PHO85_YEAST
ID PHO85_YEAST Reviewed; 305 AA.
AC P17157; D6W3Y2; Q03089; Q06888;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Cyclin-dependent protein kinase PHO85;
DE EC=2.7.11.22 {ECO:0000269|PubMed:12857883, ECO:0000269|PubMed:7973730, ECO:0000269|PubMed:7973731, ECO:0000269|PubMed:8108735, ECO:0000269|PubMed:9584169};
DE AltName: Full=Negative regulator of the PHO system;
DE AltName: Full=Serine/threonine-protein kinase PHO85;
GN Name=PHO85; Synonyms=SSG3; OrderedLocusNames=YPL031C; ORFNames=P7102.18A;
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].
RC STRAIN=ATCC 64665 / S288c / DC5;
RX PubMed=3320965; DOI=10.1093/nar/15.24.10299;
RA Uesono Y., Tanaka K., Toh-e A.;
RT "Negative regulators of the PHO system in Saccharomyces cerevisiae:
RT isolation and structural characterization of PHO85.";
RL Nucleic Acids Res. 15:10299-10309(1987).
RN [2]
RP SEQUENCE REVISION TO 1-6, AND FUNCTION.
RX PubMed=3067079; DOI=10.1007/bf00340196;
RA Toh-e A., Tanaka K., Uesono Y., Wickner R.B.;
RT "PHO85, a negative regulator of the PHO system, is a homolog of the protein
RT kinase gene, CDC28, of Saccharomyces cerevisiae.";
RL Mol. Gen. Genet. 214:162-164(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169875;
RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA Vo D.H., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL Nature 387:103-105(1997).
RN [4]
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 [5]
RP FUNCTION IN PHOSPHORYLATION OF PHO4, CATALYTIC ACTIVITY, AND INTERACTION
RP WITH PHO80.
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 [6]
RP ACTIVITY REGULATION.
RX PubMed=7939631; DOI=10.1126/science.7939631;
RA Schneider K.R., Smith R.L., O'Shea E.K.;
RT "Phosphate-regulated inactivation of the kinase PHO80-PHO85 by the CDK
RT inhibitor PHO81.";
RL Science 266:122-126(1994).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH PCL1.
RX PubMed=7973730; DOI=10.1126/science.7973730;
RA Espinoza F.H., Ogas J., Herskowitz I., Morgan D.O.;
RT "Cell cycle control by a complex of the cyclin HCS26 (PCL1) and the kinase
RT PHO85.";
RL Science 266:1388-1391(1994).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH PCL2.
RX PubMed=7973731; DOI=10.1126/science.7973731;
RA Measday V., Moore L., Ogas J., Tyers M., Andrews B.J.;
RT "The PCL2 (ORFD)-PHO85 cyclin-dependent kinase complex: a cell cycle
RT regulator in yeast.";
RL Science 266:1391-1395(1994).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF PHO4.
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 [10]
RP INTERACTION WITH CLG1; PCL1; PCL2; PCL5; PCL6; PCL7; PCL8; PCL9 AND PCL10.
RX PubMed=9032248; DOI=10.1128/mcb.17.3.1212;
RA Measday V., Moore L., Retnakaran R., Lee J., Donoviel M., Neiman A.M.,
RA Andrews B.J.;
RT "A family of cyclin-like proteins that interact with the Pho85 cyclin-
RT dependent kinase.";
RL Mol. Cell. Biol. 17:1212-1223(1997).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF RVS167.
RX PubMed=9843683; DOI=10.1016/s0960-9822(07)00561-1;
RA Lee J., Colwill K., Aneliunas V., Tennyson C.N., Moore L., Ho Y.,
RA Andrews B.J.;
RT "Interaction of yeast Rvs167 and Pho85 cyclin-dependent kinase complexes
RT may link the cell cycle to the actin cytoskeleton.";
RL Curr. Biol. 8:1310-1321(1998).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF SIC1.
RX PubMed=9725902; DOI=10.1091/mbc.9.9.2393;
RA Nishizawa M., Kawasumi M., Fujino M., Toh-e A.;
RT "Phosphorylation of Sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk
RT including Pho85 kinase is required for its prompt degradation.";
RL Mol. Biol. Cell 9:2393-2405(1998).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF GSY2, AND CATALYTIC ACTIVITY.
RX PubMed=9584169; DOI=10.1128/mcb.18.6.3289;
RA Huang D., Moffat J., Wilson W.A., Moore L., Cheng C., Roach P.J.,
RA Andrews B.J.;
RT "Cyclin partners determine Pho85 protein kinase substrate specificity in
RT vitro and in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10.";
RL Mol. Cell. Biol. 18:3289-3299(1998).
RN [14]
RP FUNCTION, AND INTERACTION WITH PCL9.
RX PubMed=9593297; DOI=10.1046/j.1365-2958.1998.00773.x;
RA Tennyson C.N., Lee J., Andrews B.J.;
RT "A role for the Pcl9-Pho85 cyclin-cdk complex at the M/G1 boundary in
RT Saccharomyces cerevisiae.";
RL Mol. Microbiol. 28:69-79(1998).
RN [15]
RP CHARACTERIZATION, PHOSPHORYLATION AT TYR-18, AND MUTAGENESIS OF GLU-53.
RX PubMed=10620010; DOI=10.1046/j.1365-2443.1999.00290.x;
RA Nishizawa M., Suzuki K., Fujino M., Oguchi T., Toh-e A.;
RT "The Pho85 kinase, a member of the yeast cyclin-dependent kinase (Cdk)
RT family, has a regulation mechanism different from Cdks functioning
RT throughout the cell cycle.";
RL Genes Cells 4:627-642(1999).
RN [16]
RP FUNCTION, INTERACTION WITH PCL10, BIOPHYSICOCHEMICAL PROPERTIES, AND LACK
RP OF PHOSPHORYLATION.
RX PubMed=10490639; DOI=10.1128/mcb.19.10.7020;
RA Wilson W.A., Mahrenholz A.M., Roach P.J.;
RT "Substrate targeting of the yeast cyclin-dependent kinase Pho85p by the
RT cyclin Pcl10p.";
RL Mol. Cell. Biol. 19:7020-7030(1999).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF SWI5.
RX PubMed=10692159; DOI=10.1046/j.1365-2958.2000.01754.x;
RA Measday V., McBride H., Moffat J., Stillman D., Andrews B.J.;
RT "Interactions between Pho85 cyclin-dependent kinase complexes and the Swi5
RT transcription factor in budding yeast.";
RL Mol. Microbiol. 35:825-834(2000).
RN [18]
RP ACTIVITY REGULATION, AND INTERACTION WITH PCL6 AND PCL7.
RX PubMed=11069666; DOI=10.1046/j.1365-2958.2000.02140.x;
RA Lee M., O'Regan S., Moreau J.-L., Johnson A.L., Johnston L.H., Goding C.R.;
RT "Regulation of the Pcl7-Pho85 cyclin-cdk complex by Pho81.";
RL Mol. Microbiol. 38:411-422(2000).
RN [19]
RP FUNCTION.
RX PubMed=11602261; DOI=10.1016/s0014-5793(01)02914-3;
RA Wang Z., Wilson W.A., Fujino M.A., Roach P.J.;
RT "The yeast cyclins Pcl6p and Pcl7p are involved in the control of glycogen
RT storage by the cyclin-dependent protein kinase Pho85p.";
RL FEBS Lett. 506:277-280(2001).
RN [20]
RP MUTAGENESIS OF PHE-82.
RX PubMed=11675494; DOI=10.1073/pnas.211195798;
RA Carroll A.S., Bishop A.C., DeRisi J.L., Shokat K.M., O'Shea E.K.;
RT "Chemical inhibition of the Pho85 cyclin-dependent kinase reveals a role in
RT the environmental stress response.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12578-12583(2001).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 200060 / W303 {ECO:0000303|PubMed:12455686};
RX PubMed=12455686; DOI=10.1128/ec.1.5.663-672.2002;
RA Pries R., Boemeke K., Irniger S., Grundmann O., Braus G.H.;
RT "Amino acid-dependent Gcn4p stability regulation occurs exclusively in the
RT yeast nucleus.";
RL Eukaryot. Cell 1:663-672(2002).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF MMR1.
RX PubMed=12006994;
RA Shi X.Z., Ao S.Z.;
RT "Phosphorylation of YLR190w by PAP1 PHO85 kinase complex.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 34:187-192(2002).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF YJL084C.
RX PubMed=12098764;
RA Shi X.Z., Ao S.Z.;
RT "Analysis of phosphorylation of YJL084c, a yeast protein.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 34:433-438(2002).
RN [24]
RP FUNCTION IN PHOSPHORYLATION OF GCN4.
RX PubMed=12101234; DOI=10.1128/mcb.22.15.5395-5404.2002;
RA Shemer R., Meimoun A., Holtzman T., Kornitzer D.;
RT "Regulation of the transcription factor Gcn4 by Pho85 cyclin PCL5.";
RL Mol. Cell. Biol. 22:5395-5404(2002).
RN [25]
RP FUNCTION IN PHOSPHORYLATION OF GLC8, CATALYTIC ACTIVITY, AND INTERACTION
RP WITH GLC8.
RX PubMed=12407105; DOI=10.1074/jbc.m208058200;
RA Tan Y.S.H., Morcos P.A., Cannon J.F.;
RT "Pho85 phosphorylates the Glc7 protein phosphatase regulator Glc8 in
RT vivo.";
RL J. Biol. Chem. 278:147-153(2003).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF RVS167.
RX PubMed=12857883; DOI=10.1091/mbc.e02-09-0613;
RA Friesen H., Murphy K., Breitkreutz A., Tyers M., Andrews B.J.;
RT "Regulation of the yeast amphiphysin homologue Rvs167p by
RT phosphorylation.";
RL Mol. Biol. Cell 14:3027-3040(2003).
RN [27]
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 [28]
RP FUNCTION IN PHOSPHORYLATION OF PHO80 AND PHO81, AND MUTAGENESIS OF LYS-36.
RX PubMed=15057567; DOI=10.1007/s00294-004-0501-0;
RA Waters N.C., Knight J.P., Creasy C.L., Bergman L.W.;
RT "The yeast Pho80-Pho85 cyclin-CDK complex has multiple substrates.";
RL Curr. Genet. 46:1-9(2004).
RN [29]
RP FUNCTION IN PHOSPHORYLATION OF HMS1; NCP1 AND NPA3.
RX PubMed=15082539; DOI=10.1534/genetics.166.3.1177;
RA Keniry M.E., Kemp H.A., Rivers D.M., Sprague G.F. Jr.;
RT "The identification of Pcl1-interacting proteins that genetically interact
RT with Cla4 may indicate a link between G1 progression and mitotic exit.";
RL Genetics 166:1177-1186(2004).
RN [30]
RP FUNCTION.
RX PubMed=15721288; DOI=10.1016/j.bbrc.2005.01.106;
RA Wilson W.A., Wang Z., Roach P.J.;
RT "Regulation of yeast glycogen phosphorylase by the cyclin-dependent protein
RT kinase Pho85p.";
RL Biochem. Biophys. Res. Commun. 329:161-167(2005).
RN [31]
RP FUNCTION IN PHOSPHORYLATION OF RIM15, AND INTERACTION WITH RIM15.
RX PubMed=16308562; DOI=10.1038/sj.emboj.7600889;
RA Wanke V., Pedruzzi I., Cameroni E., Dubouloz F., De Virgilio C.;
RT "Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex.";
RL EMBO J. 24:4271-4278(2005).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF LCB4.
RX PubMed=15598647; DOI=10.1074/jbc.m410908200;
RA Iwaki S., Kihara A., Sano T., Igarashi Y.;
RT "Phosphorylation by Pho85 cyclin-dependent kinase acts as a signal for the
RT down-regulation of the yeast sphingoid long-chain base kinase Lcb4 during
RT the stationary phase.";
RL J. Biol. Chem. 280:6520-6527(2005).
RN [33]
RP FUNCTION IN PHOSPHORYLATION OF CRZ1.
RX PubMed=16455487; DOI=10.1016/j.molcel.2005.12.011;
RA Sopko R., Huang D., Preston N., Chua G., Papp B., Kafadar K., Snyder M.,
RA Oliver S.G., Cyert M., Hughes T.R., Boone C., Andrews B.J.;
RT "Mapping pathways and phenotypes by systematic gene overexpression.";
RL Mol. Cell 21:319-330(2006).
RN [34]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-289, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
CC -!- FUNCTION: Cyclin-dependent protein kinase (CDK) catalytic subunit that
CC regulates multiple cell cycle and metabolic processes in response to
CC nutrient availability. Associates with different cyclins, that control
CC kinase activity, substrate specificity and subcellular location of the
CC kinase. Regulates metabolic processes when associated with PHO80 cyclin
CC family members (PH080, PCL6, PCL7, PCL8 and PCL10), and cell cycle and
CC morphogenesis processes when associated with PCL1,2 cyclin family
CC members (PCL1, PCL2, CLG1, PCL5 and PCL9) (PubMed:10490639,
CC PubMed:10692159, PubMed:11602261, PubMed:12006994, PubMed:12098764,
CC PubMed:12101234, PubMed:12407105, PubMed:12857883, PubMed:15057567,
CC PubMed:15082539, PubMed:15598647, PubMed:15721288, PubMed:16308562,
CC PubMed:16455487, PubMed:3067079, PubMed:7973730, PubMed:8108735,
CC PubMed:8539622, PubMed:9584169, PubMed:9593297, PubMed:9725902,
CC PubMed:9843683, PubMed:12455686). When associated with PHO80,
CC negatively regulates the expression of phosphate-starvation-responsive
CC genes under phosphate-rich conditions (PubMed:8108735, PubMed:3067079).
CC The PHO80-PHO85 cyclin-CDK holoenzyme phosphorylates and inactivates
CC the transcription factor PHO4 by promoting its export to the cytoplasm
CC (PubMed:8108735). PHO80-PHO85 phosphorylates and inactivates protein
CC kinase RIM15 by retaining it in the cytoplasm, antagonizing RIM15-
CC induced entry into stationary phase (PubMed:16308562). PHO80-PHO85 also
CC phosphorylates and inactivates the calcineurin-responsive transcription
CC factor CRZ1, linking cyclin-CDK activity to calcium signaling
CC (PubMed:16455487). PHO80-PHO85 phosphorylates MMR1 (PubMed:12006994).
CC Together with the cyclins PCL6/PCL7 and PCL8/PCL10, negatively controls
CC glycogen accumulation (PubMed:10490639, PubMed:11602261,
CC PubMed:15721288, PubMed:8539622, PubMed:9584169, PubMed:12407105). When
CC associated with cyclins PCL6 and PCL7, controls glycogen phosphorylase
CC and glycogen synthase activities (PubMed:11602261, PubMed:15721288,
CC PubMed:12407105). PCL6-PHO85 and PCL7-PHO85 phosphorylate and
CC inactivate the phosphatase PP1-2 inhibitor GLC8, causing activation of
CC PP1-2, which then dephosphorylates and activates glycogen phosphorylase
CC (PubMed:12407105). PCL7-PHO85 phosphorylate ALY2 (PubMed:12098764).
CC PCL10-PHO85 phosphorylates and negatively regulates glycogen synthase
CC GSY2 (PubMed:9584169). Association with PCL1 and PCL2 is required for
CC cell cycle progression at start in the absence of the CDC28-dependent
CC G1 cyclins CLN1 and CLN2 (PubMed:7973730, PubMed:7973731). PCL1-PHO85
CC is involved in phosphorylation of the CDK inhibitor (CKI) SIC1, which
CC is required for its ubiquitination and degradation, releasing
CC repression of b-type cyclins and promoting exit from mitosis
CC (PubMed:9725902). When associated with cyclins PCL1 and PCL2,
CC positively controls degradation of sphingoid long chain base kinase
CC LCB4 via phosphorylation of LCB4, which is required for its
CC ubiquitination and degradation (PubMed:15598647). PCL1-PHO85 also
CC phosphorylates HMS1, NCP1 and NPA3, which may all have a role in
CC mitotic exit (PubMed:15082539). PCL2-PHO85 also phosphorylates RVS167,
CC linking cyclin-CDK activity with organization of the actin cytoskeleton
CC (PubMed:9843683, PubMed:12857883). When associated with PCL5,
CC positively controls degradation of transcription factor GCN4 via
CC phosphorylation of GCN4, which is required for its degradation by the
CC E3 ubiquitin ligase complex SCF(Cdc4) (PubMed:12455686,
CC PubMed:12101234). When associated with PCL9, may have a role in bud
CC site selection in G1 phase (PubMed:9593297). PHO85 also phosphorylates
CC the transcription factor SWI5 (PubMed:10692159).
CC {ECO:0000269|PubMed:10490639, ECO:0000269|PubMed:10692159,
CC ECO:0000269|PubMed:11602261, ECO:0000269|PubMed:12006994,
CC ECO:0000269|PubMed:12098764, ECO:0000269|PubMed:12101234,
CC ECO:0000269|PubMed:12407105, ECO:0000269|PubMed:12455686,
CC ECO:0000269|PubMed:12857883, ECO:0000269|PubMed:15057567,
CC ECO:0000269|PubMed:15082539, ECO:0000269|PubMed:15598647,
CC ECO:0000269|PubMed:15721288, ECO:0000269|PubMed:16308562,
CC ECO:0000269|PubMed:16455487, ECO:0000269|PubMed:3067079,
CC ECO:0000269|PubMed:7973730, ECO:0000269|PubMed:7973731,
CC ECO:0000269|PubMed:8108735, ECO:0000269|PubMed:8539622,
CC ECO:0000269|PubMed:9584169, ECO:0000269|PubMed:9593297,
CC ECO:0000269|PubMed:9725902, ECO:0000269|PubMed:9843683}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC Evidence={ECO:0000269|PubMed:10490639, ECO:0000269|PubMed:12407105,
CC ECO:0000269|PubMed:7973730, ECO:0000269|PubMed:7973731,
CC ECO:0000269|PubMed:8108735, ECO:0000269|PubMed:9584169};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22; Evidence={ECO:0000269|PubMed:10490639,
CC ECO:0000269|PubMed:12407105, ECO:0000269|PubMed:7973730,
CC ECO:0000269|PubMed:7973731, ECO:0000269|PubMed:8108735,
CC ECO:0000269|PubMed:9584169};
CC -!- ACTIVITY REGULATION: Inhibited by the CDK inhibitor (CKI) PHO81 in
CC response to phosphate starvation. {ECO:0000269|PubMed:11069666,
CC ECO:0000269|PubMed:7939631}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.5 uM for substrate protein GSY2 (when associated with cyclin
CC PCL10) {ECO:0000269|PubMed:10490639};
CC Vmax=11.5 umol/min/mg enzyme {ECO:0000269|PubMed:10490639};
CC -!- SUBUNIT: Monomer. Forms a cyclin-CDK complex with at least 10 different
CC cyclin partners: PCL1, PCL2, PHO80, CLG1, PCL5, PCL6, PCL7, PCL8, PCL9
CC and PCL10. Interacts with GLC8 and RIM15. {ECO:0000269|PubMed:10490639,
CC ECO:0000269|PubMed:11069666, ECO:0000269|PubMed:12407105,
CC ECO:0000269|PubMed:16308562, ECO:0000269|PubMed:7973730,
CC ECO:0000269|PubMed:7973731, ECO:0000269|PubMed:8108735,
CC ECO:0000269|PubMed:9032248, ECO:0000269|PubMed:9593297}.
CC -!- INTERACTION:
CC P17157; P37366: CCL1; NbExp=2; IntAct=EBI-13327, EBI-4385;
CC P17157; P35190: CLG1; NbExp=3; IntAct=EBI-13327, EBI-4762;
CC P17157; P20437: CLN1; NbExp=2; IntAct=EBI-13327, EBI-4479;
CC P17157; P24867: PCL1; NbExp=4; IntAct=EBI-13327, EBI-4495;
CC P17157; P53124: PCL10; NbExp=6; IntAct=EBI-13327, EBI-23973;
CC P17157; P25693: PCL2; NbExp=8; IntAct=EBI-13327, EBI-4499;
CC P17157; P38794: PCL5; NbExp=2; IntAct=EBI-13327, EBI-4504;
CC P17157; P40038: PCL6; NbExp=7; IntAct=EBI-13327, EBI-22555;
CC P17157; P40186: PCL7; NbExp=8; IntAct=EBI-13327, EBI-25021;
CC P17157; Q08966: PCL8; NbExp=8; IntAct=EBI-13327, EBI-37056;
CC P17157; Q12477: PCL9; NbExp=4; IntAct=EBI-13327, EBI-38090;
CC P17157; P20052: PHO80; NbExp=4; IntAct=EBI-13327, EBI-13310;
CC P17157; P17442: PHO81; NbExp=6; IntAct=EBI-13327, EBI-13314;
CC P17157; P10591: SSA1; NbExp=2; IntAct=EBI-13327, EBI-8591;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12455686}. Nucleus
CC {ECO:0000269|PubMed:12455686}. Note=Predominantly localizes to the
CC nucleus. {ECO:0000269|PubMed:12455686}.
CC -!- PTM: Phosphorylation of Tyr-18 seems to be important to discriminate
CC between the different cyclin partners for binding.
CC {ECO:0000269|PubMed:10620010}.
CC -!- DISRUPTION PHENOTYPE: Increases GCN4 level.
CC {ECO:0000269|PubMed:12455686}.
CC -!- MISCELLANEOUS: Present with 6160 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y00867; CAA68773.1; -; Genomic_DNA.
DR EMBL; Y00867; CAA68774.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U44030; AAB68188.1; -; Genomic_DNA.
DR EMBL; BK006949; DAA11398.1; -; Genomic_DNA.
DR PIR; S62043; OKBY85.
DR RefSeq; NP_015294.1; NM_001183845.1.
DR PDB; 2PK9; X-ray; 2.91 A; A/C=1-305.
DR PDB; 2PMI; X-ray; 2.90 A; A/C=1-305.
DR PDB; 4KRC; X-ray; 2.60 A; A=1-305.
DR PDB; 4KRD; X-ray; 1.95 A; A=1-305.
DR PDBsum; 2PK9; -.
DR PDBsum; 2PMI; -.
DR PDBsum; 4KRC; -.
DR PDBsum; 4KRD; -.
DR AlphaFoldDB; P17157; -.
DR SMR; P17157; -.
DR BioGRID; 36147; 661.
DR ComplexPortal; CPX-1688; PHO80-PHO85 kinase complex.
DR ComplexPortal; CPX-1689; PCL6-PHO85 kinase complex.
DR ComplexPortal; CPX-1690; PCL7-PHO85 kinase complex.
DR ComplexPortal; CPX-1691; PCL8-PHO85 kinase complex.
DR ComplexPortal; CPX-1692; PCL10-PHO85 kinase complex.
DR ComplexPortal; CPX-1693; CLG1-PHO85 kinase complex.
DR ComplexPortal; CPX-1694; PCL2-PHO85 kinase complex.
DR ComplexPortal; CPX-1695; PCL1-PHO85 kinase complex.
DR ComplexPortal; CPX-1696; PCL5-PHO85 kinase complex.
DR ComplexPortal; CPX-1697; PCL9-PHO85 kinase complex.
DR DIP; DIP-1493N; -.
DR IntAct; P17157; 58.
DR MINT; P17157; -.
DR STRING; 4932.YPL031C; -.
DR BindingDB; P17157; -.
DR ChEMBL; CHEMBL5589; -.
DR iPTMnet; P17157; -.
DR MaxQB; P17157; -.
DR PaxDb; P17157; -.
DR PRIDE; P17157; -.
DR EnsemblFungi; YPL031C_mRNA; YPL031C; YPL031C.
DR GeneID; 856076; -.
DR KEGG; sce:YPL031C; -.
DR SGD; S000005952; PHO85.
DR VEuPathDB; FungiDB:YPL031C; -.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000173166; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P17157; -.
DR OMA; QHPWFND; -.
DR BioCyc; YEAST:G3O-33946-MON; -.
DR BRENDA; 2.7.11.22; 984.
DR EvolutionaryTrace; P17157; -.
DR PRO; PR:P17157; -.
DR Proteomes; UP000002311; Chromosome XVI.
DR RNAct; P17157; protein.
DR GO; GO:0005935; C:cellular bud neck; IPI:ComplexPortal.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IPI:SGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:1990860; C:Pho85-Pho80 CDK-cyclin complex; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:SGD.
DR GO; GO:0004672; F:protein kinase activity; HDA:SGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0044843; P:cell cycle G1/S phase transition; IC:ComplexPortal.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:SGD.
DR GO; GO:0030952; P:establishment or maintenance of cytoskeleton polarity; IC:ComplexPortal.
DR GO; GO:0031505; P:fungal-type cell wall organization; HGI:SGD.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IC:ComplexPortal.
DR GO; GO:0055088; P:lipid homeostasis; IDA:SGD.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IC:ComplexPortal.
DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; IGI:SGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:ComplexPortal.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; IMP:SGD.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:SGD.
DR GO; GO:0045936; P:negative regulation of phosphate metabolic process; IDA:ComplexPortal.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:SGD.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:SGD.
DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; IDA:SGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ComplexPortal.
DR GO; GO:0051726; P:regulation of cell cycle; IC:ComplexPortal.
DR GO; GO:1901987; P:regulation of cell cycle phase transition; IDA:SGD.
DR GO; GO:0051302; P:regulation of cell division; IDA:ComplexPortal.
DR GO; GO:0032878; P:regulation of establishment or maintenance of cell polarity; IGI:SGD.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; IC:ComplexPortal.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA:SGD.
DR GO; GO:0046822; P:regulation of nucleocytoplasmic transport; IDA:SGD.
DR GO; GO:0032880; P:regulation of protein localization; IDA:SGD.
DR GO; GO:0031647; P:regulation of protein stability; IMP:SGD.
DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IDA:ComplexPortal.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Isopeptide bond; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..305
FT /note="Cyclin-dependent protein kinase PHO85"
FT /id="PRO_0000086521"
FT DOMAIN 7..297
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 133
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 13..21
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 166
FT /note="Not phosphorylated"
FT /evidence="ECO:0000269|PubMed:10490639"
FT SITE 167
FT /note="Not phosphorylated"
FT /evidence="ECO:0000269|PubMed:10490639"
FT MOD_RES 18
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10620010"
FT CROSSLNK 289
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT MUTAGEN 18
FT /note="Y->F: Reduces kinase activity. Abolishes interaction
FT to PHO80 cyclin, but not to PCL1."
FT MUTAGEN 36
FT /note="K->R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15057567"
FT MUTAGEN 53
FT /note="E->A: Loss of kinase activity. Abolishes interaction
FT to PHO80 and PCL1 cyclins."
FT /evidence="ECO:0000269|PubMed:10620010"
FT MUTAGEN 82
FT /note="F->G: Functional kinase, that can be rapidly
FT inhibited by small, cell-permeable drugs like 1-Na PP1 (4-
FT amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-
FT d]pyrimidine)."
FT /evidence="ECO:0000269|PubMed:11675494"
FT CONFLICT 99
FT /note="G -> A (in Ref. 1; CAA68773/CAA68774)"
FT /evidence="ECO:0000305"
FT HELIX 4..6
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 7..16
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 19..26
FT /evidence="ECO:0007829|PDB:4KRD"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 32..39
FT /evidence="ECO:0007829|PDB:4KRD"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 48..55
FT /evidence="ECO:0007829|PDB:4KRD"
FT TURN 56..59
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:2PMI"
FT HELIX 107..126
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:4KRC"
FT STRAND 156..160
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 189..204
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 214..225
FT /evidence="ECO:0007829|PDB:4KRD"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 234..238
FT /evidence="ECO:0007829|PDB:4KRD"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:4KRC"
FT HELIX 254..258
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 268..277
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:4KRD"
FT HELIX 295..300
FT /evidence="ECO:0007829|PDB:4KRD"
SQ SEQUENCE 305 AA; 34906 MW; 246A4358870B00EC CRC64;
MSSSSQFKQL EKLGNGTYAT VYKGLNKTTG VYVALKEVKL DSEEGTPSTA IREISLMKEL
KHENIVRLYD VIHTENKLTL VFEFMDNDLK KYMDSRTVGN TPRGLELNLV KYFQWQLLQG
LAFCHENKIL HRDLKPQNLL INKRGQLKLG DFGLARAFGI PVNTFSSEVV TLWYRAPDVL
MGSRTYSTSI DIWSCGCILA EMITGKPLFP GTNDEEQLKL IFDIMGTPNE SLWPSVTKLP
KYNPNIQQRP PRDLRQVLQP HTKEPLDGNL MDFLHGLLQL NPDMRLSAKQ ALHHPWFAEY
YHHAS
