Format

Send to:

Choose Destination

Links from PubMed

    • Showing Current items.

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

    Gene ID: 7535, updated on 24-Jun-2016
    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 HPRD:01495; MIM:176947; Vega:OTTHUMG00000153060
    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; 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]
    Orthologs
    Location:
    2q12
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 2 NC_000002.12 (97712030..97744327)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (98330031..98356990)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1125 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

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      B Cell Receptor Signaling Pathway, organism-specific biosystemThe B cell receptor includes membrane ?? heavy chain molecules bound to a light chain and an Ig alpha (CD79A)/Ig beta (CD79B) heterodimer. Activation of the B cell receptor involves phosphorylation o...
    • Generation of second messenger molecules, organism-specific biosystem (from REACTOME)
      Generation of second messenger molecules, organism-specific biosystemIn addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have be...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Inflammatory Response Pathway, organism-specific biosystem (from WikiPathways)
      Inflammatory Response Pathway, organism-specific biosystem
      Inflammatory Response Pathway
    • Interferon type I, organism-specific biosystem (from WikiPathways)
      Interferon type I, organism-specific biosystemThe type I IFNs (IFN? family, IFN?, IFN?, IFN? and IFN?) all bind to and signal via the type I IFN receptor complex. The type I receptor consists of two main IFNAR1, IFNAR2c receptor chains and other...
    • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
      NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
    • NF-kappa B signaling pathway, conserved biosystem (from KEGG)
      NF-kappa B signaling pathway, conserved biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Primary immunodeficiency, organism-specific biosystem (from KEGG)
      Primary immunodeficiency, organism-specific biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
    • Primary immunodeficiency, conserved biosystem (from KEGG)
      Primary immunodeficiency, conserved biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
    • Prolactin Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Prolactin Signaling Pathway, organism-specific biosystemProlactin (PRL), a pleiotropic polypeptide hormone, mostly secreted by the lactotrophic cells of anterior pituitary gland and to a lesser extent expressed in numerous extra pituitary tissues such as ...
    • Ras signaling pathway, organism-specific biosystem (from KEGG)
      Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • TCR Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TCR Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
    • TCR signaling, organism-specific biosystem (from REACTOME)
      TCR signaling, organism-specific biosystemThe TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen p...
    • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
      TCR signaling in naive CD4+ T cells, organism-specific biosystem
      TCR signaling in naive CD4+ T cells
    • TCR signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
      TCR signaling in naive CD8+ T cells, organism-specific biosystem
      TCR signaling in naive CD8+ T cells
    • Translocation of ZAP-70 to Immunological synapse, organism-specific biosystem (from REACTOME)
      Translocation of ZAP-70 to Immunological synapse, organism-specific biosystemThe dual phosphorylated ITAMs recruit Syk kinase ZAP-70 via their tandem SH2 domains (step 4). ZAP-70 subsequently undergoes phosphorylation on multiple tyrosine residues for further activation. ZAP-...
    Products Interactant Other Gene Complex Source Pubs Description

    Homology

    Clone Names

    • FLJ17670, FLJ17679

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    non-membrane spanning protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    phosphotyrosine binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein tyrosine kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
     
    receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Process Evidence Code Pubs
    B cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    B cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    T cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    T cell aggregation TAS
    Traceable Author Statement
    more info
    PubMed 
    T cell differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    T cell migration TAS
    Traceable Author Statement
    more info
    PubMed 
    T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    adaptive immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    beta selection IEA
    Inferred from Electronic Annotation
    more info
     
    immune response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    intracellular signal transduction NAS
    Non-traceable Author Statement
    more info
    PubMed 
    macrophage activation involved in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    negative thymic T cell selection IEA
    Inferred from Electronic Annotation
    more info
     
    neutrophil activation involved in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    peptidyl-tyrosine autophosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    peptidyl-tyrosine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of B cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of alpha-beta T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of alpha-beta T cell proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of calcium-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of cell adhesion mediated by integrin IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of mast cell degranulation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive thymic T cell selection IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein phosphorylation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    regulation of platelet aggregation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    transmembrane receptor protein tyrosine kinase signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    T cell receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell-cell junction IEA
    Inferred from Electronic Annotation
    more info
     
    cytoplasm TAS
    Traceable Author Statement
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    extrinsic component of cytoplasmic side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    immunological synapse IEA
    Inferred from Electronic Annotation
    more info
     
    colocalizes_with membrane raft IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    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_997402.1

    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_001079.3NP_001070.2  tyrosine-protein kinase ZAP-70 isoform 1

      See identical proteins and their annotated locations for NP_001070.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      L05148
      Consensus CDS
      CCDS33254.1
      UniProtKB/Swiss-Prot
      P43403
      Related
      ENSP00000264972, OTTHUMP00000203013, ENST00000264972, OTTHUMT00000329278
      Conserved Domains (4) 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)
      pfam07714
      Location:338593
      Pkinase_Tyr; Protein tyrosine kinase
      cd05115
      Location:333601
      PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
    2. NM_207519.1NP_997402.1  tyrosine-protein kinase ZAP-70 isoform 2

      See identical proteins and their annotated locations for NP_997402.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as TZK) differs in the 5' UTR and lacks several exons in the 5' coding region, compared to variant 1. The resulting isoform (2, also known as truncated ZAP kinase) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AB083211, L05148
      Consensus CDS
      CCDS33255.1
      UniProtKB/Swiss-Prot
      P43403
      Related
      ENSP00000400475, OTTHUMP00000216626, ENST00000451498, OTTHUMT00000353475
      Conserved Domains (2) summary
      pfam07714
      Location:31286
      Pkinase_Tyr; Protein tyrosine kinase
      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 Annotation Release 108 details...

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p7 Primary Assembly

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

    mRNA and Protein(s)

    1. XM_017004869.1XP_016860358.1  

    2. XM_017004867.1XP_016860356.1  

    3. XM_017004868.1XP_016860357.1  

    4. XM_017004870.1XP_016860359.1  

    RNA

    1. XR_001738925.1 RNA Sequence

    2. XR_001738926.1 RNA Sequence

    3. XR_001738927.1 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018913.2 Alternate CHM1_1.1

      Range
      98334370..98360661
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)