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PTPA protein phosphatase 2 phosphatase activator [ Homo sapiens (human) ]

Gene ID: 5524, updated on 24-Nov-2020

Summary

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Official Symbol
PTPAprovided by HGNC
Official Full Name
protein phosphatase 2 phosphatase activatorprovided by HGNC
Primary source
HGNC:HGNC:9308
See related
Ensembl:ENSG00000119383 MIM:600756
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
PP2A; PR53; PPP2R4
Summary
Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in testis (RPKM 35.1), brain (RPKM 26.2) and 25 other tissues See more
Orthologs
mouse all

Genomic context

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See PTPA in Genome Data Viewer
Location:
9q34.11
Exon count:
13
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 9 NC_000009.12 (129110949..129148946)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (131873183..131911225)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene dolichyldiphosphatase 1 Neighboring gene carnitine O-acetyltransferase Neighboring gene Sharpr-MPRA regulatory region 13939 Neighboring gene immediate early response 5 like Neighboring gene Sharpr-MPRA regulatory region 2152

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Inhibition of PP2A enhances the osteogenic differentiation of human aortic valvular interstitial cells via ERK and p38 MAPK pathways. Xie F, et al. Life Sci, 2020 Sep 15. PMID 32679147
  2. To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling. Javadpour P, et al. Cell Mol Life Sci, 2019 Jun. PMID 30874837
  3. Hypoxia modulates protein phosphatase 2A through HIF-1α dependent and independent mechanisms in human aortic smooth muscle cells and ventricular cardiomyocytes. Elgenaidi IS, et al. Br J Pharmacol, 2019 Jun. PMID 30825189, Free PMC Article
  4. Chlamydia trachomatis Inhibits Homologous Recombination Repair of DNA Breaks by Interfering with PP2A Signaling. Mi Y, et al. mBio, 2018 Nov 6. PMID 30401777, Free PMC Article
  5. Protein phosphatase 2A regulates the p38 signaling pathway to affect the migration of astrocytes. Zhang L, et al. Mol Med Rep, 2018 Nov. PMID 30152844, Free PMC Article

See all (210) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells.
    Title: STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells.
  2. Inhibition of PP2A enhances the osteogenic differentiation of human aortic valvular interstitial cells via ERK and p38 MAPK pathways.
    Title: Inhibition of PP2A enhances the osteogenic differentiation of human aortic valvular interstitial cells via ERK and p38 MAPK pathways.
  3. Hypoxia modulates protein phosphatase 2A through HIF-1alpha dependent and independent mechanisms in human aortic smooth muscle cells and ventricular cardiomyocytes.
    Title: Hypoxia modulates protein phosphatase 2A through HIF-1α dependent and independent mechanisms in human aortic smooth muscle cells and ventricular cardiomyocytes.
  4. PP2A inhibits breast cancer metastasis via dephosphorylation of Girdin.
    Title: Dephosphorylation of Girdin by PP2A inhibits breast cancer metastasis.
  5. PP2A is critical in driving pulmonary arterial hypertension (PAH), and berberine (BBR) may alleviate PAH via PP2A signaling pathways, thereby offering a potential therapeutic option for PAH
    Title: Berberine attenuates pulmonary arterial hypertension via protein phosphatase 2A signaling pathway both in vivo and in vitro.
  6. Low PP2A expression is associated with chronic obstructive pulmonary disease
    Title: Chronic Cigarette Smoke Exposure Subdues PP2A Activity by Enhancing Expression of the Oncogene CIP2A.
  7. This review discusses the latest findings about PP2A dysregulation in Alzheimer and Parkinson diseases and possible interplay between this phosphatase and insulin signaling pathways. [review]
    Title: To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.
  8. PP2A was highly expressed in human periprosthetic interface membranes with aseptic loosening and murine osteolysis model. PP2A inhibition effectively alleviated titanium particle-induced bone destruction and decreased osteoclast numbers.
    Title: Protein phosphatase 2A as a new target for downregulating osteoclastogenesis and alleviating titanium particle-induced bone resorption.
  9. Here we show that C. trachomatis prevents activation of the key DNA damage response mediator ATM by preventing the release from PP2A, leading to a complete absence of homologous recombination repair in host cells.
    Title: <i>Chlamydia trachomatis</i> Inhibits Homologous Recombination Repair of DNA Breaks by Interfering with PP2A Signaling.
  10. study reveals that KIAA1199 promotes metastasis of colorectal cancer cells via microtubule destabilization regulated by a PP2A/stathmin pathway, and suggests that KIAA1199 may be a promising target for preventing metastasis in colorectal cancer.
    Title: KIAA1199 promotes metastasis of colorectal cancer cells via microtubule destabilization regulated by a PP2A/stathmin pathway.
Submit: New GeneRIF Correction See all GeneRIFs (111)

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

Associated conditions

Description Tests
An atlas of genetic influences on human blood metabolites.
GeneReviews: Not available
Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia.
GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat upregulates the total levels of PP2A protein and downregulates the inactive form of phosphorylated PP2A, which leads to inhibit hTERT activity directly or indirectly in CD4+ T cells PubMed
tat Protein phosphatase-2A (PP2A) and protein phosphatase-1 (PP1) regulate HIV-1 Tat-activated transcription through dephosphorylation of CDK9 PubMed
tat An increase in the amount of PP2A core enzyme with a concomitant decrease in the amount of PP2A holoenzyme inhibits HIV-1 Tat-stimulated transcription from the HIV-1 LTR promoter, indicating a role for PP2A in the modulation of HIV-1 gene expression PubMed
Vpr vpr Amino-acid peptide sequence (residues 77-92) of HIV-1 Vpr binds to PP2A1. The sequence from HIV-1 89.6 strain is a cell penetrating and death domain PubMed
vpr HIV-1 Vpr cell death causing peptide (amino acid residues 71-96) can activate the expression of PP2A when applied extracellularly to CD4+ T cells as well as cause the activation of PP2A from brain, liver, and adipose tissues PubMed
vpr HIV-1 Vpr was found to upregulate PP2A in fission yeast PubMed
vpr HIV-1 Vpr forms a complex with HIV-1 nucleocapsid that directly activates PP2A PubMed
nucleocapsid gag HIV-1 Vpr forms a complex with HIV-1 nucleocapsid that directly activates PP2A PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC2184

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
contributes_to ATPase activity IDA
Inferred from Direct Assay
more info
 PubMed 
peptidyl-prolyl cis-trans isomerase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
protein phosphatase 2A binding IDA
Inferred from Direct Assay
more info
 PubMed 
protein phosphatase regulator activity IDA
Inferred from Direct Assay
more info
 PubMed 
protein phosphatase regulator activity TAS
Traceable Author Statement
more info
 PubMed 
protein tyrosine phosphatase activator activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
protein tyrosine phosphatase activator activity IDA
Inferred from Direct Assay
more info
 PubMed 
signaling receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
mitotic spindle organization IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
negative regulation of phosphoprotein phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
negative regulation of protein dephosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of phosphoprotein phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of protein dephosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
protein peptidyl-prolyl isomerization IEA
Inferred from Electronic Annotation
more info
  
regulation of phosphoprotein phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
calcium channel complex IDA
Inferred from Direct Assay
more info
 PubMed 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
extracellular exosome HDA PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
  
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
protein phosphatase type 2A complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
protein phosphatase type 2A complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
serine/threonine-protein phosphatase 2A activator
Names
PP2A phosphatase activator
phosphotyrosyl phosphatase activator
protein phosphatase 2 regulatory subunit 4
protein phosphatase 2A activator, regulatory subunit 4
protein phosphatase 2A regulatory subunit 4
protein phosphatase 2A, regulatory subunit B' (PR 53)
serine/threonine-protein phosphatase 2A regulatory subunit B'
NP_001180326.1
NP_001258761.1
NP_066954.2
NP_821067.1
NP_821068.1
NP_821070.1
XP_011517136.1
XP_011517137.1
XP_011517138.1
XP_011517139.1
XP_011517140.1
XP_016870377.1

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

  1. NG_029370.1 RefSeqGene

    Range
    5002..42998
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001193397.2 → NP_001180326.1  serine/threonine-protein phosphatase 2A activator isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) contains a different first exon, which results in the use of an in-frame downstream start codon, and lacks an alternate coding segment, compared to variant 1. The resulting protein (isoform e) is shorter when compared to isoform a.
    Source sequence(s)
    AL158151, CD630703, DA052599, X73478
    Consensus CDS
    CCDS75917.1
    UniProtKB/Swiss-Prot
    Q15257
    UniProtKB/TrEMBL
    F6WIT2
    Related
    ENSP00000394338.3, ENST00000452489.6
    Conserved Domains (1) summary
    pfam03095
    Location:1 → 282
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  2. NM_001271832.2 → NP_001258761.1  serine/threonine-protein phosphatase 2A activator isoform f

    See identical proteins and their annotated locations for NP_001258761.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks two consecutive exons in the coding region, compared to variant 1. The resulting isoform (f) lacks an internal segment, compared to isoform a.
    Source sequence(s)
    AL158151
    Consensus CDS
    CCDS65156.1
    UniProtKB/Swiss-Prot
    Q15257
    Related
    ENSP00000349726.4, ENST00000357197.8
    Conserved Domains (1) summary
    pfam03095
    Location:26 → 288
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  3. NM_021131.5 → NP_066954.2  serine/threonine-protein phosphatase 2A activator isoform b

    See identical proteins and their annotated locations for NP_066954.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and lacks an in-frame segment of the coding region, compared to variant 1. Variants 2 and 3 encode a shorter protein (isoform b), also known as isoform alpha, that is missing an internal segment compared to isoform a.
    Source sequence(s)
    AL158151, BC002545, DB009663, X73478
    Consensus CDS
    CCDS6920.1
    UniProtKB/Swiss-Prot
    Q15257
    Related
    ENSP00000351885.4, ENST00000358994.8
    Conserved Domains (1) summary
    pfam03095
    Location:26 → 317
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  4. NM_178000.3 → NP_821067.1  serine/threonine-protein phosphatase 2A activator isoform b

    See identical proteins and their annotated locations for NP_821067.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks one of the coding exons compared to transcript variant 1. It maintains the reading frame and encodes a protein (isoform b), also known as isoform alpha, that is missing an internal segment of the protein compared to isoform a. Variants 2 and 3 encode the same isoform.
    Source sequence(s)
    AL158151
    Consensus CDS
    CCDS6920.1
    UniProtKB/Swiss-Prot
    Q15257
    Related
    ENSP00000377036.2, ENST00000393370.6
    Conserved Domains (1) summary
    pfam03095
    Location:26 → 317
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  5. NM_178001.3 → NP_821068.1  serine/threonine-protein phosphatase 2A activator isoform a

    See identical proteins and their annotated locations for NP_821068.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. It encodes the longest protein (isoform a), also known as isoform beta.
    Source sequence(s)
    AL158151
    UniProtKB/Swiss-Prot
    Q15257
    Related
    ENSP00000337448.1, ENST00000337738.5
    Conserved Domains (1) summary
    pfam03095
    Location:26 → 351
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  6. NM_178003.3 → NP_821070.1  serine/threonine-protein phosphatase 2A activator isoform d

    See identical proteins and their annotated locations for NP_821070.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter protein (isoform d), also known as isoform epsilon, that is missing an internal segment compared to isoform a.
    Source sequence(s)
    AL158151
    UniProtKB/Swiss-Prot
    Q15257
    Related
    ENSP00000347109.3, ENST00000355007.7
    Conserved Domains (1) summary
    pfam03095
    Location:26 → 275
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p13 Primary Assembly

    Range
    129110949..129148946
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011518836.2 → XP_011517138.1  serine/threonine-protein phosphatase 2A activator isoform X3

    Conserved Domains (1) summary
    pfam03095
    Location:76 → 326
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  2. XM_011518834.2 → XP_011517136.1  serine/threonine-protein phosphatase 2A activator isoform X1

    Conserved Domains (1) summary
    pfam03095
    Location:76 → 355
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  3. XM_011518838.2 → XP_011517140.1  serine/threonine-protein phosphatase 2A activator isoform X5

    Conserved Domains (1) summary
    pfam03095
    Location:76 → 337
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  4. XM_011518837.2 → XP_011517139.1  serine/threonine-protein phosphatase 2A activator isoform X4

    See identical proteins and their annotated locations for XP_011517139.1

    UniProtKB/TrEMBL
    B4DZF8
    Conserved Domains (1) summary
    pfam03095
    Location:26 → 333
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  5. XM_011518835.2 → XP_011517137.1  serine/threonine-protein phosphatase 2A activator isoform X2

    Conserved Domains (1) summary
    pfam03095
    Location:26 → 340
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  6. XM_017014888.2 → XP_016870377.1  serine/threonine-protein phosphatase 2A activator isoform X6

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_178002.1: Suppressed sequence

    Description
    NM_178002.1: This RefSeq was permanently suppressed because currently there is insufficient support for this transcript variant and PMID:10880964 indicates that the encoded isoform may not be functional.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q15257.3 GenPept UniProtKB/Swiss-Prot:Q15257

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