DIG2_YEAST
ID DIG2_YEAST Reviewed; 323 AA.
AC Q03373; D6VTA3;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Down-regulator of invasive growth 2;
DE AltName: Full=Regulator of STE12 protein 2;
DE AltName: Full=Regulator of sterile twelve 2;
GN Name=DIG2; Synonyms=RST2; OrderedLocusNames=YDR480W; ORFNames=D8035.23;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP FUNCTION, INTERACTION WITH STE12 AND KSS1, AND PHOSPHORYLATION BY KSS1.
RX PubMed=8918885; DOI=10.1101/gad.10.22.2831;
RA Cook J.G., Bardwell L., Kron S.J., Thorner J.;
RT "Two novel targets of the MAP kinase Kss1 are negative regulators of
RT invasive growth in the yeast Saccharomyces cerevisiae.";
RL Genes Dev. 10:2831-2848(1996).
RN [4]
RP FUNCTION, COMPLEX WITH DIG1; FUS3 AND STE12, AND INTERACTION WITH CLN1 AND
RP CLN2.
RX PubMed=9094309; DOI=10.1016/s0960-9822(06)00118-7;
RA Tedford K., Kim S., Sa D., Stevens K., Tyers M.;
RT "Regulation of the mating pheromone and invasive growth responses in yeast
RT by two MAP kinase substrates.";
RL Curr. Biol. 7:228-238(1997).
RN [5]
RP FUNCTION, AND COMPLEX WITH DIG1; KSS1 AND STE12.
RX PubMed=9744865; DOI=10.1101/gad.12.18.2887;
RA Bardwell L., Cook J.G., Voora D., Baggott D.M., Martinez A.R., Thorner J.;
RT "Repression of yeast Ste12 transcription factor by direct binding of
RT unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK.";
RL Genes Dev. 12:2887-2898(1998).
RN [6]
RP FUNCTION.
RX PubMed=9860980; DOI=10.1073/pnas.95.26.15400;
RA Bardwell L., Cook J.G., Zhu-Shimoni J.X., Voora D., Thorner J.;
RT "Differential regulation of transcription: repression by unactivated
RT mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:15400-15405(1998).
RN [7]
RP FUNCTION, AND INTERACTION WITH STE12.
RX PubMed=10825185; DOI=10.1128/mcb.20.12.4199-4209.2000;
RA Olson K.A., Nelson C., Tai G., Hung W., Yong C., Astell C., Sadowski I.;
RT "Two regulators of Ste12p inhibit pheromone-responsive transcription by
RT separate mechanisms.";
RL Mol. Cell. Biol. 20:4199-4209(2000).
RN [8]
RP FUNCTION, PHOSPHORYLATION BY FUS3, AND REPRESSION OF HAPLOID SPECIFIC AND
RP A-SPECIFIC GENES.
RX PubMed=12410840; DOI=10.1046/j.1365-2958.2002.03213.x;
RA Gelli A.;
RT "Rst1 and Rst2 are required for the a/alpha diploid cell type in yeast.";
RL Mol. Microbiol. 46:845-854(2002).
RN [9]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34 AND SER-225, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266 AND SER-270, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: DIG2 and DIG1 are negative regulators of the filamentation
CC and pheromone induced mating program. DIG1 and DIG2 inhibit the
CC transcriptional activity of STE12 by direct protein-protein
CC interaction. DIG2 binds to the DNA binding domain (DBD) of STE12 and
CC thus inhibits transcription when overexpressed.
CC {ECO:0000269|PubMed:10825185, ECO:0000269|PubMed:12410840,
CC ECO:0000269|PubMed:8918885, ECO:0000269|PubMed:9094309,
CC ECO:0000269|PubMed:9744865, ECO:0000269|PubMed:9860980}.
CC -!- SUBUNIT: Forms a complex with DIG1, STE12 and either FUS3 or KSS1. The
CC interaction of FUS3 with STE12 depends on the presence of both DIG1 and
CC DIG2. STE12 is lost from FUS3/DIG1/DIG2 complex after pheromone
CC treatment. DIG1 and DIG2 have also been reported to interact with CLN1
CC and CLN2.
CC -!- INTERACTION:
CC Q03373; Q03063: DIG1; NbExp=5; IntAct=EBI-34019, EBI-29752;
CC Q03373; P14681: KSS1; NbExp=5; IntAct=EBI-34019, EBI-9945;
CC Q03373; P13574: STE12; NbExp=9; IntAct=EBI-34019, EBI-18264;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- INDUCTION: By pheromone. {ECO:0000269|PubMed:12410840}.
CC -!- PTM: Phosphorylated by FUS3 and KSS1, in a pheromone-stimulated manner.
CC {ECO:0000269|PubMed:12410840, ECO:0000269|PubMed:8918885}.
CC -!- MISCELLANEOUS: Present with 1310 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; U33050; AAB64911.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA12313.1; -; Genomic_DNA.
DR PIR; S69647; S69647.
DR RefSeq; NP_010768.1; NM_001180788.1.
DR AlphaFoldDB; Q03373; -.
DR SMR; Q03373; -.
DR BioGRID; 32532; 73.
DR ComplexPortal; CPX-575; Ste12/Dig1/Dig2 transcription regulation complex.
DR DIP; DIP-1292N; -.
DR IntAct; Q03373; 28.
DR MINT; Q03373; -.
DR STRING; 4932.YDR480W; -.
DR iPTMnet; Q03373; -.
DR MaxQB; Q03373; -.
DR PaxDb; Q03373; -.
DR PRIDE; Q03373; -.
DR EnsemblFungi; YDR480W_mRNA; YDR480W; YDR480W.
DR GeneID; 852091; -.
DR KEGG; sce:YDR480W; -.
DR SGD; S000002888; DIG2.
DR VEuPathDB; FungiDB:YDR480W; -.
DR HOGENOM; CLU_074653_0_0_1; -.
DR BioCyc; YEAST:G3O-30006-MON; -.
DR PRO; PR:Q03373; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; Q03373; protein.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:1990526; C:Ste12p-Dig1p-Dig2p complex; IDA:SGD.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:SGD.
DR GO; GO:2000218; P:negative regulation of invasive growth in response to glucose limitation; IGI:SGD.
DR GO; GO:0045894; P:negative regulation of mating-type specific transcription, DNA-templated; IC:ComplexPortal.
DR GO; GO:2000221; P:negative regulation of pseudohyphal growth; IGI:SGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:SGD.
PE 1: Evidence at protein level;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..323
FT /note="Down-regulator of invasive growth 2"
FT /id="PRO_0000079898"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 11..26
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:18407956"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
SQ SEQUENCE 323 AA; 36879 MW; 8E71278ED6D3A912 CRC64;
MNKEEQEDPQ QEQISTVQEN DPRNLQQLGM LLVSPGLDED RLSEKMISKI KKSRDIEKNQ
KLLISRLSQK EEDHSGKPPT ITTSPAEKTV PFKSLNHSLK RKRVPPALNF SDIQASSHLH
GSKSAPPNIT RFPQHKNSLR VRYMGRMAPT NQDYHPSVAN SYMTATYPYP YTGLPPVPCY
PYSSTPTQTH AYEGYYSPMY PGPLYNNGII PADYHAKRKK LAGRSPHLED LTSRKRTFVS
KHHNGDPIIS KTDEDIECSV TKNSLSEGAS LNDDADDDND KERIIIGEIS LYDDVFKFEV
RDDKNDYMKA CETIWTEWHN LKK
