PPM1A

Protein identityUniProt · HPA

UniProt accession

P35813

Gene

PPM1A

Ensembl

ENSG00000100614

Chromosome

14

Canonical length

382 aa

Protein class

Enzymes, Predicted intracellular proteins

Subcellular location

Plasma membrane,Cytosol

OverviewNCBI Gene

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. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

382 residues, UniProt reviewed canonical sequence.

>P35813|PPM1A
     1  MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL ESWSFFAVYD
    61  GHAGSQVAKY CCEHLLDHIT NNQDFKGSAG APSVENVKNG IRTGFLEIDE HMRVMSEKKH
   121  GADRSGSTAV GVLISPQHTY FINCGDSRGL LCRNRKVHFF TQDHKPSNPL EKERIQNAGG
   181  SVMIQRVNGS LAVSRALGDF DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG
   241  IWDVMGNEEL CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPNAPKVSPE
   301  AVKKEAELDK YLECRVEEII KKQGEGVPDL VHVMRTLASE NIPSLPPGGE LASKRNVIEA
   361  VYNRLNPYKN DDTDSTSTDD MW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PPM1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

135 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for PPM1A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.16

gnomAD pLI

1

gnomAD missense Z

2.58

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to transforming growth factor beta stimulus
• N-terminal protein myristoylation
• negative regulation of BMP signaling pathway
• negative regulation of canonical NF-kappaB signal transduction
• negative regulation of non-canonical NF-kappaB signal transduction
• negative regulation of transcription by RNA polymerase II
• negative regulation of transforming growth factor beta receptor signaling pathway
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of canonical Wnt signaling pathway
• positive regulation of DNA-templated transcription
• positive regulation of protein export from nucleus
• protein dephosphorylation
• protein export from nucleus
• regulation of canonical NF-kappaB signal transduction
• regulation of cell cycle

Molecular functions

• calmodulin-dependent protein phosphatase activity
• magnesium ion binding
• manganese ion binding
• protein serine/threonine phosphatase activity
• R-SMAD binding

Cellular components

• cytosol
• membrane
• nucleoplasm
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• PPM-type phosphatase, divalent cation binding
• PPM-type phosphatase-like domain
• Protein serine/threonine phosphatase 2C, C-terminal
• Protein phosphatase 2C
• PPM-type phosphatase-like domain superfamily
• Phosphatase 2C, C-terminal domain superfamily
• Protein phosphatase 2C
• Protein serine/threonine phosphatase 2C, C-terminal domain

KeywordsUniProt

• Cytoplasm
• Hydrolase
• Lipoprotein
• Magnesium
• Manganese
• Membrane
• Metal-binding
• Myristate
• Nucleus
• Phosphoprotein
• Protein phosphatase

InteractionsUniProt · HPA

Protein binding partners of PPM1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SMAD2
• IKBKB
• SMAD3
• ARRB1
• ARRB2
• EGFR
• HSPB1
• IGF1R