ID PP1G_HUMAN Reviewed; 323 AA. AC P36873; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 15-JUN-2010, entry version 128. DE RecName: Full=Serine/threonine-protein phosphatase PP1-gamma catalytic subunit; DE Short=PP-1G; DE EC=3.1.3.16; DE AltName: Full=Protein phosphatase 1C catalytic subunit; GN Name=PPP1CC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GAMMA-1 AND GAMMA-2). RX MEDLINE=93349989; PubMed=8394140; DOI=10.1016/0167-4889(93)90014-G; RA Barker H.M., Craig S.P., Spurr N.K., Cohen P.T.W.; RT "Sequence of human protein serine/threonine phosphatase 1 gamma and RT localization of the gene (PPP1CC) encoding it to chromosome bands RT 12q24.1-q24.2."; RL Biochim. Biophys. Acta 1178:228-233(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA-1). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP PROTEIN SEQUENCE OF 2-15; 44-60; 99-122; 151-168 AND 247-260, CLEAVAGE RP OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [4] RP PROTEIN SEQUENCE OF 2-15; 27-36; 44-60; 99-111; 133-141; 151-187 AND RP 239-260, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND RP MASS SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Bilsland A.E., Keith W.N.; RL Submitted (JAN-2010) to UniProtKB. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-323 (ISOFORM GAMMA-1). RC TISSUE=Skeletal muscle; RX MEDLINE=94154385; PubMed=8111128; DOI=10.1007/BF00360567; RA Norman S.A., Mott D.M.; RT "Molecular cloning and chromosomal localization of a human skeletal RT muscle PP-1 gamma 1 cDNA."; RL Mamm. Genome 5:41-45(1994). RN [6] RP INTERACTION WITH MICROCYSTIN, AND MUTAGENESIS OF CYS-273. RX PubMed=7556599; DOI=10.1016/0014-5793(95)00888-G; RA MacKintosh R.W., Dalby K.N., Campbell D.G., Cohen P.T.W., Cohen P., RA MacKintosh C.; RT "The cyanobacterial toxin microcystin binds covalently to cysteine-273 RT on protein phosphatase 1."; RL FEBS Lett. 371:236-240(1995). RN [7] RP INTERACTION WITH PPP1R3D. RX MEDLINE=98074939; PubMed=9414128; DOI=10.1016/S0014-5793(97)01385-9; RA Armstrong C.G., Browne G.J., Cohen P., Cohen P.T.W.; RT "PPP1R6, a novel member of the family of glycogen-targeting subunits RT of protein phosphatase 1."; RL FEBS Lett. 418:210-214(1997). RN [8] RP SUBCELLULAR LOCATION, INTERACTION WITH PPP1R8, AND MUTAGENESIS OF RP HIS-125. RX PubMed=11739654; RA Trinkle-Mulcahy L., Sleeman J.E., Lamond A.I.; RT "Dynamic targeting of protein phosphatase 1 within the nuclei of RT living mammalian cells."; RL J. Cell Sci. 114:4219-4228(2001). RN [9] RP INTERACTION WITH PPP1R15A. RX PubMed=11564868; DOI=10.1128/MCB.21.20.6841-6850.2001; RA Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., Shenolikar S.; RT "Growth arrest and DNA damage-inducible protein GADD34 assembles a RT novel signaling complex containing protein phosphatase 1 and inhibitor RT 1."; RL Mol. Cell. Biol. 21:6841-6850(2001). RN [10] RP INTERACTION WITH PPP1R7. RX PubMed=12226088; DOI=10.1074/jbc.M206838200; RA Ceulemans H., Vulsteke V., De Maeyer M., Tatchell K., Stalmans W., RA Bollen M.; RT "Binding of the concave surface of the Sds22 superhelix to the alpha RT 4/alpha 5/alpha 6-triangle of protein phosphatase-1."; RL J. Biol. Chem. 277:47331-47337(2002). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=12529430; DOI=10.1091/mbc.E02-07-0376; RA Trinkle-Mulcahy L., Andrews P.D., Wickramasinghe S., Sleeman J., RA Prescott A., Lam Y.W., Lyon C., Swedlow J.R., Lamond A.I.; RT "Time-lapse imaging reveals dynamic relocalization of PP1gamma RT throughout the mammalian cell cycle."; RL Mol. Biol. Cell 14:107-117(2003). RN [12] RP ENZYME REGULATION. RX PubMed=15705855; DOI=10.1126/science.1101902; RA Boyce M., Bryant K.F., Jousse C., Long K., Harding H.P., Scheuner D., RA Kaufman R.J., Ma D., Coen D.M., Ron D., Yuan J.; RT "A selective inhibitor of eIF2alpha dephosphorylation protects cells RT from ER stress."; RL Science 307:935-939(2005). RN [13] RP INTERACTION WITH CDCA2. RX PubMed=16492807; DOI=10.1083/jcb.200508154; RA Trinkle-Mulcahy L., Andersen J., Lam Y.W., Moorhead G., Mann M., RA Lamond A.I.; RT "Repo-Man recruits PP1 gamma to chromatin and is essential for cell RT viability."; RL J. Cell Biol. 172:679-692(2006). RN [14] RP SUBCELLULAR LOCATION, AND INTERACTION WITH NOM1. RX PubMed=17965019; DOI=10.1074/jbc.M706708200; RA Gunawardena S.R., Ruis B.L., Meyer J.A., Kapoor M., Conklin K.F.; RT "NOM1 targets protein phosphatase I to the nucleolus."; RL J. Biol. Chem. 283:398-404(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-307, AND MASS RP SPECTROMETRY. RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP IDENTIFICATION IN THE MLL5-L COMPLEX. RX PubMed=19377461; DOI=10.1038/nature07954; RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G., RA Kitagawa H., Kato S.; RT "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced RT granulopoiesis."; RL Nature 459:455-459(2009). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-147, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). RX MEDLINE=96107380; PubMed=7500362; DOI=10.1006/jmbi.1995.0667; RA Egloff M.-P., Cohen P.T.W., Reinemer P., Barford D.; RT "Crystal structure of the catalytic subunit of human protein RT phosphatase 1 and its complex with tungstate."; RL J. Mol. Biol. 254:942-959(1995). CC -!- FUNCTION: Protein phosphatase 1 (PP1) is essential for cell CC division, and participates in the regulation of glycogen CC metabolism, muscle contractility and protein synthesis. Involved CC in regulation of ionic conductances and long-term synaptic CC plasticity. May play an important role in dephosphorylating CC substrates such as the postsynaptic density-associated CC Ca(2+)/calmodulin dependent protein kinase II. CC -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein + CC phosphate. CC -!- COFACTOR: Binds 1 iron ion per subunit. CC -!- COFACTOR: Binds 1 manganese ion per subunit. CC -!- ENZYME REGULATION: The phosphatase activity of the PPP1R15A-PP1 CC complex toward EIF2S1 is specifically inhibited by Salubrinal, a CC drug that protects cells from endoplasmic reticulum stress. CC -!- SUBUNIT: PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or CC PPP1CC, which is folded into its native form by inhibitor 2 and CC glycogen synthetase kinase 3, and then complexed to one or several CC targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C CC mediate binding to myosin. PPP1R3A, PPP1R3B, PPP1R3C and PPP1R3D CC mediate binding to glycogen. Interacts with cyanobacterial toxin CC microcystin; disulfide-linked. Interacts with PPP1R3B and PPP1R7. CC Isoform gamma-2 interacts with SPZ1 (By similarity). Component of CC the MLL5-L complex, at least composed of MLL5, STK38, PPP1CA, CC PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with CDCA2. CC PPP1R15A and PPP1R15B mediate binding to EIF2S1. Part of a complex CC containing PPP1R15B, PP1 and NCK1/2. Interacts with IKFZ1; the CC interaction targets PPP1CC to pericentromeric heterochromatin, CC dephosphorylates IKAROS, stabilizes it and prevents it from CC degradation (By similarity). Interacts with NOM1 and PPP1R8. CC -!- INTERACTION: CC Q13315:ATM; NbExp=1; IntAct=EBI-356289, EBI-495465; CC P10415:BCL2; NbExp=1; IntAct=EBI-356289, EBI-77694; CC Q07817:BCL2L1; NbExp=1; IntAct=EBI-356289, EBI-78035; CC O15392:BIRC5; NbExp=1; IntAct=EBI-356289, EBI-518823; CC P38398:BRCA1; NbExp=2; IntAct=EBI-356283, EBI-349905; CC P24385:CCND1; NbExp=1; IntAct=EBI-356289, EBI-375001; CC P30281:CCND3; NbExp=1; IntAct=EBI-356289, EBI-375013; CC P06493:CDC2; NbExp=1; IntAct=EBI-356289, EBI-444308; CC P49427:CDC34; NbExp=1; IntAct=EBI-356289, EBI-975634; CC P24941:CDK2; NbExp=1; IntAct=EBI-356289, EBI-375096; CC P11802:CDK4; NbExp=1; IntAct=EBI-356289, EBI-295644; CC Q8N726:CDKN2A; NbExp=1; IntAct=EBI-356289, EBI-625922; CC P05198:EIF2S1; NbExp=1; IntAct=EBI-356289, EBI-1056162; CC P03372:ESR1; NbExp=1; IntAct=EBI-356283, EBI-78473; CC P61244:MAX; NbExp=1; IntAct=EBI-356289, EBI-878388; CC P12004:PCNA; NbExp=1; IntAct=EBI-356289, EBI-358311; CC P63208:SKP1; NbExp=1; IntAct=EBI-356289, EBI-307486; CC P04637:TP53; NbExp=2; IntAct=EBI-356289, EBI-366083; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, nucleolus. CC Note=Colocalizes with SPZ1 in the nucleus (By similarity). Rapidly CC exchanges between the nucleolar, nucleoplasmic and cytoplasmic CC compartments. Highly mobile in cells and can be relocalized CC through interaction with targeting subunits. In the presence of CC PPP1R8 relocalizes from the nucleolus to nuclear speckles. Shows a CC dynamic targeting to specific sites throughout the cell cycle. CC Highly concentrated in nucleoli of interphase cells and localizes CC at kinetochores early in mitosis. Relocalization to chromosome- CC containing regions occurs at the transition from early to late CC anaphase. Also accumulates at the cleavage furrow and midbody by CC telophase. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Gamma-1; CC IsoId=P36873-1; Sequence=Displayed; CC Name=Gamma-2; CC IsoId=P36873-2; Sequence=VSP_005094; CC -!- MISCELLANEOUS: Microcystin toxin is bound to Cys-273 through a CC thioether bond. CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The things we forget - CC Issue 32 of March 2003; CC URL="http://www.expasy.org/spotlight/back_issues/sptlt032.shtml"; 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; X74008; CAA52169.1; -; mRNA. DR EMBL; BC014073; AAH14073.1; -; mRNA. DR EMBL; L07395; AAA19823.1; -; mRNA. DR IPI; IPI00005705; -. DR IPI; IPI00218187; -. DR PIR; S35699; S35699. DR PIR; S35700; S35700. DR RefSeq; NP_002701.1; -. DR UniGene; Hs.79081; -. DR PDB; 1IT6; X-ray; 2.00 A; A/B=1-323. DR PDB; 1JK7; X-ray; 1.90 A; A=1-323. DR PDB; 1U32; X-ray; 2.00 A; A=6-298. DR PDB; 2BCD; X-ray; 2.10 A; A=1-323. DR PDB; 2BDX; X-ray; 2.30 A; A=1-323. DR PDBsum; 1IT6; -. DR PDBsum; 1JK7; -. DR PDBsum; 1U32; -. DR PDBsum; 2BCD; -. DR PDBsum; 2BDX; -. DR DIP; DIP-749N; -. DR IntAct; P36873; 22. DR STRING; P36873; -. DR PhosphoSite; P36873; -. DR PRIDE; P36873; -. DR Ensembl; ENST00000335007; ENSP00000335084; ENSG00000186298; Homo sapiens. DR GeneID; 5501; -. DR KEGG; hsa:5501; -. DR UCSC; uc001tru.1; human. DR CTD; 5501; -. DR GeneCards; GC12M109620; -. DR HGNC; HGNC:9283; PPP1CC. DR HPA; CAB022645; -. DR MIM; 176914; gene. DR PharmGKB; PA33611; -. DR eggNOG; prNOG08140; -. DR HOVERGEN; HBG000216; -. DR OMA; VGWSEND; -. DR OrthoDB; EOG9T4GFC; -. DR PhylomeDB; P36873; -. DR BRENDA; 3.1.3.16; 247. DR Pathway_Interaction_DB; aurora_b_pathway; Aurora B signaling. DR Pathway_Interaction_DB; insulin_glucose_pathway; Insulin-mediated glucose transport. DR Reactome; REACT_152; Cell Cycle, Mitotic. DR Reactome; REACT_602; Metabolism of lipids and lipoproteins. DR NextBio; 21286; -. DR ArrayExpress; P36873; -. DR Bgee; P36873; -. DR CleanEx; HS_PPP1CC; -. DR Genevestigator; P36873; -. DR GermOnline; ENSG00000186298; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0070688; C:MLL5-L complex; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IMP:UniProtKB. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-KW. DR InterPro; IPR004843; M-pesterase. DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase. DR PANTHER; PTHR11668; T_phtase_apaH; 1. DR Pfam; PF00149; Metallophos; 1. DR PRINTS; PR00114; STPHPHTASE. DR SMART; SM00156; PP2Ac; 1. DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; KW Carbohydrate metabolism; Cell cycle; Cell division; Complete proteome; KW Cytoplasm; Direct protein sequencing; Disulfide bond; KW Glycogen metabolism; Hydrolase; Iron; Manganese; Metal-binding; KW Nucleus; Phosphoprotein; Polymorphism; Protein phosphatase. FT INIT_MET 1 1 Removed. FT CHAIN 2 323 Serine/threonine-protein phosphatase PP1- FT gamma catalytic subunit. FT /FTId=PRO_0000058787. FT ACT_SITE 125 125 Proton donor. FT METAL 64 64 Iron. FT METAL 66 66 Iron. FT METAL 92 92 Iron. FT METAL 92 92 Manganese. FT METAL 124 124 Manganese. FT METAL 173 173 Manganese. FT METAL 248 248 Manganese. FT SITE 273 273 Inhibition by microcystin toxin binding. FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 147 147 N6-acetyllysine. FT MOD_RES 307 307 Phosphothreonine. FT VAR_SEQ 315 323 GMITKQAKK -> VASGLNPSIQKASNYRNNTVLYE (in FT isoform Gamma-2). FT /FTId=VSP_005094. FT VARIANT 152 152 F -> S (in dbSNP:rs11558237). FT /FTId=VAR_051734. FT MUTAGEN 125 125 H->A: Loss of activity. FT MUTAGEN 273 273 C->A,S,L: Abolishes interaction with FT microcystin toxin. FT HELIX 9 18 FT TURN 19 21 FT HELIX 32 48 FT STRAND 51 55 FT STRAND 57 62 FT HELIX 69 79 FT STRAND 87 89 FT STRAND 94 98 FT HELIX 100 113 FT TURN 115 117 FT STRAND 118 120 FT HELIX 128 131 FT HELIX 136 143 FT HELIX 146 156 FT STRAND 162 165 FT TURN 166 168 FT STRAND 169 174 FT HELIX 183 187 FT STRAND 197 199 FT HELIX 200 206 FT STRAND 214 218 FT STRAND 222 227 FT HELIX 229 239 FT STRAND 242 246 FT STRAND 254 258 FT TURN 259 262 FT STRAND 263 267 FT HELIX 272 274 FT STRAND 280 285 FT STRAND 291 296 SQ SEQUENCE 323 AA; 36984 MW; 0EEEF0E842188536 CRC64; MADLDKLNID SIIQRLLEVR GSKPGKNVQL QENEIRGLCL KSREIFLSQP ILLELEAPLK ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS LETICLLLAY KIKYPENFFL LRGNHECASI NRIYGFYDEC KRRYNIKLWK TFTDCFNCLP IAAIVDEKIF CCHGGLSPDL QSMEQIRRIM RPTDVPDQGL LCDLLWSDPD KDVLGWGEND RGVSFTFGAE VVAKFLHKHD LDLICRAHQV VEDGYEFFAK RQLVTLFSAP NYCGEFDNAG AMMSVDETLM CSFQILKPAE KKKPNATRPV TPPRGMITKQ AKK //