PP1A_RABIT
ID PP1A_RABIT Reviewed; 330 AA.
AC P62139; P08128; 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 138.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP TISSUE SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Skeletal muscle;
RX PubMed=2822491; DOI=10.1016/0014-5793(87)80316-2;
RA Berndt N., Campbell D.G., Caudwell F.B., Cohen P., da Cruz e Silva E.F.,
RA da Cruz e Silva O.B., Cohen P.T.W.;
RT "Isolation and sequence analysis of a cDNA clone encoding a type-1 protein
RT phosphatase catalytic subunit: homology with protein phosphatase 2A.";
RL FEBS Lett. 223:340-346(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Muscle;
RX PubMed=2846396; DOI=10.1096/fasebj.2.14.2846396;
RA Bai G., Zhang Z., Amin J., Deans-Zirattu S.A., Lee E.Y.C.;
RT "Molecular cloning of a cDNA for the catalytic subunit of rabbit muscle
RT phosphorylase phosphatase.";
RL FASEB J. 2:3010-3016(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=New Zealand white; TISSUE=Skeletal muscle;
RX PubMed=2835264; DOI=10.1016/0014-5793(88)80378-8;
RA Cohen P.T.W.;
RT "Two isoforms of protein phosphatase 1 may be produced from the same
RT gene.";
RL FEBS Lett. 232:17-23(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=2541784; DOI=10.1016/0167-4781(89)90181-4;
RA Cohen P.T.W., Schelling D.L., da Cruz e Silva O.B., Barker H.M., Cohen P.;
RT "The major type-1 protein phosphatase catalytic subunits are the same gene
RT products in rabbit skeletal muscle and rabbit liver.";
RL Biochim. Biophys. Acta 1008:125-128(1989).
RN [5]
RP INTERACTION WITH PPP1R39.
RX PubMed=19945436; DOI=10.1016/j.bbrc.2009.11.123;
RA Chen C.Y., Lai N.S., Yang J.J., Huang H.L., Hung W.C., Li C., Lin T.H.,
RA Huang H.B.;
RT "FLJ23654 encodes a heart protein phosphatase 1-binding protein (Hepp1).";
RL Biochem. Biophys. Res. Commun. 391:698-702(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS, AND
RP COFACTOR.
RX PubMed=7651533; DOI=10.1038/376745a0;
RA Goldberg J., Huang H.B., Kwon Y.G., Greengard P., Nairn A.C., Kuriyan J.;
RT "Three-dimensional structure of the catalytic subunit of protein
RT serine/threonine phosphatase-1.";
RL Nature 376:745-753(1995).
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;
CC Evidence={ECO:0000269|PubMed:7651533};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:7651533};
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 PPP1R9A, PPP1R9B and PPP1R7. Interacts with YLPM1. Forms a complex with
CC ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and
CC PPP1R8. Interacts with PPP1R16B. Interacts with RPSA only in the
CC presence of PPP1R16B. Component of the PTW/PP1 phosphatase complex,
CC composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC.
CC Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the
CC presence of PPP1R10/PNUTS. 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 PPP1R39. Interacts with
CC NEK2. Interacts with PHACTR4; which acts as an activator of PP1
CC activity. Interacts with FER; this promotes phosphorylation at Thr-320
CC (By similarity). Interacts with BTBD10 (By similarity). Interacts with
CC KCTD20 (By similarity). Interacts with FOXP3 (By similarity). Interacts
CC with CENPA (By similarity). Interacts with ATG16L1 (By similarity).
CC Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity).
CC {ECO:0000250|UniProtKB:P62136, ECO:0000250|UniProtKB:P62137,
CC ECO:0000269|PubMed:19945436}.
CC -!- INTERACTION:
CC P62139; Q13224: GRIN2B; Xeno; NbExp=2; IntAct=EBI-2008988, EBI-2256942;
CC P62139; O60927: PPP1R11; Xeno; NbExp=2; IntAct=EBI-2008988, EBI-1048104;
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 this protein to the
CC nucleolus. In the presence of PPP1R8 relocalizes from the nucleus to
CC nuclear speckles (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=1-alpha-2;
CC IsoId=P62139-1, P08129-1;
CC Sequence=Displayed;
CC Name=1; Synonyms=1-alpha-1;
CC IsoId=P62139-2, P08128-1;
CC Sequence=VSP_010642;
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle (at protein level).
CC Detected in skeletal muscle. {ECO:0000269|PubMed:2822491}.
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; Y00701; CAA68693.1; -; mRNA.
DR EMBL; X07798; CAA30645.1; -; mRNA.
DR EMBL; X14832; CAA32941.1; -; mRNA.
DR PIR; S04335; PARB11.
DR RefSeq; NP_001095176.1; NM_001101706.1.
DR PDB; 1FJM; X-ray; 2.10 A; A/B=1-330.
DR PDB; 7NZM; EM; 3.96 A; B=7-300.
DR PDBsum; 1FJM; -.
DR PDBsum; 7NZM; -.
DR AlphaFoldDB; P62139; -.
DR SMR; P62139; -.
DR BioGRID; 1172319; 81.
DR ELM; P62139; -.
DR IntAct; P62139; 5.
DR MINT; P62139; -.
DR STRING; 9986.ENSOCUP00000008007; -.
DR ChEMBL; CHEMBL5458; -.
DR iPTMnet; P62139; -.
DR PRIDE; P62139; -.
DR GeneID; 100009298; -.
DR KEGG; ocu:100009298; -.
DR CTD; 5499; -.
DR eggNOG; KOG0374; Eukaryota.
DR InParanoid; P62139; -.
DR OrthoDB; 766640at2759; -.
DR EvolutionaryTrace; P62139; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; IDA:CAFA.
DR GO; GO:0072357; C:PTW/PP1 phosphatase complex; ISS:UniProtKB.
DR GO; GO:1901567; F:fatty acid derivative binding; IDA:CAFA.
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:ParkinsonsUK-UCL.
DR GO; GO:0072542; F:protein phosphatase activator activity; IDA:CAFA.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; IDA:ParkinsonsUK-UCL.
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:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:CAFA.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0036496; P:regulation of translational initiation by eIF2 alpha dephosphorylation; IDA:ParkinsonsUK-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 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Carbohydrate metabolism; Cell cycle; Cell division; Cytoplasm;
KW Direct protein sequencing; Glycogen metabolism; Hydrolase; Manganese;
KW Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW 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_0000058776"
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 BINDING 66
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT BINDING 92
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT BINDING 92
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT BINDING 124
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT BINDING 173
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT BINDING 248
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
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"
FT VAR_SEQ 1..33
FT /note="MSDSEKLNLDSIIGRLLEVQGSRPGKNVQLTEN -> MVTIMTTSEYLSGY
FT (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:2822491"
FT /id="VSP_010642"
FT CONFLICT 309
FT /note="F -> L (in Ref. 1; CAA68693 and 3; CAA30645)"
FT /evidence="ECO:0000305"
FT HELIX 9..18
FT /evidence="ECO:0007829|PDB:1FJM"
FT TURN 19..22
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 32..48
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 69..79
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 100..113
FT /evidence="ECO:0007829|PDB:1FJM"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 146..156
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:1FJM"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 169..174
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 183..188
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:1FJM"
FT HELIX 229..239
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:1FJM"
FT TURN 259..262
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 280..285
FT /evidence="ECO:0007829|PDB:1FJM"
FT STRAND 291..296
FT /evidence="ECO:0007829|PDB:1FJM"
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
