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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
    mouse all
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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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    NEW Try the new Transcript table

    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

    Gene LinkOut

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