PPM1A protein phosphatase, Mg2+/Mn2+ dependent 1A [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPM1Aprovided by HGNC
Official Full Name: protein phosphatase, Mg2+/Mn2+ dependent 1Aprovided by HGNC
Primary source: HGNC:HGNC:9275
See related: Ensembl:ENSG00000100614 MIM:606108; AllianceGenome:HGNC:9275
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: PP2CA; PP2Calpha; PP2C-ALPHA
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. 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]
Expression: Ubiquitous expression in bone marrow (RPKM 10.2), brain (RPKM 9.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q23.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (60245750..60299087)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (54452043..54505381)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (60712468..60765805)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Extracellular PPM1A promotes mineralization of osteoblasts differentiation in ankylosing spondylitis via the FOXO1A-RUNX2 pathway.
Title: Extracellular PPM1A promotes mineralization of osteoblasts differentiation in ankylosing spondylitis via the FOXO1A-RUNX2 pathway.
Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage.
Title: Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage.
Knockdown of TRIM65 suppressed the proliferation and invasiveness of gastric cancer cells by restricting the ubiquitin degradation of PPM1A.
Title: Knockdown of TRIM65 suppressed the proliferation and invasiveness of gastric cancer cells by restricting the ubiquitin degradation of PPM1A.
A comprehensive overview of PPM1A: From structure to disease.
Title: A comprehensive overview of PPM1A: From structure to disease.
lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p.
Title: lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p.
Role of active site arginine residues in substrate recognition by PPM1A.
Title: Role of active site arginine residues in substrate recognition by PPM1A.
MicroRNA-487a-3p inhibits the growth and invasiveness of oral squamous cell carcinoma by targeting PPM1A.
Title: MicroRNA-487a-3p inhibits the growth and invasiveness of oral squamous cell carcinoma by targeting PPM1A.
PPM1A suppresses the proliferation and invasiveness of RCC cells via Smad2/3 signaling inhibition.
Title: PPM1A suppresses the proliferation and invasiveness of RCC cells via Smad2/3 signaling inhibition.
Hepatitis B Virus-Encoded MicroRNA (HBV-miR-3) Regulates Host Gene PPM1A Related to Hepatocellular Carcinoma.
Title: Hepatitis B Virus-Encoded MicroRNA (HBV-miR-3) Regulates Host Gene PPM1A Related to Hepatocellular Carcinoma.
PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARgamma at Ser273.
Title: PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARγ at Ser273.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of protein phosphatase, Mg2+/Mn2+ dependent, 1A (PPM1A) by siRNA ehnahces HIV-1 gene expression in resting CD4+ T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D14S656E (e-PCR)
- UniSTS:151554

RH17916 (e-PCR)
- UniSTS:17424

RH98675 (e-PCR)
- UniSTS:83994

RH102741 (e-PCR)
- UniSTS:97075

D14S1259 (e-PCR)
- UniSTS:54325

RH92556 (e-PCR)
- UniSTS:85591

RH124067 (e-PCR)
- UniSTS:138877

STS-AA034525 (e-PCR)
- UniSTS:49825

PPM1A__5759 (e-PCR)
- UniSTS:471723

D14S794 (e-PCR)
- UniSTS:153531

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables R-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables calmodulin-dependent protein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info
enables manganese ion binding	IEA Inferred from Electronic Annotation more info
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine phosphatase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in N-terminal protein myristoylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to transforming growth factor beta stimulus	IEA Inferred from Electronic Annotation more info
involved_in dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of non-canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-threonine dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-threonine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	HMP more info	PubMed
involved_in positive regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein export from nucleus	IEA Inferred from Electronic Annotation more info
involved_in protein dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein export from nucleus	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell cycle	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: protein phosphatase 1A

NP_066283.1

EC 3.1.3.16

NP_808820.1

EC 3.1.3.16

NP_808821.2

EC 3.1.3.16

XP_011535183.1

EC 3.1.3.16

XP_011535185.1

EC 3.1.3.16

XP_016876872.1

EC 3.1.3.16

XP_024305405.1

EC 3.1.3.16

XP_047287455.1

EC 3.1.3.16

XP_047287456.1

EC 3.1.3.16

XP_047287457.1

EC 3.1.3.16

XP_047287458.1

EC 3.1.3.16

XP_047287459.1

EC 3.1.3.16

XP_047287460.1

EC 3.1.3.16

XP_047287461.1

EC 3.1.3.16

XP_047287462.1

EC 3.1.3.16

XP_047287463.1

EC 3.1.3.16

XP_047287464.1

EC 3.1.3.16

XP_047287465.1

EC 3.1.3.16

XP_047287466.1

EC 3.1.3.16

XP_047287467.1

EC 3.1.3.16

XP_047287468.1

EC 3.1.3.16

XP_047287469.1

EC 3.1.3.16

XP_047287470.1

EC 3.1.3.16

XP_047287471.1

EC 3.1.3.16

XP_047287472.1

EC 3.1.3.16

XP_054232229.1

EC 3.1.3.16

XP_054232230.1

EC 3.1.3.16

XP_054232231.1

EC 3.1.3.16

XP_054232232.1

EC 3.1.3.16

XP_054232233.1

EC 3.1.3.16

XP_054232234.1

EC 3.1.3.16

XP_054232235.1

EC 3.1.3.16

XP_054232236.1

EC 3.1.3.16

XP_054232237.1

EC 3.1.3.16

XP_054232238.1

EC 3.1.3.16

XP_054232239.1

EC 3.1.3.16

XP_054232240.1

EC 3.1.3.16

XP_054232241.1

EC 3.1.3.16

XP_054232242.1

EC 3.1.3.16

XP_054232243.1

EC 3.1.3.16

XP_054232244.1

EC 3.1.3.16

XP_054232245.1

EC 3.1.3.16

XP_054232246.1

EC 3.1.3.16

XP_054232247.1

EC 3.1.3.16

XP_054232248.1

EC 3.1.3.16

XP_054232249.1

EC 3.1.3.16

XP_054232250.1

EC 3.1.3.16

NCBI Reference Sequences (RefSeq)

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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_029698.1 RefSeqGene

Range

8470..58336

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_021003.5 → NP_066283.1 protein phosphatase 1A isoform 1

See identical proteins and their annotated locations for NP_066283.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longest transcript and encodes isoform 1.

Source sequence(s)

AI076736, AL132778, AL157756, BC063243, DA439296

Consensus CDS

CCDS9744.1

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813

UniProtKB/TrEMBL

B2R8E4, B5BUD5

Related

ENSP00000378514.4, ENST00000395076.9

Conserved Domains (2) summary

cd00143
Location:23 → 291

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 ...

pfam07830
Location:285 → 363

PP2C_C; Protein serine/threonine phosphatase 2C, C-terminal domain
NM_177951.3 → NP_808820.1 protein phosphatase 1A isoform 2

See identical proteins and their annotated locations for NP_808820.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an additional exon within the 5' UTR and lacks a few of 3' exons but has an alternate 3' segment, as compared to variant 1. The resulting isoform (2) has a distinct and shorter C-terminus, as compared to isoform 1.

Source sequence(s)

AF070670, AL157756, CB156710, DA439296

Consensus CDS

CCDS9745.1

UniProtKB/TrEMBL

B2R8E4, B5BUD5

Related

ENSP00000314850.3, ENST00000325658.3

Conserved Domains (2) summary

pfam00481
Location:22 → 284

PP2C; Protein phosphatase 2C

cl29762
Location:285 → 317

PP2C_C; Protein serine/threonine phosphatase 2C, C-terminal domain
NM_177952.3 → NP_808821.2 protein phosphatase 1A isoform 3

See identical proteins and their annotated locations for NP_808821.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate 5' exon, as compared to variant 1. It encodes isoform 3, which has a distinct and longer N-terminus, as compared to isoform 1.

Source sequence(s)

AI076736, AK097843, AK313337, AL132778, AL157756, BC063243

Consensus CDS

CCDS45120.1

UniProtKB/TrEMBL

B2R8E4, B5BUD5

Related

ENSP00000327255.3, ENST00000325642.7

Conserved Domains (2) summary

pfam00481
Location:95 → 357

PP2C; Protein phosphatase 2C

pfam07830
Location:358 → 433

PP2C_C; Protein serine/threonine phosphatase 2C, C-terminal domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

60245750..60299087

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047431505.1 → XP_047287461.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431508.1 → XP_047287464.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431511.1 → XP_047287467.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431512.1 → XP_047287468.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431516.1 → XP_047287472.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431499.1 → XP_047287455.1 protein phosphatase 1A isoform X1
XM_047431501.1 → XP_047287457.1 protein phosphatase 1A isoform X1
XM_017021383.2 → XP_016876872.1 protein phosphatase 1A isoform X1

UniProtKB/TrEMBL

B2R8E4, B5BUD5
XM_047431507.1 → XP_047287463.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431513.1 → XP_047287469.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431515.1 → XP_047287471.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_024449637.2 → XP_024305405.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813

UniProtKB/TrEMBL

B2R8E4, B5BUD5

Conserved Domains (2) summary

cd00143
Location:23 → 291

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 ...

pfam07830
Location:285 → 363

PP2C_C; Protein serine/threonine phosphatase 2C, C-terminal domain
XM_047431500.1 → XP_047287456.1 protein phosphatase 1A isoform X1
XM_047431510.1 → XP_047287466.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431506.1 → XP_047287462.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431514.1 → XP_047287470.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_011536883.2 → XP_011535185.1 protein phosphatase 1A isoform X3

See identical proteins and their annotated locations for XP_011535185.1

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813

UniProtKB/TrEMBL

B2R8E4, B5BUD5

Conserved Domains (2) summary

cd00143
Location:23 → 291

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 ...

pfam07830
Location:285 → 363

PP2C_C; Protein serine/threonine phosphatase 2C, C-terminal domain
XM_047431509.1 → XP_047287465.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431503.1 → XP_047287459.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_047431504.1 → XP_047287460.1 protein phosphatase 1A isoform X3

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813
XM_011536881.4 → XP_011535183.1 protein phosphatase 1A isoform X3

See identical proteins and their annotated locations for XP_011535183.1

UniProtKB/Swiss-Prot

B5BU11, J3KNM0, O75551, P35813

UniProtKB/TrEMBL

B2R8E4, B5BUD5

Conserved Domains (2) summary

cd00143
Location:23 → 291

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 ...

pfam07830
Location:285 → 363

PP2C_C; Protein serine/threonine phosphatase 2C, C-terminal domain
XM_047431502.1 → XP_047287458.1 protein phosphatase 1A isoform X2