PP4C_RABIT
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 03-AUG-2022, entry version 140.
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 GeneID; 100009163; -.
DR KEGG; ocu:100009163; -.
DR CTD; 5531; -.
DR eggNOG; KOG0372; Eukaryota.
DR InParanoid; P11084; -.
DR OrthoDB; 808922at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; 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 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 Pfam; PF00149; Metallophos; 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; 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
