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Identifying novel protein phenotype annotations by hybridizing protein–protein interactions and protein sequence similarities

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Abstract

Studies of protein phenotypes represent a central challenge of modern genetics in the post-genome era because effective and accurate investigation of protein phenotypes is one of the most critical procedures to identify functional biological processes in microscale, which involves the analysis of multifactorial traits and has greatly contributed to the development of modern biology in the post genome era. Therefore, we have developed a novel computational method that identifies novel proteins associated with certain phenotypes in yeast based on the protein–protein interaction network. Unlike some existing network-based computational methods that identify the phenotype of a query protein based on its direct neighbors in the local network, the proposed method identifies novel candidate proteins for a certain phenotype by considering all annotated proteins with this phenotype on the global network using a shortest path (SP) algorithm. The identified proteins are further filtered using both a permutation test and their interactions and sequence similarities to annotated proteins. We compared our method with another widely used method called random walk with restart (RWR). The biological functions of proteins for each phenotype identified by our SP method and the RWR method were analyzed and compared. The results confirmed a large proportion of our novel protein phenotype annotation, and the RWR method showed a higher false positive rate than the SP method. Our method is equally effective for the prediction of proteins involving in all the eleven clustered yeast phenotypes with a quite low false positive rate. Considering the universality and generalizability of our supporting materials and computing strategies, our method can further be applied to study other organisms and the new functions we predicted can provide pertinent instructions for the further experimental verifications.

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References

  • Acevedo-Torres K, Fonseca-Williams S, Ayala-Torres S, Torres-Ramos CA (2009) Requirement of the Saccharomyces cerevisiae APN1 gene for the repair of mitochondrial DNA alkylation damage. Environ Mol Mutagen 50:317–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aguilar C, Davidson C, Dix M, Stead K, Zheng K, Hartman T, Guacci V (2005) Topoisomerase II suppresses the temperature sensitivity of Saccharomyces cerevisiae pds5 mutants, but not the defect in sister chromatid cohesion. Cell Cycle 4:1294–1304

    Article  CAS  PubMed  Google Scholar 

  • Ali M, Chernova TA, Newnam GP, Yin L, Shanks J, Karpova TS, Lee A, Laur O, Subramanian S, Kim D, McNally JG, Seyfried NT, Chernoff YO, Wilkinson KD (2014) Stress-dependent proteolytic processing of the actin assembly protein Lsb1 modulates a yeast prion. J Biol Chem 289:27625–27639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  CAS  PubMed  Google Scholar 

  • Attanapola SL, Alexander CJ, Mulvihill DP (2009) Ste20-kinase-dependent TEDS-site phosphorylation modulates the dynamic localisation and endocytic function of the fission yeast class I myosin, Myo1. J Cell Sci 122:3856–3861

    Article  CAS  PubMed  Google Scholar 

  • Avendaño A, Riego L, DeLuna A, Aranda C, Romero G, Ishida C, Vázquez-Acevedo M, Rodarte B, Recillas-Targa F, Valenzuela L (2005) Swi/SNF-GCN5-dependent chromatin remodelling determines induced expression of GDH3, one of the paralogous genes responsible for ammonium assimilation and glutamate biosynthesis in Saccharomyces cerevisiae. Mol Microbiol 57:291–305

    Article  PubMed  CAS  Google Scholar 

  • Baranwal S, Azad GK, Singh V, Tomar RS (2014) Signaling of chloroquine-induced stress in the yeast Saccharomyces cerevisiae requires the Hog1 and Slt2 mitogen-activated protein kinase pathways. Antimicrob Agents Chemother 58:5552–5566

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Beach D, Rodgers L, Gould J (1985) ran1+ controls the transition from mitotic division to meiosis in fission yeast. Curr Genet 10:297–311

    Article  CAS  PubMed  Google Scholar 

  • Bin-Umer MA, McLaughlin JE, Butterly MS, McCormick S, Tumer NE (2014) Elimination of damaged mitochondria through mitophagy reduces mitochondrial oxidative stress and increases tolerance to trichothecenes. Proc Natl Acad Sci USA 111:11798–11803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biswas TK, Getz GS (1999) The single amino acid changes in the yeast mitochondrial S4 ribosomal protein cause temperature-sensitive defect in the accumulation of mitochondrial 15S rRNA. Biochemistry 38:13042–13054

    Article  CAS  PubMed  Google Scholar 

  • Bohovych I, Donaldson G, Christianson S, Zahayko N, Khalimonchuk O (2014) Stress-triggered activation of the metalloprotease Oma1 involves its C-terminal region and is important for mitochondrial stress protection in yeast. J Biol Chem 289:13259–13272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bohr VA (2013) Mitochondrial genome integrity and neurodegeneration. J Neurochem 125:92-92

    Google Scholar 

  • Boon-Unge K, Yu Q, Zou T, Zhou A, Govitrapong P, Zhou J (2007) Emetine regulates the alternative splicing of Bcl-x through a protein phosphatase 1-dependent mechanism. Chem Biol 14:1386–1392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braun M, Fountoulakis M, Papadopoulou A, Vougas K, Seidel I, Höller T, Yeghiazaryan K, Schild HH, Kuhn W, Golubnitschaja O (2009) Down-regulation of microfilamental network-associated proteins in leukocytes of breast cancer patients: potential application to predictive diagnosis. Cancer Genomics Proteomics 6:31–40

    CAS  PubMed  Google Scholar 

  • Čabart P, Jin H, Li L, Kaplan CD (2014) Activation and reactivation of the RNA polymerase II trigger loop for intrinsic RNA cleavage and catalysis. Transcription 5:e28869

    Article  PubMed  PubMed Central  Google Scholar 

  • Canepa A, Divino JC, Forsberg AM, Perfumo F, Carrea A, Verrina E, Podesta E, Gusmano R, Bergstrom J (1996) Children on continuous ambulatorial peritoneal dialysis: muscle and plasma proteins, amino acids and nutritional status. Clin Nephrol 46:125–131

    CAS  PubMed  Google Scholar 

  • Cao LW, Yu L, Guo ZM, Shen AJ, Guo YN, Liang XM (2014) N-Glycosylation site analysis of proteins from Saccharomyces cerevisiae by using hydrophilic interaction liquid chromatography-based enrichment, parallel deglycosylation, and mass spectrometry. J Proteome Res 13:1485–1493

    Article  CAS  PubMed  Google Scholar 

  • Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, Turay AM, Frauwirth KA (2010) Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J Immunol 185:1037–1044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chanklan R, Mizunuma M, Kongkathip N, Hasitapan K, Kongkathip B, Miyakawa T (2008) Identification of Saccharomyces cerevisiae Tub1 α-tubulin as a potential target for NKH-7, a cytotoxic 1-naphthol derivative compound. Biosci Biotechnol Biochem 72:1023–1031

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Lu L, Feng KR, Li WJ, Song J, Zheng LL, Yuan YL, Zeng ZB, Feng KY, Lu WC, Cai YD (2009) Multiple classifier integration for the prediction of protein structural classes. J Comput Chem 30:2248–2254

    CAS  PubMed  Google Scholar 

  • Chen D, Chia JY, Liu SQ (2014a) Impact of addition of aromatic amino acids on non-volatile and volatile compounds in lychee wine fermented with Saccharomyces cerevisiae MERIT.ferm. Int J Food Microbiol 170:12–20

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Li J, Wang W, Guo X, Li Y, Mao X, Chen X, Guan W (2014b) Mutations adjacent to the end of transmembrane helices 6 and 7 independently affect drug efflux capacity of yeast ABC transporter Pdr5p. Biochim Biophys Acta 1838:932–939

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Xing Z, Huang T, Shu Y, Huang G, Li HP (2014c) Application of the shortest path algorithm for the discovery of breast cancer related genes. Curr Bioinform. doi:10.2174/1574893611666151119220024

  • Chen L, Chu C, Kong X, Huang G, Huang T (2015) A hybrid computational method for the discovery of novel reproduction-related genes. PLoS One 10:e0117090

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheng C, Shou C, Yip KY, Gerstein MB (2011) Genome-wide analysis of chromatin features identifies histone modification sensitive and insensitive yeast transcription factors. Genome Biol 12:R111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng XY, Huang WJ, Hu SC, Zhang HL, Wang H, Zhang JX, Lin HH, Chen YZ, Zou Q, Ji ZL (2012) A global characterization and identification of multifunctional enzymes. PLoS One 7:e38979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colby G, Ishii Y, Tzagoloff A (1998) Suppression of sdh1 mutations by the SDH1b gene of Saccharomyces cerevisiae. Yeast 14:1001–1006

    Article  CAS  PubMed  Google Scholar 

  • Colley A, Beggs JD, Tollervey D, Lafontaine DL (2000) Dhr1p, a putative DEAH-box RNA helicase, is associated with the box C+ D snoRNP U3. Mol Cell Biol 20:7238–7246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coudreuse D, van Bakel H, Dewez M, Soutourina J, Parnell T, Vandenhaute J, Cairns B, Werner M, Hermand D (2010) A gene-specific requirement of RNA polymerase II CTD phosphorylation for sexual differentiation in S. pombe. Curr Biol 20:1053–1064

    Article  CAS  PubMed  Google Scholar 

  • Crapeau M, Merhi A, André B (2014) Stress conditions promote yeast Gap1 permease ubiquitylation and down-regulation via the arrestin-like bul and aly proteins. J Biol Chem 289:22103–22116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cunha TF, Moreira JB, Paixao NA, Campos JC, Monteiro AW, Bacurau AV, Bueno CR Jr, Ferreira JC, Brum PC (2012) Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice. J Appl Physiol (1985) 112:1839–1846

    Article  CAS  Google Scholar 

  • Daraba A, Gali VK, Halmai M, Haracska L, Unk I (2014) Def1 promotes the degradation of Pol3 for polymerase exchange to occur during DNA-damage-induced mutagenesis in Saccharomyces cerevisiae. PLoS Biol 12:e1001771

    Article  PubMed  PubMed Central  Google Scholar 

  • De Zoysa P, Connerton I, Watson D, Johnston J (1991) Cloning, sequencing and expression of the Schwanniomyces occidentalis NADP-dependent glutamate dehydrogenase gene. Curr Genet 20:219–224

    Article  PubMed  Google Scholar 

  • Dekanty A, Barrio L, Milan M (2015) Contributions of DNA repair, cell cycle checkpoints and cell death to suppressing the DNA damage-induced tumorigenic behavior of Drosophila epithelial cells. Oncogene 34:978–985

    Article  CAS  PubMed  Google Scholar 

  • Dembowski JA, Kuo B, Woolford JL (2013) Has1 regulates consecutive maturation and processing steps for assembly of 60S ribosomal subunits. Nucleic Acids Res 41:7889–7904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Díaz-Blanco NL, Rodríguez-Medina JR (2007) Dosage rescue by UBC4 restores cell wall integrity in Saccharomyces cerevisiae lacking the myosin type II gene MYO1. Yeast 24:343–355

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dikicioglu D, Pir P, Oliver SG (2013) Predicting complex phenotype–genotype interactions to enable yeast engineering: Saccharomyces cerevisiae as a model organism and a cell factory. Biotechnol J 8:1017–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Domkin V, Thelander L, Chabes A (2002) Yeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex. J Biol Chem 277:18574–18578

    Article  CAS  PubMed  Google Scholar 

  • Doucette CD, Greenshields AL, Liwski RS, Hoskin DW (2015) Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways. Toxicol Lett 234:1–12

    Article  CAS  PubMed  Google Scholar 

  • Dunn CD, Jensen RE (2003) Suppression of a defect in mitochondrial protein import identifies cytosolic proteins required for viability of yeast cells lacking mitochondrial DNA. Genetics 165:35–45

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eren Z, Gurol Y, Sonmezoglu M, Eren HS, Celik G, Kantarci G (2014) Saccharomyces cerevisiae fungemia in an elderly patient following probiotic treatment. Mikrobiyol Bul 48:351–355

    Article  PubMed  Google Scholar 

  • Færgeman NJ, Black PN, Zhao XD, Knudsen J, DiRusso CC (2001) The Acyl-CoA synthetases encoded within FAA1 and FAA4 in Saccharomyces cerevisiae function as components of the fatty acid transport system linking import, activation, and intracellular utilization. J Biol Chem 276:37051–37059

    Article  PubMed  Google Scholar 

  • Ferreira C, Silva S, Faria-Oliveira F, Pinho E, Henriques M, Lucas C (2010) Candida albicans virulence and drug-resistance requires the O-acyltransferase Gup1p. BMC Microbiol 10:238

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41:D808–D815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fritz BR, Jewett MC (2014) The impact of transcriptional tuning on in vitro integrated rRNA transcription and ribosome construction. Nucleic Acids Res 42:6774–6785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujimura H (2000) The immunosuppressive drug leflunomide affects mating-pheromone response and sporu lation by different mechanisms in Saccharomyces cerevisiae. FEMS Microbiol Lett 191:57–60

    Article  CAS  PubMed  Google Scholar 

  • Fujimura M, Ochiai N, Oshima M, Motoyama T, Ichiishi A, Usami R, Horikoshi K, Yamaguchi I (2003) Putative homologs of SSK22 MAPKK kinase and PBS2 MAPK kinase of Saccharomyces cerevisiae encoded by os-4 and os-5 genes for osmotic sensitivity and fungicide…. Biosci Biotechnol Biochem 67:186–191

    Article  CAS  PubMed  Google Scholar 

  • Gagneur J, Stegle O, Zhu C, Jakob P, Tekkedil MM, Aiyar RS, Schuon A-K, Pe’er D, Steinmetz LM (2013) Genotype-environment interactions reveal causal pathways that mediate genetic effects on phenotype. PLoS Genet 9:e1003803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao P, Wang QP, Chen L, Huang T (2012a) Prediction of human genes regulatory functions based on proteinprotein interaction network. Protein Pept Lett 19:910–916

    Article  CAS  PubMed  Google Scholar 

  • Gao YF, Chen L, Cai YD, Feng KY, Huang T, Jiang Y (2012b) Predicting metabolic pathways of small molecules and enzymes based on interaction information of chemicals and proteins. PLoS One 7:e45944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • García-Gómez JJ, Lebaron S, Froment C, Monsarrat B, Henry Y, De La Cruz J (2011) Dynamics of the putative RNA helicase Spb4 during ribosome assembly in Saccharomyces cerevisiae. Mol Cell Biol 31:4156–4164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gari E, Volpe T, Wang H, Gallego C, Futcher B, Aldea M (2001) Whi3 binds the mRNA of the G1 cyclin CLN3 to modulate cell fate in budding yeast. Genes Dev 15:2803–2808

    CAS  PubMed  PubMed Central  Google Scholar 

  • Geng C, Paukstelis PJ (2014) An in vitro peptide complementation assay for CYT-18-dependent group I intron splicing reveals a new role for the N-terminus. Biochemistry 53:1311–1319

    Article  CAS  PubMed  Google Scholar 

  • Ghodke I, Muniyappa K (2013) Processing of DNA double-stranded breaks and intermediates of recombination and repair by Saccharomyces cerevisiae Mre11 and its stimulation by Rad50, Xrs2, and Sae2 proteins. J Biol Chem 288:11273–11286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghosh K, Tagore DM, Anumula R, Lakshmaiah B, Kumar PPBS, Singaram S, Matan T, Kallipatti S, Selvam S, Krishnamurthy P, Ramarao M (2013) Crystal structure of rat intestinal alkaline phosphatase—role of crown domain in mammalian alkaline phosphatases. J Struct Biol 184:182–192

    Article  CAS  PubMed  Google Scholar 

  • Gonçalves DL, Matsushika A, Belisa B, Goshima T, Bon EP, Stambuk BU (2014) Xylose and xylose/glucose co-fermentation by recombinant Saccharomyces cerevisiae strains expressing individual hexose transporters. Enzyme Microb Technol 63:13–20

    Article  PubMed  CAS  Google Scholar 

  • Gormen TH, Leiserson CE, Rivest RL, Stein C (eds) (1990) Introduction to algorithms. MIT press, Cambridge

    Google Scholar 

  • Grisvard J, Aubusson-Fleury A, Baroin-Tourancheau A (2010) Multiple uses of Lys63-polyubiquitination in the ciliate Sterkiella histriomuscorum. Protist 161:479–488

    Article  CAS  PubMed  Google Scholar 

  • Gritenaite D, Princz LN, Szakal B, Bantele SC, Wendeler L, Schilbach S, Habermann BH, Matos J, Lisby M, Branzei D, Pfander B (2014) A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication. Genes Dev 28:1604–1619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guacci V, Koshland D (2012) Cohesin-independent segregation of sister chromatids in budding yeast. Mol Biol Cell 23:729–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Güldener U, Münsterkötter M, Kastenmüller G, Strack N, Van Helden J, Lemer C, Richelles J, Wodak S, Garcia-Martinez J, Perez-Ortin J (2005) CYGD: the comprehensive yeast genome database. Nucleic Acids Res 33:D364–D368

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo S, Shen X, Yan G, Ma D, Bai X, Li S, Jiang Y (2009) A MAP kinase dependent feedback mechanism controls Rho1 GTPase and actin distribution in yeast. PLoS One 4:e6089

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo M, Wang R, Wang J, Hua K, Wang Y, Liu X, Yao S (2014) ALT1, a Snf2 family chromatin remodeling atpase, negatively regulates alkaline tolerance through enhanced defense against oxidative stress in rice. PLoS One 9:e112515

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harries E, Carmona L, Munoz A, Ibeas JI, Read ND, Gandia M, Marcos JF (2013) Genes involved in protein glycosylation determine the activity and cell internalization of the antifungal peptide PAF26 in Saccharomyces cerevisiae. Fungal Genet Biol 58–59:105–115

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto TB, Nagasaki M, Kojima K, Miyano S (2009) BFL: a node and edge betweenness based fast layout algorithm for large scale networks. BMC Bioinform 10:19

    Article  Google Scholar 

  • He X, Zhu X, Wang X, Wang W, Dai Y, Yan Q (2013) Nuclear modifier MTO2 modulates the aminoglycoside-sensitivity of mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae. PLoS One 8:e81490

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hofmeister-Brix A, Lenzen S, Baltrusch S (2013) The ubiquitin-proteasome system regulates the stability and activity of the glucose sensor glucokinase in pancreatic beta-cells. Biochem J 456:173–184

    Article  PubMed  CAS  Google Scholar 

  • Horton MJ, Brandon CA, Morris TJ, Braun TW, Yaw KM, Sciote JJ (2001) Abundant expression of myosin heavy-chain IIB RNA in a subset of human masseter muscle fibres. Arch Oral Biol 46:1039–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hota SK, Bhardwaj SK, Deindl S, Y-c Lin, Zhuang X, Bartholomew B (2013) Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains. Nat Struct Mol Biol 20:222–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou Y, Zhang Z, Xu Q, Wang H, Xu Y, Chen K (2014) Inhibitor of growth 4 induces NF-kappaB/p65 ubiquitin-dependent degradation. Oncogene 33:1997–2003

    Article  CAS  PubMed  Google Scholar 

  • Hu L, Huang T, Liu XJ, Cai YD (2011a) Predicting protein phenotypes based on protein-protein interaction network. PLoS One 6:e17668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu L, Huang T, Shi X, Lu WC, Cai YD, Chou KC (2011b) Predicting functions of proteins in mouse based on weighted protein-protein interaction network and protein hybrid properties. PLoS One 6:e14556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu YT, Ming F, Chen WW, Yan JY, Xu ZY, Li GX, Xu CY, Yang JL, Zheng SJ (2012) TcOPT3, a member of oligopeptide transporters from the hyperaccumulator Thlaspi caerulescens, is a novel Fe/Zn/Cd/Cu transporter. PLoS One 7:e38535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Igual IQJC (2012) Molecular basis of the functional distinction between Cln1 and Cln2 cyclins. Cell Cycle 11:3117–3131

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Invernizzi F, Lamantea E, Lauria G, Galassi G, Onofrj M, Palmieri L, Spinazzola A, Zeviani M (2008) Instability of the mitochondrial genome and neurodegeneration. Neurology 70:A482–A483

    Google Scholar 

  • Jiang YW, Kang CM (2003) Induction of S. cerevisiae filamentous differentiation by slowed DNA synthesis involves Mec1, Rad53 and Swe1 checkpoint proteins. Mol Biol Cell 14:5116–5124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang R, Gan MX, He P (2011) Constructing a gene semantic similarity network for the inference of disease genes. BMC Syst Biol 5:S2

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang J-X, Gao S, Pan Y-Z, Yu C, Sun C-Y (2014) Overexpression of microRNA-125b sensitizes human hepatocellular carcinoma cells to 5-fluorouracil through inhibition of glycolysis by targeting hexokinase II. Mol Med Rep 10:995–1002

    CAS  PubMed  Google Scholar 

  • Kaleta C, Centler F, di Fenizio PS, Dittrich P (2008) Phenotype prediction in regulated metabolic networks. BMC Syst Biol 2:37

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kawai M, Nakashima A, Ueno M, Ushimaru T, Aiba K, Doi H, Uritani M (2001) Fission yeast tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high temperature. Curr Genet 39:166–174

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Rose MD (2012) A mechanism for the coordination of proliferation and differentiation by spatial regulation of Fus2p in budding yeast. Genes Dev 26:1110–1121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitchen CM, Leung SW, Corbett AH, Murphy TJ (2009) The mating response cascade does not modulate changes in the steady-state level of target mRNAs through control of mRNA stability. Yeast 26:261–272

    Article  CAS  PubMed  Google Scholar 

  • Kiyomitsu T, Cheeseman IM (2013) Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell 154:391–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohler S, Bauer S, Horn D, Robinson PN (2008) Walking the interactome for prioritization of candidate disease genes. Am J Hum Genet 82:949–958

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kossinova O, Malygin A, Krol A, Karpova G (2014) The SBP2 protein central to selenoprotein synthesis contacts the human ribosome at expansion segment 7L of the 28S rRNA. RNA 20:1046–1056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubota T, Stead DA, Hiraga S, ten Have S, Donaldson AD (2012) Quantitative proteomic analysis of yeast DNA replication proteins. Methods 57:196–202

    Article  CAS  PubMed  Google Scholar 

  • Kursu VA, Pietikainen LP, Fontanesi F, Aaltonen MJ, Suomi F, Raghavan Nair R, Schonauer MS, Dieckmann CL, Barrientos A, Hiltunen JK, Kastaniotis AJ (2013) Defects in mitochondrial fatty acid synthesis result in failure of multiple aspects of mitochondrial biogenesis in Saccharomyces cerevisiae. Mol Microbiol 90:824–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lager S, Jansson T, Powell TL (2014) Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids. Am J Physiol Cell Physiol 307:C738–C744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laha S, Das SP, Hajra S, Sanyal K, Sinha P (2011) Functional characterization of the Saccharomyces cerevisiae protein Chl1 reveals the role of sister chromatid cohesion in the maintenance of spindle length during S-phase arrest. BMC Genet 12:83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lajoie P, Moir RD, Willis IM, Snapp EL (2012) Kar2p availability defines distinct forms of endoplasmic reticulum stress in living cells. Mol Biol Cell 23:955–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lang GI, Parsons L, Gammie AE (2013) Mutation rates, spectra, and genome-wide distribution of spontaneous mutations in mismatch repair deficient yeast. G3 (Bethesda) 3:1453–1465

    Article  PubMed Central  CAS  Google Scholar 

  • Lardenois A, Becker E, Walther T, Law MJ, Xie B, Demougin P, Strich R, Primig M (2015) Global alterations of the transcriptional landscape during yeast growth and development in the absence of Ume6-dependent chromatin modification. Mol Genet Genomics 290:2031–2046

    Article  CAS  PubMed  Google Scholar 

  • Lee YJ, Kim KJ, Kang HY, Kim H-R, Maeng PJ (2012) Involvement of GDH3-encoded NADP+-dependent glutamate dehydrogenase in yeast cell resistance to stress-induced apoptosis in stationary phase cells. J Biol Chem 287:44221–44233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewinska A, Miedziak B, Kulak K, Molon M, Wnuk M (2014) Links between nucleolar activity, rDNA stability, aneuploidy and chronological aging in the yeast Saccharomyces cerevisiae. Biogerontology 15:289–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li YJ, Patra JC (2010) Genome-wide inferring gene-phenotype relationship by walking on the heterogeneous network. Bioinformatics 26:1219–1224

    Article  CAS  PubMed  Google Scholar 

  • Liao SY, Lin X, Christiani DC (2014) Genome-wide association and network analysis of lung function in the Framingham heart study. Genet Epidemiol 38:572–578

    Article  PubMed  PubMed Central  Google Scholar 

  • Liesegang H, Kaster A-K, Wiezer A, Goenrich M, Wollherr A, Seedorf H, Gottschalk G, Thauer RK (2010) Complete genome sequence of Methanothermobacter marburgensis, a methanoarchaeon model organism. J Bacteriol 192:5850–5851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin C, Zou Y, Qin J, Liu X, Jiang Y, Ke C, Zou Q (2013) Hierarchical classification of protein folds using a novel ensemble classifier. PLoS One 8:e56499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liou L-C, Ren Q, Gao Q, Zhang Z (2014) Sro7 and Sro77, the yeast homologues of the Drosophila lethal giant larvae (Lgl), regulate cell proliferation via the Rho1Tor1 pathway. Microbiology 160:2208–2214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo J, Liang S (2014) Prioritization of potential candidate disease genes by topological similarity of protein–protein interaction network and phenotype data. J Biomed Inform 53:229–236

    Article  PubMed  Google Scholar 

  • Ma GX, Zhou RQ, Huang HC, Hu SJ, Lin J (2014) Tissue-specific distribution of serine/threonine protein phosphatase 1 of Toxocara canis. Vet parasitol 205:551–557

    Article  CAS  PubMed  Google Scholar 

  • Macropol K, Can T, Singh AK (2009) RRW: repeated random walks on genome-scale protein networks for local cluster discovery. BMC Bioinform 10:283

    Article  CAS  Google Scholar 

  • Madeira JB, Masuda CA, Maya-Monteiro CM, Matos GS, Montero-Lomeli M, Bozaquel-Morais BL (2015) TORC1 inhibition induces lipid droplet replenishment in yeast. Mol Cell Biol 35:737–746

    PubMed  PubMed Central  Google Scholar 

  • Magasanik B (2005) The transduction of the nitrogen regulation signal in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 102:16537–16538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makio T, Stanton LH, Lin C-C, Goldfarb DS, Weis K, Wozniak RW (2009) The nucleoporins Nup170p and Nup157p are essential for nuclear pore complex assembly. J Cell Biol 185:459–473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mao K, Klionsky DJ (2013) Mitochondrial fission facilitates mitophagy in Saccharomyces cerevisiae. Autophagy 9:1900–1901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marshall PA, Netzel N, Guintchev JW (2012) Assessing compensation for loss of vacuolar function in Saccharomyces cerevisiae. Can J Microbiol 58:132–144

    Article  CAS  PubMed  Google Scholar 

  • Mascaraque V, Hernaez ML, Jimenez-Sanchez M, Hansen R, Gil C, Martin H, Cid VJ, Molina M (2013) Phosphoproteomic analysis of protein kinase C signaling in Saccharomyces cerevisiae reveals Slt2 mitogen-activated protein kinase (MAPK)-dependent phosphorylation of eisosome core components. Mol Cell Proteomics 12:557–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuda F, Tsugawa H, Fukusaki E (2013) Method for assessing the statistical significance of mass spectral similarities using basic local alignment search tool statistics. Anal Chem 85:8291–8297

    Article  CAS  PubMed  Google Scholar 

  • McMurray MA, Thorner J (2009) Reuse, replace, recycle. Specificity in subunit inheritance and assembly of higher-order septin structures during mitotic and meiotic division in budding yeast. Cell Cycle 8:195–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehla J, Ernst R, Moore R, Wakschlag A, Marquis MK, Ambudkar SV, Golin J (2014) Evidence for a molecular diode-based mechanism in a multispecific ATP-binding cassette (ABC) exporter: SER-1368 as a gatekeeping residue in the yeast multidrug transporter Pdr5. J Biol Chem 289:26597–26606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melton EM, Cerny RL, DiRusso CC, Black PN (2013) Overexpression of human fatty acid transport protein 2/very long chain acyl-CoA synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous fatty acids. Biochem Biophys Res Commun 440:743–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Michaeli S, Fait A, Lagor K, Nunes-Nesi A, Grillich N, Yellin A, Bar D, Khan M, Fernie AR, Turano FJ, Fromm H (2011) A mitochondrial GABA permease connects the GABA shunt and the TCA cycle, and is essential for normal carbon metabolism. Plant J 67:485–498

    Article  CAS  PubMed  Google Scholar 

  • Milani L, Ghiselli F, Iannello M, Passamonti M (2014) Evidence for somatic transcription of male-transmitted mitochondrial genome in the DUI species Ruditapes philippinarum (Bivalvia: Veneridae). Curr Genet 60:163–173

    Article  CAS  PubMed  Google Scholar 

  • Mirel DB, Marder K, Graziano J, Freyer G, Zhao Q, Mayeux R, Wilhelmsen KC (1998) Characterization of the human mitochondrial aconitase gene (ACO2). Gene 213:205–218

    Article  CAS  PubMed  Google Scholar 

  • Molon M, Zadrag-Tecza R, Bilinski T (2015) The longevity in the yeast Saccharomyces cerevisiae: a comparison of two approaches for assessment the lifespan. Biochem Biophys Res Commun 460:651–656

    Article  CAS  PubMed  Google Scholar 

  • Monroy MA, Ruhl DD, Xu X, Granner DK, Yaciuk P, Chrivia JC (2001) Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP. J Biol Chem 276:40721–40726

    Article  CAS  PubMed  Google Scholar 

  • Morano KA, Santoro N, Koch KA, Thiele DJ (1999) A trans-activation domain in yeast heat shock transcription factor is essential for cell cycle progression during stress. Mol Cell Biol 19:402–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moulos P, Klein J, Jupp S, Stevens R, Bascands J-L, Schanstra JP (2013) The KUPNetViz: a biological network viewer for multiple-omics datasets in kidney diseases. BMC Bioinform 14:235

    Article  Google Scholar 

  • Mulla W, Zhu J, Li R (2014) Yeast: a simple model system to study complex phenomena of aneuploidy. FEMS Microbiol Rev 38:201–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mulvihill DP, Hyams JS (2003) Role of the two type II myosins, Myo2 and Myp2, in cytokinetic actomyosin ring formation and function in fission yeast. Cell Motil Cytoskelet 54:208–216

    Article  CAS  Google Scholar 

  • Nguyen TTM, Kitajima S, Izawa S (2014) Importance of glucose-6-phosphate dehydrogenase (G6PDH) for vanillin tolerance in Saccharomyces cerevisiae. J Biosci Bioeng 118:263–269

    Article  CAS  PubMed  Google Scholar 

  • Nicastro R, Tripodi F, Guzzi C, Reghellin V, Khoomrung S, Capusoni C, Compagno C, Airoldi C, Nielsen J, Alberghina L, Coccetti P (2015) Enhanced amino acid utilization sustains growth of cells lacking Snf1/AMPK. Biochim Biophys Acta 1853:1615–1625

    Article  CAS  PubMed  Google Scholar 

  • Nishant KT, Plys AJ, Alani E (2008) A mutation in the putative MLH3 endonuclease domain confers a defect in both mismatch repair and meiosis in Saccharomyces cerevisiae. Genetics 179:747–755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohtsubo M, Yoshida T, Seino H, Nishitani H, Clark KL, Sprague GF Jr, Frasch M, Nishimoto T (1991) Mutation of the hamster cell cycle gene RCC1 is complemented by the homologous genes of Drosophila and S.cerevisiae. EMBO J 10:1265–1273

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ohyama K, Suzuki M, Masuda K, Yoshida S, Muranaka T (2007) Chemical phenotypes of the hmg1 and hmg2 mutants of Arabidopsis demonstrate the in-planta role of HMG-CoA reductase in triterpene biosynthesis. Chem Pharm Bull (Tokyo) 55:1518–1521

    Article  CAS  Google Scholar 

  • Okuzaki D, Watanabe T, Tanaka S, Nojima H (2003) The Saccharomyces cerevisiae bud-neck proteins Kcc4 and Gin4 have distinct but partially-overlapping cellular functions. Genes Genet syst 78:113–126

    Article  CAS  PubMed  Google Scholar 

  • Olmo VN, Grote E (2010) Prm1 targeting to contact sites enhances fusion during mating in Saccharomyces cerevisiae. Eukaryot Cell 9:1538–1548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Onuki R, Shibuya T, Kanehisa M (2010) New kernel methods for phenotype prediction from genotype data. In: Genome informatics International Conference on Genome Informatics. World Scientific, pp 132–141

  • Orij R, Urbanus ML, Vizeacoumar FJ, Giaever G, Boone C, Nislow C, Brul S, Smits GJ (2012) Genome-wide analysis of intracellular pH reveals quantitative control of cell division rate by pH(c) in Saccharomyces cerevisiae. Genome Biol 13:R80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pareek G, Samaddar M, D’Silva P (2011) Primary sequence that determines the functional overlap between mitochondrial heat shock protein 70 Ssc1 and Ssc3 of Saccharomyces cerevisiae. J Biol Chem 286:19001–19013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park S-K, Hartnell LM, Jackson CL (2005) Mutations in a highly conserved region of the Arf1p activator GEA2 block anterograde Golgi transport but not COPI recruitment to membranes. Mol Biol Cell 16:3786–3799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul L (2011) Diet, nutrition and telomere length. J Nutr Biochem 22:895–901

    Article  CAS  PubMed  Google Scholar 

  • Pebernard S, McDonald WH, Pavlova Y, Yates JR 3rd, Boddy MN (2004) Nse1, Nse2, and a novel subunit of the Smc5-Smc6 complex, Nse3, play a crucial role in meiosis. Mol Biol Cell 15:4866–4876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez-Gallardo RV, Briones LS, Diaz-Perez AL, Gutierrez S, Rodriguez-Zavala JS, Campos-Garcia J (2013) Reactive oxygen species production induced by ethanol in Saccharomyces cerevisiae increases because of a dysfunctional mitochondrial iron-sulfur cluster assembly system. FEMS Yeast Res 13:804–819

    Article  CAS  PubMed  Google Scholar 

  • Pestov DG, Shcherbik N (2012) Rapid cytoplasmic turnover of yeast ribosomes in response to rapamycin inhibition of TOR. Mol Cell Biol 32:2135–2144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prager S, Wollmann HA, Mergenthaler S, Mavany M, Eggermann K, Ranke MB, Eggermann T (2003) Characterization of genomic variants in CSH1 and GH2, two candidate genes for Silver-Russell syndrome in 17q24-q25. Genet Test 7:259–263

    Article  CAS  PubMed  Google Scholar 

  • Quek NCH, Matthews JH, Bloor SJ, Jones DA, Bircham PW, Heathcott RW, Atkinson PH (2013) The novel equisetin-like compound, TA-289, causes aberrant mitochondrial morphology which is independent of the production of reactive oxygen species in Saccharomyces cerevisiae. Mol Biosyst 9:2125–2133

    Article  CAS  PubMed  Google Scholar 

  • Raspelli E, Cassani C, Chiroli E, Fraschini R (2015) Budding yeast Swe1 is involved in the control of mitotic spindle elongation and is regulated by Cdc14 phosphatase during mitosis. J Biol Chem 290:1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raymond M, Ruetz S, Thomas DY, Gros P (1994) Functional expression of P-glycoprotein in Saccharomyces cerevisiae confers cellular resistance to the immunosuppressive and antifungal agent FK520. Mol Cell Biol 14:277–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reck-Peterson SL, Tyska MJ, Novick PJ, Mooseker MS (2001) The yeast class V myosins, Myo2p and Myo4p, are nonprocessive actin-based motors. J Cell Biol 153:1121–1126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reiter A, Steinbauer R, Philippi A, Gerber J, Tschochner H, Milkereit P, Griesenbeck J (2011) Reduction in ribosomal protein synthesis is sufficient to explain major effects on ribosome production after short-term TOR inactivation in Saccharomyces cerevisiae. Mol Cell Biol 31:803–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren Y, Wang Z-X, Wei Q (2009) Mechanism of activation of Saccharomyces cerevisiae calcineurin by Mn2+. Biol Chem 390:1155–1162

    Article  CAS  PubMed  Google Scholar 

  • Ruiz A, Ariño J (2007) Function and regulation of the Saccharomyces cerevisiae ENA sodium ATPase system. Eukaryot cell 6:2175–2183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Casalongue ME, Lee J, Diamond A, Shuldiner S, Moir RD, Willis IM (2015) Differential phosphorylation of a regulatory subunit of protein kinase CK2 by target of rapamycin complex 1 signaling and the Cdc-like kinase Kns1. J Biol Chem 290:7221–7233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scazzari M, Amm I, Wolf DH (2015) Quality control of a cytoplasmic protein complex: chaperone motors and the ubiquitin-proteasome system govern the fate of orphan fatty acid synthase subunit Fas2 of yeast. J Biol Chem 290:4677–4687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shan J, Balasubramanian MN, Donelan W, Fu L, Hayner J, Lopez MC, Baker HV, Kilberg MS (2014) A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation. J Biol Chem 289:24665–24679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma S, Watzinger P, Kotter P, Entian KD (2013) Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res 41:5428–5443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shcherbik N (2013) Golgi-mediated glycosylation determines residency of the T2 RNase Rny1p in Saccharomyces cerevisiae. Traffic 14:1209–1227

    Article  CAS  PubMed  Google Scholar 

  • Sheltzer JM, Rose MD (2009) The class V myosin Myo2p is required for Fus2p transport and actin polarization during the yeast mating response. Mol Biol Cell 20:2909–2919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shepperd LA, Meadows JC, Sochaj AM, Lancaster TC, Zou J, Buttrick GJ, Rappsilber J, Hardwick KG, Millar JB (2012) Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Curr Biol 22:891–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva GM, Finley D, Vogel C (2015) K63 polyubiquitination is a new modulator of the oxidative stress response. Nat Struct Mol Biol 22:116–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smedley D, Köhler S, Czeschik JC, Amberger J, Bocchini C, Hamosh A, Veldboer J, Zemojtel T, Robinson PN (2014) Walking the interactome for candidate prioritization in exome sequencing studies of Mendelian diseases. Bioinformatics 30:3215–3222

    Article  PubMed  PubMed Central  Google Scholar 

  • Smolle M, Venkatesh S, Gogol MM, Li H, Zhang Y, Florens L, Washburn MP, Workman JL (2012) Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange. Nat Struct Mol Biol 19:884–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song L, Li D, Zeng X, Wu Y, Guo L, Zou Q (2014) nDNA-prot: identification of DNA-binding proteins based on unbalanced classification. BMC Bioinform 15:298

    Article  CAS  Google Scholar 

  • Soudet J, Jolivet P, Teixeira MT (2014) Elucidation of the DNA end-replication problem in Saccharomyces cerevisiae. Mol Cell 53:954–964

    Article  CAS  PubMed  Google Scholar 

  • Spiegel R, Pines O, Ta-Shma A, Burak E, Shaag A, Halvardson J, Edvardson S, Mahajna M, Zenvirt S, Saada A (2012) Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. Am J Hum Genet 90:518–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • St Charles JA, Liberti SE, Williams JS, Lujan SA, Kunkel TA (2015) Quantifying the contributions of base selectivity, proofreading and mismatch repair to nuclear DNA replication in Saccharomyces cerevisiae. DNA Repair (Amst) 31:41–51

    Article  CAS  Google Scholar 

  • Stark C, Breitkreutz B-J, Reguly T, Boucher L, Breitkreutz A, Tyers M (2006) BioGRID: a general repository for interaction datasets. Nucleic Acids Res 34:D535–D539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stevens SK, Strehle AP, Miller RL, Gammons SH, Hoffman KJ, McCarty JT, Miller ME, Stultz LK, Hanson PK (2013) The anticancer ruthenium complex KP1019 induces DNA damage, leading to cell cycle delay and cell death in Saccharomyces cerevisiae. Mol Pharmacol 83:225–234

    Article  CAS  PubMed  Google Scholar 

  • Stewart EV, Lloyd SJ-A, Burg JS, Nwosu CC, Lintner RE, Daza R, Russ C, Ponchner K, Nusbaum C, Espenshade PJ (2012) Yeast sterol regulatory element-binding protein (SREBP) cleavage requires Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing subunit of the Golgi Dsc E3 ligase. J Biol Chem 287:672–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strathern J, Malagon F, Irvin J, Gotte D, Shafer B, Kireeva M, Lubkowska L, Jin DJ, Kashlev M (2013) The fidelity of transcription: RPB1 (RPO21) mutations that increase transcriptional slippage in S. cerevisiae. J Biol Chem 288:2689–2699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Striebeck A, Robinson DA, Schüttelkopf AW, van Aalten DM (2013) Yeast Mnn9 is both a priming glycosyltransferase and an allosteric activator of mannan biosynthesis. Open Biol 3:130022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Suzuki M, Kamide Y, Nagata N, Seki H, Ohyama K, Kato H, Masuda K, Sato S, Kato T, Tabata S (2004) Loss of function of 3-hydroxy-3-methylglutaryl coenzyme A reductase 1 (HMG1) in Arabidopsis leads to dwarfing, early senescence and male sterility, and reduced sterol levels. Plant J 37:750–761

    Article  CAS  PubMed  Google Scholar 

  • Tahara EB, Cezario K, Souza-Pinto NC, Barros MH, Kowaltowski AJ (2011) Respiratory and TCA cycle activities affect S. cerevisiae lifespan, response to caloric restriction and mtDNA stability. J Bioenerg Biomembr 43:483–491

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi M, Kimata Y, Hirata A, Oka M, Kohno K (2006) Saccharomyces cerevisiae Rot1p is an ER-localized membrane protein that may function with BiP/Kar2p in protein folding. J Biochem 139:597–605

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, Tatebayashi K, Nishimura A, Yamamoto K, Yang HY, Saito H (2014) Yeast osmosensors Hkr1 and Msb2 activate the Hog1 MAPK cascade by different mechanisms. Sci Signal 7:ra21

    Article  PubMed  CAS  Google Scholar 

  • Tatebayashi K, Takekawa M, Saito H (2003) A docking site determining specificity of Pbs2 MAPKK for Ssk2/Ssk22 MAPKKKs in the yeast HOG pathway. EMBO J 22:3624–3634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taxis C, Keller P, Kavagiou Z, Jensen LJ, Colombelli J, Bork P, Stelzer EH, Knop M (2005) Spore number control and breeding in Saccharomyces cerevisiae: a key role for a self-organizing system. J Cell Biol 171:627–640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teixeira MC, Sá-Correia I (2002) Saccharomyces cerevisiae resistance to chlorinated phenoxyacetic acid herbicides involves Pdr1p-mediated transcriptional activation of TPO1 and PDR5 genes. Biochem Biophys Res Commun 292:530–537

    Article  CAS  PubMed  Google Scholar 

  • Tennen RI, Haye JE, Wijayatilake HD, Arlow T, Ponzio D, Gammie AE (2013) Cell-cycle and DNA damage regulation of the DNA mismatch repair protein Msh2 occurs at the transcriptional and post-transcriptional level. DNA Repair (Amst) 12:97–109

    Article  CAS  Google Scholar 

  • Theesfeld CL, Pourmand D, Davis T, Garza RM, Hampton RY (2011) The sterol-sensing domain (SSD) directly mediates signal-regulated endoplasmic reticulum-associated degradation (ERAD) of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase isozyme Hmg2. J Biol Chem 286:26298–26307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thevelein JM (1992) The RAS-adenylate cyclase pathway and cell cycle control in Saccharomyces cerevisiae. Antonie Van Leeuwenhoek 62:109–130

    Article  CAS  PubMed  Google Scholar 

  • Tourasse NJ, Stabell FB, Kolsto AB (2014) Survey of chimeric IStron elements in bacterial genomes: multiple molecular symbioses between group I intron ribozymes and DNA transposons. Nucleic Acids Res 42:12333–12351

    Article  PubMed  PubMed Central  Google Scholar 

  • Trobos M, Christensen H, Sunde M, Nordentoft S, Agersø Y, Simonsen GS, Hammerum AM, Olsen JE (2009) Characterization of sulphonamide-resistant Escherichia coli using comparison of sul2 gene sequences and multilocus sequence typing. Microbiology 155:831–836

    Article  CAS  PubMed  Google Scholar 

  • Tsabar M, Haber JE (2013) Chromatin modifications and chromatin remodeling during DNA repair in budding yeast. Curr Opin Genet Dev 23:166–173

    Article  CAS  PubMed  Google Scholar 

  • Tsai IT, Lin JL, Chiang YH, Chuang YC, Liang SS, Chuang CN, Huang TN, Wang TF (2014) Interorganelle interactions and inheritance patterns of nuclei and vacuoles in budding yeast meiosis. Autophagy 10:285–295

    Article  CAS  PubMed  Google Scholar 

  • Tsujimoto Y, Takase D, Okano H, Tomari N, Watanabe K, Matsui H (2013) Functional roles of YPT31 and YPT32 in clotrimazole resistance of Saccharomyces cerevisiae through effects on vacuoles and ATP-binding cassette transporter(s). J Biosci Bioeng 115:4–11

    Article  CAS  PubMed  Google Scholar 

  • Tsukamoto Y, Katayama C, Shinohara M, Shinohara A, Maekawa S, Miyamoto M (2013) The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast. Biochem Biophys Res Commun 441:867–872

    Article  CAS  PubMed  Google Scholar 

  • Turnbull HE, Lax NZ, Diodato D, Ansorge O, Turnbull DM (2010) The mitochondrial brain: from mitochondrial genome to neurodegeneration. BBA-Mol Basis Dis 1802:111–121

    Article  CAS  Google Scholar 

  • Vallabhaneni H, O’Callaghan N, Sidorova J, Liu Y (2013) Defective repair of oxidative base lesions by the DNA glycosylase Nth1 associates with multiple telomere defects. PLoS Genet 9:e1003639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Zeebroeck G, Bonini BM, Versele M, Thevelein JM (2009) Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor. Nat Chem Biol 5:45–52

    Article  PubMed  CAS  Google Scholar 

  • Wang TF, Kleckner N, Hunter N (1999) Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Proc Natl Acad Sci USA 96:13914–13919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y-C, Huang S-H, Lan C-Y, Chen B-S (2012) Prediction of phenotype-associated genes via a cellular network approach: a Candida albicans infection case study. PLoS One 7:e35339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Q, Vaupel P, Ziegler SI, Shi K (2015) Exploring the quantitative relationship between metabolism and enzymatic phenotype by physiological modeling of glucose metabolism and lactate oxidation in solid tumors. Phys Med Biol 60:2547–2571

    Article  CAS  PubMed  Google Scholar 

  • Wery M, Ruidant S, Schillewaert S, Leporé N, Lafontaine DL (2009) The nuclear poly (A) polymerase and Exosome cofactor Trf5 is recruited cotranscriptionally to nucleolar surveillance. RNA 15:406–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wloka C, Nishihama R, Onishi M, Oh Y, Hanna J, Pringle JR, Krauss M, Bi EF (2011) Evidence that a septin diffusion barrier is dispensable for cytokinesis in budding yeast. Biol Chem 392:813–829

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Feng X, Stein L (2010) Research a human functional protein interaction network and its application to cancer data analysis. Genome Biol 11:R53

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xenarios I, Rice DW, Salwinski L, Baron MK, Marcotte EM, Eisenberg D (2000) DIP: the database of interacting proteins. Nucleic Acids Res 28:289–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamoto A, Hiraoka Y (2003) Monopolar spindle attachment of sister chromatids is ensured by two distinct mechanisms at the first meiotic division in fission yeast. Embo J 22:2284–2296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye M, Chen Y, Zou S, Yu S, Liang Y (2014) Ypt1 suppresses defects of vesicle trafficking and autophagy in Ypt6 related mutants. Cell Biol Int 38:663–674

    Article  CAS  PubMed  Google Scholar 

  • Yorimitsu T, Nair U, Yang ZF, Klionsky DJ (2006) Endoplasmic reticulum stress triggers autophagy. J Biol Chem 281:30299–30304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida S, Bartolini S, Pellman D (2009) Mechanisms for concentrating Rho1 during cytokinesis. Genes Dev 23:810–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida K, Bacal J, Desmarais D, Padioleau I, Tsaponina O, Chabes A, Pantesco V, Dubois E, Parrinello H, Skrzypczak M, Ginalski K, Lengronne A, Pasero P (2014) The histone deacetylases sir2 and rpd3 act on ribosomal DNA to control the replication program in budding yeast. Mol Cell 54:691–697

    Article  CAS  PubMed  Google Scholar 

  • Young ET, Zhang C, Shokat KM, Parua PK, Braun KA (2012) The AMP-activated protein kinase Snf1 regulates transcription factor binding, RNA polymerase ii activity, and mRNA stability of glucose-repressed genes in Saccharomyces cerevisiae. J Biol Chem 287:29021–29034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu SL, Kang MS, Kim HY, Gorospe CM, Kim TS, Lee SK (2014) The PCNA binding domain of Rad2p plays a role in mutagenesis by modulating the cell cycle in response to DNA damage. DNA Repair (Amst) 16:1–10

    Article  CAS  Google Scholar 

  • Zhang NS, Wu J, Oliver SG (2009) Gis1 is required for transcriptional reprogramming of carbon metabolism and the stress response during transition into stationary phase in yeast. Microbiology 155:1690–1698

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Zhang C, Gao R, Yang R (2015) An ensemble method to distinguish bacteriophage virion from non-virion proteins based on protein sequence characteristics. Int J Mol Sci 16:21734–21758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Q, Wang W, He X, Zhu X, Shen Y, Yu Z, Wang X, Qi X, Zhang X, Fan M, Dai Y, Yang S, Yan Q (2014) Mechanistic study on the nuclear modifier gene MSS1 mutation suppressing neomycin sensitivity of the mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae. PLoS One 9:e90336

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu G, Saleh AA, Bahwal SA, Wang K, Wang M, Wang D, Ge T, Sun J (2014) Overexpression of four fatty acid synthase genes elevated the efficiency of long-chain polyunsaturated fatty acids biosynthesis in mammalian cells. Sheng Wu Gong Cheng Xue Bao 30:1464–1472

    CAS  PubMed  Google Scholar 

  • Zou Q, Wang Z, Guan X, Liu B, Wu Y, Lin Z (2013) An approach for identifying cytokines based on a novel ensemble classifier. Biomed Res Int 2013:686090

    PubMed  PubMed Central  Google Scholar 

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Correspondence to Lei Chen or Yu-Dong Cai.

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This study was supported by the National Basic Research Program of China (2011CB510101, 2011CB510102), the National Natural Science Foundation of China (61202021, 31371335, 61373028, 11371008), the Innovation Program of the Shanghai Municipal Education Commission (12ZZ087), and the Shanghai Educational Development Foundation (12CG55).

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Communicated by S. Hohmann.

L. Chen and Y.-H. Zhang contributed equally to this work.

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Chen, L., Zhang, YH., Huang, T. et al. Identifying novel protein phenotype annotations by hybridizing protein–protein interactions and protein sequence similarities. Mol Genet Genomics 291, 913–934 (2016). https://doi.org/10.1007/s00438-015-1157-9

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