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Protein

Protein phosphatase 1D

Gene

PPM1D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the negative regulation of p53 expression (PubMed:23242139). Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins (PubMed:15870257, PubMed:16311512). Mediates MAPK14 dephosphorylation and inactivation (PubMed:21283629). Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity (By similarity).By similarity4 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium or manganese ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi105Manganese 1By similarity1
Metal bindingi105Manganese 2By similarity1
Metal bindingi106Manganese 1; via carbonyl oxygenBy similarity1
Metal bindingi314Manganese 2By similarity1
Metal bindingi366Manganese 2By similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • mitogen-activated protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: Reactome
  • protein serine/threonine phosphatase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processCell cycle
LigandMagnesium, Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-8878166 Transcriptional regulation by RUNX2
SIGNORiO15297

Names & Taxonomyi

Protein namesi
Recommended name:
Protein phosphatase 1D (EC:3.1.3.16)
Alternative name(s):
Protein phosphatase 2C isoform delta
Short name:
PP2C-delta
Protein phosphatase magnesium-dependent 1 delta
p53-induced protein phosphatase 1
Gene namesi
Name:PPM1D
Synonyms:WIP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000170836.11
HGNCiHGNC:9277 PPM1D
MIMi605100 gene
neXtProtiNX_O15297

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold (IDDGIP)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurodevelopmental disorder characterized by mild to severe intellectual disability, psychomotor developmental delay, speech delay, and behavioral manifestations including attention deficit-hyperactivity disorder, autism and anxiety disorders. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold, hypersensitivity to sound, hypotonia, broad-based gait, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet.
See also OMIM:617450
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080081404 – 605Missing in IDDGIP. 1 PublicationAdd BLAST202
Natural variantiVAR_080082407 – 605Missing in IDDGIP. 1 PublicationAdd BLAST199
Natural variantiVAR_080083427 – 605Missing in IDDGIP. 1 PublicationAdd BLAST179
Natural variantiVAR_080085447 – 605Missing in IDDGIP. 1 PublicationAdd BLAST159
Natural variantiVAR_080090552 – 605Missing in IDDGIP. 1 PublicationAdd BLAST54
Breast cancer (BC)1 Publication
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionA common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
See also OMIM:114480
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080086462 – 605Missing in BC; may be associated with disease susceptibility; gain-of-function mutation that results in increased negative regulation of p53 expression in response to ionizing radiation exposure. 1 PublicationAdd BLAST144
Natural variantiVAR_080087478 – 605Missing in BC; may be associated with disease susceptibility. 1 PublicationAdd BLAST128
Natural variantiVAR_080088484 – 605Missing in BC; may be associated with disease susceptibility. 1 PublicationAdd BLAST122
Natural variantiVAR_080089538 – 605Missing in BC; may be associated with disease susceptibility. 1 PublicationAdd BLAST68
Ovarian cancer (OC)1 Publication
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionThe term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
See also OMIM:167000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080084446 – 605Missing in OC; may be associated with disease susceptibility. 1 PublicationAdd BLAST160

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi314D → A: Abrogates phosphatase activity. 1 Publication1

Keywords - Diseasei

Autism spectrum disorder, Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi8493
MalaCardsiPPM1D
MIMi114480 phenotype
167000 phenotype
617450 phenotype
OpenTargetsiENSG00000170836
PharmGKBiPA33605

Chemistry databases

ChEMBLiCHEMBL1938224

Polymorphism and mutation databases

BioMutaiPPM1D

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000577521 – 605Protein phosphatase 1DAdd BLAST605

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40PhosphoserineCombined sources1
Modified residuei85PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO15297
MaxQBiO15297
PaxDbiO15297
PeptideAtlasiO15297
PRIDEiO15297
ProteomicsDBi48570

PTM databases

DEPODiO15297
iPTMnetiO15297
PhosphoSitePlusiO15297

Expressioni

Tissue specificityi

Expressed in fetal and adult brain. Also detected in fetal liver and skeletal muscle, but not in their adult counterparts.1 Publication

Inductioni

By p53/TP53.2 Publications

Gene expression databases

BgeeiENSG00000170836 Expressed in 206 organ(s), highest expression level in chorionic villus
CleanExiHS_PPM1D
ExpressionAtlasiO15297 baseline and differential
GenevisibleiO15297 HS

Organism-specific databases

HPAiHPA022277

Interactioni

Subunit structurei

Interacts with CHEK1 and CHEK2; dephosphorylates them. Interacts with MAPK14 (PubMed:21283629).3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114065, 28 interactors
CORUMiO15297
DIPiDIP-38281N
IntActiO15297, 40 interactors
MINTiO15297
STRINGi9606.ENSP00000306682

Chemistry databases

BindingDBiO15297

Structurei

3D structure databases

ProteinModelPortaliO15297
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 375PPM-type phosphatasePROSITE-ProRule annotationAdd BLAST368

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 101Interaction with CHEK11 PublicationAdd BLAST101

Sequence similaritiesi

Belongs to the PP2C family.

Phylogenomic databases

eggNOGiKOG0698 Eukaryota
COG0631 LUCA
GeneTreeiENSGT00920000149079
HOGENOMiHOG000231949
HOVERGENiHBG058897
InParanoidiO15297
KOiK10147
OMAiPLLHQHR
OrthoDBiEOG091G08LU
PhylomeDBiO15297
TreeFamiTF313481

Family and domain databases

CDDicd00143 PP2Cc, 1 hit
InterProiView protein in InterPro
IPR015655 PP2C
IPR000222 PP2C_BS
IPR036457 PPM-type_dom_sf
IPR001932 PPM-type_phosphatase_dom
PANTHERiPTHR13832 PTHR13832, 1 hit
PfamiView protein in Pfam
PF00481 PP2C, 1 hit
SMARTiView protein in SMART
SM00332 PP2Cc, 1 hit
SUPFAMiSSF81606 SSF81606, 2 hits
PROSITEiView protein in PROSITE
PS01032 PPM_1, 1 hit
PS51746 PPM_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O15297-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAGLYSLGVS VFSDQGGRKY MEDVTQIVVE PEPTAEEKPS PRRSLSQPLP
60 70 80 90 100
PRPSPAALPG GEVSGKGPAV AAREARDPLP DAGASPAPSR CCRRRSSVAF
110 120 130 140 150
FAVCDGHGGR EAAQFAREHL WGFIKKQKGF TSSEPAKVCA AIRKGFLACH
160 170 180 190 200
LAMWKKLAEW PKTMTGLPST SGTTASVVII RGMKMYVAHV GDSGVVLGIQ
210 220 230 240 250
DDPKDDFVRA VEVTQDHKPE LPKERERIEG LGGSVMNKSG VNRVVWKRPR
260 270 280 290 300
LTHNGPVRRS TVIDQIPFLA VARALGDLWS YDFFSGEFVV SPEPDTSVHT
310 320 330 340 350
LDPQKHKYII LGSDGLWNMI PPQDAISMCQ DQEEKKYLMG EHGQSCAKML
360 370 380 390 400
VNRALGRWRQ RMLRADNTSA IVICISPEVD NQGNFTNEDE LYLNLTDSPS
410 420 430 440 450
YNSQETCVMT PSPCSTPPVK SLEEDPWPRV NSKDHIPALV RSNAFSENFL
460 470 480 490 500
EVSAEIAREN VQGVVIPSKD PEPLEENCAK ALTLRIHDSL NNSLPIGLVP
510 520 530 540 550
TNSTNTVMDQ KNLKMSTPGQ MKAQEIERTP PTNFKRTLEE SNSGPLMKKH
560 570 580 590 600
RRNGLSRSSG AQPASLPTTS QRKNSVKLTM RRRLRGQKKI GNPLLHQHRK

TVCVC
Length:605
Mass (Da):66,675
Last modified:January 1, 1998 - v1
Checksum:iE6C5884CF04008B7
GO
Isoform 2 (identifier: O15297-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     421-430: SLEEDPWPRV → DFGFELDSRK
     431-605: Missing.

Note: No experimental confirmation available.
Show »
Length:430
Mass (Da):47,211
Checksum:iFD242857BFE6D5D9
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EJH1K7EJH1_HUMAN
Protein phosphatase 1D
PPM1D
125Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070430322P → Q1 PublicationCorresponds to variant dbSNP:rs17855093Ensembl.1
Natural variantiVAR_080081404 – 605Missing in IDDGIP. 1 PublicationAdd BLAST202
Natural variantiVAR_080082407 – 605Missing in IDDGIP. 1 PublicationAdd BLAST199
Natural variantiVAR_080083427 – 605Missing in IDDGIP. 1 PublicationAdd BLAST179
Natural variantiVAR_080084446 – 605Missing in OC; may be associated with disease susceptibility. 1 PublicationAdd BLAST160
Natural variantiVAR_080085447 – 605Missing in IDDGIP. 1 PublicationAdd BLAST159
Natural variantiVAR_080086462 – 605Missing in BC; may be associated with disease susceptibility; gain-of-function mutation that results in increased negative regulation of p53 expression in response to ionizing radiation exposure. 1 PublicationAdd BLAST144
Natural variantiVAR_080087478 – 605Missing in BC; may be associated with disease susceptibility. 1 PublicationAdd BLAST128
Natural variantiVAR_080088484 – 605Missing in BC; may be associated with disease susceptibility. 1 PublicationAdd BLAST122
Natural variantiVAR_080089538 – 605Missing in BC; may be associated with disease susceptibility. 1 PublicationAdd BLAST68
Natural variantiVAR_080090552 – 605Missing in IDDGIP. 1 PublicationAdd BLAST54

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056377421 – 430SLEEDPWPRV → DFGFELDSRK in isoform 2. 1 Publication10
Alternative sequenceiVSP_056378431 – 605Missing in isoform 2. 1 PublicationAdd BLAST175

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78305 mRNA Translation: AAB61637.1
BT009780 mRNA Translation: AAP88782.1
AC011921 Genomic DNA No translation available.
AC110602 Genomic DNA No translation available.
AC111155 Genomic DNA No translation available.
CH471179 Genomic DNA Translation: EAW51408.1
CH471179 Genomic DNA Translation: EAW51409.1
BC016480 mRNA Translation: AAH16480.1
BC042418 mRNA Translation: AAH42418.1
BC060877 mRNA Translation: AAH60877.1
CCDSiCCDS11625.1 [O15297-1]
RefSeqiNP_003611.1, NM_003620.3 [O15297-1]
UniGeneiHs.286073

Genome annotation databases

EnsembliENST00000305921; ENSP00000306682; ENSG00000170836 [O15297-1]
ENST00000392995; ENSP00000376720; ENSG00000170836 [O15297-2]
ENST00000629650; ENSP00000486573; ENSG00000170836 [O15297-2]
GeneIDi8493
KEGGihsa:8493
UCSCiuc002iyt.3 human [O15297-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78305 mRNA Translation: AAB61637.1
BT009780 mRNA Translation: AAP88782.1
AC011921 Genomic DNA No translation available.
AC110602 Genomic DNA No translation available.
AC111155 Genomic DNA No translation available.
CH471179 Genomic DNA Translation: EAW51408.1
CH471179 Genomic DNA Translation: EAW51409.1
BC016480 mRNA Translation: AAH16480.1
BC042418 mRNA Translation: AAH42418.1
BC060877 mRNA Translation: AAH60877.1
CCDSiCCDS11625.1 [O15297-1]
RefSeqiNP_003611.1, NM_003620.3 [O15297-1]
UniGeneiHs.286073

3D structure databases

ProteinModelPortaliO15297
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114065, 28 interactors
CORUMiO15297
DIPiDIP-38281N
IntActiO15297, 40 interactors
MINTiO15297
STRINGi9606.ENSP00000306682

Chemistry databases

BindingDBiO15297
ChEMBLiCHEMBL1938224

PTM databases

DEPODiO15297
iPTMnetiO15297
PhosphoSitePlusiO15297

Polymorphism and mutation databases

BioMutaiPPM1D

Proteomic databases

EPDiO15297
MaxQBiO15297
PaxDbiO15297
PeptideAtlasiO15297
PRIDEiO15297
ProteomicsDBi48570

Protocols and materials databases

DNASUi8493
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305921; ENSP00000306682; ENSG00000170836 [O15297-1]
ENST00000392995; ENSP00000376720; ENSG00000170836 [O15297-2]
ENST00000629650; ENSP00000486573; ENSG00000170836 [O15297-2]
GeneIDi8493
KEGGihsa:8493
UCSCiuc002iyt.3 human [O15297-1]

Organism-specific databases

CTDi8493
DisGeNETi8493
EuPathDBiHostDB:ENSG00000170836.11
GeneCardsiPPM1D
HGNCiHGNC:9277 PPM1D
HPAiHPA022277
MalaCardsiPPM1D
MIMi114480 phenotype
167000 phenotype
605100 gene
617450 phenotype
neXtProtiNX_O15297
OpenTargetsiENSG00000170836
PharmGKBiPA33605
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0698 Eukaryota
COG0631 LUCA
GeneTreeiENSGT00920000149079
HOGENOMiHOG000231949
HOVERGENiHBG058897
InParanoidiO15297
KOiK10147
OMAiPLLHQHR
OrthoDBiEOG091G08LU
PhylomeDBiO15297
TreeFamiTF313481

Enzyme and pathway databases

ReactomeiR-HSA-8878166 Transcriptional regulation by RUNX2
SIGNORiO15297

Miscellaneous databases

GeneWikiiPPM1D
GenomeRNAii8493
PROiPR:O15297
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170836 Expressed in 206 organ(s), highest expression level in chorionic villus
CleanExiHS_PPM1D
ExpressionAtlasiO15297 baseline and differential
GenevisibleiO15297 HS

Family and domain databases

CDDicd00143 PP2Cc, 1 hit
InterProiView protein in InterPro
IPR015655 PP2C
IPR000222 PP2C_BS
IPR036457 PPM-type_dom_sf
IPR001932 PPM-type_phosphatase_dom
PANTHERiPTHR13832 PTHR13832, 1 hit
PfamiView protein in Pfam
PF00481 PP2C, 1 hit
SMARTiView protein in SMART
SM00332 PP2Cc, 1 hit
SUPFAMiSSF81606 SSF81606, 2 hits
PROSITEiView protein in PROSITE
PS01032 PPM_1, 1 hit
PS51746 PPM_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPPM1D_HUMAN
AccessioniPrimary (citable) accession number: O15297
Secondary accession number(s): Q53XP4, Q6P991, Q8IVR6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: September 12, 2018
This is version 169 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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