PPM1D

Gene Information

Official Symbol: PPM1D
Official Name: protein phosphatase, Mg2+/Mn2+ dependent 1D
Aliases and Previous Symbols: N/A
Entrez ID: 8493
UniProt: O15297
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez 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].
UniProt Summary: 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). {ECO:0000250|UniProtKB:Q9QZ67, ECO:0000269|PubMed:15870257, ECO:0000269|PubMed:16311512, ECO:0000269|PubMed:21283629, ECO:0000269|PubMed:23242139}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Nutlin-3A 1.6μM R06 exp294	-2.88
DABN racemic mixture R03 exp93	-2.27
GSK626616 14μM R08 exp485	-2.21
SNS-032 25μM R07 exp401	-2.12
Rotenone 2μM R00 exp33	-2.05
Atovaquone 15μM R08 exp451	-2.01
Vitamin-D3 40μM R08 exp536	-1.88
Erlotinib 10μM R05 exp216	1.7
TNF-alpha 44ng/ml R08 exp533	1.7
Cycloheximide 0.2μM R00 exp15	1.76
Doxycycline 10μM R00 exp18	1.82
YM155 0.001μM R08 exp432	1.94
CCCP 0.1μM R00 exp10	1.95
Cycloheximide 0.02μM R00 exp14	2.05

Gene	Correlation
PSMA7	0.48
NARFL	0.475
RPL6	0.468
RAD51	0.467
DISP2	0.458
TCEB3C	0.457
CIAPIN1	0.457
PSMB4	0.448
RPL35	0.447
KRT78	0.446
PSMC1	0.444
ORC6	0.443
CCDC116	0.442
CDC73	0.442
SF3A3	0.44
WDR75	0.44
RPL8	0.44
SMG7	0.438
ACBD4	0.438
TICRR	0.437
NOP16	0.435
PSMA6	0.435
TCEB3CL2	0.435
TCEB3CL	0.434
NCL	0.434
CTR9	0.433
TERF2	0.432
PSMC5	0.43
TERF1	0.43
PAN3	0.429
RPL17	0.429
TSG101	0.427
CCDC64B	0.426
DTL	0.425
COPB1	0.424
CDT1	0.423
RPLP1	0.422
PSMB1	0.421
TIMELESS	0.42
GOLGA6L1	0.417
ESCO1	0.416
XYLT2	0.415
EXOSC9	0.414
RPS12	0.412
RPS7	0.412
RPL14	0.411
ZNF574	0.411
COL2A1	0.41
USP37	0.409
TBC1D3L	0.408
EBNA1BP2	0.408
NOL12	0.408
TBC1D3E	0.407
TBC1D3K	0.407
SMG1	0.406
TBC1D3I	0.406
CGB2	0.406
CDC6	0.406
PSME3	0.405
RRN3	0.404
C14orf93	0.404
TBC1D3F	0.401
ZNF655	0.401
CDCA3	0.401
TAF1	0.401
IK	0.4
WDR87	0.4

Global Fraction of Cell Lines Where Essential: 3/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 1353
Expression level (log2 read counts): 5.55

Expression Distribution

peptidyl-threonine dephosphorylation
magnesium-dependent protein serine/threonine phosphatase activity
mitogen-activated protein kinase binding
DNA methylation
DNA alkylation
chromatin silencing
chromatin organization involved in negative regulation of transcription
protein serine/threonine phosphatase activity
DNA methylation or demethylation
chromatin organization involved in regulation of transcription
DNA damage response, signal transduction by p53 class mediator
negative regulation of gene expression, epigenetic
DNA modification
signal transduction in response to DNA damage
signal transduction by p53 class mediator
G2/M transition of mitotic cell cycle
cell cycle G2/M phase transition
cellular response to starvation
gene silencing
transcription initiation from RNA polymerase II promoter
response to starvation
protein dephosphorylation
DNA-templated transcription, initiation
cellular response to nutrient levels
regulation of gene expression, epigenetic
macromolecule methylation
cellular response to extracellular stimulus
mitotic cell cycle phase transition
cell cycle phase transition
dephosphorylation
methylation
cellular response to external stimulus
protein serine/threonine kinase activity
response to radiation
transcription by RNA polymerase II
response to nutrient levels
response to extracellular stimulus
mitotic cell cycle process
transcription, DNA-templated
nucleic acid-templated transcription