MET4_YEAST
ID MET4_YEAST Reviewed; 672 AA.
AC P32389; D6W176;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Transcriptional activator of sulfur metabolism MET4;
DE AltName: Full=Methionine-requiring protein 4;
GN Name=MET4; OrderedLocusNames=YNL103W; ORFNames=N2177;
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 [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 26786 / X2180-1A;
RX PubMed=1549123; DOI=10.1128/mcb.12.4.1719-1727.1992;
RA Thomas D., Jacquemin I., Surdin-Kerjan Y.;
RT "MET4, a leucine zipper protein, and centromere-binding factor 1 are both
RT required for transcriptional activation of sulfur metabolism in
RT Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 12:1719-1727(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8446029; DOI=10.1111/j.1365-2958.1993.tb01113.x;
RA Mountain H.A., Bystroem A.S., Korch C.;
RT "The general amino acid control regulates MET4, which encodes a methionine-
RT pathway-specific transcriptional activator of Saccharomyces cerevisiae.";
RL Mol. Microbiol. 7:215-228(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8701612;
RX DOI=10.1002/(sici)1097-0061(19960330)12:4<403::aid-yea923>3.0.co;2-h;
RA Saiz J.E., Buitrago M.J., Soler A., del Rey F., Revuelta J.L.;
RT "The sequence of a 21.3 kb DNA fragment from the left arm of yeast
RT chromosome XIV reveals LEU4, MET4, POL1, RAS2, and six new open reading
RT frames.";
RL Yeast 12:403-409(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(1997).
RN [5]
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 [6]
RP FUNCTION, AND FUNCTIONAL REGIONS.
RX PubMed=7799928; DOI=10.1128/mcb.15.1.208;
RA Kuras L., Thomas D.;
RT "Functional analysis of Met4, a yeast transcriptional activator responsive
RT to S-adenosylmethionine.";
RL Mol. Cell. Biol. 15:208-216(1995).
RN [7]
RP INTERACTION WITH MET30.
RX PubMed=8524217; DOI=10.1128/mcb.15.12.6526;
RA Thomas D., Kuras L., Barbey R., Cherest H., Blaiseau P.L.,
RA Surdin-Kerjan Y.;
RT "Met30p, a yeast transcriptional inhibitor that responds to S-
RT adenosylmethionine, is an essential protein with WD40 repeats.";
RL Mol. Cell. Biol. 15:6526-6534(1995).
RN [8]
RP FUNCTION, AND SUBUNIT.
RX PubMed=8665859; DOI=10.1002/j.1460-2075.1996.tb00609.x;
RA Kuras L., Cherest H., Surdin-Kerjan Y., Thomas D.;
RT "A heteromeric complex containing the centromere binding factor 1 and two
RT basic leucine zipper factors, Met4 and Met28, mediates the transcription
RT activation of yeast sulfur metabolism.";
RL EMBO J. 15:2519-2529(1996).
RN [9]
RP FUNCTION, AND SUBUNIT.
RX PubMed=9171357; DOI=10.1093/emboj/16.9.2441;
RA Kuras L., Barbey R., Thomas D.;
RT "Assembly of a bZIP-bHLH transcription activation complex: formation of the
RT yeast Cbf1-Met4-Met28 complex is regulated through Met28 stimulation of
RT Cbf1 DNA binding.";
RL EMBO J. 16:2441-2451(1997).
RN [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=9799240; DOI=10.1093/emboj/17.21.6327;
RA Blaiseau P.L., Thomas D.;
RT "Multiple transcriptional activation complexes tether the yeast activator
RT Met4 to DNA.";
RL EMBO J. 17:6327-6336(1998).
RN [11]
RP FUNCTION, AND SUBUNIT.
RX PubMed=10637232; DOI=10.1093/emboj/19.2.282;
RA Rouillon A., Barbey R., Patton E.E., Tyers M., Thomas D.;
RT "Feedback-regulated degradation of the transcriptional activator Met4 is
RT triggered by the SCF(Met30) complex.";
RL EMBO J. 19:282-294(2000).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [13]
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 [14]
RP FUNCTION, ACTIVATION BY CADMIUM AND ARSENIC, AND INACTIVATION BY HYDROGEN
RP PEROXIDE.
RX PubMed=15689486; DOI=10.1091/mbc.e04-12-1130;
RA Yen J.L., Su N.Y., Kaiser P.;
RT "The yeast ubiquitin ligase SCFMet30 regulates heavy metal response.";
RL Mol. Biol. Cell 16:1872-1882(2005).
RN [15]
RP INTERACTION WITH MET30.
RX PubMed=15883825; DOI=10.1007/s00438-005-1137-6;
RA Brunson L.E., Dixon C., LeFebvre A., Sun L., Mathias N.;
RT "Identification of residues in the WD-40 repeat motif of the F-box protein
RT Met30p required for interaction with its substrate Met4p.";
RL Mol. Genet. Genomics 273:361-370(2005).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564, AND IDENTIFICATION BY
RP 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 [17]
RP IDENTIFICATION BY 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416 AND SER-564, 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 [20]
RP 9AATAD MOTIF.
RX PubMed=31375868; DOI=10.1007/s00018-019-03251-w;
RA Piskacek M., Havelka M., Jendruchova K., Knight A., Keegan L.P.;
RT "The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with
RT valines and intron reservoirs.";
RL Cell. Mol. Life Sci. 77:1793-1810(2020).
CC -!- FUNCTION: Positive trans-acting factor capable of stimulating the
CC transcription of the MET genes from the methionine biosynthetic
CC pathway. MET4, MET28 and CBF1 are required for full induction of MET25
CC and MET16 gene transcription. MET4 controls as well the derepression of
CC MET6. Required for the transcription of genes necessary for sulfur
CC amino acid biosynthesis. Involved in the transcription activation of
CC MET28 and MET30. Required for MET3 gene expression via assembly of the
CC MET4-MET28-MET31 and MET4-MET28-MET32 complexes. Involved in response
CC to cadmium and arsenic. Cadmium-activated MET4 also induces glutathione
CC biosynthesis. {ECO:0000269|PubMed:10637232, ECO:0000269|PubMed:1549123,
CC ECO:0000269|PubMed:15689486, ECO:0000269|PubMed:7799928,
CC ECO:0000269|PubMed:8446029, ECO:0000269|PubMed:8665859,
CC ECO:0000269|PubMed:9171357, ECO:0000269|PubMed:9799240}.
CC -!- SUBUNIT: Interacts with MET30. Tethered to DNA through two alternate
CC complexes associating MET4 with MET28 and either MET31 or MET32.
CC Interacts with MET28 and CBF1 through its leucine zipper to form a
CC heteromeric complex. {ECO:0000269|PubMed:10637232,
CC ECO:0000269|PubMed:15883825, ECO:0000269|PubMed:8524217,
CC ECO:0000269|PubMed:8665859, ECO:0000269|PubMed:9171357,
CC ECO:0000269|PubMed:9799240}.
CC -!- INTERACTION:
CC P32389; P40573: MET28; NbExp=5; IntAct=EBI-10757, EBI-11503;
CC P32389; P39014: MET30; NbExp=7; IntAct=EBI-10757, EBI-11507;
CC P32389; P32389: MET4; NbExp=2; IntAct=EBI-10757, EBI-10757;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}.
CC -!- INDUCTION: Regulated by the general amino acid control.
CC {ECO:0000269|PubMed:8446029}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000269|PubMed:31375868}.
CC -!- MISCELLANEOUS: Present with 1300 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- MISCELLANEOUS: Transcriptional activation function is inhibited by the
CC elevation of intracellular S-adenosylmethionine (AdoMet), but is
CC activated by cadmium and arsenic which leads to phosphorylation and
CC prevents ubiquitination. Inactivation by oxidative stress induced by
CC hydrogen peroxide promotes ubiquitination.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA34776.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA78109.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA90523.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M84455; AAA34776.1; ALT_FRAME; Genomic_DNA.
DR EMBL; Z12126; CAA78109.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z50161; CAA90523.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z71379; CAA95979.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10442.1; -; Genomic_DNA.
DR PIR; S63043; S63043.
DR RefSeq; NP_014296.4; NM_001182941.3.
DR AlphaFoldDB; P32389; -.
DR SMR; P32389; -.
DR BioGRID; 35720; 45.
DR ComplexPortal; CPX-1015; MET4-MET28-MET32 sulfur metabolism transcription factor complex.
DR ComplexPortal; CPX-1016; CBF1-MET4-MET28 sulfur metabolism transcription factor complex.
DR ComplexPortal; CPX-999; MET4-MET28-MET31 sulfur metabolism transcription factor complex.
DR DIP; DIP-2241N; -.
DR IntAct; P32389; 10.
DR MINT; P32389; -.
DR STRING; 4932.YNL103W; -.
DR iPTMnet; P32389; -.
DR MaxQB; P32389; -.
DR PaxDb; P32389; -.
DR PRIDE; P32389; -.
DR TopDownProteomics; P32389; -.
DR GeneID; 855620; -.
DR KEGG; sce:YNL103W; -.
DR SGD; S000005047; MET4.
DR eggNOG; ENOG502QSA8; Eukaryota.
DR HOGENOM; CLU_022093_0_0_1; -.
DR InParanoid; P32389; -.
DR BioCyc; YEAST:G3O-33131-MON; -.
DR PRO; PR:P32389; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P32389; protein.
DR GO; GO:0089713; C:Cbf1-Met4-Met28 complex; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IPI:SGD.
DR GO; GO:0005667; C:transcription regulator complex; IC:ComplexPortal.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:SGD.
DR GO; GO:0019344; P:cysteine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:SGD.
DR GO; GO:0042762; P:regulation of sulfur metabolic process; IC:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0046685; P:response to arsenic-containing substance; IDA:SGD.
DR GO; GO:0046686; P:response to cadmium ion; IDA:SGD.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; IMP:SGD.
PE 1: Evidence at protein level;
KW Activator; Amino-acid biosynthesis; Coiled coil; Cysteine biosynthesis;
KW DNA-binding; Methionine biosynthesis; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..672
FT /note="Transcriptional activator of sulfur metabolism MET4"
FT /id="PRO_0000076519"
FT DOMAIN 586..649
FT /note="bZIP"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..144
FT /note="Transcriptional activation"
FT REGION 157..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..235
FT /note="Inhibitory region; AdoMet responsiveness; required
FT for interaction with MET30"
FT REGION 299..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..375
FT /note="Auxiliary; required for high transcriptional
FT activity under nonrepressive growth conditions"
FT REGION 375..403
FT /note="Required for interaction with MET31 and MET32"
FT REGION 475..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 601..612
FT /note="Basic motif"
FT /evidence="ECO:0000250"
FT REGION 614..642
FT /note="Leucine-zipper"
FT /evidence="ECO:0000250"
FT COILED 609..648
FT /evidence="ECO:0000255"
FT MOTIF 89..97
FT /note="9aaTAD 1"
FT /evidence="ECO:0000269|PubMed:31375868"
FT MOTIF 102..110
FT /note="9aaTAD 2"
FT /evidence="ECO:0000269|PubMed:31375868"
FT MOTIF 109..117
FT /note="9aaTAD 3"
FT /evidence="ECO:0000269|PubMed:31375868"
FT COMPBIAS 10..44
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..265
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..502
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 503..517
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..565
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT CONFLICT 441..442
FT /note="RG -> AA (in Ref. 1; AAA34776 and 4; DAA10442)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 672 AA; 74373 MW; D65745E1FA40C09D CRC64;
MKQEQSHEGD SYSTEFINLF GKDTATHPSS NNGANNNGMG STNSLDQFVA TASSSSSLVT
SSENRRPLIG DVTNRGNTNL YDHAVTPEIL LEQLAYVDNF IPSLDNEFSN VDWNVNTTHN
NANNNGADTF SSINANPFDL DEQLAIELSA FADDSFIFPD EDKPSNNNNN SNNGNDDHSN
HDVLHEDPST NNRQRNPHFL TQRRNTFLTS QYDQSKSRFS SKNKRNGNNG ETNNFGDNMQ
NNHPFEPNFM GSPSQFPADA TNMTSIDHGG FTNVDITSTE NNTTGDNGVD ALSNLLHRTT
HTPNRSSPLS NVTSAQNSSS QQRKHSESKV DSNSDNNSSN KAPNITVPDY SIIPTSVLVT
LLPRVNVPNG AYNSLISAGF DNDQIDAIAA IMAYHHQKKI RENNSNNNKN INTNDSQEAP
ILKNINELLS VLIPPSPAET RGPTTLSTSP SFNEHGVVAE ASFLSSILEL GIKHPKSNNI
HNQRQPSRND HKISRESDGN NGNDNVHHNN AVIKSSTTRG DEIAKIRSEP TLNASSSDHK
ENSLKRSHSG DLKNKKVPVD RKYSDNEDDE YDDADLHGFE KKQLIKKELG DDDEDLLIQS
KKSHQKKKLK EKELESSIHE LTEIAASLQK RIHTLETENK LLKNLVLSSG ETEGIKKAES
LKKQIFEKVQ KE
