ID   PP4C_RABIT              Reviewed;         307 AA.
AC   P11084;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 2.
DT   27-MAR-2024, entry version 147.
DE   RecName: Full=Serine/threonine-protein phosphatase 4 catalytic subunit;
DE            Short=PP4C;
DE            Short=Pp4;
DE            EC=3.1.3.16;
DE   AltName: Full=Protein phosphatase X;
DE            Short=PP-X;
GN   Name=PPP4C;
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].
RC   STRAIN=New Zealand white; TISSUE=Liver;
RX   PubMed=2166691; DOI=10.1016/0014-5793(90)81285-v;
RA   Cohen P.T.W., Brewis N.D., Hughes V., Mann D.J.;
RT   "Protein serine/threonine phosphatases; an expanding family.";
RL   FEBS Lett. 268:355-359(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=New Zealand white; TISSUE=Liver;
RX   PubMed=8384557; DOI=10.1002/j.1460-2075.1993.tb05739.x;
RA   Brewis N.D., Street A.J., Prescott A.R., Cohen P.T.W.;
RT   "PPX, a novel protein serine/threonine phosphatase localized to
RT   centrosomes.";
RL   EMBO J. 12:987-996(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 105-307.
RC   STRAIN=New Zealand white; TISSUE=Liver;
RX   PubMed=2849555; DOI=10.1016/0014-5793(88)80995-5;
RA   da Cruz e Silva O.B., da Cruz e Silva E.F., Cohen P.T.W.;
RT   "Identification of a novel protein phosphatase catalytic subunit by cDNA
RT   cloning.";
RL   FEBS Lett. 242:106-110(1988).
RN   [4]
RP   METHYLATION AT LEU-307.
RX   PubMed=9359419; DOI=10.1042/bj3270481;
RA   Kloeker S., Bryant J.C., Strack S., Colbran R.J., Wadzinski B.E.;
RT   "Carboxymethylation of nuclear protein serine/threonine phosphatase X.";
RL   Biochem. J. 327:481-486(1997).
RN   [5]
RP   INTERACTION WITH PPP4R2.
RX   PubMed=10769191; DOI=10.1042/bj3470845;
RA   Hastie C.J., Carnegie G.K., Morrice N., Cohen P.T.W.;
RT   "A novel 50 kDa protein forms complexes with protein phosphatase 4 and is
RT   located at centrosomal microtubule organizing centres.";
RL   Biochem. J. 347:845-855(2000).
CC   -!- FUNCTION: Protein phosphatase that is involved in many processes such
CC       as microtubule organization at centrosomes, maturation of spliceosomal
CC       snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha
CC       signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of
CC       histone acetylation, DNA damage checkpoint signaling, NF-kappa-B
CC       activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a
CC       role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-
CC       PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated
CC       on Ser-140 (gamma-H2AX) generated during DNA replication and required
CC       for DNA DSB repair. Dephosphorylates NDEL1 at CDK1 phosphorylation
CC       sites and negatively regulates CDK1 activity in interphase (By
CC       similarity). In response to DNA damage, catalyzes RPA2
CC       dephosphorylation, an essential step for DNA repair since it allows the
CC       efficient RPA2-mediated recruitment of RAD51 to chromatin (By
CC       similarity). {ECO:0000250}.
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: Serine/threonine-protein phosphatase 4 (PP4) occurs in
CC       different assemblies of the catalytic and one or more regulatory
CC       subunits. Component of the PP4 complexes PPP4C-PPP4R1, PPP4C-PPP4R2,
CC       PPP4C-PPP4R2-PPP4R3A, PPP4C-PPP4R2-PPP4R3B and PPP4C-PPP4R4. The PPP4C-
CC       PPP4R2 complex appears to be a tetramer composed of 2 molecules of
CC       PPP4C and 2 molecules of PPP4R2. Interacts with REL, NFKB1/p50 and
CC       RELA. Interacts with SMN1 and GEMIN4. Interacts with IRS4
CC       (phosphorylated). Interacts with SMEK1/PPP4R3A; the interaction
CC       requires PP4R2. Interacts with HDAC3 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, cytoskeleton,
CC       microtubule organizing center, centrosome.
CC   -!- PTM: Methylation at the C-terminal Leu-307 is critical for interactions
CC       with regulatory subunits and functions in DNA repair.
CC       {ECO:0000250|UniProtKB:P60510}.
CC   -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-4 (PP-X)
CC       subfamily. {ECO:0000305}.
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DR   EMBL; X14031; CAA32191.1; -; mRNA.
DR   EMBL; S57412; AAB25913.1; -; mRNA.
DR   PIR; S36193; PARBA2.
DR   RefSeq; NP_001075792.1; NM_001082323.1.
DR   AlphaFoldDB; P11084; -.
DR   SMR; P11084; -.
DR   STRING; 9986.ENSOCUP00000005480; -.
DR   PaxDb; 9986-ENSOCUP00000005480; -.
DR   GeneID; 100009163; -.
DR   KEGG; ocu:100009163; -.
DR   CTD; 5531; -.
DR   eggNOG; KOG0372; Eukaryota.
DR   InParanoid; P11084; -.
DR   OrthoDB; 19833at2759; -.
DR   Proteomes; UP000001811; Unplaced.
DR   GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR   CDD; cd07415; MPP_PP2A_PP4_PP6; 1.
DR   Gene3D; 3.60.21.10; -; 1.
DR   InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR   InterPro; IPR029052; Metallo-depent_PP-like.
DR   InterPro; IPR047129; PPA2-like.
DR   InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR   PANTHER; PTHR45619; SERINE/THREONINE-PROTEIN PHOSPHATASE PP2A-RELATED; 1.
DR   PANTHER; PTHR45619:SF8; SERINE_THREONINE-PROTEIN PHOSPHATASE 4 CATALYTIC SUBUNIT; 1.
DR   Pfam; PF00149; Metallophos; 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   Acetylation; Cytoplasm; Cytoskeleton; Hydrolase; Manganese; Metal-binding;
KW   Methylation; Nucleus; Protein phosphatase; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P60510"
FT   CHAIN           2..307
FT                   /note="Serine/threonine-protein phosphatase 4 catalytic
FT                   subunit"
FT                   /id="PRO_0000058885"
FT   ACT_SITE        115
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   BINDING         54
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         56
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         82
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         82
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         114
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         164
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         238
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-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P60510"
FT   MOD_RES         307
FT                   /note="Leucine methyl ester"
FT                   /evidence="ECO:0000269|PubMed:9359419"
SQ   SEQUENCE   307 AA;  35037 MW;  364A1641F8B22B41 CRC64;
     MAEISDLDRQ IEQLLRCELI KESEVKALCA KAREILVEES NVQRVDSPVT VCGDIHGQFY
     DLKELFRVGG DVPETNYLFM GDFVDRGFYS VETFLLLLAL KVRYPDRITL IRGNHESRQI
     TQVYGFYDEC LRKYGSVTVW RYCTEIFDYL SLSAIIDGKI FCVHGGLSPS IQTLDQIRTI
     DRKQEVPHDG PMCDLLWSDP EDTTGWGVSP RGAGYLFGSD VVAQFNAAND IDMICRAHQL
     VMEGYKWHFN ETVLTVWSAP NYCYRCGNVA AILELDEHLQ KDFIIFEAAP QETRGIPSKK
     PVADYFL
//