PPM1D_MOUSE
ID PPM1D_MOUSE Reviewed; 598 AA.
AC Q9QZ67; B1B0B0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Protein phosphatase 1D;
DE EC=3.1.3.16;
DE AltName: Full=Protein phosphatase 2C isoform delta;
DE Short=PP2C-delta;
DE AltName: Full=Protein phosphatase magnesium-dependent 1 delta;
DE AltName: Full=p53-induced protein phosphatase 1;
GN Name=Ppm1d; Synonyms=Wip1;
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], AND TISSUE SPECIFICITY.
RC STRAIN=129/SvJ;
RX PubMed=10756097; DOI=10.1006/geno.2000.6134;
RA Choi J., Appella E., Donehower L.A.;
RT "The structure and expression of the murine wildtype p53-induced
RT phosphatase 1 (Wip1) gene.";
RL Genomics 64:298-306(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24135283; DOI=10.1016/j.ccr.2013.08.022;
RA Filipponi D., Muller J., Emelyanov A., Bulavin D.V.;
RT "Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA
RT methylation.";
RL Cancer Cell 24:528-541(2013).
CC -!- FUNCTION: Involved in the negative regulation of p53 expression.
CC Required for the relief of p53-dependent checkpoint mediated cell cycle
CC arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of
CC CHEK1 which contributes to the functional inactivation of these
CC proteins. Mediates MAPK14 dephosphorylation and inactivation (By
CC similarity). Is also an important regulator of global heterochromatin
CC silencing and critical in maintaining genome integrity
CC (PubMed:24135283). {ECO:0000250|UniProtKB:O15297,
CC ECO:0000269|PubMed:24135283}.
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=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};
CC -!- SUBUNIT: Interacts with CHEK1 and CHEK2; dephosphorylates them.
CC Interacts with MAPK14. {ECO:0000250|UniProtKB:O15297}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O15297}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:O15297}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:10756097}.
CC -!- INDUCTION: By p53.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show defective spermatogenesis. On
CC histological sections, testes display an abnormal architecture and
CC considerably narrower seminiferous tubules than those of wild-type
CC mice, accompanied by changes in heterochromatin structure and globally
CC altered gene expression in germ cells, and depletion of the most
CC differentiated germ cell types. {ECO:0000269|PubMed:24135283}.
CC -!- SIMILARITY: Belongs to the PP2C family.
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DR EMBL; AF200464; AAF09251.1; -; mRNA.
DR EMBL; BX323026; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25194.1; -.
DR RefSeq; NP_058606.3; NM_016910.3.
DR AlphaFoldDB; Q9QZ67; -.
DR SMR; Q9QZ67; -.
DR STRING; 10090.ENSMUSP00000020835; -.
DR iPTMnet; Q9QZ67; -.
DR PhosphoSitePlus; Q9QZ67; -.
DR EPD; Q9QZ67; -.
DR MaxQB; Q9QZ67; -.
DR PaxDb; Q9QZ67; -.
DR PRIDE; Q9QZ67; -.
DR ProteomicsDB; 289737; -.
DR Antibodypedia; 4007; 294 antibodies from 31 providers.
DR DNASU; 53892; -.
DR Ensembl; ENSMUST00000020835; ENSMUSP00000020835; ENSMUSG00000020525.
DR GeneID; 53892; -.
DR KEGG; mmu:53892; -.
DR UCSC; uc007krl.2; mouse.
DR CTD; 8493; -.
DR MGI; MGI:1858214; Ppm1d.
DR VEuPathDB; HostDB:ENSMUSG00000020525; -.
DR eggNOG; KOG0698; Eukaryota.
DR GeneTree; ENSGT00940000155672; -.
DR HOGENOM; CLU_036050_0_0_1; -.
DR InParanoid; Q9QZ67; -.
DR OMA; NTIMDQK; -.
DR OrthoDB; 1344250at2759; -.
DR PhylomeDB; Q9QZ67; -.
DR TreeFam; TF313481; -.
DR Reactome; R-MMU-8878166; Transcriptional regulation by RUNX2.
DR BioGRID-ORCS; 53892; 12 hits in 78 CRISPR screens.
DR PRO; PR:Q9QZ67; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9QZ67; protein.
DR Bgee; ENSMUSG00000020525; Expressed in seminiferous tubule of testis and 241 other tissues.
DR ExpressionAtlas; Q9QZ67; baseline and differential.
DR Genevisible; Q9QZ67; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:MGI.
DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IDA:MGI.
DR GO; GO:0006306; P:DNA methylation; IDA:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0031507; P:heterochromatin assembly; IDA:UniProtKB.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; ISO:MGI.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IMP:MGI.
DR CDD; cd00143; PP2Cc; 1.
DR Gene3D; 3.60.40.10; -; 1.
DR InterPro; IPR000222; PP2C_BS.
DR InterPro; IPR036457; PPM-type_dom_sf.
DR InterPro; IPR001932; PPM-type_phosphatase_dom.
DR Pfam; PF00481; PP2C; 1.
DR SMART; SM00332; PP2Cc; 1.
DR SUPFAM; SSF81606; SSF81606; 1.
DR PROSITE; PS01032; PPM_1; 1.
DR PROSITE; PS51746; PPM_2; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cytoplasm; Hydrolase; Magnesium; Manganese; Metal-binding;
KW Nucleus; Phosphoprotein; Protein phosphatase; Reference proteome.
FT CHAIN 1..598
FT /note="Protein phosphatase 1D"
FT /id="PRO_0000057753"
FT DOMAIN 57..368
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT REGION 1..94
FT /note="Interaction with CHEK1"
FT /evidence="ECO:0000250"
FT REGION 49..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 398..412
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..567
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 568..584
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 98
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 99
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 307
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 359
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15297"
FT CONFLICT 532
FT /note="E -> K (in Ref. 1; AAF09251)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 598 AA; 65723 MW; 4DB70375685BBC15 CRC64;
MAGLYSLGVS VFSDQGGRKY MEDVTQIVVE PEPAAEDKPA PVPRRALGLP ATPTLAGVGP
SEKGPAAARD PAPDAAASLP AGRCCRRRSS VAFFAVCDGH GGREAAQFAR EHLWGFIKKQ
KGFTSSEPAK VCAAIRKGFL ACHLAMWKKL AEWPKTMTGL PSTSGTTASV VIIRGMKMYV
AHVGDSGVVL GIQDDPKDDF VRAVEVTQDH KPELPKERER IEGLGGSVMN KSGVNRVVWK
RPRLTHSGPV RRSTVIDQIP FLAVARALGD LWSYDFFSGK FVVSPEPDTS VHTLDPRKHK
YIILGSDGLW NMVPPQDAIS MCQDQEEKKY LMGEQGQSCA KMLVNRALGR WRQRMLRADN
TSAIVICISP EVDNQGNFTN EDELFLNLTD SPTYNSQETC VMTSSPSSTP PIKSPEEDAW
PRLSSKDHIP ALVRSNAFSE KFLEVPAEIA RGNIQTVVMT SKDSETLEEN CPKALTLRIH
DSLNNTLSVG LIPTNSTNTI MDQKNLKMST PGQMKAQEVE RTPPANFKRT LEESNSGPLM
KKHRRNGLSR SSGAQASSLP TASQRRHSVK LTLRRRLRGQ RKMGNPLLHQ HRKTVCVC
