PPM1D protein phosphatase, Mg2+/Mn2+ dependent, 1D [Homo sapiens] - Gene

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Summary

Official Symbol: PPM1Dprovided by HGNC
Official Full Name: protein phosphatase, Mg2+/Mn2+ dependent, 1Dprovided by HGNC
Primary source: HGNC:9277
See related: Ensembl:ENSG00000170836; HPRD:05482; MIM:605100
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: WIP1; PP2C-DELTA
Summary: The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 17q23.2

Sequence :: Chromosome: 17; NC_000017.10 (58677544..58743641)

See PPM1D in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Wip1 provides ample time for cells to be ready for mitosis, which is at least mediated through increased inhibitory phospho-tyrosine level on CDC2.
Title: Wip1 contributes to cell homeostasis maintained by the steady-state level of Wtp53.
Wip1 over-expression correlated with TP53/p14(ARF) pathway disruption in human astrocytomas.
Title: Wip1 over-expression correlated with TP53/p14(ARF) pathway disruption in human astrocytomas.
the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1
Title: LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating p38 association with the wild-type p53 induced phosphatase 1 (WIP1).
the increased expression of Wip1 in cancer epithelial cells has significant value for tumor progression and the clinical prognosis of patients with primary lung adenocarcinoma
Title: Oncogenic phosphatase Wip1 is a novel prognostic marker for lung adenocarcinoma patient survival.
PPM1D is consistently overexpressed when amplified in breast cancer; however, PPM1D overexpression is more pervasive than gene amplification.
Title: PPM1D gene amplification and overexpression in breast cancer: a qRT-PCR and chromogenic in situ hybridization study.
results suggest an important role of miR-16 in the regulation of Wip1 phosphatase in the DNA damage response and mammary tumorigenesis.
Title: Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway.
The high expression of Wip1 mRNA and its protein in breast cancer tissue may promote the growth of breast cancer.
Title: [Expression of proto-oncogene Wip1 in breast cancer and its clinical significance].
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair.
Title: Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair.
Wip1 has an essential role in dephosphorylation of gamma-H2AX to silence the checkpoint and restore chromatin structure once DNA damage is repaired.
Title: Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition.

Submit: New GeneRIF Correction See all (42)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Products	Interactant	Other Gene	Source	Pubs	Description
NP_003611.1	NP_550433.1	UNG	BIND	PubMed	PPM1D interacts with and dephosphorylates UNG2.
O15297	P19338	NCL	HPRD	PubMed
O15297	P46777	RPL5	HPRD	PubMed
BioGRID:114065	BioGRID:107424	CDC5L	BioGRID	PubMed	Affinity Capture-MS; Co-purification
BioGRID:114065	BioGRID:109268	H2AFX	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:114065	BioGRID:110358	MDM2	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
hydrolase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info
protein serine/threonine phosphatase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
G2/M transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
cell cycle	IEA Inferred from Electronic Annotation more info
negative regulation of cell proliferation	TAS Traceable Author Statement more info	PubMed
peptidyl-threonine dephosphorylation	IDA Inferred from Direct Assay more info
protein dephosphorylation	IEA Inferred from Electronic Annotation more info
protein dephosphorylation	TAS Traceable Author Statement more info	PubMed
response to bacterium	IEA Inferred from Electronic Annotation more info
response to radiation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
nucleus	TAS Traceable Author Statement more info	PubMed
protein serine/threonine phosphatase complex	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: protein phosphatase 1D

Names: protein phosphatase 1D; protein phosphatase Wip1; wild-type p53-induced phosphatase 1; protein phosphatase 2C delta isoform; protein phosphatase magnesium-dependent 1 delta; protein phosphatase 1D magnesium-dependent, delta isoform

NP_003611.1

EC 3.1.3.16

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023265.1 RefSeqGene

Range

4991..71088

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003620.3 → NP_003611.1 protein phosphatase 1D

Status: REVIEWED

Source sequence(s)

AC110602, BC060877, BU616782, U78305

Consensus CDS

CCDS11625.1

UniProtKB/Swiss-Prot

O15297

UniProtKB/TrEMBL

Q6P991

Related

ENSP00000306682, ENST00000305921

Conserved Domains (2) summary

cd00143
Location:98 – 375
Blast Score: 485

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...

pfam00481
Location:67 – 368
Blast Score: 527

PP2C; Protein phosphatase 2C

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p5 Primary Assembly

Range

58677544..58743641

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

54048263..54112992

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC011921.14 (152660..153921)	None
genomic	AC110602.8 (94136..138692)	None
genomic	AC111155.11 (12346..32600)	None
genomic	CH471179.1	EAW51408.1
		EAW51409.1
mRNA	AA326266.1	None
mRNA	AK054573.1	None
mRNA	AK299773.1	BAG61656.1
mRNA	AK312902.1	BAG35748.1
mRNA	AU280469.1	None
mRNA	BC016480.1	AAH16480.1
mRNA	BC032826.1	None
mRNA	BC033893.2	AAH33893.1
mRNA	BC042418.1	AAH42418.1
mRNA	BC060877.1	AAH60877.1
mRNA	BT009780.1	AAP88782.1
mRNA	BU616782.1	None
mRNA	U78305.1	AAB61637.1
other-genetic	DQ891047.2	ABM81973.1
other-genetic	EU176552.1	ABW03353.1

Protein Accession	Links
Protein Accession	GenePept Link	UniProtKB Link
O15297.1	GenPept	UniProtKB/Swiss-Prot:O15297
Q6P991	GenPept	UniProtKB/TrEMBL:Q6P991
Q8IVR6	GenPept	UniProtKB/TrEMBL:Q8IVR6
Q8NEA7	GenPept	UniProtKB/TrEMBL:Q8NEA7