PHO4_YEAST
ID PHO4_YEAST Reviewed; 312 AA.
AC P07270; D6VTR7;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Phosphate system positive regulatory protein PHO4;
GN Name=PHO4; OrderedLocusNames=YFR034C;
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].
RX PubMed=3008105; DOI=10.1093/nar/14.7.3059;
RA Legrain M., de Wilde M., Hilger F.;
RT "Isolation, physical characterization and expression analysis of the
RT Saccharomyces cerevisiae positive regulatory gene PHO4.";
RL Nucleic Acids Res. 14:3059-3073(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2505053; DOI=10.1007/bf00330939;
RA Yoshida K., Kuromitsu Z., Ogawa N., Oshima Y.;
RT "Mode of expression of the positive regulatory genes PHO2 and PHO4 of the
RT phosphatase regulon in Saccharomyces cerevisiae.";
RL Mol. Gen. Genet. 217:31-39(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8686381;
RX DOI=10.1002/(sici)1097-0061(199602)12:2<177::aid-yea896>3.0.co;2-a;
RA Eki T., Naitou M., Hagiwara H., Abe M., Ozawa M., Sasanuma S., Sasanuma M.,
RA Tsuchiya Y., Shibata T., Watanabe K., Ono A., Yamazaki M., Tashiro H.,
RA Hanaoka F., Murakami Y.;
RT "Fifteen open reading frames in a 30.8 kb region of the right arm of
RT chromosome VI from Saccharomyces cerevisiae.";
RL Yeast 12:177-190(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7670463; DOI=10.1038/ng0795-261;
RA Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA Eki T.;
RT "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT cerevisiae.";
RL Nat. Genet. 10:261-268(1995).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [7]
RP DOMAINS.
RX PubMed=2183025; DOI=10.1128/mcb.10.5.2224-2236.1990;
RA Ogawa N., Oshima Y.;
RT "Functional domains of a positive regulatory protein, PHO4, for
RT transcriptional control of the phosphatase regulon in Saccharomyces
RT cerevisiae.";
RL Mol. Cell. Biol. 10:2224-2236(1990).
RN [8]
RP HELIX-LOOP-HELIX MOTIF.
RX PubMed=2220078; DOI=10.1002/yea.320060510;
RA Berben G.H.F., Legrain M., Gilliquet V., Hilger F.;
RT "The yeast regulatory gene PHO4 encodes a helix-loop-helix motif.";
RL Yeast 6:451-454(1990).
RN [9]
RP INTERACTION WITH PHO80.
RX PubMed=8187772; DOI=10.1002/j.1460-2075.1994.tb06496.x;
RA Jayaraman P.-S., Hirst K., Goding C.R.;
RT "The activation domain of a basic helix-loop-helix protein is masked by
RT repressor interaction with domains distinct from that required for
RT transcription regulation.";
RL EMBO J. 13:2192-2199(1994).
RN [10]
RP INTERACTION WITH PHO2; PHO80 AND PHO81.
RX PubMed=7957107; DOI=10.1002/j.1460-2075.1994.tb06876.x;
RA Hirst K., Fisher F., McAndrew P.C., Goding C.R.;
RT "The transcription factor, the Cdk, its cyclin and their regulator:
RT directing the transcriptional response to a nutritional signal.";
RL EMBO J. 13:5410-5420(1994).
RN [11]
RP PHOSPHORYLATION.
RX PubMed=8108735; DOI=10.1126/science.8108735;
RA Kaffman A., Herskowitz I., Tjian R., O'Shea E.K.;
RT "Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex,
RT PHO80-PHO85.";
RL Science 263:1153-1156(1994).
RN [12]
RP PHOSPHORYLATION AT SER-100; SER-114; SER-128; SER-152 AND SER-223, AND
RP SUBCELLULAR LOCATION.
RX PubMed=8539622; DOI=10.1126/science.271.5246.209;
RA O'Neill E.M., Kaffman A., Jolly E.R., O'Shea E.K.;
RT "Regulation of PHO4 nuclear localization by the PHO80-PHO85 cyclin-CDK
RT complex.";
RL Science 271:209-212(1996).
RN [13]
RP PHOSPHORYLATION AT SER-100; SER-114; SER-128; SER-152 AND SER-223.
RX PubMed=10320381; DOI=10.1126/science.284.5416.977;
RA Komeili A., O'Shea E.K.;
RT "Roles of phosphorylation sites in regulating activity of the transcription
RT factor Pho4.";
RL Science 284:977-980(1999).
RN [14]
RP DOMAIN.
RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003;
RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.;
RT "Nine-amino-acid transactivation domain: establishment and prediction
RT utilities.";
RL Genomics 89:756-768(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-242 AND SER-243, AND
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204, 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, AND IDENTIFICATION BY
RP 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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 251-312.
RX PubMed=9303313; DOI=10.1093/emboj/16.15.4689;
RA Shimizu T., Toumoto A., Ihara K., Shimizu M., Kyogoku Y., Ogawa N.,
RA Oshima Y., Hakoshima T.;
RT "Crystal structure of PHO4 bHLH domain-DNA complex: flanking base
RT recognition.";
RL EMBO J. 16:4689-4697(1997).
CC -!- FUNCTION: Transcriptional activator that regulates the expression of
CC repressible phosphatase under phosphate starvation conditions. Binds to
CC the upstream activating sequence (UAS) of several phosphatase encoding
CC PHO genes. Inhibited by the cyclin-CDK PHO80-PHO85 under high-phosphate
CC conditions.
CC -!- SUBUNIT: Binds DNA as a homodimer. Interacts with transcription factor
CC PHO2 and binds cooperatively to PHO5 UAS. Interacts with the cyclin-CDK
CC PHO80-PHO85 and the CDK inhibitor (CKI) PHO81.
CC {ECO:0000269|PubMed:7957107, ECO:0000269|PubMed:8187772}.
CC -!- INTERACTION:
CC P07270; P52918: MSN5; NbExp=2; IntAct=EBI-13378, EBI-11420;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8539622}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:8539622}.
CC Note=Predominantly cytoplasmic under high-phosphate conditions and
CC localized to the nucleus upon phosphate starvation.
CC -!- DOMAIN: The 9aaTAD motif (residues 75 to 83) is a transactivation
CC domain present in a large number of yeast and animal transcription
CC factors. {ECO:0000269|PubMed:17467953, ECO:0000269|PubMed:2183025}.
CC -!- PTM: Phosphorylated by the cyclin-CDK PHO80-PHO85 at five residues
CC under high-phosphate conditions, preventing PHO4 from activating the
CC structural PHO genes. Phosphorylation of Ser-114 and Ser-128 promotes
CC nuclear export. Phosphorylation of Ser-152 decreases nuclear import.
CC Phosphorylation of Ser-223 decreases the binding affinity for PHO2.
CC {ECO:0000269|PubMed:10320381, ECO:0000269|PubMed:8108735,
CC ECO:0000269|PubMed:8539622}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA27345.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X03719; CAA27345.1; ALT_FRAME; Genomic_DNA.
DR EMBL; D50617; BAA09273.1; -; Genomic_DNA.
DR EMBL; AY692776; AAT92795.1; -; Genomic_DNA.
DR EMBL; BK006940; DAA12477.1; -; Genomic_DNA.
DR PIR; S56289; S56289.
DR RefSeq; NP_116692.1; NM_001179999.1.
DR PDB; 1A0A; X-ray; 2.80 A; A/B=251-312.
DR PDB; 3W3X; X-ray; 2.90 A; B=140-166.
DR PDBsum; 1A0A; -.
DR PDBsum; 3W3X; -.
DR AlphaFoldDB; P07270; -.
DR SMR; P07270; -.
DR BioGRID; 31191; 257.
DR DIP; DIP-911N; -.
DR ELM; P07270; -.
DR IntAct; P07270; 115.
DR MINT; P07270; -.
DR STRING; 4932.YFR034C; -.
DR iPTMnet; P07270; -.
DR MaxQB; P07270; -.
DR PaxDb; P07270; -.
DR PRIDE; P07270; -.
DR EnsemblFungi; YFR034C_mRNA; YFR034C; YFR034C.
DR GeneID; 850594; -.
DR KEGG; sce:YFR034C; -.
DR SGD; S000001930; PHO4.
DR VEuPathDB; FungiDB:YFR034C; -.
DR eggNOG; ENOG502S1Z7; Eukaryota.
DR GeneTree; ENSGT00940000173160; -.
DR HOGENOM; CLU_077481_0_0_1; -.
DR InParanoid; P07270; -.
DR OMA; DFNEQND; -.
DR BioCyc; YEAST:G3O-30481-MON; -.
DR EvolutionaryTrace; P07270; -.
DR PRO; PR:P07270; -.
DR Proteomes; UP000002311; Chromosome VI.
DR RNAct; P07270; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:SGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0016036; P:cellular response to phosphate starvation; IDA:SGD.
DR GO; GO:0006338; P:chromatin remodeling; IMP:SGD.
DR GO; GO:0045937; P:positive regulation of phosphate metabolic process; IGI:SGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:SGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..312
FT /note="Phosphate system positive regulatory protein PHO4"
FT /id="PRO_0000127422"
FT DOMAIN 250..306
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..31
FT /note="Interaction with PHO80"
FT REGION 35..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 75..99
FT /note="Transcription activation domain"
FT REGION 138..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 156..200
FT /note="Interaction with PHO80"
FT REGION 201..218
FT /note="Interaction with PHO2"
FT /evidence="ECO:0000269|PubMed:7957107"
FT REGION 203..227
FT /note="Involved in oligomerization"
FT MOTIF 75..83
FT /note="9aaTAD"
FT MOTIF 140..166
FT /note="Nuclear localization signal"
FT COMPBIAS 35..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..68
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..156
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..241
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..259
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 100
FT /note="Phosphoserine; by PHO85"
FT /evidence="ECO:0000269|PubMed:10320381,
FT ECO:0000269|PubMed:8539622"
FT MOD_RES 114
FT /note="Phosphoserine; by PHO85"
FT /evidence="ECO:0000269|PubMed:10320381,
FT ECO:0000269|PubMed:8539622"
FT MOD_RES 128
FT /note="Phosphoserine; by PHO85"
FT /evidence="ECO:0000269|PubMed:10320381,
FT ECO:0000269|PubMed:8539622"
FT MOD_RES 152
FT /note="Phosphoserine; by PHO85"
FT /evidence="ECO:0000269|PubMed:10320381,
FT ECO:0000269|PubMed:8539622"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 223
FT /note="Phosphoserine; by PHO85"
FT /evidence="ECO:0000269|PubMed:10320381,
FT ECO:0000269|PubMed:8539622, ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358"
FT CONFLICT 269
FT /note="A -> P (in Ref. 1; CAA27345 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="V -> G (in Ref. 2)"
FT /evidence="ECO:0000305"
FT HELIX 254..258
FT /evidence="ECO:0007829|PDB:1A0A"
FT HELIX 260..275
FT /evidence="ECO:0007829|PDB:1A0A"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:1A0A"
FT HELIX 294..306
FT /evidence="ECO:0007829|PDB:1A0A"
SQ SEQUENCE 312 AA; 34089 MW; 6DB93C0DDDB4D741 CRC64;
MGRTTSEGIH GFVDDLEPKS SILDKVGDFI TVNTKRHDGR EDFNEQNDEL NSQENHNSSE
NGNENENEQD SLALDDLDRA FELVEGMDMD WMMPSHAHHS PATTATIKPR LLYSPLIHTQ
SAVPVTISPN LVATATSTTS ANKVTKNKSN SSPYLNKRRG KPGPDSATSL FELPDSVIPT
PKPKPKPKQY PKVILPSNST RRVSPVTAKT SSSAEGVVVA SESPVIAPHG SSHSRSLSKR
RSSGALVDDD KRESHKHAEQ ARRNRLAVAL HELASLIPAE WKQQNVSAAP SKATTVEAAC
RYIRHLQQNV ST
