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    PTPN4 protein tyrosine phosphatase non-receptor type 4 [ Homo sapiens (human) ]

    Gene ID: 5775, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PTPN4provided by HGNC
    Official Full Name
    protein tyrosine phosphatase non-receptor type 4provided by HGNC
    Primary source
    HGNC:HGNC:9656
    See related
    Ensembl:ENSG00000088179 MIM:176878; AllianceGenome:HGNC:9656
    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
    MEG; PTPMEG; PTPMEG1
    Summary
    The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 7.2), brain (RPKM 5.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PTPN4 in Genome Data Viewer
    Location:
    2q14.2
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (119759922..119984899)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (120193967..120419641)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (120517498..120742475)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:120457784-120458983 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:120459450-120460055 Neighboring gene transmembrane protein 177 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:120460663-120461267 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:120472887-120473388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:120473389-120473888 Neighboring gene ribosomal protein L17 pseudogene 15 Neighboring gene uncharacterized LOC101927764 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11912 Neighboring gene Sharpr-MPRA regulatory region 5959 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:120517730-120518354 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16454 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11914 Neighboring gene MPRA-validated peak3834 silencer Neighboring gene small nucleolar RNA U13 Neighboring gene Sharpr-MPRA regulatory region 12882 Neighboring gene uncharacterized LOC107985817 Neighboring gene ribosomal protein L27 pseudogene 7

    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. Identification, cloning, and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1. Gu MX, et al. Proc Natl Acad Sci U S A, 1991 Jul 1. PMID 1648233, Free PMC Article
    2. The effect of overexpression of the protein tyrosine phosphatase PTPMEG on cell growth and on colony formation in soft agar in COS-7 cells. Gu M, et al. Proc Natl Acad Sci U S A, 1996 Nov 12. PMID 8917530, Free PMC Article
    3. Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein. Lee HS, et al. J Microbiol, 2022 Apr. PMID 35089587
    4. Regulation of the Human Phosphatase PTPN4 by the inter-domain linker connecting the PDZ and the phosphatase domains. Caillet-Saguy C, et al. Sci Rep, 2017 Aug 11. PMID 28801650, Free PMC Article
    5. Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma. Xiao X, et al. Comput Biol Chem, 2017 Feb. PMID 27923202

    See all (40) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LncRNA SH3BP5-AS1 promotes hepatocellular carcinoma progression by sponging miR-6838-5p and activation of PTPN4.
      Title: LncRNA SH3BP5-AS1 promotes hepatocellular carcinoma progression by sponging miR-6838-5p and activation of PTPN4.
    2. circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood-brain barrier integrity and cognitive function in uremic encephalopathy.
      Title: circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood-brain barrier integrity and cognitive function in uremic encephalopathy.
    3. E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.
      Title: E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.
    4. MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis.
      Title: MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis.
    5. Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein.
      Title: Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein.
    6. Study identified a nonsense mutation of PTPN4 with mutation ratio of 90.90% from 1 case of rectal cancer. Overexpression of PTPN4 suppressed the growth of colorectal cancer cells. PTPN4 dephosphorylates pSTAT3 at the Tyr705 residue with a direct interaction and depresses the transcriptional activity of STAT3.
      Title: Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer.
    7. Data show that mutations affect the regulation of the protein tyrosine phosphatase non-receptor type 4 (PTPN4) bidomain and indicate that the PDZ-PDZ ligand regulation of PTPN4 is a linker-mediated mechanism.
      Title: Regulation of the Human Phosphatase PTPN4 by the inter-domain linker connecting the PDZ and the phosphatase domains.
    8. Binding assays confirmed that three (Cyto8-mtxd-1, Cyto8-mtxk-4 and Cyto8-mtxd-1k-4) out of the five designed peptides exhibit moderately or considerably increased affinity as compared to the native peptide Cyto8-RETEV
      Title: Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma.
    9. the p38gamma.PTPN4 interaction promotes cellular signaling, preventing cell death induction.
      Title: Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ.
    10. Deletion of PTPN4 has been reported in monozygotic twins with a Rett syndrome-like phenotype.
      Title: Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    • FLJ21893

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytoskeletal protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables glutamate receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXY142 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables non-membrane spanning protein tyrosine phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein tyrosine phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein tyrosine phosphatase activity, metal-dependent IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein dephosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasmic side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasmic side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoskeleton IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    tyrosine-protein phosphatase non-receptor type 4
    Names
    PTPase-MEG1
    megakaryocyte phosphatase
    megakaryocyte protein-tyrosine phosphatase
    protein tyrosine phosphatase MEG1
    protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte)
    NP_002821.1

    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.

    mRNA and Protein(s)

    1. NM_002830.4 → NP_002821.1  tyrosine-protein phosphatase non-receptor type 4

      See identical proteins and their annotated locations for NP_002821.1

      Status: REVIEWED

      Source sequence(s)
      AC016691, BC010674, M68941
      Consensus CDS
      CCDS2129.1
      UniProtKB/Swiss-Prot
      B2RBV8, P29074, Q9UDA7
      Related
      ENSP00000263708.2, ENST00000263708.7
      Conserved Domains (5) summary
      smart00295
      Location:30 → 222
      B41; Band 4.1 homologues
      cd00047
      Location:682 → 909
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
      cd00992
      Location:515 → 602
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      cd13189
      Location:216 → 310
      FERM_C_PTPN4_PTPN3_like; FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 3 and 4 (PTPN4 and PTPN3)
      pfam08736
      Location:325 → 365
      FA; FERM adjacent (FA)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      119759922..119984899
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      120193967..120419641
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P29074.1 GenPept UniProtKB/Swiss-Prot:P29074

    Gene LinkOut

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