules and immuno logically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen, such as a polypeptide complex. Such antibodies include, e.g., polyclonal, monoclonal, chimeric, single chain, Fab and F(ab')2 fragments, and an Fab expression library. In specific embodiments, antibodies to human ortholog complexes.
Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies. For example, for the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by injection with the native protein, or a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, recombinantly expressed polypeptide complex. Alternatively, the immunogenic polypeptides or complex may be chemically synthesized, as discussed above. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, e.g., Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), human adjuvants such as Bacille Calmette-Guerin and Corγnebacterium parvum, or similar immunostimulatory agents. If desired, the antibody molecules directed against complex can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as protein A chromatography to obtain the IgG fraction.
The term "monoclonal antibody" or "monoclonal antibody composition", as used herein, refers to a population of antibody molecules that contain only one species of an antigen binding site capable of immunoreacting with a particular epitope of a polypeptide complex. A monoclonal antibody composition thus typically displays a single binding affinity for a particular protein with which it immunoreacts. For preparation of monoclonal antibodies directed towards a particular complex, or polypeptide, any technique that provides for the production of antibody molecules by continuous cell line culture may be utilized. Such techniques include, e.g., the hybridoma technique (see Kohler & Milstein, Nature 256: 495-497 (1975)); the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al, Immunol Today 4: 72 (1983)); and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al, In: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., (1985) pp. 77-96). If desired, human monoclonal antibodies may be prepared by using human hybridomas (see Cote, et al, Proc. Natl. Acad. Sci. USA 80: 2026-2030 (1983)) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al. In: Monoclonal Antibodies and Cancer Therapy, supra).
Methods can be adapted for the construction of Fab expression libraries (see e.g., Huse, et al, Science 246: 1275-1281 (1989)) to allow rapid and effective identification of monoclonal Fab fragments with the desired specificity for the desired protein or derivatives, fragments, analogs or homologs thereof. Non-human antibodies can be "humanized" by techniques well known in the art. See e.g., U.S. Patent No. 5,225,539. Antibody fragments that contain the idiotypes to a polypeptide or polypeptide complex may be produced by techniques known in the art including, e.g.: (i) an F(ab')2 fragment produced by pepsin digestion of an antibody molecule; (ii) an Fab fragment generated by reducing the disulfide bridges of an F(ab')2 fragment; (/ ) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) Fv fragments.
Chimeric and humanized monoclonal antibodies against the polypeptide complexes, or polypeptides, described herein are also within the scope of the invention, and can be produced by recombinant DNA techniques known in the art, for example using methods described in PCT International Application No. PCT/US86/02269; European Patent Application No. 184,187; European Patent Application No. 171,496; European Patent Application No. 173,494; PCT International Publication No. WO 86/01533; U.S. Pat. No. 4,816,567; European Patent Application No. 125,023; Better et al., Science 240: 1041-1043 (1988); Liu et al., Proc. Nat. Acad. Sci. USA 84: 3439-3443 (1987); Liu et al., J. Immunol. 139: 3521-3526 (1987); Sun et al, Proc. Nat. Acad. Sci. USA 84: 214-218 (1987); Nishimura et al, Cancer Res. 47: 999-1005 (1987); Wood et al., Nature 314: 446-449 (1985); Shaw et al., J. Natl. Cancer Inst. 80: 1553-1559 (1988); Morrison, Science 229: 1202-1207 (1985); Oi et al, BioTechniques 4: 214 (1986); U.S. Pat. No. 5,225,539; Jones et al, Nature 321: 552-525 (1986); Verhoeyan et al., Science 239: 1534 (1988); and Beidler et al., J. Immunol. 141: 4053-4060 (1988).
Methods for the screening of antibodies that possess the desired specificity include, e.g., enzyme-linked immunosorbent assay (ELISA) and other immunologically-mediated techniques known within the art. For example, selection of antibodies that are specific to a particular domain of a polypeptide complex is facilitated by generation of hybridomas that bind to the complex, or fragment thereof, possessing such a domain.
In certain embodiments of the invention, antibodies specific for the polypeptide complexes described herein may be used in various methods, such as detection of complex, and identification of agents which disrupt complexes. These methods are described in more detail, below. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I,
Figure imgf000083_0001
Polypeptide complex-specific, or polypeptide-specific antibodies, can also be used to isolate complexes using standard techniques, such as affinity chromatography or immunoprecipitation. Thus, the antibodies disclosed herein can facilitate the purification of specific polypeptide complexes from cells, as well as recombinantly produced complexes expressed in host cells.
Kits
In a specific embodiment, the invention provides kits containing a reagent, for example, an antibody described above, which can specifically detect a polypeptide complex, or a constituent polypeptide, described herein. Such kits can contain, for example, reaction vessels, reagents for detecting complex in sample, and reagents for development of detected complex, e.g. a secondary antibody coupled to a detectable marker. The label incorporated into the anti- complex, or anti -polypeptide antibody may include, e.g., a chemiluminescent, enzymatic, fluorescent, colorimetric or radioactive moiety. Kits of the present invention may be employed in diagnostic and/or clinical screening assays.
Pharmaceutical Compositions
The invention further provides pharmaceutical compositions of purified complexes suitable for administration to a subject, most preferably, a human, in the treatment of disorders involving altered levels of such complexes. Such preparations include a therapeutically- effective amount of a complex, and a pharmaceutically acceptable carrier. As utilized herein, the term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals and, more particularly, in humans. The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic is administered and includes, but is not limited to such sterile liquids as water and oils. The therapeutic amount of a complex which will be effective in the treatment of a particular disorder or condition will depend on the nature of the disorder or condition, and may be determined by standard clinical techniques by those of average skill within the art. In addition, in vitro assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the formulation will also depend on the route of administration, and the overall seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each patient's circumstances. //However, suitable dosage ranges for intravenous administration of the complexes of the present invention are generally about 20-500 micrograms (μg) of active compound per kilogram (Kg) body weight. Suitable dosage ranges for intranasal administration are generally about 0.01 pg kg body weight to 1 mg/kg body weight. Effective doses may be extrapolated from dose- response curves derived from in vitro or animal model test systems. Suppositories generally contain active ingredient in the range of 0.5% to 10% by weight; oral formulations preferably contain 10% to 95% active ingredient.
Various delivery systems are known and can be used to administer a pharmaceutical preparation of a complex of the invention including, e.g.: (/) encapsulation in liposomes, microparticles, microcapsules; (//) recombinant cells capable of expressing the polypeptides of the complex; (Hi) receptor-mediated endocytosis (see, e.g., Wu et al, J. Biol. Chem. 262: 4429-4432 (1987)); (iv) construction of a nucleic acid encoding the polypeptides of the complex as part of a retroviral or other vector, and the like. Methods of administration include, e.g., intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes. The pharmaceutical preparations of the present invention may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically-active agents. Administration can be systemic or local. In addition, it may be advantageous to administer the pharmaceutical preparation into the central nervous system by any suitable route, including intraventricular and intrathecal injection. Intraventricular injection may be facilitated by an intraventricular catheter attached to a reservoir (e.g., an Ommaya reservoir). Pulmonary administration may also be employed by use of an inhaler or nebulizer, and formulation with an aerosolizing agent. It may also be desirable to administer the pharmaceutical preparation locally to the area in need of treatment; this may be achieved by, for example, and not by way of limitation, local infusion during surgery, topical application, by injection, by means of a catheter, by means of a suppository, or by means of an implant. In a specific embodiment, administration may be by direct injection at the site (or former site) of a malignant tumor or neoplastic or pre-neoplastic tissue.
Alternatively, pharmaceutical preparations of the invention may be delivered in a vesicle, in particular a liposome, (see, e.g., Langer, Science 249:1527-1533 (1990)) or via a controlled release system including, e.g., a delivery pump (see, e.g., Saudek, et al, New Engl. J. Med. 321: 574 (1989) and a semi-permeable polymeric material (see, e.g., Howard, et al, J. Neurosurg. 71: 105 (1989)). Additionally, the controlled release system can be placed in proximity of the therapeutic target (e.g., the brain), thus requiring only a fraction of the systemic dose. See, e.g., Goodson, In: Medical Applications of Controlled Release, 1984 (CRC Press, Bocca Raton, FL).
Screening, Diagnostic, and Therapeutic Methods
The invention further provides methods of identifying an agent which modulate formation or stability a polypeptide complex described herein. By modulate is meant to increase or decrease the rate at which the complex is assembled or dissembled, or to increase or decrease the stability of an assembled complex. Thus, an agent can be tested for its ability to disrupt a complex, or to promote formation or stability of a complex.
In one embodiment, the invention provides a method of identifying an agent that promotes disruption of a complex. The method includes providing a polypeptide complex, contacting the complex with a test agent, and detecting the presence of a polypeptide displaced from the complex. The presence of displaced polypeptide indicates the disruption of the complex by the agent. In some embodiments, the complex is a human ortholog complex, as described above, which includes "bait" and "prey" proteins selected from those recited in Table 7. In other embodiments, the complex contains at least one microtubule or microtubule-associated protein, as described above, and is selected from the complexes recited in Table 4. In other embodiments, the complex contains at least one heme biosynthesis protein, as described above, and is the complex recited in Table 5. In yet another embodiment, the complex contains at least one cell wall or cell wall-synthesis protein, as described above, and is selected from the complexes recited in Table 6. Agents which disrupt complexes of the invention may present novel modulators of cell processes and pathways in which the complexes participate. For example, agents which disrupt complexes involving microtubule proteins may be selected as potential anti-fungal therapeutics. Any compound or other molecule (or mixture or aggregate thereof) can be used as a test agent. In some embodiments, the agent can be a small peptide, or other small molecule produced by e.g., combinatorial synthetic methods known in the art. Disruption of the complex by the test agent, e.g. binding of the agent to the complex, can be determined using art recognized methods, e.g., detection of polypeptide using polypeptide-specific antibodies, as described above. Bound agents can alternatively be identified by comparing the relative electrophoretic mobility of complexes exposed to the test agent to the mobility of complexes that have not been exposed to the test agent.
Agents identified in the screening assays can be further tested for their ability to alter and/or modulate cellular functions, particularly those functions in which the complex has been implicated. These functions include, e.g., control of cell-cycle progression; regulation of transcription; control of intracellular signal transduction, etc., as described in detail above.
In another embodiment, the invention provides methods for inhibiting the interaction of a polypeptide with a ligand, by contacting a complex of the protein and the ligand with an agent that disrupts the complex, as described above. In certain embodiments, the polypeptides are microtubule or microtubule-associated proteins, heme biosynthesis proteins, or cell wall or cell wall-synthesis proteins. In certain embodiments, the ligand is an interacting polypeptide, and the polypeptide and ligands are selected from those recited in Tables 4-6. Inhibition of complex formation allows for modulation of cellular functions and pathways in which the targeted complexes participate. In another embodiment, the invention provides a method for identifying a polypeptide complex in a subject. The method includes the steps of providing a biological sample from the subject, detecting, if present, the level of polypeptide complex. In some embodiments, the complex includes a first polypeptide (a "bait" polypeptide) selected from the polypeptides recited in Table 7, column 2, and a second polypeptide ("prey" polypeptide) selected from the polypeptides recited in Table 7, column 6. Any suitable biological sample potentially containing the complex may be employed, e.g. blood, urine, cerebral-spinal fluid, plasma, etc. Complexes may be detected by, e.g., using complex-specific antibodies as described above. The method provides for diagnostic screening, including in the clinical setting, using, e.g., the kits described above.
In still another embodiment, the present invention provides methods for detecting a polypeptide in a biological sample, by providing a biological sample containing the polypeptide, contacting the sample with a corresponding polypeptide to form a complex under suitable conditions, and detecting the presence of the complex. A complex will form if the sample does, indeed, contain the first polypeptide. In some embodiments, the polypeptide being detecting is a "prey" protein selected from the polypeptides recited in Table 7, column 6, and is detected by complexing with the corresponding "bait" protein recited in Table 7, column 2. Conversely, in other embodiments the polypeptide being detected is the "bait" protein. Alternatively, a yeast "bait" or "prey" ortholog may be employed to form a chimeric complex with the polypeptide in the biological sample.
In still another embodiment, the invention provides methods for removing a first polypeptide from a biological sample by contacting the biological sample with the corresponding second peptide to form a complex under conditions suitable for such formation. The complex is then removed from the sample, effectively removing the first polypeptide. As with the methods of detecting polypeptide described above, the polypeptide being removed may be either a "bait" or "prey" protein, and the second corresponding polypeptide used to remove it may be either a yeast or human ortholog polypeptide.
Methods of determining altered expression of a polypeptide in a subject, e.g. for diagnostic purposes, are also provided by the invention. Altered expression of proteins involved in cell processes and pathways can lead to deleterious effects in the subject. Altered expression of a polypeptide in a given pathway leads to altered formation of complexes which include the polypeptide, hence providing a means for indirect detection of the polypeptide level. The method involves providing a biological sample from a subject, measuring the level of a polypeptide complex of the invention in the sample, and comparing the level to the level of complex in a reference sample having known polypeptide expression. A higher or lower complex level in the sample versus the reference indicates altered expression of either of the polypeptides that forms the complex. The detection of altered expression of a polypeptide can be use to diagnose a given disease state, and or used to identify a subject with a predisposition for a disease state. Any suitable reference sample may be employed, but preferably the test sample and the reference sample are derived from the same medium, e.g. both are urine, etc. The reference sample should be suitably representative of the level polypeptide expressed in a control population.
In a certain embodiment, the polypeptide complex contains a "bait" polypeptide selected from the polypeptides recited in Table 7, column 2, and a "prey" polypeptide selected from the polypeptides recited in Table 7, column 6.
The invention further provides methods for treating or preventing a disease or disorder involving altered levels of a polypeptide complex, or polypeptide, disclosed herein, by administering to a subject a therapeutically-effective amount of at least one molecule that modulates the function of the complex. As discussed above, altered levels of polypeptide. complexes described herein may be implicated in disease states resulting from a deviation in normal function of the pathway in which a complex is implicated. For example, altered levels of the observed complex between YGROlOWp and YLR328Wp may be implicated in disruptions in arginine metabolism, leading to retinal atrophy, for example. In subjects with a deleteriously high level of complex, modulation may consist, for example, by administering an agent which disrupts the complex, or an agent which does not disrupt, but down-regulates, the functional activity of the complex. Alternatively, modulation in subjects with a deleteriously low level of complex may be achieved by pharmaceutical administration of complex, constituent polypeptide, or an agent which up-regulates the functional activity of complex. Pharmaceutical preparations suitable for administration of complex are described above. In one embodiment, a disease or disorder involving altered levels of a polypeptide selected from the polypeptides recited in Table 7, column 2 or the corresponding polypeptides in column 4, is treated by administering a molecule that modulates the function of the polypeptide. In certain embodiments, the modulating molecule is the corresponding polypeptide, e.g. administering a "prey" protein corresponding to a "bait" protein modulates the latter by forming a complex with it.
The details of one or more embodiments of the invention are set forth in the description above. Although any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred methods and materials are now described. For example, additional interactions can be identified using other two-hybrid systems (i.e. using a LexA binding domain fusion or HIS3 as a reporter gene), including variables such as different protein domains or genomic activation domain libraries. Other features, objects, and advantages of the invention will be apparent from the description and from the claims. The following examples are presented in order to more fully illustrate the preferred embodiments of the invention. These examples should in no way be construed as limiting the scope of the invention, as defined by the appended claims.
EXAMPLE 1 —CLONING OF S. CEREVISIAE OPEN-READING FRAMES
6144 potential yeast open-reading frames (ORFs) have been previously described. See Goffeau et al, supra. These ORFs were amplified by PCR as full-length fragments, and each fragment was fused to sequences encoding the Gal4 DNA binding domain and the Gal4 activation domain by gap-repair cloning into the vectors pOBD2 and pOAD. PCR amplified products of the 6144 yeast ORFs were made by amplification of yeast cDNA using 70 oligonucleotide primers to allow recombination with centromeric plasmids pO3D2 and pOAD. See Hudson et al, Genome Res 7: 1169 (1997). The yeast strains used were YULH (MATa ura3-52 trpl lys2 his3 leu2 gal4 gal80 GAL1-URA3 GALl-LacZ) for the Gal4 binding domain fusion in pOBD2 and N106r (MATa ura3-52 his 3 ade2 trpl leu2 gal4 gal80 cyh2 lys2::GALl-HIS3 ura3::GALl-LacZ) for the Gal4 AD fusion in pOAD. Yeast transformations were performed in a 96-well format using the lithium acetate procedure. See Ito et al, J. Bacteriol. 153: 163 (1983). Five μl from individual transformations were grown on selective media lacking leucine (Sc-Leu) or tryptophan (Sc-Trp) for two days and grown at 30°C. Patches of transformants were manually transferred into individual wells on micro-assay plates, to generate 64 barcoded 96-well plates for further use.
Of the 6144 ORFs, 5345 (87%) were successfully cloned into both plasmids (Table 1). Transformants from the Gal4 activation domain array were pooled to form an activation domain library. As yeast strains of opposite mating type were used to generate the two arrays, each binding domain fusion transformant was mated in duplicate to the activation domain library, and diploid cells that expressed interacting pairs were selected. Mating reactions were performed on 96-well filter plates (Millipore MAHV S45) by mixing 107 MATa cells (Gal4 binding domain fusion) with 5xl06 MATa cells (activation domain library) from liquid cultures in complete media (YPAD). After filtration, the 96-well filter plates were incubated overnight at 30°C on rectangular YPAD solid media plates. Cells were collected from each filter with sterile water and the diploids containing potential interactors were selected on media lacking uracil and simultaneously screened by the addition of X-gal by incubating 4 days at 30°C. Each mating generated 5x105 to 106 diploids per well, and was performed in duplicate to insure the reproducibility of the results. Up to 12 blue colonies were picked per mating and submitted for PCR and sequencing. A total of 8676 blue colonies were picked from the screen, 6909 (80%) passed PCR, sequencing, vector trimming, and annotation quality control, and 6215 (72%) passed interaction quality control. To conduct transformation and mating reactions on such a large scale in a timely fashion, 96-well assay plates and a semi-automated Zymark® work station were used throughout the cloning and screening procedures. Sample handling and manipulation during the screens were tracked by computer, and data analysis was carried out using web-based software developed at CuraGen (GeneScape®). The final product of the screening process was a collection of 96-well plates of diploid clones. The activation domain fusion plasmids were sequenced to identify the yeast ORF. The resulting sequences were compared to the yeast sequence database using Blast2. See Altschul et al, J. Mol. Biol. 215: 403 (1990). Using these results, a list of interactors was obtained, as discussed above (see Table 3).
Results from this screen were also compared with a compilation of previously described interactions. Thirty-one protein pairs identified in the present screen were previously reported as two-hybrid interactions, and an additional 18 pairs confirmed interactions previously identified by biochemical assays (co-immunoprecipitation, copurification, affinity column). See MIPS Yeast Genome Database (MYGD) Functional Catalogue, supra.; Mewes et al, supra.; YPD™ information available at www.proteome.com/YPDhome.html. Thus, 49 out of the 692 interactions identified in this screen overlap the approximately 700 interactions in S cerevisiae reported in the literature. See id.
The limited overlap between the results described herein and the literature (7%) can be attributed to specifics of the screen: the exclusive use of full-length proteins as both binding and activation domain fusions and the version of the two-hybrid system used, which includes Gal4 as the binding domain fusion protein, centromeric plasmids, and a stringent reporter gene (URA3). Each of these components can affect the sensitivity of the assay. See Legrain et al, Nucl. Acid. Res. 22: 3241 (1994).

Claims

CLAIMSWE CLAIM:
1. A purified complex comprising a first polypeptide and a second polypeptide, wherein said first polypeptide comprises an amino acid sequence of a polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 1, and wherein said second polypeptide comprises an amino acid sequence of the corresponding polypeptide recited in Table 3, column 5; or said first polypeptide comprises an amino acid sequence of a polypeptide selected from the group consisting of the polypeptides recited in Table 7, column 2, and wherein said second polypeptide comprises the amino acid sequence of the corresponding polypeptide recited in Table 7, column 6; or said first and second polypeptide comprise the amino acid sequences of a first polypeptide-second polypeptide selected from the group consisting of APG7-AUT7,
DUO1-BIM1, BUB3-MAD3, KAR4-MUM2, CLN3-MAD3, EBS1-MAD2, MSB2-MAD2, MSB2-MAD3, NUP157-MAD2, SAP4-MAD2, SAP4-MAD3, SIN4-MAD2, SIN4-MAD3, YDR214W-MAD2, YNL218W-MAD2, MCM16-MCM22, CYP2-JSN1, SPC34-JSN1, YIL065C-JSN1, YLR392C-JSN1, SED1-HEM13, CDC11-SPR28, YFR042W-KRE6, YDR482C-SCW11, SMI1-BAS1, and WSC3-PEX14.
2. The complex of claim 1, wherein said first polypeptide is selected from the group consisting of the polypeptides recited in Table 3, column 1, and wherein said second polypeptide is the corresponding polypeptide recited in Table 3, column 5.
3. The complex of claim 1, wherein said first polypeptide is labeled.
4. The complex of claim 1, wherein said second polypeptide is labeled.
5. The complex of claim 3, wherein said second polypeptide is labeled.
6. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair la- 128a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair lb-128b.
7. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 129a- 140a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 129b- 140b.
8. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 141a-144a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 141b-141b.
9. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 145a-154a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 145b-154b.
10. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 155a-170a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 155b- 170b.
11. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 171a-177a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 171b-177b.
12. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 178a-194a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 178b- 194b.
13. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 195a-310a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 195b-310b.
14. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 31 la-35 la, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 311b-351b.
15. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 352a-367a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 352b-367b.
16. The complex of claim 1 , wherein said first polypeptide is the polypeptide recited in Table 3, column 1, which is denoted as ProPair 368a, and wherein said second polypeptide is the corresponding polypeptide recited in Table 3, column 5, which is denoted as ProPair 368b.
17. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 369a-374aa, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 369b-374b.
18. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 375a-431a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 375b-431b.
19. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 432a-440a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 432b-440b.
20. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 441 a-580a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 441b-580b.
21. The complex of claim 1, wherein said first polypeptide is selected from the group of polypeptides recited in Table 3, column 1, which are denoted as ProPair 581a-692a, and wherein said second polypeptide is the corresponding polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 5, which are denoted as ProPair 581b-692b.
22. The complex of claim 1, wherein said first and second polypeptide comprise the amino acid sequences of a first polypeptide-second polypeptide selected from the group consisting of APG7-AUT7, DUO1-BIM1, BUB3-MAD3, KAR4-MUM2, CLN3-MAD3, EBS1-MAD2, MSB2-MAD2, MSB2-MAD3, NUP157-MAD2, SAP4-MAD2, SAP4-MAD3, SIN4-MAD2, SIN4-MAD3, YDR214W-MAD2, YNL218W-MAD2, MCM16-MCM22, CYP2-JSN1, SPC34-JSN1, YIL065C-JSN1, YLR392C-JSN1, SED1-HEM13, CDC11-SPR28, YFR042W-KRE6, YDR482C-SCW11, SMI1-BAS1, and WSC3-PEX14.
23. The complex of claim 1, wherein said first polypeptide comprises an amino acid sequence of a polypeptide selected from the group consisting of the polypeptides recited in Table 7, column 2, and wherein said second polypeptide comprises the amino acid sequence of the corresponding polypeptide recited in Table 7, column 6.
24. The complex of claim 1, wherein said first polypeptide is selected from the group consisting of the polypeptides recited in Table 7, column 2, and wherein said second polypeptide is the corresponding polypeptide recited in Table 7, column 6.
25. A purified complex comprising a first polypeptide and a second polypeptide, wherein said first polypeptide comprises a region of amino acids of a polypeptide selected from the group consisting of the polypeptides recited in Table 3, column 1 sufficient to allow said first polypeptide to bind said second polypeptide, and wherein said second polypeptide comprises a region of amino acids of the corresponding polypeptide recited in Table 3, column 5 sufficient to bind said first polypeptide.
26. A chimeric polypeptide comprising six or more amino acids of the first polypeptide of claim 1 covalently linked to six or more amino acids of the second polypeptide of claim 1.
27. A nucleic acid encoding the chimeric polypeptide of claim 26.
28. A vector comprising the nucleic acid of claim 27.
29. A cell comprising the vector of claim 28.
30. An antibody which specifically binds the complex of claim 1.
31. The antibody of claim 30, wherein said antibody binds to the complex of claim 1 with higher affinity than it binds to said first or second polypeptide when said polypeptides are not complexed.
32. A pharmaceutical composition comprising the complex of claim 1.
33. A kit comprising a reagent which can specifically detect the complex of claim 1.
34. The kit of claim 33, wherein said reagent is selected from the group consisting of an antibody specific for said complex, an antibody specific for said first polypeptide, and an antibody specific for said second polypeptide.
35. A method of identifying an agent which disrupts a polypeptide complex, the method comprising:
(a) providing the complex of claim 1;
(b) contacting the complex with a test agent; and (c) detecting the presence of a polypeptide displaced from said complex, wherein the presence of displaced polypeptide indicates said agent disrupts said complex.
36. A method for identifying an agent which disrupts a polypeptide complex comprising at least one microtubule/microtubule-associated protein, heme biosynthesis protein, or cell wall/cell-wall synthesis protein, the method comprising:
(a) providing the complex of claim 22;
(b) contacting said complex with a test agent; and
(c) detecting the presence of a polypeptide displaced from said complex, wherein the presence of displaced polypeptide indicates said agent disrupts said complex.
37. A method for inhibiting interaction of a microtubule or microtubule-associated protein, with a ligand, the method comprising: contacting a complex comprising said protein and said ligand with an agent that disrupts said complex, wherein said complex is selected from the group consisting of APG7-AUT7, DUO1-BIM1, BUB3-MAD3, KAR4-MUM2, CLN3-MAD3, EBS1-MAD2, MSB2-MAD2, MSB2-MAD3, NUP157-MAD2, SAP4-MAD2, SAP4-MAD3, SIN4-MAD2, SIN4-MAD3, YDR214W-MAD2, YNL218W-MAD2, MCM16-MCM22, CYP2-JSN1, SPC34-JSN1, YIL065C-JSN1, and YLR392C-JSN1, thereby inhibiting interaction of said protein with said ligand.
38. A method for inhibiting interaction of a heme biosynthesis protein with a ligand, the method comprising: contacting a complex comprising said protein and said ligand with an agent that disrupts said complex, wherein said complex comprises SED1-HEM13, thereby inhibiting interaction of said protein with said ligand.
39. A method for inhibiting interaction of a cell wall or cell wall-synthesis protein with a ligand, said method comprising the step of: contacting a complex comprising said protein and said ligand with an agent that disrupts said complex, wherein said complex is selected from the group consisting of
CDC11-SPR28, YFR042W-KRE6, YDR482C-SCW11, SMI1-BAS1, and
WSC3-PEX14, thereby inhibiting interaction of said protein with said ligand.
40. A method of identifying a polypeptide complex in a subject, the method comprising:
(a) providing a biological sample from said subject, and
(b) detecting, if present, the polypeptide complex of claim 1 in said sample, thereby identifying said complex.
41. A method of detecting a polypeptide in a biological sample, the method comprising:
(a) providing a biological sample comprising the first polypeptide of claim 1 ;
(b) contacting said biological sample with the second polypeptide of claim 1 under conditions suitable for formation of a complex comprising said first and second polypeptides; and (c) detecting the presence of a complex of said first and second polypeptide, wherein the presence of said complex indicates the presence of said first polypeptide in said sample.
42. A method of detecting a polypeptide in a biological sample, the method comprising: (a) providing a biological sample comprising the second polypeptide of claim 1 ;
(b) contacting said biological sample with the first polypeptide of claim 1 under conditions suitable for formation of a complex comprising said first and second polypeptides; and
(c) detecting the presence of a complex of said first and second polypeptide, wherein the presence of said complex indicates the presence of said second polypeptide in said sample.
43. A method of removing a polypeptide from a biological sample, the method comprising:
(a) providing a biological sample comprising the first polypeptide of claim 1 ;
(b) contacting said biological sample with the second polypeptide of claim 1 under conditions suitable for formation of a complex comprising said first and second polypeptide; and
(c) removing said complex from said sample, thereby removing said first polypeptide from said sample.
44. A method of determining altered expression of a polypeptide in a subject, the method comprising:
(a) providing a biological sample from said subject,
(b) measuring the level of the complex of claim 1 in said sample; and
(c) comparing the level of said complex from step (b) to the level of said complex in a reference sample whose level of the complex of claim 1 is known, thereby determining whether said subject has altered expression of said first or second polypeptide.
45. A method of treating or preventing a disease or disorder involving altered levels of the complex of claim 1, the method comprising: administering a therapeutically-effective amount of least one molecule that modulates the function of said complex to a subject in need thereof.
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