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ZAP70 zeta-chain (TCR) associated protein kinase 70kDa [ Homo sapiens (human) ]

Gene ID: 7535, updated on 6-Jul-2014
Official Symbol
ZAP70provided by HGNC
Official Full Name
zeta-chain (TCR) associated protein kinase 70kDaprovided by HGNC
Primary source
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]
See ZAP70 in Epigenomics, MapViewer
Location:
2q12
Exon count :
15
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 2 NC_000002.12 (97713568..97739860)
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 transmembrane protein 131 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 36 Neighboring gene von Willebrand factor A domain containing 3B Neighboring gene ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide pseudogene 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Protein interactions

Protein Gene Interaction Pubs
Env, gp160, envelope glycoprotein 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
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
Gag, Pr55 gag Intracellular Gag localization is regulated by the presence of ZAP70 in lymphocytes PubMed
Nef, p27 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

Go to the HIV-1, Human Protein 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...
  • 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

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
 
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
 
Process Evidence Code Pubs
B cell activation TAS
Traceable Author Statement
more info
 
T cell activation TAS
Traceable Author Statement
more info
 
T cell aggregation TAS
Traceable Author Statement
more info
 
T cell differentiation NAS
Non-traceable Author Statement
more info
PubMed 
T cell migration TAS
Traceable Author Statement
more info
 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
adaptive immune response TAS
Traceable Author Statement
more info
 
beta selection IEA
Inferred from Electronic Annotation
more info
 
immune response IDA
Inferred from Direct Assay
more info
PubMed 
intracellular signal transduction NAS
Non-traceable Author Statement
more info
PubMed 
negative thymic T cell selection IEA
Inferred from Electronic Annotation
more info
 
peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
 
peptidyl-tyrosine phosphorylation IMP
Inferred from Mutant Phenotype
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 IEA
Inferred from Electronic Annotation
more info
 
positive regulation of calcium-mediated signaling IEA
Inferred from Electronic Annotation
more info
 
positive thymic T cell selection IDA
Inferred from Direct Assay
more info
PubMed 
protein autophosphorylation IEA
Inferred from Electronic Annotation
more info
 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein phosphorylation NAS
Non-traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
T cell receptor complex IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm TAS
Traceable Author Statement
more info
PubMed 
cytosol TAS
Traceable Author Statement
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
 
Preferred Names
tyrosine-protein kinase ZAP-70
Names
tyrosine-protein kinase ZAP-70
syk-related tyrosine kinase
70 kDa zeta-associated protein
70 kDa zeta-chain associated protein
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 

    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 proteins identical to 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
    cd05115
    Location:342598
    Blast Score: 1465
    PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
    cd09938
    Location:8111
    Blast Score: 549
    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
    Blast Score: 579
    SH2_C-SH2_Zap70; C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70)
    pfam07714
    Location:338593
    Blast Score: 942
    Pkinase_Tyr; Protein tyrosine kinase
  2. NM_207519.1NP_997402.1  tyrosine-protein kinase ZAP-70 isoform 2

    See proteins identical to 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
    Conserved Domains (2) summary
    cd05115
    Location:35291
    Blast Score: 1425
    PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
    pfam07714
    Location:31286
    Blast Score: 929
    Pkinase_Tyr; Protein tyrosine kinase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000002.12 

    Range
    97713568..97739860
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005264015.2XP_005264072.1  

    Conserved Domains (4) summary
    cd05115
    Location:336592
    Blast Score: 1463
    PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
    cd09938
    Location:8111
    Blast Score: 549
    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
    Blast Score: 579
    SH2_C-SH2_Zap70; C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70)
    pfam07714
    Location:332587
    Blast Score: 941
    Pkinase_Tyr; Protein tyrosine kinase
  2. XM_006712728.1XP_006712791.1  

    Conserved Domains (4) summary
    cd09938
    Location:8111
    Blast Score: 548
    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
    Blast Score: 581
    SH2_C-SH2_Zap70; C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70)
    pfam07714
    Location:338581
    Blast Score: 920
    Pkinase_Tyr; Protein tyrosine kinase
    cl09925
    Location:342578
    Blast Score: 1357
    PKc_like; Protein Kinases, catalytic domain
  3. XM_006712729.1XP_006712792.1  

    See proteins identical to XP_006712792.1

    UniProtKB/Swiss-Prot
    P43403
    Conserved Domains (2) summary
    cd05115
    Location:35291
    Blast Score: 1425
    PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
    pfam07714
    Location:31286
    Blast Score: 929
    Pkinase_Tyr; Protein tyrosine kinase

Alternate HuRef

Genomic

  1. AC_000134.1 

    Range
    92095689..92121947
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018913.2 

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

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