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O15297 (PPM1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PPM1D
Synonyms:WIP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length605 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6

Catalytic activity

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

Cofactor

Binds 2 magnesium or manganese ions per subunit By similarity.

Subunit structure

Interacts with CHEK1 and CHEK2; dephosphorylates them. Ref.5 Ref.6

Induction

By p53/TP53. Ref.1 Ref.5

Sequence similarities

Belongs to the PP2C family.

Contains 1 PP2C-like domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 605605Protein phosphatase 1D
PRO_0000057752

Regions

Domain61 – 378318PP2C-like
Region1 – 101101Interaction with CHEK1

Sites

Metal binding1051Manganese 1 By similarity
Metal binding1051Manganese 2 By similarity
Metal binding1061Manganese 1; via carbonyl oxygen By similarity
Metal binding3141Manganese 2 By similarity
Metal binding3661Manganese 2 By similarity

Amino acid modifications

Modified residue401Phosphoserine Ref.7

Natural variations

Natural variant3221P → Q. Ref.4
Corresponds to variant rs17855093 [ dbSNP | Ensembl ].
VAR_070430

Experimental info

Mutagenesis3141D → A: Abrogates phosphatase activity. Ref.5

Sequences

Sequence LengthMass (Da)Tools
O15297 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: E6C5884CF04008B7

FASTA60566,675
        10         20         30         40         50         60 
MAGLYSLGVS VFSDQGGRKY MEDVTQIVVE PEPTAEEKPS PRRSLSQPLP PRPSPAALPG 

        70         80         90        100        110        120 
GEVSGKGPAV AAREARDPLP DAGASPAPSR CCRRRSSVAF FAVCDGHGGR EAAQFAREHL 

       130        140        150        160        170        180 
WGFIKKQKGF TSSEPAKVCA AIRKGFLACH LAMWKKLAEW PKTMTGLPST SGTTASVVII 

       190        200        210        220        230        240 
RGMKMYVAHV GDSGVVLGIQ DDPKDDFVRA VEVTQDHKPE LPKERERIEG LGGSVMNKSG 

       250        260        270        280        290        300 
VNRVVWKRPR LTHNGPVRRS TVIDQIPFLA VARALGDLWS YDFFSGEFVV SPEPDTSVHT 

       310        320        330        340        350        360 
LDPQKHKYII LGSDGLWNMI PPQDAISMCQ DQEEKKYLMG EHGQSCAKML VNRALGRWRQ 

       370        380        390        400        410        420 
RMLRADNTSA IVICISPEVD NQGNFTNEDE LYLNLTDSPS YNSQETCVMT PSPCSTPPVK 

       430        440        450        460        470        480 
SLEEDPWPRV NSKDHIPALV RSNAFSENFL EVSAEIAREN VQGVVIPSKD PEPLEENCAK 

       490        500        510        520        530        540 
ALTLRIHDSL NNSLPIGLVP TNSTNTVMDQ KNLKMSTPGQ MKAQEIERTP PTNFKRTLEE 

       550        560        570        580        590        600 
SNSGPLMKKH RRNGLSRSSG AQPASLPTTS QRKNSVKLTM RRRLRGQKKI GNPLLHQHRK 


TVCVC 

« Hide

References

« Hide 'large scale' references
[1]"Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner."
Fiscella M., Zhang H., Fan S., Sakaguchi K., Shen S., Mercer W.E., Vande Woude G.F., O'Connor P.M., Appella E.
Proc. Natl. Acad. Sci. U.S.A. 94:6048-6053(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-322.
Tissue: Brain and Skin.
[5]"PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints."
Lu X., Nannenga B., Donehower L.A.
Genes Dev. 19:1162-1174(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CHEK1, INDUCTION, MUTAGENESIS OF ASP-314.
[6]"Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase."
Fujimoto H., Onishi N., Kato N., Takekawa M., Xu X.Z., Kosugi A., Kondo T., Imamura M., Oishi I., Yoda A., Minami Y.
Cell Death Differ. 13:1170-1180(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS, FUNCTION IN DEPHOSPHORYLATION OF CHEK2, INTERACTION WITH CHEK2.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U78305 mRNA. Translation: AAB61637.1.
BT009780 mRNA. Translation: AAP88782.1.
CH471179 Genomic DNA. Translation: EAW51408.1.
BC016480 mRNA. Translation: AAH16480.1.
BC060877 mRNA. Translation: AAH60877.1.
RefSeqNP_003611.1. NM_003620.3.
UniGeneHs.286073.

3D structure databases

ProteinModelPortalO15297.
SMRO15297. Positions 6-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114065. 6 interactions.
DIPDIP-38281N.
IntActO15297. 4 interactions.
MINTMINT-7944722.
STRING9606.ENSP00000306682.

Chemistry

BindingDBO15297.
ChEMBLCHEMBL1938224.

PTM databases

PhosphoSiteO15297.

Proteomic databases

PaxDbO15297.
PRIDEO15297.

Protocols and materials databases

DNASU8493.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000305921; ENSP00000306682; ENSG00000170836.
GeneID8493.
KEGGhsa:8493.
UCSCuc002iyt.2. human.

Organism-specific databases

CTD8493.
GeneCardsGC17P058677.
HGNCHGNC:9277. PPM1D.
HPACAB009474.
HPA022277.
MIM605100. gene.
neXtProtNX_O15297.
PharmGKBPA33605.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0631.
HOGENOMHOG000231949.
HOVERGENHBG058897.
InParanoidO15297.
KOK10147.
OMAVIPSKDP.
OrthoDBEOG7Z95M0.
PhylomeDBO15297.
TreeFamTF313481.

Gene expression databases

ArrayExpressO15297.
BgeeO15297.
CleanExHS_PPM1D.
GenevestigatorO15297.

Family and domain databases

Gene3D3.60.40.10. 2 hits.
InterProIPR001932. PP2C-like_dom.
IPR000222. PP2C_Mn2_Asp60_BS.
IPR015655. Protein_Pase_2C.
[Graphical view]
PANTHERPTHR13832. PTHR13832. 1 hit.
PfamPF00481. PP2C. 1 hit.
[Graphical view]
SMARTSM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMSSF81606. SSF81606. 2 hits.
PROSITEPS01032. PP2C. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPPM1D.
GenomeRNAi8493.
NextBio31775.
PROO15297.
SOURCESearch...

Entry information

Entry namePPM1D_HUMAN
AccessionPrimary (citable) accession number: O15297
Secondary accession number(s): Q53XP4, Q6P991
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM