PP1A_RAT
ID PP1A_RAT Reviewed; 330 AA.
AC P62138; P08129; P20653; P22802;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Serine/threonine-protein phosphatase PP1-alpha catalytic subunit;
DE Short=PP-1A;
DE EC=3.1.3.16;
GN Name=Ppp1ca; Synonyms=Ppp1a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=1650776;
RA Kitamura K., Mizuno Y., Sasaki A., Yasui A., Tsuiki S., Kikuchi K.;
RT "Molecular cloning and sequence analysis of cDNA for the catalytic subunit
RT 1 alpha of rat kidney type 1 protein phosphatase, and detection of the gene
RT expression at high levels in hepatoma cells and regenerating livers as
RT compared to rat livers.";
RL J. Biochem. 109:307-310(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2177460; DOI=10.1111/j.1349-7006.1990.tb02690.x;
RA Sasaki K., Shima H., Kitagawa Y., Irino S., Sugimura T., Nagao M.;
RT "Identification of members of the protein phosphatase 1 gene family in the
RT rat and enhanced expression of protein phosphatase 1 alpha gene in rat
RT hepatocellular carcinomas.";
RL Jpn. J. Cancer Res. 81:1272-1280(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7751917; DOI=10.1523/jneurosci.15-05-03375.1995;
RA da Cruz e Silva E.F., Fox C.A., Ouimet C.C., Gustafson E., Watson S.J.,
RA Greengard P.;
RT "Differential expression of protein phosphatase 1 isoforms in mammalian
RT brain.";
RL J. Neurosci. 15:3375-3389(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 7-26 AND 212-234, AND INTERACTION WITH PPP1R9A AND
RP PPP1R9B.
RC STRAIN=Sprague-Dawley;
RX PubMed=10504266; DOI=10.1021/bi991227d;
RA McAvoy T., Allen P.B., Obaishi H., Nakanishi H., Takai Y., Greengard P.,
RA Nairn A.C., Hemmings H.C. Jr.;
RT "Regulation of neurabin I interaction with protein phosphatase 1 by
RT phosphorylation.";
RL Biochemistry 38:12943-12949(1999).
RN [6]
RP PROTEIN SEQUENCE OF 44-60 AND 112-122, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [7]
RP INTERACTION WITH YLPM1.
RX PubMed=17890166; DOI=10.1016/j.bbapap.2007.07.015;
RA Ulke-Lemee A., Trinkle-Mulcahy L., Chaulk S., Bernstein N.K., Morrice N.,
RA Glover M., Lamond A.I., Moorhead G.B.G.;
RT "The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside
RT kinase that complexes with SAM68, CIA, NF110/45, and HNRNP-G.";
RL Biochim. Biophys. Acta 1774:1339-1350(2007).
CC -!- FUNCTION: Protein phosphatase that associates with over 200 regulatory
CC proteins to form highly specific holoenzymes which dephosphorylate
CC hundreds of biological targets. Protein phosphatase 1 (PP1) is
CC essential for cell division, and participates in the regulation of
CC glycogen metabolism, muscle contractility and protein synthesis.
CC Involved in regulation of ionic conductances and long-term synaptic
CC plasticity. May play an important role in dephosphorylating substrates
CC such as the postsynaptic density-associated Ca(2+)/calmodulin dependent
CC protein kinase II. Component of the PTW/PP1 phosphatase complex, which
CC plays a role in the control of chromatin structure and cell cycle
CC progression during the transition from mitosis into interphase.
CC Regulates NEK2 function in terms of kinase activity and centrosome
CC number and splitting, both in the presence and absence of radiation-
CC induced DNA damage. Regulator of neural tube and optic fissure closure,
CC and enteric neural crest cell (ENCCs) migration during development. In
CC balance with CSNK1D and CSNK1E, determines the circadian period length,
CC through the regulation of the speed and rhythmicity of PER1 and PER2
CC phosphorylation. May dephosphorylate CSNK1D and CSNK1E (By similarity).
CC Dephosphorylates CENPA (By similarity). Dephosphorylates the 'Ser-139'
CC residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex,
CC thereby inhibiting autophagy (By similarity).
CC {ECO:0000250|UniProtKB:P62136, ECO:0000250|UniProtKB:P62137}.
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: PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC,
CC which is folded into its native form by inhibitor 2 and glycogen
CC synthetase kinase 3, and then complexed to one or several targeting or
CC regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to
CC myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C,
CC PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts
CC with PPP1R15A and PPP1R15B; the interactions mediate binding to EIF2S1.
CC Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with
CC PPP1R7. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and
CC NCOA5. Interacts with NOM1 and PPP1R8. Interacts with PPP1R16B.
CC Interacts with RPSA only in the presence of PPP1R16B. Component of the
CC PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82,
CC and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and
CC PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS.
CC Interacts with PPP1R39. Interacts with TRIM28; the interaction
CC dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21
CC promoter site (By similarity). Interacts with PPP1R9A, PPP1R9B and
CC YLPM1. Interacts with NEK2. Interacts with PHACTR4; which acts as an
CC activator of PP1 activity. Interacts with FER; this promotes
CC phosphorylation at Thr-320 (By similarity). Interacts with BTBD10 (By
CC similarity). Interacts with KCTD20 (By similarity). Interacts with
CC FOXP3 (By similarity). Interacts with CENPA (By similarity). Interacts
CC with ATG16L1 (By similarity). Found in a complex with PPP1CA, PPP1CC,
CC SHC1 and PEAK1 (By similarity). {ECO:0000250|UniProtKB:P62136,
CC ECO:0000250|UniProtKB:P62137, ECO:0000250|UniProtKB:P62139,
CC ECO:0000269|PubMed:10504266, ECO:0000269|PubMed:17890166}.
CC -!- INTERACTION:
CC P62138; Q5PQX1: Tor1aip1; NbExp=2; IntAct=EBI-357231, EBI-15644430;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Nucleus, nucleoplasm {ECO:0000250}. Nucleus, nucleolus {ECO:0000250}.
CC Note=Primarily nuclear and largely excluded from the nucleolus. Highly
CC mobile in cells and can be relocalized through interaction with
CC targeting subunits. NOM1 plays a role in targeting it to the nucleolus.
CC In the presence of PPP1R8 relocalizes from the nucleus to nuclear
CC speckles (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:7751917}.
CC -!- PTM: Phosphorylated. Dephosphorylated at Thr-320 in the presence of
CC ionizing radiation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The things we forget - Issue
CC 32 of March 2003;
CC URL="https://web.expasy.org/spotlight/back_issues/032";
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DR EMBL; D00859; BAA00732.1; -; mRNA.
DR EMBL; D90163; BAA14194.1; -; mRNA.
DR EMBL; BC070517; AAH70517.1; -; mRNA.
DR PIR; JX0157; JX0157.
DR RefSeq; NP_113715.1; NM_031527.1.
DR AlphaFoldDB; P62138; -.
DR SMR; P62138; -.
DR BioGRID; 246800; 8.
DR CORUM; P62138; -.
DR ELM; P62138; -.
DR IntAct; P62138; 5.
DR MINT; P62138; -.
DR STRING; 10116.ENSRNOP00000025282; -.
DR iPTMnet; P62138; -.
DR PhosphoSitePlus; P62138; -.
DR SwissPalm; P62138; -.
DR jPOST; P62138; -.
DR PaxDb; P62138; -.
DR PRIDE; P62138; -.
DR Ensembl; ENSRNOT00000025282; ENSRNOP00000025282; ENSRNOG00000018708.
DR Ensembl; ENSRNOT00000098712; ENSRNOP00000087498; ENSRNOG00000018708.
DR GeneID; 24668; -.
DR KEGG; rno:24668; -.
DR UCSC; RGD:3375; rat.
DR CTD; 5499; -.
DR RGD; 3375; Ppp1ca.
DR eggNOG; KOG0374; Eukaryota.
DR GeneTree; ENSGT00940000153472; -.
DR HOGENOM; CLU_004962_8_1_1; -.
DR InParanoid; P62138; -.
DR OMA; YLVMESR; -.
DR OrthoDB; 766640at2759; -.
DR PhylomeDB; P62138; -.
DR TreeFam; TF354243; -.
DR Reactome; R-RNO-180024; DARPP-32 events.
DR PRO; PR:P62138; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000018708; Expressed in thymus and 19 other tissues.
DR ExpressionAtlas; P62138; baseline and differential.
DR Genevisible; P62138; RN.
DR GO; GO:0005912; C:adherens junction; ISO:RGD.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0042587; C:glycogen granule; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; IDA:RGD.
DR GO; GO:0072357; C:PTW/PP1 phosphatase complex; ISS:UniProtKB.
DR GO; GO:0098641; F:cadherin binding involved in cell-cell adhesion; ISO:RGD.
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:0016791; F:phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:RGD.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IPI:RGD.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IPI:RGD.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; ISO:RGD.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; IDA:RGD.
DR GO; GO:0005981; P:regulation of glycogen catabolic process; IDA:RGD.
DR GO; GO:0010288; P:response to lead ion; IDA:ARUK-UCL.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR037979; PPP1CA.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR InterPro; IPR031675; STPPase_N.
DR PANTHER; PTHR11668:SF377; PTHR11668:SF377; 1.
DR Pfam; PF00149; Metallophos; 1.
DR Pfam; PF16891; STPPase_N; 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 Acetylation; Biological rhythms; Carbohydrate metabolism; Cell cycle;
KW Cell division; Cytoplasm; Direct protein sequencing; Glycogen metabolism;
KW Hydrolase; Manganese; Metal-binding; Nucleus; Phosphoprotein;
KW Protein phosphatase; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P62136"
FT CHAIN 2..330
FT /note="Serine/threonine-protein phosphatase PP1-alpha
FT catalytic subunit"
FT /id="PRO_0000058777"
FT REGION 306..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 66
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 248
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P62136"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62136"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62136"
FT MOD_RES 305
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62137"
FT MOD_RES 306
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P62137"
FT MOD_RES 320
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62136"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62136"
SQ SEQUENCE 330 AA; 37512 MW; 60C37E1AD9831DAC CRC64;
MSDSEKLNLD SIIGRLLEVQ GSRPGKNVQL TENEIRGLCL KSREIFLSQP ILLELEAPLK
ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS LETICLLLAY KIKYPENFFL
LRGNHECASI NRIYGFYDEC KRRYNIKLWK TFTDCFNCLP IAAIVDEKIF CCHGGLSPDL
QSMEQIRRIM RPTDVPDQGL LCDLLWSDPD KDVQGWGEND RGVSFTFGAE VVAKFLHKHD
LDLICRAHQV VEDGYEFFAK RQLVTLFSAP NYCGEFDNAG AMMSVDETLM CSFQILKPAD
KNKGKYGQFS GLNPGGRPIT PPRNSAKAKK
