PP4C_YEAST
ID PP4C_YEAST Reviewed; 308 AA.
AC P32345; D6VS61;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Serine/threonine-protein phosphatase 4 catalytic subunit;
DE Short=PP4C;
DE EC=3.1.3.16;
DE AltName: Full=Phosphatase PP2A-like catalytic subunit PPH3;
GN Name=PPH3; OrderedLocusNames=YDR075W; ORFNames=D4421;
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 208353 / W303-1A;
RX PubMed=1656215; DOI=10.1128/mcb.11.10.4876-4884.1991;
RA Ronne H., Carlberg M., Hu G.-Z., Nehlin J.O.;
RT "Protein phosphatase 2A in Saccharomyces cerevisiae: effects on cell growth
RT and bud morphogenesis.";
RL Mol. Cell. Biol. 11:4876-4884(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RX PubMed=7941742; DOI=10.1002/yea.320100502;
RA Hoffmann R., Jung S., Ehrmann M., Hofer H.W.;
RT "The Saccharomyces cerevisiae gene PPH3 encodes a protein phosphatase with
RT properties different from PPX, PP1 and PP2A.";
RL Yeast 10:567-578(1994).
RN [3]
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 [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 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 [6]
RP FUNCTION IN GLN3 DEPHOSPHORYLATION.
RX PubMed=10940301; DOI=10.1074/jbc.m004235200;
RA Bertram P.G., Choi J.H., Carvalho J., Ai W., Zeng C., Chan T.-F.,
RA Zheng X.F.S.;
RT "Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases.";
RL J. Biol. Chem. 275:35727-35733(2000).
RN [7]
RP INTERACTION WITH TAP42.
RX PubMed=14551259; DOI=10.1091/mbc.e03-02-0072;
RA Wang H., Wang X., Jiang Y.;
RT "Interaction with Tap42 is required for the essential function of Sit4 and
RT type 2A phosphatases.";
RL Mol. Biol. Cell 14:4342-4351(2003).
RN [8]
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 [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 INTERACTION WITH PPE1 AND RRD1.
RX PubMed=15447631; DOI=10.1042/bj20040887;
RA Van Hoof C., Martens E., Longin S., Jordens J., Stevens I., Janssens V.,
RA Goris J.;
RT "Specific interactions of PP2A and PP2A-like phosphatases with the yeast
RT PTPA homologues, Ypa1 and Ypa2.";
RL Biochem. J. 386:93-102(2005).
RN [11]
RP IDENTIFICATION IN HTP-C COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP INTERACTION WITH SPT5.
RX PubMed=16085932; DOI=10.1074/mcp.m500231-mcp200;
RA Gingras A.-C., Caballero M., Zarske M., Sanchez A., Hazbun T.R., Fields S.,
RA Sonenberg N., Hafen E., Raught B., Aebersold R.;
RT "A novel, evolutionarily conserved protein phosphatase complex involved in
RT cisplatin sensitivity.";
RL Mol. Cell. Proteomics 4:1725-1740(2005).
RN [12]
RP FUNCTION, IDENTIFICATION IN HTP-C COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16299494; DOI=10.1038/nature04384;
RA Keogh M.-C., Kim J.-A., Downey M., Fillingham J., Chowdhury D.,
RA Harrison J.C., Onishi M., Datta N., Galicia S., Emili A., Lieberman J.,
RA Shen X., Buratowski S., Haber J.E., Durocher D., Greenblatt J.F.,
RA Krogan N.J.;
RT "A phosphatase complex that dephosphorylates gamma-H2AX regulates DNA
RT damage checkpoint recovery.";
RL Nature 439:497-501(2006).
RN [13]
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: Forms the histone H2A phosphatase complex in association with
CC the regulatory subunits PSY2 and PSY4, which dephosphorylates H2AS128ph
CC (gamma-H2A) that has been displaced from sites of DNA lesions in the
CC double-stranded DNA break repair process. Dephosphorylation is
CC necessary for efficient recovery from the DNA damage checkpoint. PPH3
CC is directly involved in the dephosphorylation and activation of the
CC transcription factor GLN3 in response to nutrient availability.
CC {ECO:0000269|PubMed:10940301, ECO:0000269|PubMed:16299494}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000250};
CC -!- SUBUNIT: Catalytic subunit of the histone H2A phosphatase complex (HTP-
CC C) containing PPH3, PSY2 and PSY4. Inactivated in a complex with
CC phosphatase methylesterase PPE1 (PP2Ai). Interacts with phosphatase 2A
CC activator RRD1, which can reactivate PP2Ai by dissociating the
CC catalytic subunit from the complex. Interacts with SPT5 and TAP42.
CC {ECO:0000269|PubMed:14551259, ECO:0000269|PubMed:15447631,
CC ECO:0000269|PubMed:16085932, ECO:0000269|PubMed:16299494}.
CC -!- INTERACTION:
CC P32345; P40164: PSY2; NbExp=10; IntAct=EBI-12759, EBI-29107;
CC P32345; P38193: PSY4; NbExp=10; IntAct=EBI-12759, EBI-21239;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus
CC {ECO:0000269|PubMed:14562095}.
CC -!- PTM: Reversibly methyl esterified on Leu-308 by leucine carboxyl
CC methyltransferase 1 (PPM1) and protein phosphatase methylesterase 1
CC (PPE1). Carboxyl methylation influences the affinity of the catalytic
CC subunit for the different regulatory subunits, thereby modulating the
CC PP2A holoenzyme's substrate specificity, enzyme activity and cellular
CC localization (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Present with 2840 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-4 (PP-X)
CC subfamily. {ECO:0000305}.
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DR EMBL; Z46796; CAA86797.1; -; Genomic_DNA.
DR EMBL; X58858; CAA41662.1; -; Genomic_DNA.
DR EMBL; X82086; CAA57602.1; -; Genomic_DNA.
DR EMBL; Z74371; CAA98894.1; -; Genomic_DNA.
DR EMBL; AY557686; AAS56012.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11921.1; -; Genomic_DNA.
DR PIR; S44331; PABY3.
DR RefSeq; NP_010360.1; NM_001180383.1.
DR AlphaFoldDB; P32345; -.
DR SMR; P32345; -.
DR BioGRID; 32130; 373.
DR ComplexPortal; CPX-1846; Histone H2A phosphatase complex.
DR DIP; DIP-3905N; -.
DR IntAct; P32345; 36.
DR MINT; P32345; -.
DR STRING; 4932.YDR075W; -.
DR MaxQB; P32345; -.
DR PaxDb; P32345; -.
DR PRIDE; P32345; -.
DR TopDownProteomics; P32345; -.
DR EnsemblFungi; YDR075W_mRNA; YDR075W; YDR075W.
DR GeneID; 851647; -.
DR KEGG; sce:YDR075W; -.
DR SGD; S000002482; PPH3.
DR VEuPathDB; FungiDB:YDR075W; -.
DR eggNOG; KOG0372; Eukaryota.
DR GeneTree; ENSGT00930000151040; -.
DR HOGENOM; CLU_004962_8_1_1; -.
DR InParanoid; P32345; -.
DR OMA; FKCFGPS; -.
DR BioCyc; YEAST:G3O-29680-MON; -.
DR PRO; PR:P32345; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P32345; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0034399; C:nuclear periphery; IDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0030289; C:protein phosphatase 4 complex; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:SGD.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IGI:SGD.
DR GO; GO:0051598; P:meiotic recombination checkpoint signaling; IMP:SGD.
DR GO; GO:2000002; P:negative regulation of DNA damage checkpoint; IMP:SGD.
DR GO; GO:1902660; P:negative regulation of glucose mediated signaling pathway; IMP:SGD.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IMP:SGD.
DR GO; GO:0051173; P:positive regulation of nitrogen compound metabolic process; IMP:SGD.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:CACAO.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Manganese; Metal-binding; Methylation; Nucleus;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1..308
FT /note="Serine/threonine-protein phosphatase 4 catalytic
FT subunit"
FT /id="PRO_0000058875"
FT ACT_SITE 112
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 51
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 53
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 161
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT CONFLICT 245
FT /note="M -> I (in Ref. 1; CAA41662)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 308 AA; 35264 MW; AFE99582C7F44052 CRC64;
MMDLDKIIAS LRDGKHIPEE TVFRLCLNSQ ELLMNEGNVT QVDTPVTICG DIHGQLHDLL
TLFEKSGGVE KTRYIFLGDF VDRGFYSLES FLLLLCYKLR YPDRITLIRG NHETRQITKV
YGFYDEVVRK YGNSNVWRYC CEVFDYLSLG AIINNSIFCV HGGLSPDMTT VDEIRTIDRK
QEVPHEGAMC DLLWSDPEDV DTWSLSPRGA GFLFGKREVD QFLEKNNVEL IARAHQLVME
GYKEMFDGGL VTVWSAPNYC YRCGNVAAVL KIDDDLNREY TIFEAVQAQN EVGNAIIPTK
KSQMDYFL
