MGP Database

MGP002388

UniProt Annotations

Entry Information
Gene Nameprotein phosphatase 1, catalytic subunit, alpha isozyme
Protein EntryPP1A_HUMAN
UniProt IDP62136
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P62136-1; Sequence=Displayed; Name=2; IsoId=P62136-2; Sequence=VSP_043377; Note=No experimental confirmation available.; Name=3; IsoId=P62136-3; Sequence=VSP_046754; Note=No experimental confirmation available. Gene prediction based on EST data.;
Catalytic Activity[a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate.
CofactorName=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250}; Note=Binds 1 Fe cation per subunit. {ECO:0000250};
CofactorName=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:18992256}; Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:18992256};
Enzyme RegulationThe phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress. {ECO:0000269|PubMed:15705855}.
FunctionProtein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. {ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:21712997}.
InteractionP31749:AKT1; NbExp=6; IntAct=EBI-357253, EBI-296087; O14727:APAF1; NbExp=2; IntAct=EBI-357253, EBI-446492; O15169:AXIN1; NbExp=4; IntAct=EBI-357253, EBI-710484; P38398:BRCA1; NbExp=2; IntAct=EBI-357253, EBI-349905; Q8NG31:CASC5; NbExp=2; IntAct=EBI-357253, EBI-1001161; O95400:CD2BP2; NbExp=2; IntAct=EBI-357253, EBI-768015; P12830:CDH1; NbExp=2; IntAct=EBI-357253, EBI-727477; Q8TEP8:CEP192; NbExp=2; IntAct=EBI-357253, EBI-2339778; Q9NX63:CHCHD3; NbExp=2; IntAct=EBI-357253, EBI-743375; O08785:Clock (xeno); NbExp=2; IntAct=EBI-357253, EBI-79859; Q6PJW8:CNST; NbExp=3; IntAct=EBI-357253, EBI-750390; Q9H175:CSRNP2; NbExp=3; IntAct=EBI-357253, EBI-5235958; Q92796:DLG3; NbExp=2; IntAct=EBI-357253, EBI-80440; P55199:ELL; NbExp=2; IntAct=EBI-357253, EBI-1245868; Q5S007:LRRK2; NbExp=6; IntAct=EBI-357253, EBI-5323863; O00566:MPHOSPH10; NbExp=2; IntAct=EBI-357253, EBI-5235884; Q96KQ4:PPP1R13B; NbExp=5; IntAct=EBI-357253, EBI-1105153; Q8WUF5:PPP1R13L; NbExp=4; IntAct=EBI-357253, EBI-5550163; Q5SWA1:PPP1R15B; NbExp=3; IntAct=EBI-357253, EBI-2815482; P41236:PPP1R2; NbExp=2; IntAct=EBI-357253, EBI-1056517; Q5T8A7:PPP1R26; NbExp=2; IntAct=EBI-357253, EBI-308500; Q86WC6:PPP1R27; NbExp=2; IntAct=EBI-357253, EBI-5235602; Q7Z5V6:PPP1R32; NbExp=3; IntAct=EBI-357253, EBI-4311771; O75864:PPP1R37; NbExp=2; IntAct=EBI-357253, EBI-5235692; Q12972:PPP1R8; NbExp=3; IntAct=EBI-357253, EBI-716633; Q96SB3:PPP1R9B; NbExp=5; IntAct=EBI-357253, EBI-351275; P60484:PTEN; NbExp=2; IntAct=EBI-357253, EBI-696162; P06400:RB1; NbExp=2; IntAct=EBI-357253, EBI-491274; P36313:RL1 (xeno); NbExp=4; IntAct=EBI-357253, EBI-6149234; A8K8P3:SFI1; NbExp=2; IntAct=EBI-357253, EBI-743371; Q562F6:SGOL2; NbExp=4; IntAct=EBI-357253, EBI-989213; Q9H788:SH2D4A; NbExp=2; IntAct=EBI-357253, EBI-747035; Q8TEC5:SH3RF2; NbExp=3; IntAct=EBI-357253, EBI-2130111; P63208:SKP1; NbExp=3; IntAct=EBI-357253, EBI-307486; Q7Z699:SPRED1; NbExp=4; IntAct=EBI-357253, EBI-5235340; Q9HCH5:SYTL2; NbExp=2; IntAct=EBI-357253, EBI-2690103; Q14C87:TMEM132D; NbExp=2; IntAct=EBI-357253, EBI-5235567; Q13625:TP53BP2; NbExp=7; IntAct=EBI-357253, EBI-77642; Q8TEL6:TRPC4AP; NbExp=2; IntAct=EBI-357253, EBI-2559060; P49815:TSC2; NbExp=2; IntAct=EBI-357253, EBI-396587; Q9H4A3:WNK1; NbExp=2; IntAct=EBI-357253, EBI-457907; Q9HBF4:ZFYVE1; NbExp=2; IntAct=EBI-357253, EBI-4401611; O95405:ZFYVE9; NbExp=3; IntAct=EBI-357253, EBI-296817;
PtmPhosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation. {ECO:0000269|PubMed:16732323, ECO:0000269|PubMed:18088087, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:20068231}.
SimilarityBelongs to the PPP phosphatase family. PP-1 subfamily. {ECO:0000305}.
Subcellular LocationCytoplasm. Nucleus. Nucleus, nucleoplasm. Nucleus, nucleolus. Note=Primarily nuclear and largely excluded from the nucleolus. Highly mobile in cells and can be relocalized through interaction with targeting subunits. NOM1 plays a role in targeting this protein to the nucleolus. In the presence of PPP1R8 relocalizes from the nucleus to nuclear speckles.
SubunitPP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R39 (By similarity). Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity)Interacts with PPP1R9A and PPP1R9B. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PHACTR4; which acts as an activator of PP1 activity (By similarity). Interacts with PPP1R15A and PPP1R15B; the interactions mediate binding to EIF2S1. Component of the MLL5-L complex, at least composed of KMT2E/MLL5, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with PPP1R7. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with HHV-1 ICP34.5. Interacts with PPP1R16B. Interacts with RPSA only in the presence of PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site. Interacts with isoform 1 and isoform 4 of NEK2. Interacts with FER; this promotes phosphorylation at Thr-320. Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction. {ECO:0000250, ECO:0000250|UniProtKB:P62137, ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:12226088, ECO:0000269|PubMed:16263087, ECO:0000269|PubMed:16732323, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:17890166, ECO:0000269|PubMed:17965019, ECO:0000269|PubMed:18992256, ECO:0000269|PubMed:19377461, ECO:0000269|PubMed:19581931, ECO:0000269|PubMed:20305656, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20516061, ECO:0000269|PubMed:9023344}.
Web ResourceName=Protein Spotlight; Note=The things we forget - Issue 32 of March 2003; URL="http://web.expasy.org/spotlight/back_issues/032";
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