A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae

Uetz, Peter; Giot, Loic; Cagney, Gerard; Mansfield, Traci A.; Judson, Richard S.; Knight, James R.; Lockshon, Daniel; Narayan, Vaibhav; Srinivasan, Maithreyan; Pochart, Pascale; Qureshi-Emili, Alia; Li, Ying; Godwin, Brian; Conover, Diana; Kalbfleisch, Theodore; Vijayadamodar, Govindan; Yang, Meijia; Johnston, Mark; Fields, Stanley; Rothberg, Jonathan M.

doi:10.1038/35001009

Cited by 4,706Bioinformatics and Genomic NetworksFungal and yeast genetics researchAdvanced Proteomics Techniques and Applications

A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae

Uetz, Peter, Giot, Loic, Cagney, Gerard, Mansfield, Traci A., Judson, Richard S., Knight, James R., Lockshon, Daniel, Narayan, Vaibhav +12 more·2000·Nature

DOI 10.1038/35001009

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Abstract

Two large-scale yeast two-hybrid screens were undertaken to identify protein-protein interactions between full-length open reading frames predicted from the Saccharomyces cerevisiae genome sequence. In one approach, we constructed a protein array of about 6,000 yeast transformants, with each transformant expressing one of the open reading frames as a fusion to an activation domain. This array was screened by a simple and automated procedure for 192 yeast proteins, with positive responses identified by their positions in the array. In a second approach, we pooled cells expressing one of about 6,000 activation domain fusions to generate a library. We used a high-throughput screening procedure to screen nearly all of the 6,000 predicted yeast proteins, expressed as Gal4 DNA-binding domain fusion proteins, against the library, and characterized positives by sequence analysis. These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. These data reveal interactions that place functionally unclassified proteins in a biological context, interactions between proteins involved in the same biological function, and interactions that link biological functions together into larger cellular processes. The results of these screens are shown here.

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High-throughput experimental techniques designed to identify interacting protein partners have results that are far from complete and often mutually inconsistent.
“Several high-throughput experimental techniques have been designed to identify interacting protein partners23–26, but their results are far from complete and are often mutually inconsistent.”
From AF2Complex predicts direct physical interactions in multimeric proteins with deep learning (2022) · cites this paper as [23]
Y2H, APMS, and other high-throughput experimental approaches have identified many pairs of interacting proteins in yeast and other organisms, but there are discrepancies between sets generated using different methods and considerable false positive and false negative rates.
“Yeast two hybrid (Y2H), affinity-purification mass spectrometry (APMS), and other high-throughput experimental approaches have identified many pairs of interacting proteins in yeast and other organisms (1–5), but there are discrepancies between sets generated using the different methods and considerable false positive and false negative rates (6–8).”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [4]

Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
Methods in yeast genetics
Sherman, F., Fink, G. R., & Hicks, J. B. (1979) · Cold Spring Harbor Laboratory eBooks · Cited by 7,543 · see citing works
Transformation of intact yeast cells treated with alkali cations
Ito, H., Fukuda, Y., Murata, K., & Kimura, A. (1983) · Journal of Bacteriology · doi:10.1128/jb.153.1.163-168.1983 · Cited by 7,518 · see citing works
A novel genetic system to detect protein–protein interactions
Fields, S., & Song, O.-K. (1989) · Nature · doi:10.1038/340245a0 · Cited by 6,152 · see citing works
Self-citation
Methods in Yeast Genetics
Jacob, H. (1988) · Bioelectrochemistry and Bioenergetics · doi:10.1016/0302-4598(88)80052-7 · Cited by 4,911 · see citing works
Life with 6000 Genes
Goffeau, A., Barrell, B., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., Galibert, F., Hoheisel, J., Jacq, C., Johnston, M., et al. (1996) · Science · doi:10.1126/science.274.5287.546 · Cited by 4,420 · see citing works
Self-citation
Genomic Libraries and a Host Strain Designed for Highly Efficient Two-Hybrid Selection in Yeast
James, P. M., Halladay, J. T., & Craig, E. A. (1996) · Genetics · doi:10.1093/genetics/144.4.1425 · Cited by 2,638 · see citing works
DMC1: A meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression
Bishop, D. K., Park, D., Xu, L., & Kleckner, N. (1992) · Cell · doi:10.1016/0092-8674(92)90446-j · Cited by 1,144 · see citing works
S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function
Hoyt, M. A., Totis, L., & Roberts, B. T. (1991) · Cell · doi:10.1016/0092-8674(81)90014-3 · Cited by 1,138 · see citing works
Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens
Fromont‐Racine, M., Rain, J., & Legrain, P. (1997) · Nature Genetics · doi:10.1038/ng0797-277 · Cited by 913 · see citing works
THE STRUCTURE AND FUNCTION OF PROTEINS INVOLVED IN MAMMALIAN PRE-mRNA SPLICING
Krämer, A. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.002055 · Cited by 691 · see citing works
Budding Yeast Cdc20: A Target of the Spindle Checkpoint
Hwang, L. H., Lau, L. F., Smith, D. L., Mistrot, C., Hardwick, K., Hwang, E. S., Amon, A., & Murray, A. W. (1998) · Science · doi:10.1126/science.279.5353.1041 · Cited by 567 · see citing works
Plasmid construction by homologous recombination in yeast
Ma, H., Kunes, S. M., Schatz, P. J., & Botstein, D. (1987) · Gene · doi:10.1016/0378-1119(87)90376-3 · Cited by 563 · see citing works
A three-hybrid system to detect RNA-protein interactions in vivo.
SenGupta, D. J., Zhang, B., Kraemer, B. C., Pochart, P., Fields, S., & Wickens, M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8496 · Cited by 510 · see citing works
Self-citation
Control of the yeast cell cycle by the Cdc28 protein kinase
Nasmyth, K. (1993) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(93)90099-c · Cited by 490 · see citing works
Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex
Neubauer, G., King, A., Rappsilber, J., Calvio, C., Watson, M. A., Ajuh, P., Sleeman, J., Lamond, A. I., & Mann, M. (1998) · Nature Genetics · doi:10.1038/1700 · Cited by 478 · see citing works
Crystal Structures of Two Sm Protein Complexes and Their Implications for the Assembly of the Spliceosomal snRNPs
Kambach, C., Walke, S., Young, R., Avis, J. M., Fortelle, E. D. L., Raker, V. A., Lührmann, R., Li, J., & Nagai, K. (1999) · Cell · doi:10.1016/s0092-8674(00)80550-4 · Cited by 475 · see citing works
Isolation of ORC6 , a Component of the Yeast Origin Recognition Complex by a One-Hybrid System
Li, J. J., & Herskowitz, I. (1993) · Science · doi:10.1126/science.8266075 · Cited by 426 · see citing works
Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast
Wang, M. M., & Reed, R. R. (1993) · Nature · doi:10.1038/364121a0 · Cited by 418 · see citing works
MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair.Preprint
Hollingsworth, N. M., Ponte, L. D., & Halsey, C. (1995) · Genes & Development · doi:10.1101/gad.9.14.1728 · Cited by 414 · see citing works
A Biochemical Genomics Approach for Identifying Genes by the Activity of Their Products
Martzen, M. R., McCraith, S. M., Spinelli, S. L., Torres, F. M., Fields, S., Grayhack, E. J., & Phizicky, E. M. (1999) · Science · doi:10.1126/science.286.5442.1153 · Cited by 407 · see citing works
Self-citation
Complex Formation and Functional Versatility of Mre11 of Budding Yeast in Recombination
Usui, T., Ohta, T., Oshiumi, H., Tomizawa, J.-I., Ogawa, H., & Ogawa, T. (1998) · Cell · doi:10.1016/s0092-8674(00)81640-2 · Cited by 372 · see citing works
A protein linkage map of Escherichia coli bacteriophage T7
Bartel, P. L., Roecklein, J. A., SenGupta, D., & Fields, S. (1996) · Nature Genetics · doi:10.1038/ng0196-72 · Cited by 333 · see citing works
Self-citation
A three-hybrid system for detecting small ligand–protein receptor interactions
Licitra, E. J., & Liu, J. O. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.12817 · Cited by 299 · see citing works
Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins.
Belshaw, P. J., Ho, S. N., Crabtree, G. R., & Schreiber, S. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4604 · Cited by 278 · see citing works
Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole.
Scott, S. V., Hefner-Gravink, A., Morano, K. A., Noda, T., Ohsumi, Y., & Klionsky, D. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12304 · Cited by 263 · see citing works
Mammalian p55CDC Mediates Association of the Spindle Checkpoint Protein Mad2 with the Cyclosome/Anaphase-promoting Complex, and is Involved in Regulating Anaphase Onset and Late Mitotic Events
Kallio, M. J., Weinstein, J., Daum, J. R., Burke, D. J., & Gorbsky, G. J. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.6.1393 · Cited by 240 · see citing works
Characterization of Sm‐like proteins in yeast and their association with U6 snRNA
Mayes, A. E., Verdone, L., Legrain, P., & Beggs, J. D. (1999) · The EMBO Journal · doi:10.1093/emboj/18.15.4321 · Cited by 239 · see citing works
MIPS: a database for protein sequences, homology data and yeast genome information
Mewes, H., Albermann, K., Heumann, K., Liebl, S., & Pfeiffer, F. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.1.28 · Cited by 227 · see citing works
The Yeast Proteome Database (YPD): a model for the organization and presentation of genome-wide functional data
Hodges, P. E., McKee, A. H. Z., Davis, B. P., et al. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.69 · Cited by 215 · see citing works
Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae
Funakoshi, T., Matsuura, A., Noda, T., & Ohsumi, Y. (1997) · Gene · doi:10.1016/s0378-1119(97)00031-0 · Cited by 166 · see citing works
The major yeast poly(A)-binding protein is associated with cleavage factor IA and functions in premessenger RNA 3′-end formation
Minvielle-Sébastia, L., Preker, P., Wiederkehr, T., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.7897 · Cited by 159 · see citing works
Isolation and characterization of Saccharomyces cerevisiae mRNA transport-defective (mtr) mutants [published erratum appears in J Cell Biol 1994 Sep;126(6):1627]
Kadowaki, T. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.126.3.649 · Cited by 156 · see citing works
Transport of a Large Oligomeric Protein by the Cytoplasm to Vacuole Protein Targeting Pathway
Kim, J., Scott, S. V., Oda, M. N., & Klionsky, D. J. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.3.609 · Cited by 144 · see citing works
A protein–protein interaction map of yeast RNA polymerase III
Flores, A., Briand, J.-F., Gadal, O., Andrau, J., Rubbi, L., Mullem, V. V., Boschiero, C., Goussot, M., Marck, C., Carles, C., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.7815 · Cited by 142 · see citing works
Capped mRNA Degradation Intermediates Accumulate in the Yeast spb8-2 Mutant
Boeck, R., Lapeyre, B., Brown, C. E., & Sachs, A. B. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.9.5062 · Cited by 135 · see citing works
The Complete Set of Predicted Genes from Saccharomyces cerevisiae in a Readily Usable FormPreprint
Hudson, J. R., Dawson, E. P., Rushing, K. L., Jackson, C. H., Lockshon, D., Conover, D., Lanciault, C., Harris, J. R., Simmons, S. J., Rothstein, R. J., et al. (1997) · Genome Research · doi:10.1101/gr.7.12.1169 · Cited by 120 · see citing works
Self-citation
Delivery of proteins and organelles to the vacuole from the cytoplasm
Scott, S. V., & Klionsky, D. J. (1998) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(98)80068-9 · Cited by 108 · see citing works
Detection of protein - protein interactions using different vectors in the two-hybrid system
Legrain, P., Dokhélar, M., & Transy, C. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.15.3241 · Cited by 73 · see citing works
Phosphorylation of Human MAD1 by the BUB1 Kinasein Vitro
Seeley, T. W., Wang, L., & Zhen, J. Y. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0514 · Cited by 47 · see citing works
Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency.
Ramesh, V., Gusella, J. F., & Shih, V. E. (1991) · PubMed · Cited by 22 · see citing works
Suppression of a conditional mutation in alpha-tubulin by overexpression of two checkpoint genes
Guénette, S. Y., Magendantz, M., & Solomon, F. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.3.1195 · Cited by 16 · see citing works

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Huh, W.-K., Falvo, J. V., Gerke, L. C., Carroll, A. S., Howson, R. W., Weissman, J. S., & O'Shea, E. K. (2003) · Nature · doi:10.1038/nature02026 · Cited by 4,248 · see citing works
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Edwards, A. M., Kus, B., Jansen, R., Greenbaum, D., Greenblatt, J., & Gerstein, M. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02763-4 · Cited by 276 · see citing works
Trans-Omics: How To Reconstruct Biochemical Networks Across Multiple ‘Omic’ Layers
Yugi, K., Kubota, H., Hatano, A., & Kuroda, S. (2016) · Trends in Biotechnology · doi:10.1016/j.tibtech.2015.12.013 · Cited by 258 · see citing works
The S. cerevisiae SET3 complex includes two histone deacetylases, Hos2 and Hst1, and is a meiotic-specific repressor of the sporulation gene program
Pijnappel, W. W. M. P., Schaft, D., Roguev, A., Shevchenko, A., Tekotte, H., Wilm, M., Rigaut, G., Séraphin, B., Aasland, R., & Stewart, A. F. (2001) · Genes & Development · doi:10.1101/gad.207401 · Cited by 265 · see citing works
AF2Complex predicts direct physical interactions in multimeric proteins with deep learning
Gao, M., Nakajima An, D., Parks, J. M., & Skolnick, J. (2022) · Nature Communications · doi:10.1038/s41467-022-29394-2 · Cited by 252 · see citing works
A Systems Biology Approach for the Investigation of the Heparin/Heparan Sulfate Interactome
Ori, A., Wilkinson, M. C., & Fernig, D. G. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.228114 · Cited by 251 · see citing works
Combining biological networks to predict genetic interactions
Wong, S. L., Zhang, L. V., Tong, A. H. Y., Li, Z., Goldberg, D. S., King, O. D., Lesage, G., Vidal, M., Andrews, B., Bussey, H., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406614101 · Cited by 245 · see citing works
Probabilistic assembly of human protein interaction networks from label-free quantitative proteomics
Sardiu, M. E., Cai, Y., Jin, J., Swanson, S. K., Conaway, R. C., Conaway, J. W., Florens, L., & Washburn, M. P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706983105 · Cited by 226 · see citing works
The Conserved Transmembrane Nucleoporin NDC1 Is Required for Nuclear Pore Complex Assembly in Vertebrate Cells
Mansfeld, J., Güttinger, S., Hawryluk-Gara, L. A., Panté, N., Mall, M., Galy, V., Haselmann, U., Mühlhäusser, P., Wozniak, R. W., Mattaj, I. W., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.015 · Cited by 221 · see citing works
Integrating physical and genetic maps: from genomes to interaction networks
Beyer, A., Bandyopadhyay, S., & Ideker, T. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2144 · Cited by 207 · see citing works
Integrating diverse data for structure determination of macromolecular assemblies
Alber, F., Förster, F., Korkin, D., Topf, M., & Sali, A. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.060407.135530 · Cited by 206 · see citing works
Protein-protein interaction networks and biology—what's the connection?
Hakes, L., Pinney, J. W., Robertson, D. L., & Lovell, S. C. (2008) · Nature Biotechnology · doi:10.1038/nbt0108-69 · Cited by 200 · see citing works
Protein-protein interaction networks: probing disease mechanisms using model systems
Kuzmanov, U., & Emili, A. (2013) · Genome Medicine · doi:10.1186/gm441 · Cited by 197 · see citing works
Self-citation
Correlation between gene expression profiles and protein-protein interactions within and across genomes
Bhardwaj, N., & Lu, H. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti398 · Cited by 186 · see citing works
Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps
Huang, H., Jedynak, B. M., & Bader, J. S. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030214 · Cited by 182 · see citing works
A Physical Interaction Network of Dengue Virus and Human Proteins
Khadka, S., Vangeloff, A. D., Zhang, C., Siddavatam, P., Heaton, N. S., Wang, L., Sengupta, R., Sahasrabudhe, S., Randall, G., Gribskov, M., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.012187 · Cited by 175 · see citing works
Geometric De-noising of Protein-Protein Interaction Networks
Kuchaiev, O., Rašajski, M., Higham, D. J., & Pržulj, N. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000454 · Cited by 180 · see citing works
Antiviral Protein Ski8 Is a Direct Partner of Spo11 in Meiotic DNA Break Formation, Independent of Its Cytoplasmic Role in RNA Metabolism
Arora, C., Kee, K., Maleki, S., & Keeney, S. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00063-2 · Cited by 173 · see citing works
A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p).
Millson, S. H., Truman, A. W., King, V., Prodromou, C., Pearl, L. H., & Piper, P. W. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.5.849-860.2005 · Cited by 172 · see citing works
Biochemical approaches for discovering protein–protein interactions
Miernyk, J. A., & Thelen, J. J. (2008) · The Plant Journal · doi:10.1111/j.1365-313x.2007.03316.x · Cited by 165 · see citing works
Molecular architecture of the yeast Mediator complex
Robinson, P. J., Trnka, M. J., Pellarin, R., Greenberg, C. H., Bushnell, D. A., Davis, R., Burlingame, A. L., Sali, A., & Kornberg, R. D. (2015) · eLife · doi:10.7554/elife.08719 · Cited by 150 · see citing works
Identification of Protein Interactions Involved in Cellular Signaling
Westermarck, J., Ivaska, J., & Corthals, G. L. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r113.027771 · Cited by 143 · see citing works
Structural space of protein–protein interfaces is degenerate, close to complete, and highly connected
Gao, M., & Skolnick, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012820107 · Cited by 139 · see citing works
Protein–protein interaction networks: how can a hub protein bind so many different partners?
Tsai, C.-J., Ma, B., & Nussinov, R. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.07.007 · Cited by 138 · see citing works
Localization and roles of Ski8p protein in Sordaria meiosis and delineation of three mechanistically distinct steps of meiotic homolog juxtaposition
Tessé, S., Storlazzi, A., Kleckner, N., Gargano, S., & Zickler, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2034282100 · Cited by 132 · see citing works
Robotic cloning and protein production platform of the northeast structural genomics consortium
Acton, T. B., Gunsalus, K. C., Xiao, R., Ma, L. C., Aramini, J., Baran, M. C., Chiang, Y.-W., Climent, T., Cooper, B., Denissova, N. G., et al. (2005) · Methods in Enzymology · doi:10.1016/s0076-6879(05)94008-1 · Cited by 129 · see citing works
Eukaryotic DNA damage checkpoint activation in response to double-strand breaks
Finn, K., Lowndes, N. F., & Grenon, M. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0875-3 · Cited by 127 · see citing works
The GPI Transamidase Complex ofSaccharomyces cerevisiaeContains Gaa1p, Gpi8p, and Gpi16p
Fraering, P., Imhof, I., Meyer, U., Strub, J.-M., van Dorsselaer, A., Vionnet, C., & Conzelmann, A. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.10.3295 · Cited by 111 · see citing works
Aspergillus fumigatus Survival in Alkaline and Extreme Zinc-Limiting Environments Relies on the Induction of a Zinc Homeostasis System Encoded by the zrfC and aspf2 Genes
Amich, J., Vicentefranqueira, R., Leal, F., & Calera, J. A. (2010) · Eukaryotic Cell · doi:10.1128/ec.00348-09 · Cited by 105 · see citing works
A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs
Ramani, A. K., Li, Z., Hart, G. T., Carlson, M. W., Boutz, D. R., & Marcotte, E. M. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.19 · Cited by 78 · see citing works
Prism: Protein-Protein Interaction Prediction by Structural Matching
Keskin, O., Nussinov, R., & Gursoy, A. (2008) · Methods in Molecular Biology · doi:10.1007/978-1-59745-398-1_30 · Cited by 80 · see citing works
Integrative structure modeling of macromolecular assemblies from proteomics data
Lasker, K., Phillips, J. L., Russel, D., Velázquez-Muriel, J., Schneidman-Duhovny, D., Tjioe, E., Webb, B., Schlessinger, A., & Sali, A. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r110.000067 · Cited by 71 · see citing works
A domain of Rad9 specifically required for activation of Chk1 in budding yeast
Blankley, R. T., & Lydall, D. (2004) · Journal of Cell Science · doi:10.1242/jcs.00907 · Cited by 69 · see citing works
Temporal patterns of genes in scientific publications
Pfeiffer, T., & Hoffmann, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701315104 · Cited by 64 · see citing works
M-TASSER: An Algorithm for Protein Quaternary Structure Prediction
Chen, H., & Skolnick, J. (2008) · Biophysical Journal · doi:10.1529/biophysj.107.114280 · Cited by 68 · see citing works
In the yeast heat shock response, Hsf1-directed induction of Hsp90 facilitates the activation of the Slt2 (Mpk1) mitogen-activated protein kinase required for cell integrity.
Truman, A. W., Millson, S. H., Nuttall, J. M., Mollapour, M., Prodromou, C., & Piper, P. W. (2007) · Eukaryotic Cell · doi:10.1128/ec.00009-07 · Cited by 59 · see citing works
Systems biology in neuroscience: bridging genes to cognition
Grant, S. G. (2003) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2003.09.016 · Cited by 53 · see citing works
Higher-order molecular organization as a source of biological function
Gaudelet, T., Malod-Dognin, N., & Pržulj, N. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty570 · Cited by 46 · see citing works
New benchmark metrics for protein‐protein docking methods
Gao, M., & Skolnick, J. (2011) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.22987 · Cited by 42 · see citing works
Functional interactions among members of the meiotic initiation complex in fission yeast
Steiner, S., Kohli, J., & Ludin, K. (2010) · Current Genetics · doi:10.1007/s00294-010-0296-0 · Cited by 34 · see citing works
Beyond hairballs: The use of quantitative mass spectrometry data to understand protein–protein interactions
Gingras, A.-C., & Raught, B. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.03.065 · Cited by 34 · see citing works
Protein-Protein Interactions and Aggregation Inhibitors in Alzheimer’s Disease
Ganeshpurkar, A., Swetha, R., Kumar, D., Gangaram, G. P., Singh, R., Gutti, G., Jana, S., Kumar, D., Kumar, A., & Singh, S. K. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190304153353 · Cited by 30 · see citing works
Introduction
Janin, J., & Wodak, S. J. (2002) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(02)61000-9 · Cited by 31 · see citing works

Defining Viral Protein Interactomes Using the Yeast Two-Hybrid Assay
Diefenbach, E., Cunningham, A. L., & Diefenbach, R. J. (2005) · Current Proteomics · doi:10.2174/157016405774641138 · Cited by 1 · see citing works
Yeast Split-Ubiquitin-Based Cytosolic Screening System to Detect Interactions Between Transcriptionally Active Proteins
Möckli, N., Deplazes‐Zemp, A., Hassa, P. O., et al. (2007) · BioTechniques · doi:10.2144/000112455 · Cited by 85 · see citing works
Two‐Hybrid Systems to Measure Protein–Protein Interactions
Finley, R. L., & Mairiang, D. (2018) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0005980.pub3 · Cited by 3 · see citing works
Two‐Hybrid Systems to Measure Protein–Protein Interactions
Finley, R. L., & Mairiang, D. (2014) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0005980.pub2 · Cited by 1 · see citing works
Detection of Protein-Protein Interactions Using Protein-Fragment Complementation Assays (PCA)
Barnard, E., McFerran, N. V., Nelson, J., & Timson, D. J. (2007) · Current Proteomics · doi:10.2174/157016407781387348 · Cited by 11 · see citing works

Authors: Uetz, P., Giot, L., Cagney, G., Mansfield, T. A., Judson, R. S., Knight, J. R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., Qureshi-Emili, A., Li, Y., Godwin, B., Conover, D., Kalbfleisch, T., Vijayadamodar, G., Yang, M., Johnston, M., Fields, S., & Rothberg, J. M.
Affiliations: University of Washington (US)
Howard Hughes Medical Institute (US)
Washington University in St. Louis (US)
Corresponding author: Fields, Stanley
ORCID: Uetz, Peter
Cagney, Gerard
Judson, Richard S.
Knight, James R.
Narayan, Vaibhav
Srinivasan, Maithreyan
Li, Ying
Yang, Meijia
Johnston, Mark
Fields, Stanley
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2000-02
Volume: 403
Issue: 6770
Pages: 623-627
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35001009
OpenAlex: W2065304353
Cited by: 4,706
References: 42
Citations by year: 2026: 30 · 2025: 27 · 2024: 44 · 2023: 35 · 2022: 61 · 2021: 62 · 2020: 56 · 2019: 79 · 2018: 83 · 2017: 83 · 2016: 78 · 2015: 119 · 2014: 130 · 2013: 174 · 2012: 193
FWCI: 116.43
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords: protein-protein interaction, Saccharomyces cerevisiae, yeast two-hybrid screen, protein microarrays, GAL4 DNA-binding domain, high-throughput screening, protein-protein interaction network, cellular processes
MeSH terms: Fungal Proteins, Protein Binding, Saccharomyces cerevisiae, Open Reading Frames, Protein Structure, Tertiary, Peptide Library, Two-Hybrid System Techniques

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A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae

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