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   27-MAR-2024, entry version 144.
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       Interacts with tensin TNS1 (By similarity). Interacts with SAXO4,
CC       PPP1R21, PPP1R26, PPP1R27, PPP1R35, PPP1R36, PPP1R37, SH3RF2, ELFN1 and
CC       ELFN2 (By similarity). {ECO:0000250|UniProtKB:P62136,
CC       ECO:0000250|UniProtKB:P62137, 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; Sequence=Displayed;
CC       Name=1; Synonyms=1-alpha-1;
CC         IsoId=P62139-2, P08128-1; 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   EMDB; EMD-12665; -.
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   PaxDb; 9986-ENSOCUP00000008007; -.
DR   GeneID; 100009298; -.
DR   KEGG; ocu:100009298; -.
DR   CTD; 5499; -.
DR   eggNOG; KOG0374; Eukaryota.
DR   InParanoid; P62139; -.
DR   OrthoDB; 19833at2759; -.
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: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: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   CDD; cd07414; MPP_PP1_PPKL; 1.
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   InterPro; IPR031675; STPPase_N.
DR   PANTHER; PTHR11668; SERINE/THREONINE PROTEIN PHOSPHATASE; 1.
DR   PANTHER; PTHR11668:SF377; SERINE_THREONINE-PROTEIN PHOSPHATASE PP1-ALPHA CATALYTIC SUBUNIT; 1.
DR   Pfam; PF00149; Metallophos; 1.
DR   Pfam; PF16891; STPPase_N; 1.
DR   PRINTS; PR00114; STPHPHTASE.
DR   SMART; SM00156; PP2Ac; 1.
DR   SUPFAM; SSF56300; Metallo-dependent phosphatases; 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
//