PPM1D_HUMAN
ID PPM1D_HUMAN Reviewed; 605 AA.
AC O15297; Q53XP4; Q6P991; Q8IVR6;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 191.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9177166; DOI=10.1073/pnas.94.12.6048;
RA Fiscella M., Zhang H., Fan S., Sakaguchi K., Shen S., Mercer W.E.,
RA Vande Woude G.F., O'Connor P.M., Appella E.;
RT "Wip1, a novel human protein phosphatase that is induced in response to
RT ionizing radiation in a p53-dependent manner.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:6048-6053(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP GLN-322.
RC TISSUE=Brain, and Skin;
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 [6]
RP FUNCTION, INTERACTION WITH CHEK1, INDUCTION, AND MUTAGENESIS OF ASP-314.
RX PubMed=15870257; DOI=10.1101/gad.1291305;
RA Lu X., Nannenga B., Donehower L.A.;
RT "PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle
RT checkpoints.";
RL Genes Dev. 19:1162-1174(2005).
RN [7]
RP FUNCTION IN APOPTOSIS, FUNCTION IN DEPHOSPHORYLATION OF CHEK2, AND
RP INTERACTION WITH CHEK2.
RX PubMed=16311512; DOI=10.1038/sj.cdd.4401801;
RA Fujimoto H., Onishi N., Kato N., Takekawa M., Xu X.Z., Kosugi A., Kondo T.,
RA Imamura M., Oishi I., Yoda A., Minami Y.;
RT "Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1
RT phosphatase.";
RL Cell Death Differ. 13:1170-1180(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP FUNCTION, AND INTERACTION WITH MAPK14.
RX PubMed=21283629; DOI=10.1371/journal.pone.0016427;
RA An H., Lu X., Liu D., Yarbrough W.G.;
RT "LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating
RT p38 association with the wild-type p53 induced phosphatase 1 (WIP1).";
RL PLoS ONE 6:E16427-E16427(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP FUNCTION, INVOLVEMENT IN BC, INVOLVEMENT IN OC, VARIANT OC 446-SER--CYS-605
RP DEL, VARIANTS BC 462-GLN--CYS-605 DEL; 478-CYS--CYS-605 DEL;
RP 484-LEU--CYS-605 DEL AND 538-LEU--CYS-605 DEL, AND CHARACTERIZATION OF
RP VARIANT BC 462-GLN--CYS-605 DEL.
RX PubMed=23242139; DOI=10.1038/nature11725;
RG Breast and Ovarian Cancer Susceptibility Collaboration;
RG Wellcome Trust Case Control Consortium;
RA Ruark E., Snape K., Humburg P., Loveday C., Bajrami I., Brough R.,
RA Rodrigues D.N., Renwick A., Seal S., Ramsay E., Del Vechio Duarte S.,
RA Rivas M.A., Warren-Perry M., Zachariou A., Campion-Flora A., Hanks S.,
RA Murray A., Ansari Pour N., Douglas J., Gregory L., Rimmer A., Walker N.M.,
RA Yang T.P., Adlard J.W., Barwell J., Berg J., Brady A.F., Brewer C.,
RA Brice G., Chapman C., Cook J., Davidson R., Donaldson A., Douglas F.,
RA Eccles D., Evans D.G., Greenhalgh L., Henderson A., Izatt L., Kumar A.,
RA Lalloo F., Miedzybrodzka Z., Morrison P.J., Paterson J., Porteous M.,
RA Rogers M.T., Shanley S., Walker L., Gore M., Houlston R., Brown M.A.,
RA Caufield M.J., Deloukas P., McCarthy M.I., Todd J.A., Turnbull C.,
RA Reis-Filho J.S., Ashworth A., Antoniou A.C., Lord C.J., Donnelly P.,
RA Rahman N.;
RT "Mosaic PPM1D mutations are associated with predisposition to breast and
RT ovarian cancer.";
RL Nature 493:406-410(2013).
RN [12]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN JDVS, AND VARIANTS
RP JDVS 404-GLN--CYS-605 DEL; 407-CYS--CYS-605 DEL; 427-TRP--CYS-605 DEL;
RP 447-GLU--CYS-605 DEL AND 552-ARG--CYS-605 DEL.
RX PubMed=28343630; DOI=10.1016/j.ajhg.2017.02.005;
RG Deciphering Developmental Disorders Study;
RA Jansen S., Geuer S., Pfundt R., Brough R., Ghongane P., Herkert J.C.,
RA Marco E.J., Willemsen M.H., Kleefstra T., Hannibal M., Shieh J.T.,
RA Lynch S.A., Flinter F., FitzPatrick D.R., Gardham A., Bernhard B.,
RA Ragge N., Newbury-Ecob R., Bernier R., Kvarnung M., Magnusson E.A.,
RA Wessels M.W., van Slegtenhorst M.A., Monaghan K.G., de Vries P.,
RA Veltman J.A., Lord C.J., Vissers L.E., de Vries B.B.;
RT "De novo truncating mutations in the last and penultimate exons of PPM1D
RT cause an intellectual disability syndrome.";
RL Am. J. Hum. Genet. 100:650-658(2017).
CC -!- FUNCTION: Involved in the negative regulation of p53 expression
CC (PubMed:23242139). Required for the relief of p53-dependent checkpoint
CC mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of
CC TP53 and 'Ser-345' of CHEK1 which contributes to the functional
CC inactivation of these proteins (PubMed:15870257, PubMed:16311512).
CC Mediates MAPK14 dephosphorylation and inactivation (PubMed:21283629).
CC Is also an important regulator of global heterochromatin silencing and
CC critical in maintaining genome integrity (By similarity).
CC {ECO:0000250|UniProtKB:Q9QZ67, ECO:0000269|PubMed:15870257,
CC ECO:0000269|PubMed:16311512, ECO:0000269|PubMed:21283629,
CC ECO:0000269|PubMed:23242139}.
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 (PubMed:21283629). {ECO:0000269|PubMed:15870257,
CC ECO:0000269|PubMed:16311512, ECO:0000269|PubMed:21283629}.
CC -!- INTERACTION:
CC O15297; P16104: H2AX; NbExp=3; IntAct=EBI-1551512, EBI-494830;
CC O15297; Q00987: MDM2; NbExp=4; IntAct=EBI-1551512, EBI-389668;
CC O15297; Q13950: RUNX2; NbExp=4; IntAct=EBI-1551512, EBI-976402;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28343630,
CC ECO:0000269|PubMed:9177166}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:28343630}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15297-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15297-2; Sequence=VSP_056377, VSP_056378;
CC -!- TISSUE SPECIFICITY: Expressed in fetal and adult brain. Also detected
CC in fetal liver and skeletal muscle, but not in their adult
CC counterparts. {ECO:0000269|PubMed:28343630}.
CC -!- INDUCTION: By p53/TP53. {ECO:0000269|PubMed:15870257,
CC ECO:0000269|PubMed:9177166}.
CC -!- DISEASE: Jansen-de Vries syndrome (JDVS) [MIM:617450]: An autosomal
CC dominant neurodevelopmental disorder characterized by mild to severe
CC intellectual disability, psychomotor developmental delay, speech delay,
CC and behavioral manifestations including attention deficit-hyperactivity
CC disorder, autism and anxiety disorders. Most patients have variable
CC additional features, including feeding and gastrointestinal
CC difficulties, high pain threshold, hypersensitivity to sound,
CC hypotonia, broad-based gait, and dysmorphic features, including mild
CC facial abnormalities, strabismus, and small hands and feet.
CC {ECO:0000269|PubMed:28343630}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy
CC originating from breast epithelial tissue. Breast neoplasms can be
CC distinguished by their histologic pattern. Invasive ductal carcinoma is
CC by far the most common type. Breast cancer is etiologically and
CC genetically heterogeneous. Important genetic factors have been
CC indicated by familial occurrence and bilateral involvement. Mutations
CC at more than one locus can be involved in different families or even in
CC the same case. {ECO:0000269|PubMed:23242139}. Note=Disease
CC susceptibility may be associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer
CC defines malignancies originating from ovarian tissue. Although many
CC histologic types of ovarian tumors have been described, epithelial
CC ovarian carcinoma is the most common form. Ovarian cancers are often
CC asymptomatic and the recognized signs and symptoms, even of late-stage
CC disease, are vague. Consequently, most patients are diagnosed with
CC advanced disease. {ECO:0000269|PubMed:23242139}. Note=Disease
CC susceptibility may be associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the PP2C family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PPM1DID41803ch17q23.html";
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DR EMBL; U78305; AAB61637.1; -; mRNA.
DR EMBL; BT009780; AAP88782.1; -; mRNA.
DR EMBL; AC011921; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110602; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC111155; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471179; EAW51408.1; -; Genomic_DNA.
DR EMBL; CH471179; EAW51409.1; -; Genomic_DNA.
DR EMBL; BC016480; AAH16480.1; -; mRNA.
DR EMBL; BC042418; AAH42418.1; -; mRNA.
DR EMBL; BC060877; AAH60877.1; -; mRNA.
DR CCDS; CCDS11625.1; -. [O15297-1]
DR RefSeq; NP_003611.1; NM_003620.3. [O15297-1]
DR AlphaFoldDB; O15297; -.
DR SMR; O15297; -.
DR BioGRID; 114065; 54.
DR CORUM; O15297; -.
DR DIP; DIP-38281N; -.
DR IntAct; O15297; 45.
DR MINT; O15297; -.
DR STRING; 9606.ENSP00000306682; -.
DR BindingDB; O15297; -.
DR ChEMBL; CHEMBL1938224; -.
DR GuidetoPHARMACOLOGY; 3134; -.
DR DEPOD; PPM1D; -.
DR iPTMnet; O15297; -.
DR MetOSite; O15297; -.
DR PhosphoSitePlus; O15297; -.
DR BioMuta; PPM1D; -.
DR EPD; O15297; -.
DR jPOST; O15297; -.
DR MassIVE; O15297; -.
DR MaxQB; O15297; -.
DR PaxDb; O15297; -.
DR PeptideAtlas; O15297; -.
DR PRIDE; O15297; -.
DR ProteomicsDB; 48570; -. [O15297-1]
DR ProteomicsDB; 70754; -.
DR Antibodypedia; 4007; 294 antibodies from 31 providers.
DR DNASU; 8493; -.
DR Ensembl; ENST00000305921.8; ENSP00000306682.2; ENSG00000170836.13. [O15297-1]
DR Ensembl; ENST00000392995.7; ENSP00000376720.3; ENSG00000170836.13. [O15297-2]
DR GeneID; 8493; -.
DR KEGG; hsa:8493; -.
DR MANE-Select; ENST00000305921.8; ENSP00000306682.2; NM_003620.4; NP_003611.1.
DR UCSC; uc002iyt.3; human. [O15297-1]
DR CTD; 8493; -.
DR DisGeNET; 8493; -.
DR GeneCards; PPM1D; -.
DR HGNC; HGNC:9277; PPM1D.
DR HPA; ENSG00000170836; Low tissue specificity.
DR MalaCards; PPM1D; -.
DR MIM; 114480; phenotype.
DR MIM; 167000; phenotype.
DR MIM; 605100; gene.
DR MIM; 617450; phenotype.
DR neXtProt; NX_O15297; -.
DR OpenTargets; ENSG00000170836; -.
DR Orphanet; 227535; Hereditary breast cancer.
DR PharmGKB; PA33605; -.
DR VEuPathDB; HostDB:ENSG00000170836; -.
DR eggNOG; KOG0698; Eukaryota.
DR GeneTree; ENSGT00940000155672; -.
DR InParanoid; O15297; -.
DR OMA; NTIMDQK; -.
DR PhylomeDB; O15297; -.
DR TreeFam; TF313481; -.
DR PathwayCommons; O15297; -.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR SignaLink; O15297; -.
DR SIGNOR; O15297; -.
DR BioGRID-ORCS; 8493; 98 hits in 1087 CRISPR screens.
DR ChiTaRS; PPM1D; human.
DR GeneWiki; PPM1D; -.
DR GenomeRNAi; 8493; -.
DR Pharos; O15297; Tchem.
DR PRO; PR:O15297; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O15297; protein.
DR Bgee; ENSG00000170836; Expressed in secondary oocyte and 185 other tissues.
DR ExpressionAtlas; O15297; baseline and differential.
DR Genevisible; O15297; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:UniProtKB.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:Reactome.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0006306; P:DNA methylation; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0031507; P:heterochromatin assembly; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IMP:UniProtKB.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR GO; GO:0060260; P:regulation of transcription initiation from RNA polymerase II promoter; TAS:Reactome.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0009314; P:response to radiation; TAS:ProtInc.
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 1: Evidence at protein level;
KW Alternative splicing; Autism spectrum disorder; Cell cycle; Cytoplasm;
KW Disease variant; Hydrolase; Intellectual disability; Magnesium; Manganese;
KW Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1..605
FT /note="Protein phosphatase 1D"
FT /id="PRO_0000057752"
FT DOMAIN 8..375
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT REGION 1..101
FT /note="Interaction with CHEK1"
FT /evidence="ECO:0000269|PubMed:15870257"
FT REGION 28..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 516..591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..575
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..591
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 105
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 105
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 314
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 366
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 421..430
FT /note="SLEEDPWPRV -> DFGFELDSRK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056377"
FT VAR_SEQ 431..605
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056378"
FT VARIANT 322
FT /note="P -> Q (in dbSNP:rs17855093)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_070430"
FT VARIANT 404..605
FT /note="Missing (in JDVS)"
FT /evidence="ECO:0000269|PubMed:28343630"
FT /id="VAR_080081"
FT VARIANT 407..605
FT /note="Missing (in JDVS)"
FT /evidence="ECO:0000269|PubMed:28343630"
FT /id="VAR_080082"
FT VARIANT 427..605
FT /note="Missing (in JDVS)"
FT /evidence="ECO:0000269|PubMed:28343630"
FT /id="VAR_080083"
FT VARIANT 446..605
FT /note="Missing (in OC; may be associated with disease
FT susceptibility)"
FT /evidence="ECO:0000269|PubMed:23242139"
FT /id="VAR_080084"
FT VARIANT 447..605
FT /note="Missing (in JDVS)"
FT /evidence="ECO:0000269|PubMed:28343630"
FT /id="VAR_080085"
FT VARIANT 462..605
FT /note="Missing (in BC; may be associated with disease
FT susceptibility; gain-of-function mutation that results in
FT increased negative regulation of p53 expression in response
FT to ionizing radiation exposure)"
FT /evidence="ECO:0000269|PubMed:23242139"
FT /id="VAR_080086"
FT VARIANT 478..605
FT /note="Missing (in BC; may be associated with disease
FT susceptibility)"
FT /evidence="ECO:0000269|PubMed:23242139"
FT /id="VAR_080087"
FT VARIANT 484..605
FT /note="Missing (in BC; may be associated with disease
FT susceptibility)"
FT /evidence="ECO:0000269|PubMed:23242139"
FT /id="VAR_080088"
FT VARIANT 538..605
FT /note="Missing (in BC; may be associated with disease
FT susceptibility)"
FT /evidence="ECO:0000269|PubMed:23242139"
FT /id="VAR_080089"
FT VARIANT 552..605
FT /note="Missing (in JDVS)"
FT /evidence="ECO:0000269|PubMed:28343630"
FT /id="VAR_080090"
FT MUTAGEN 314
FT /note="D->A: Abrogates phosphatase activity."
FT /evidence="ECO:0000269|PubMed:15870257"
SQ SEQUENCE 605 AA; 66675 MW; E6C5884CF04008B7 CRC64;
MAGLYSLGVS VFSDQGGRKY MEDVTQIVVE PEPTAEEKPS PRRSLSQPLP PRPSPAALPG
GEVSGKGPAV AAREARDPLP DAGASPAPSR CCRRRSSVAF FAVCDGHGGR EAAQFAREHL
WGFIKKQKGF TSSEPAKVCA AIRKGFLACH LAMWKKLAEW PKTMTGLPST SGTTASVVII
RGMKMYVAHV GDSGVVLGIQ DDPKDDFVRA VEVTQDHKPE LPKERERIEG LGGSVMNKSG
VNRVVWKRPR LTHNGPVRRS TVIDQIPFLA VARALGDLWS YDFFSGEFVV SPEPDTSVHT
LDPQKHKYII LGSDGLWNMI PPQDAISMCQ DQEEKKYLMG EHGQSCAKML VNRALGRWRQ
RMLRADNTSA IVICISPEVD NQGNFTNEDE LYLNLTDSPS YNSQETCVMT PSPCSTPPVK
SLEEDPWPRV NSKDHIPALV RSNAFSENFL EVSAEIAREN VQGVVIPSKD PEPLEENCAK
ALTLRIHDSL NNSLPIGLVP TNSTNTVMDQ KNLKMSTPGQ MKAQEIERTP PTNFKRTLEE
SNSGPLMKKH RRNGLSRSSG AQPASLPTTS QRKNSVKLTM RRRLRGQKKI GNPLLHQHRK
TVCVC
