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Protein

Protein phosphatase 1D

Gene

PPM1D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi105 – 1051Manganese 1By similarity
Metal bindingi105 – 1051Manganese 2By similarity
Metal bindingi106 – 1061Manganese 1; via carbonyl oxygenBy similarity
Metal bindingi314 – 3141Manganese 2By similarity
Metal bindingi366 – 3661Manganese 2By similarity

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein serine/threonine phosphatase activity Source: UniProtKB

GO - Biological processi

  • G2/M transition of mitotic cell cycle Source: Ensembl
  • negative regulation of cell proliferation Source: ProtInc
  • peptidyl-threonine dephosphorylation Source: UniProtKB
  • protein dephosphorylation Source: ProtInc
  • response to bacterium Source: Ensembl
  • response to radiation Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

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
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:9277. PPM1D.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: ProtInc
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi314 – 3141D → A: Abrogates phosphatase activity. 1 Publication

Organism-specific databases

PharmGKBiPA33605.

Polymorphism and mutation databases

BioMutaiPPM1D.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 605605Protein phosphatase 1DPRO_0000057752Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei40 – 401Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO15297.
PaxDbiO15297.
PRIDEiO15297.

PTM databases

DEPODiO15297.
PhosphoSiteiO15297.

Expressioni

Inductioni

By p53/TP53.2 Publications

Gene expression databases

BgeeiO15297.
CleanExiHS_PPM1D.
ExpressionAtlasiO15297. baseline and differential.
GenevisibleiO15297. HS.

Organism-specific databases

HPAiCAB009474.
HPA022277.

Interactioni

Subunit structurei

Interacts with CHEK1 and CHEK2; dephosphorylates them.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
H2AFXP161046EBI-1551512,EBI-494830
MDM2Q009874EBI-1551512,EBI-389668

Protein-protein interaction databases

BioGridi114065. 5 interactions.
DIPiDIP-38281N.
IntActiO15297. 18 interactions.
MINTiMINT-7944722.
STRINGi9606.ENSP00000306682.

Structurei

3D structure databases

ProteinModelPortaliO15297.
SMRiO15297. Positions 99-374.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 375368PPM-type phosphatasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 101101Interaction with CHEK1Add
BLAST

Sequence similaritiesi

Belongs to the PP2C family.Curated
Contains 1 PPM-type phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0631.
GeneTreeiENSGT00770000120571.
HOGENOMiHOG000231949.
HOVERGENiHBG058897.
InParanoidiO15297.
KOiK10147.
OMAiNTIMDQK.
OrthoDBiEOG7Z95M0.
PhylomeDBiO15297.
TreeFamiTF313481.

Family and domain databases

Gene3Di3.60.40.10. 2 hits.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81606. SSF81606. 2 hits.
PROSITEiPS01032. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti322 – 3221P → Q.1 Publication
Corresponds to variant rs17855093 [ dbSNP | Ensembl ].
VAR_070430

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei421 – 43010SLEEDPWPRV → DFGFELDSRK in isoform 2. 1 PublicationVSP_056377
Alternative sequencei431 – 605175Missing in isoform 2. 1 PublicationVSP_056378Add
BLAST

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.2. human. [O15297-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
SMRiO15297. Positions 99-374.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114065. 5 interactions.
DIPiDIP-38281N.
IntActiO15297. 18 interactions.
MINTiMINT-7944722.
STRINGi9606.ENSP00000306682.

Chemistry

BindingDBiO15297.
ChEMBLiCHEMBL1938224.

PTM databases

DEPODiO15297.
PhosphoSiteiO15297.

Polymorphism and mutation databases

BioMutaiPPM1D.

Proteomic databases

MaxQBiO15297.
PaxDbiO15297.
PRIDEiO15297.

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.2. human. [O15297-1]

Organism-specific databases

CTDi8493.
GeneCardsiGC17P058677.
HGNCiHGNC:9277. PPM1D.
HPAiCAB009474.
HPA022277.
MIMi605100. gene.
neXtProtiNX_O15297.
PharmGKBiPA33605.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0631.
GeneTreeiENSGT00770000120571.
HOGENOMiHOG000231949.
HOVERGENiHBG058897.
InParanoidiO15297.
KOiK10147.
OMAiNTIMDQK.
OrthoDBiEOG7Z95M0.
PhylomeDBiO15297.
TreeFamiTF313481.

Miscellaneous databases

GeneWikiiPPM1D.
GenomeRNAii8493.
NextBioi31775.
PROiO15297.
SOURCEiSearch...

Gene expression databases

BgeeiO15297.
CleanExiHS_PPM1D.
ExpressionAtlasiO15297. baseline and differential.
GenevisibleiO15297. HS.

Family and domain databases

Gene3Di3.60.40.10. 2 hits.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81606. SSF81606. 2 hits.
PROSITEiPS01032. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 1), 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] (ISOFORM 1).
  3. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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] (ISOFORMS 1 AND 2), VARIANT GLN-322.
    Tissue: Brain and Skin.
  6. "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.
  7. "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.
  8. "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.

Entry informationi

Entry nameiPPM1D_HUMAN
AccessioniPrimary (citable) accession number: O15297
Secondary accession number(s): Q53XP4, Q6P991, Q8IVR6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: June 24, 2015
This is version 140 of the entry and version 1 of the sequence. [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 chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.