PP4C_MOUSE
ID PP4C_MOUSE Reviewed; 307 AA.
AC P97470; P33172;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 175.
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; Synonyms=Ppp4, Ppx;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9837938; DOI=10.1074/jbc.273.50.33561;
RA Hu M.C.-T., Tang-Oxley Q., Qiu W.R., Wang Y.-P., Mihindukulasuriya K.A.,
RA Afshar R., Tan T.-H.;
RT "Protein phosphatase X interacts with c-Rel and stimulates c-Rel/nuclear
RT factor kappaB activity.";
RL J. Biol. Chem. 273:33561-33565(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=11707325; DOI=10.1016/s0378-1119(01)00734-x;
RA Hu M.C.-T., Shui J.W., Mihindukulasuriya K.A., Tan T.-H.;
RT "Genomic structure of the mouse PP4 gene: a developmentally regulated
RT protein phosphatase.";
RL Gene 278:89-99(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 79-293.
RC STRAIN=BALB/cJ;
RA Sussman D.J.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH PPP4C.
RX PubMed=18715871; DOI=10.1074/jbc.m803443200;
RA Chen G.I., Tisayakorn S., Jorgensen C., D'Ambrosio L.M., Goudreault M.,
RA Gingras A.-C.;
RT "PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein
RT phosphatase 4.";
RL J. Biol. Chem. 283:29273-29284(2008).
RN [6]
RP FUNCTION.
RX PubMed=18347064; DOI=10.1083/jcb.200705148;
RA Toyo-oka K., Mori D., Yano Y., Shiota M., Iwao H., Goto H., Inagaki M.,
RA Hiraiwa N., Muramatsu M., Wynshaw-Boris A., Yoshiki A., Hirotsune S.;
RT "Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and
RT microtubule organization via NDEL1 dephosphorylation.";
RL J. Cell Biol. 180:1133-1147(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 double strand break repair (By similarity). Dephosphorylates
CC NDEL1 at CDK1 phosphorylation sites and negatively regulates CDK1
CC activity in interphase. 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, ECO:0000269|PubMed:18347064}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB38494.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF088911; AAC96297.1; -; mRNA.
DR EMBL; AF378669; AAL35110.1; -; Genomic_DNA.
DR EMBL; BC001993; AAH01993.1; -; mRNA.
DR EMBL; U79747; AAB38494.1; ALT_FRAME; mRNA.
DR CCDS; CCDS21844.1; -.
DR RefSeq; NP_062648.1; NM_019674.3.
DR AlphaFoldDB; P97470; -.
DR SMR; P97470; -.
DR BioGRID; 207966; 55.
DR ComplexPortal; CPX-157; PPP4C-PPP4R1 protein phosphatase 4 complex.
DR ComplexPortal; CPX-158; PPP4C-PPP4R2-PPP4R3A protein phosphatase 4 complex.
DR ComplexPortal; CPX-163; PPP4C-PPP4R2 protein phosphatase 4 complex.
DR ComplexPortal; CPX-164; PPP4C-PPP4R2-PPP4R3B protein phosphatase 4 complex.
DR ComplexPortal; CPX-165; PPP4C-PPP4R4 protein phosphatase 4 complex.
DR IntAct; P97470; 32.
DR STRING; 10090.ENSMUSP00000032936; -.
DR iPTMnet; P97470; -.
DR PhosphoSitePlus; P97470; -.
DR EPD; P97470; -.
DR jPOST; P97470; -.
DR PaxDb; P97470; -.
DR PeptideAtlas; P97470; -.
DR PRIDE; P97470; -.
DR ProteomicsDB; 289375; -.
DR Antibodypedia; 26991; 440 antibodies from 40 providers.
DR DNASU; 56420; -.
DR Ensembl; ENSMUST00000032936; ENSMUSP00000032936; ENSMUSG00000030697.
DR Ensembl; ENSMUST00000206570; ENSMUSP00000146245; ENSMUSG00000030697.
DR GeneID; 56420; -.
DR KEGG; mmu:56420; -.
DR UCSC; uc009jss.1; mouse.
DR CTD; 5531; -.
DR MGI; MGI:1891763; Ppp4c.
DR VEuPathDB; HostDB:ENSMUSG00000030697; -.
DR eggNOG; KOG0372; Eukaryota.
DR GeneTree; ENSGT00930000151040; -.
DR HOGENOM; CLU_004962_8_1_1; -.
DR InParanoid; P97470; -.
DR OMA; HGQFWDM; -.
DR OrthoDB; 808922at2759; -.
DR PhylomeDB; P97470; -.
DR TreeFam; TF105559; -.
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR BioGRID-ORCS; 56420; 46 hits in 111 CRISPR screens.
DR ChiTaRS; Ppp4c; mouse.
DR PRO; PR:P97470; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P97470; protein.
DR Bgee; ENSMUSG00000030697; Expressed in mandibular prominence and 262 other tissues.
DR ExpressionAtlas; P97470; baseline and differential.
DR Genevisible; P97470; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0030289; C:protein phosphatase 4 complex; IDA:MGI.
DR GO; GO:0005521; F:lamin binding; ISO:MGI.
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:0004704; F:NF-kappaB-inducing kinase activity; NAS:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; ISO:MGI.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0016311; P:dephosphorylation; ISO:MGI.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0033128; P:negative regulation of histone phosphorylation; ISO:MGI.
DR GO; GO:2000779; P:regulation of double-strand break repair; ISO:MGI.
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_0000058884"
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:0000250|UniProtKB:P60510"
FT CONFLICT 95..96
FT /note="LL -> FF (in Ref. 2; AAB38494)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 307 AA; 35080 MW; D6FE470A5C6CBCAC CRC64;
MAEISDLDRQ IEQLRRCELI 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
