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

Gene ID: 5524, updated on 3-Apr-2024

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; AllianceGenome:HGNC:9308
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; PARK25; 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
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Genomic context

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Location:
9q34.11
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (129110950..129148946)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (141314397..141352390)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (131873229..131911225)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20359 Neighboring gene dolichyldiphosphatase 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:131864095-131864840 Neighboring gene carnitine O-acetyltransferase Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20360 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:131873890-131874430 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131889125-131890047 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131893809-131894363 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:131895457-131895957 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131900767-131901394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29104 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131902025-131902652 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131902653-131903282 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29107 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131905799-131906426 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131907685-131908314 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29108 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:131910837-131911337 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131929576-131930565 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20363 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131937384-131938105 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20365 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20366 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20367 Neighboring gene Sharpr-MPRA regulatory region 13939 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131941425-131942348 Neighboring gene uncharacterized LOC105376289 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. PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability. Fevga C, et al. Brain, 2023 Apr 19. PMID 36073231, Free PMC Article
  2. A new paradigm for regulation of protein phosphatase 2A function via Src and Fyn kinase-mediated tyrosine phosphorylation. Sontag JM, et al. J Biol Chem, 2022 Aug. PMID 35820485, Free PMC Article
  3. Protein Phosphatase 2A (PP2A) mutations in brain function, development, and neurologic disease. Verbinnen I, et al. Biochem Soc Trans, 2021 Aug 27. PMID 34241636
  4. PP2A and E3 ubiquitin ligase deficiencies: Seminal biological drivers in endometrial cancer. Gonzalez-Bosquet J, et al. Gynecol Oncol, 2021 Jul. PMID 33867147
  5. PP2A-C may be a promising candidate for postmortem interval estimation. Wang J, et al. Int J Legal Med, 2021 May. PMID 33409557

See all (255) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PR55alpha-controlled protein phosphatase 2A inhibits p16 expression and blocks cellular senescence induction by gamma-irradiation.
    Title: PR55α-controlled protein phosphatase 2A inhibits p16 expression and blocks cellular senescence induction by γ-irradiation.
  2. PP2A inhibitor SET promotes mTORC1 and Bmi1 signaling through Akt activation and maintains the colony-formation ability of cancer cells.
    Title: PP2A inhibitor SET promotes mTORC1 and Bmi1 signaling through Akt activation and maintains the colony-formation ability of cancer cells.
  3. PP2A drives the stemness in colorectal cancer cells by decreasing the Hippo signaling pathway.
    Title: PP2A drives the stemness in colorectal cancer cells by decreasing the Hippo signaling pathway.
  4. PP2A inhibition causes synthetic lethality in BRCA2-mutated prostate cancer models via spindle assembly checkpoint reactivation.
    Title: PP2A inhibition causes synthetic lethality in BRCA2-mutated prostate cancer models via spindle assembly checkpoint reactivation.
  5. PTPA variants are rare in early-onset and familial Parkinson's disease.
    Title: PTPA variants are rare in early-onset and familial Parkinson's disease.
  6. Regulation and role of the PP2A-B56 holoenzyme family in cancer.
    Title: Regulation and role of the PP2A-B56 holoenzyme family in cancer.
  7. Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.
    Title: Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.
  8. Protein phosphatase 2A propels follicular T helper cell development in lupus.
    Title: Protein phosphatase 2A propels follicular T helper cell development in lupus.
  9. Cross-Ethnic Variant Screening and Burden Analysis of PTPA in Parkinson's Disease.
    Title: Cross-Ethnic Variant Screening and Burden Analysis of PTPA in Parkinson's Disease.
  10. PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.
    Title: PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.
Submit: New GeneRIF Correction See all GeneRIFs (150)

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
Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development
MedGen: CN372710 OMIM: 620482 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia.
EBI GWAS Catalog

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
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables peptidyl-prolyl cis-trans isomerase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
contributes_to phosphoprotein phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein phosphatase 2A binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein phosphatase regulator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein phosphatase regulator activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein tyrosine phosphatase activator activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein tyrosine phosphatase activator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables signaling receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in mitotic spindle organization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of phosphoprotein phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of protein dephosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of phosphoprotein phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of protein dephosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of phosphoprotein phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of ATPase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of calcium channel complex IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
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 
part_of protein phosphatase type 2A complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of 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_011517138.1
XP_011517140.1
XP_047279515.1
XP_047279516.1
XP_054219193.1
XP_054219194.1
XP_054219195.1
XP_054219196.1
XP_054219197.1

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_029370.2 RefSeqGene

    Range
    5467..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/TrEMBL
    A6PVN5, 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/TrEMBL
    A6PVN5
    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/TrEMBL
    A6PVN5
    Related
    ENSP00000351885.5, ENST00000358994.9
    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/TrEMBL
    A6PVN5
    Related
    ENSP00000377036.2, ENST00000393370.7
    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
    A2A347, A9IZU4, B4DXM4, Q15257, Q15258, Q53GZ3, Q5TZQ2, Q9BUK1, Q9NNZ7, Q9NNZ8, Q9NNZ9
    UniProtKB/TrEMBL
    A6PVN5
    Related
    ENSP00000337448.1, ENST00000337738.6
    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/TrEMBL
    A6PVN5
    Related
    ENSP00000347109.3, ENST00000355007.7
    Conserved Domains (1) summary
    pfam03095
    Location:26 → 275
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

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

  1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

    Range
    129110950..129148946
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047423560.1 → XP_047279516.1  serine/threonine-protein phosphatase 2A activator isoform X4

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

    UniProtKB/TrEMBL
    A6PVN5
    Conserved Domains (1) summary
    pfam03095
    Location:76 → 337
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  3. XM_047423559.1 → XP_047279515.1  serine/threonine-protein phosphatase 2A activator isoform X1

  4. XM_011518834.3 → XP_011517136.1  serine/threonine-protein phosphatase 2A activator isoform X2

    UniProtKB/TrEMBL
    B4DLX5
    Conserved Domains (1) summary
    pfam03095
    Location:76 → 355
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

  5. XM_011518836.3 → XP_011517138.1  serine/threonine-protein phosphatase 2A activator isoform X3

    UniProtKB/TrEMBL
    B4DLX5
    Conserved Domains (1) summary
    pfam03095
    Location:76 → 326
    PTPA; Phosphotyrosyl phosphate activator (PTPA) protein

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    141314397..141352390
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054363221.1 → XP_054219196.1  serine/threonine-protein phosphatase 2A activator isoform X4

  2. XM_054363222.1 → XP_054219197.1  serine/threonine-protein phosphatase 2A activator isoform X5

  3. XM_054363218.1 → XP_054219193.1  serine/threonine-protein phosphatase 2A activator isoform X6

  4. XM_054363219.1 → XP_054219194.1  serine/threonine-protein phosphatase 2A activator isoform X7

  5. XM_054363220.1 → XP_054219195.1  serine/threonine-protein phosphatase 2A activator isoform X8

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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