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    ZAP70 zeta chain of T cell receptor associated protein kinase 70 [ Homo sapiens (human) ]

    Gene ID: 7535, updated on 6-Sep-2021

    Summary

    Official Symbol
    ZAP70provided by HGNC
    Official Full Name
    zeta chain of T cell receptor associated protein kinase 70provided by HGNC
    Primary source
    HGNC:HGNC:12858
    See related
    Ensembl:ENSG00000115085 MIM:176947
    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
    SRK; STD; TZK; STCD; IMD48; ADMIO2; ZAP-70
    Summary
    This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in lymph node (RPKM 11.2), spleen (RPKM 7.9) and 11 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See ZAP70 in Genome Data Viewer
    Location:
    2q11.2
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (97712030..97744327)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (98330039..98356323)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene actin related protein 1B Neighboring gene chromosome 2 open reading frame 92 Neighboring gene RNA, U4 small nuclear 8, pseudogene Neighboring gene uncharacterized LOC107985921 Neighboring gene transmembrane protein 131 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 36

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Binding of HIV-1 gp120 to CD4 induces p56lck activation and zeta-chain (TCR) associated protein kinase 70kDa desensitization independent of TCR tyrosine phosphorylation PubMed
    env Lck is recuited to a virological synapse (VS) interface and is highly colocalized with gp120 when cells interact with gp120+ICAM-1 bilayers, leading to activation of ZAP70, LAT, SLP76, and PLCgamma PubMed
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 alone or CD4/gp160 cross-linking induces tyrosine phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also leads to ras activation PubMed
    Nef nef Diaminoquinoxaline benzenesulfonamide (DQBS) treatment reduces the amount of both HCK and the p85 regulatory subunit of PI3K associated with HIV-1 Nef and completely blocks Nef-dependent activation of ZAP-70 PubMed
    nef HIV-1 Nef inhibits colocalization of activated ZAP70 with SLP76 in microclusters (MCs) PubMed
    nef Nef/Hck complex recruits and phosphorylates the tyrosine kinase ZAP-70, which binds class I PI3K to trigger MHC-I downregulation in primary CD4+ T cells PubMed
    Pr55(Gag) gag Intracellular Gag localization is regulated by the presence of ZAP70 in lymphocytes PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Homology

    Clone Names

    • FLJ17670, FLJ17679

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in B cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in T cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in T cell aggregation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in T cell differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in T cell migration TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in adaptive immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in beta selection IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in immune response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in intracellular signal transduction NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative thymic T cell selection IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within peptidyl-tyrosine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of alpha-beta T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of alpha-beta T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of calcium-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within positive thymic T cell selection IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein autophosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein phosphorylation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in transmembrane receptor protein tyrosine kinase signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of T cell receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cell-cell junction IEA
    Inferred from Electronic Annotation
    more info
     
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    is_active_in extrinsic component of cytoplasmic side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in immunological synapse IEA
    Inferred from Electronic Annotation
    more info
     
    colocalizes_with membrane raft IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    tyrosine-protein kinase ZAP-70
    Names
    70 kDa zeta-associated protein
    70 kDa zeta-chain associated protein
    syk-related tyrosine kinase
    zeta chain of T cell receptor associated protein kinase 70kDa
    zeta-chain (TCR) associated protein kinase 70kDa
    zeta-chain associated protein kinase, 70kD
    NP_001070.2
    NP_001365523.1
    NP_997402.1
    XP_016860356.1
    XP_016860357.1
    XP_016860358.1
    XP_016860359.1

    NCBI Reference Sequences (RefSeq)

    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_007727.1 RefSeqGene

      Range
      5001..31293
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_126

    mRNA and Protein(s)

    1. NM_001079.4NP_001070.2  tyrosine-protein kinase ZAP-70 isoform 1

      See identical proteins and their annotated locations for NP_001070.2

      Status: REVIEWED

      Source sequence(s)
      AC016699, AC017099
      Consensus CDS
      CCDS33254.1
      UniProtKB/Swiss-Prot
      P43403
      Related
      ENSP00000264972.5, ENST00000264972.10
      Conserved Domains (3) summary
      cd09938
      Location:8111
      SH2_N-SH2_Zap70_Syk_like; N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins
      cd10402
      Location:152255
      SH2_C-SH2_Zap70; C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70)
      cd05115
      Location:333601
      PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
    2. NM_001378594.1NP_001365523.1  tyrosine-protein kinase ZAP-70 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016699, AC017099
      Conserved Domains (3) summary
      cd09938
      Location:8111
      SH2_N-SH2_Zap70_Syk_like; N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins
      cd10402
      Location:152255
      SH2_C-SH2_Zap70; C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70)
      cd05115
      Location:333601
      PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
    3. NM_207519.2NP_997402.1  tyrosine-protein kinase ZAP-70 isoform 2

      See identical proteins and their annotated locations for NP_997402.1

      Status: REVIEWED

      Source sequence(s)
      AC016699
      Consensus CDS
      CCDS33255.1
      UniProtKB/Swiss-Prot
      P43403
      Related
      ENSP00000400475.2, ENST00000451498.2
      Conserved Domains (1) summary
      cd05115
      Location:26294
      PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

      Range
      97712030..97744327
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017004869.1XP_016860358.1  tyrosine-protein kinase ZAP-70 isoform X3

    2. XM_017004867.1XP_016860356.1  tyrosine-protein kinase ZAP-70 isoform X1

    3. XM_017004868.1XP_016860357.1  tyrosine-protein kinase ZAP-70 isoform X2

    4. XM_017004870.1XP_016860359.1  tyrosine-protein kinase ZAP-70 isoform X4

    RNA

    1. XR_001738925.1 RNA Sequence

    2. XR_001738926.1 RNA Sequence

    3. XR_001738927.1 RNA Sequence

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