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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

ZAP70 Gene

protein-coding   GIFtS: 75
GCID: GC02P098331

Zeta-Chain (TCR) Associated Protein Kinase 70kDa

(Previous name: zeta-chain (TCR) associated protein kinase (70 kD))
(Previous symbol: SRK)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Zeta-Chain (TCR) Associated Protein Kinase 70kDa1 2     70 KDa Zeta-Associated Protein2
SRK1 2 3 5     STCD2
Syk-Related Tyrosine Kinase2 3     TZK2
70 KDa Zeta-Chain Associated Protein2 3     ZAP-702
EC 2.7.10.23 8     Tyrosine-Protein Kinase ZAP-702
STD2 5     Zeta-Chain Associated Protein Kinase, 70kD2
Zeta-Chain (TCR) Associated Protein Kinase (70 KD)1     EC 2.7.108

External Ids:    HGNC: 128581   Entrez Gene: 75352   Ensembl: ENSG000001150857   OMIM: 1769475   UniProtKB: P434033   

Export aliases for ZAP70 gene to outside databases

Previous GC identifers: GC02P096211 GC02P096782 GC02P097934 GC02P097951 GC02P097788 GC02P097696 GC02P092095


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for ZAP70 Gene:
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)

GeneCards Summary for ZAP70 Gene: 
ZAP70 (zeta-chain (TCR) associated protein kinase 70kDa) is a protein-coding gene. Diseases associated with ZAP70 include zap-70 deficiency, and cll/sll, and among its related super-pathways are Immune response Role of DAP12 receptors in NK cells and T cell receptor signaling pathway. GO annotations related to this gene include phosphotyrosine binding and protein tyrosine kinase activity. An important paralog of this gene is SYK.

UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403
Function: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates
motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also
to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell
receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR
component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the
stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further
stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter
proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to
lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton
modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC.
ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3
ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation
switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70
promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are
still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary
B-cells formation and activation through B-cell receptor (BCR)

Gene Wiki entry for ZAP70 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000002.11  NT_022171.15  NC_018913.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the ZAP70 gene promoter:
         GR   STAT1   AP-1   STAT3   GR-alpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidZAP70 promoter sequence
   Search SABiosciences Chromatin IP Primers for ZAP70

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ZAP70


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q12   Ensembl cytogenetic band:  2q11.2   HGNC cytogenetic band: 2q11-q13

ZAP70 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ZAP70 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02P098331:  view genomic region     (about GC identifiers)

Start:
98,330,023 bp from pter      End:
98,356,325 bp from pter
Size:
26,303 bases      Orientation:
plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403 (See protein sequence)
Recommended Name: Tyrosine-protein kinase ZAP-70  
Size: 619 amino acids; 69872 Da
Subunit: Interacts with NFAM1. Interacts with adapter proteins SLA and SLA2; these interactions negatively
regulates T-cell receptor signaling. Interacts with CBLB (By similarity). Interacts with DEF6. Interacts (via SH2
domains) with RHOH; this interaction regulates ZAP70 subcellular localization (By similarity). Interacts with
FCRL3. Interacts with VAV1. Interacts with CD247/CD3Z; this interaction docks ZAP70 at the stimulated TCR.
Interacts with CBL; this interaction promotes ubiquitination, internalization and subsequent degradation of
CD247/CD3Z. Identified in a complex with CBL and UBE2L3
Subcellular location: Cytoplasm. Cell membrane; Peripheral membrane protein. Note=In quiescent T-lymphocytes, it
is cytoplasmic. Upon TCR activation, it is recruited at the plasma membrane by interacting with CD247/CD3Z.
Co-localizes together with RHOH in the immunological synapse. RHOH is required for its proper localization to the
cell membrane and cytoskeleton fractions in the thymocytes (By similarity)
6/10 PDB 3D structures from and Proteopedia for ZAP70 (see all 10):
1FBV (3D)        1M61 (3D)        1U59 (3D)        2CBL (3D)        2OQ1 (3D)        2OZO (3D)    
Secondary accessions: A6NFP4 Q6PIA4 Q8IXD6 Q9UBS6
Alternative splicing: 3 isoforms:  P43403-1   P43403-2   P43403-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ZAP70: NX_P43403

Explore proteomics data for ZAP70 at MOPED 

Post-translational modifications:

  • UniProtKB: Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Phosphorylation of Tyr-315 and
    Tyr-319 are essential for ZAP70 positive function on T-lymphocyte activation whereas Tyr-292 has a negative
    regulatory role. Within the C-terminal kinase domain, Tyr-492 and Tyr-493 are phosphorylated after TCR induction,
    Tyr-492 playing a negative regulatory role and Tyr-493 a positive. Tyr-493 is dephosphorylated by PTN22
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P43403

  • 4/12 DME Specific Peptides for ZAP70 (P43403) (see all 12)
     FVHRDLA  AARNVLL  RDLAARN  SYGQKPY 

    ZAP70 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    ZAP70 Protein Expression
    REFSEQ proteins (2 alternative transcripts): 
    NP_001070.2  NP_997402.1  

    ENSEMBL proteins: 
     ENSP00000264972   ENSP00000400475   ENSP00000411141  
    Reactome Protein details: P43403
    Human Recombinant Protein Products for ZAP70: 
    EMD Millipore Purified and/or Recombinant ZAP70 Protein
    R&D Systems Recombinant & Natural Proteins for ZAP70
    Enzo Life Sciences proteins for ZAP70
    OriGene Purified Protein for ZAP70
    OriGene Protein Over-expression Lysate for ZAP70
    OriGene MassSpec for ZAP70 
    OriGene Custom Protein Services for ZAP70
    GenScript Custom Purified and Recombinant Proteins Services for ZAP70
    Novus Biologicals ZAP70 Proteins
    Novus Biologicals ZAP70 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001772immunological synapse IEA--
    GO:0005737cytoplasm TAS12359715
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane TAS--
    GO:0042101T cell receptor complex IDA8176201

    ZAP70 for ontologies           About GeneDecksing



    ZAP70 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of ZAP70
    R&D Systems Antibodies for ZAP70
    Cell Signaling Technology (CST) Antibodies for ZAP70 
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    Novus Biologicals ZAP70 Antibodies
    Abcam antibodies for ZAP70
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    ThermoFisher Antibody for ZAP70
    LSBio Antibodies in human, mouse, rat for ZAP70 

    Assay Products for ZAP70: 
    EMD Millipore Kits and Assays for the Analysis of ZAP70
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    GenScript ZAP70-Activity-based Kinase Assay for Compound Screening
    Cell Signaling Technology (CST) Sandwich ELISA Kits for ZAP70
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp. 
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    SH2D: SH2 domain containing

    IUPHAR Guide to PHARMACOLOGY protein family classification: zeta-chain (TCR) associated protein kinase 70kDa 
    Syk family

    5/9 InterPro protein domains (see all 9):
     IPR012234 Tyr_kinase_non-rcpt_SYK/ZAP70
     IPR017441 Protein_kinase_ATP_BS
     IPR001245 Ser-Thr/Tyr_kinase_cat_dom
     IPR011009 Kinase-like_dom
     IPR000980 SH2

    Graphical View of Domain Structure for InterPro Entry P43403

    ProtoNet protein and cluster: P43403

    2 Blocks protein domains:
    IPB000980 SH2 domain signature
    IPB008266 Tyrosine protein kinase


    UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403
    Domain: Composed of 2 N-terminal SH2 domains and a C-terminal kinase domain. The tandem SH2 domains bind to the
    doubly phosphorylated tyrosine-based activation motif (ITAM) of CD247/CD3Z and the non-canonical phosphorylated
    tyrosine-based activation motif (TAM) of RHOH (By similarity). The interdomain B located between the second SH2
    and the kinase domain contains 3 tyrosines (Tyr-292, Tyr-315, Tyr-319) that are phosphorylated following TCR
    activation. These sites have been implicated in binding to other signaling molecules including CBL or VAV1. Thus,
    ZAP70 can also function as a scaffold by recruiting additional factors to the stimulated TCR complex
    Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily
    Similarity: Contains 1 protein kinase domain
    Similarity: Contains 2 SH2 domains


    ZAP70 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ZAP70_HUMAN, P43403
    Function: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates
    motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also
    to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell
    receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR
    component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the
    stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further
    stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter
    proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to
    lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton
    modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC.
    ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3
    ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation
    switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70
    promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are
    still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary
    B-cells formation and activation through B-cell receptor (BCR)
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
    Enzyme regulation: Activated by phosphorylation at Tyr-493 in the activation loop. Inhibited by staurosporine

         Genatlas biochemistry entry for ZAP70:
    CD3 zeta associated tyrosine kinase,SYK (non SRC) family,expressed in T and NK cells,involved in signal
    transduction

         Enzyme Numbers (IUBMB): EC 2.7.10.21 2 EC 2.7.102

         Gene Ontology (GO): 5/7 molecular function terms (GO ID links to tree view) (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001784phosphotyrosine binding IEA--
    GO:0004672protein kinase activity ----
    GO:0004713protein tyrosine kinase activity TAS--
    GO:0004715non-membrane spanning protein tyrosine kinase activity TAS--
    GO:0005515protein binding IPI10318843
         
    ZAP70 for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for ZAP70:
     Decreased mitotic index  Gemcitabine induced cell-death  Increased resistance to Trastu 

         7 MGI mutant phenotypes (inferred from 12 alleles(MGI details for Zap70):
     cellular  hematopoietic system  immune system  integument  normal 
     respiratory system  skeleton 

    ZAP70 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for ZAP70: Zap70tm1Dlo Zap70tm1Weis

       inGenious Targeting Laboratory - Custom generated mouse model solutions for ZAP70 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for ZAP70

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ZAP70 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ZAP70 

    miRNA
    Products:
        
    miRTarBase miRNAs that target ZAP70:
    hsa-mir-34a (MIRT005760), hsa-mir-34c-5p (MIRT005762), hsa-mir-34b (MIRT005761)

    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ZAP70
    Search QIAGEN for miScript miRNA Assays for microRNAs that regulate ZAP70
    SwitchGear 3'UTR luciferase reporter plasmidZAP70 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for ZAP70
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat ZAP70

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ZAP70
    Sirion Biotech Customized adenovirus for overexpression of ZAP70

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for ZAP70 (see all 12)
    OriGene ORF clones in mouse, rat for ZAP70
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): ZAP70 (NM_001079)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ZAP70
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                         Customized lentivirus expression plasmids for stable overexpression of ZAP70 

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ZAP70


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for ZAP70 About   (see all 33)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Immune response Fc epsilon RI pathway
    Immune response Role of DAP12 receptors in NK cells0.32
    Natural killer cell mediated cytotoxicity0.31
    Immune response CD16 signaling in NK cells0.32
    2B cell receptor signaling pathway
    T cell receptor signaling pathway0.38
    TCR Signaling Pathway0.35
    3PKC-Theta Pathway
    TCR Signaling0.68
    ITK and TCR Signaling0.54
    PKC-Theta Pathway0.68
    4Translocation of ZAP-70 to Immunological synapse
    Translocation of ZAP-70 to Immunological synapse0.85
    Generation of second messenger molecules0.64
    5ICos-ICosL Pathway in T-Helper Cell
    ICos-ICosL Pathway in T-Helper Cell0.66
    CD28 Signaling in T-Helper Cell0.66

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5/12 EMD Millipore Pathways for ZAP70 (see all 12)
        Immune response CD16 signaling in NK cells
    Immune response Role of DAP12 receptors in NK cells
    Signal transduction IP3 signaling
    Immune response NFAT in immune response
    Immune response CD28 signaling

    5/13 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for ZAP70 (see all 13)
        ICos-ICosL Pathway in T-Helper Cell
    Rap1 Pathway
    CD28 Signaling in T-Helper Cell
    NF-KappaB Family Pathway
    CTLA4 Signaling

    2 Cell Signaling Technology (CST) Pathways for ZAP70
        Lymphocyte Signaling
    Tyrosine Kinases / Adaptors

    5/12 GeneGo (Thomson Reuters) Pathways for ZAP70 (see all 12)
        G-protein signaling Regulation of RAC1 activity
    Immune response CD28 signaling
    Immune response CD16 signaling in NK cells
    G-protein signaling N-RAS regulation pathway
    Immune response NFAT in immune response

    5/6 BioSystems Pathways for ZAP70 (see all 6)
        TCR Signaling Pathway
    B Cell Receptor Signaling Pathway
    Prolactin Signaling Pathway
    TCR signaling in naive CD4+ T cells
    TCR signaling in naive CD8+ T cells

    5        Reactome Pathways for ZAP70
        Translocation of ZAP-70 to Immunological synapse
    Adaptive Immune System
    TCR signaling
    Generation of second messenger molecules
    Immune System


    4         Kegg Pathways  (Kegg details for ZAP70):
        NF-kappa B signaling pathway
    Natural killer cell mediated cytotoxicity
    T cell receptor signaling pathway
    Primary immunodeficiency


    ZAP70 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for ZAP70

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/128 Interacting proteins for ZAP70 (P434031, 2, 3 ENSP000002649724) via UniProtKB, MINT, STRING, and/or I2D (see all 128)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CD247P209632, 3, ENSP000003547824MINT-8027153 MINT-8033018 MINT-8036100 MINT-8036025 MINT-8027168 MINT-8036085 MINT-8036010 MINT-8031499 MINT-8034584 MINT-8034599 MINT-8031468 MINT-8032988 MINT-8033003 MINT-8036055 MINT-8031453 MINT-8034614 MINT-8032973 MINT-8033033 MINT-8032943 MINT-8036070 MINT-8032958 MINT-8036040 I2D: score=5 STRING: ENSP00000354782
    CD3EP077662, 3, ENSP000003545664MINT-8031576 MINT-8031519 MINT-8035855 I2D: score=4 STRING: ENSP00000354566
    LCKP062392, 3, ENSP000003378254MINT-8038418 MINT-59476 I2D: score=7 STRING: ENSP00000337825
    CRKP461082, 3, ENSP000003005744MINT-8035366 I2D: score=7 STRING: ENSP00000300574
    VAV1P154982, 3, ENSP000003022694MINT-8035351 I2D: score=4 STRING: ENSP00000302269
    About this table

    Gene Ontology (GO): 5/21 biological process terms (GO ID links to tree view) (see all 21):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002250adaptive immune response TAS--
    GO:0006468protein phosphorylation NAS1423621
    GO:0006955immune response IDA1423621
    GO:0007243intracellular protein kinase cascade NAS1423621
    GO:0018108peptidyl-tyrosine phosphorylation IDA--

    ZAP70 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    ZAP70 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for ZAP70

    2 HMDB Compounds for ZAP70    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    1 DrugBank Compound for ZAP70    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Staurosporine-- 62996-74-1target--17139284 17016423

    10/38 Novoseek inferred chemical compound relationships for ZAP70 gene (see all 38)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 84.3 489 11744042 (8), 8530437 (5), 7760813 (5), 7642520 (5) (see all 99)
    fludarabine 68.3 6 17051411 (2), 18587576 (1), 16284990 (1), 17283363 (1) (see all 5)
    phosphotyrosine 63.4 8 8196616 (1), 12356870 (1), 7822334 (1), 8520027 (1) (see all 7)
    piceatannol 49.6 3 17250586 (1), 9723676 (1)
    rituximab 48.9 1 16284990 (1)
    thiosemicarbazide 31.7 2 10779765 (1), 10979964 (1)
    calcium 30.5 19 10748099 (1), 19018007 (1), 8096851 (1), 11588032 (1) (see all 18)
    phosphatidylinositol 29.1 7 15100278 (2), 8096851 (1), 9195899 (1), 11418612 (1) (see all 6)
    okt3 23.8 3 10576607 (1), 16219325 (1), 18548611 (1)
    phenylalanine 20 6 10779765 (1), 10318843 (1), 11046020 (1), 15100278 (1) (see all 6)

    Search CenterWatch for drugs/clinical trials and news about ZAP70

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for ZAP70 gene (2 alternative transcripts): 
    NM_001079.3  NM_207519.1  

    Unigene Cluster for ZAP70:

    Zeta-chain (TCR) associated protein kinase 70kDa
    Hs.234569  [show with all ESTs]
    Unigene Representative Sequence: BC053878
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000264972(uc002syd.1) ENST00000483781 ENST00000463643(uc002sye.1)
    ENST00000498836 ENST00000487283(uc010yvf.1 uc002syf.1) ENST00000451498
    ENST00000495754 ENST00000489250 ENST00000442208
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    Additional mRNA sequence: 

    AB083211.1 AK303341.1 AK310637.1 BC039039.1 BC053878.1 L05148.1 

    8 DOTS entries:

    DT.302578  DT.100019754  DT.100019752  DT.95142057  DT.100019753  DT.100750057  DT.100727964  DT.97782684 

    24/54 AceView cDNA sequences (see all 54):

    NM_207519 BC039039 L05148 NM_001079 BQ054223 BE254072 BX092836 AI382267 
    BM916976 BC053878 AJ346204 AI473901 BQ051966 AB083211 AL832287 AA353108 
    AW590195 BX421713 AW136108 AJ573211 BM917637 BG231716 BI826450 AW448979 

    GeneLoc Exon Structure

    5/9 Alternative Splicing Database (ASD) splice patterns (SP) for ZAP70 (see all 9)    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16a · 16b · 16c ^ 17a ·
    SP1:        -                       -     -           -                                   -                 -                                         -         
    SP2:                                                  -                                   -                 -                                         -         
    SP3:                                                                                                                                                  -         
    SP4:                                                  -                                   -     -                                                               
    SP5:                                                                                                        -                                         -         

    ExUns: 17b
    SP1:      
    SP2:      
    SP3:      
    SP4:      
    SP5:      


    ECgene alternative splicing isoforms for ZAP70

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    ZAP70 expression in normal human tissues (normalized intensities)      ZAP70 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CGAGCCTGTT
    ZAP70 Expression
    About this image


    ZAP70 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/8 selected tissues (see all 8) fully expand
     
     Blood (Hematopoietic System)    fully expand to see all 4 entries
             Hematopoietic Stem Cells Hematopoietic Bone Marrow
             Peripheral blood Pan-T Cells   
     
     Lymph (Hematopoietic System)    fully expand to see all 3 entries
             lymph node ; non-germinal center cells   
             LYMPH NODE   
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 2 entries
             Endoderm progenitor-like cells ( Generation and expansion of endodermal progenitor...
     
     Umbilical Cord (Extraembryonic Tissues)    fully expand to see all 2 entries
             Cord Blood Pan-T Cells   
     
     Tonsil (Hematopoietic System)    fully expand to see all 2 entries
             tonsil ; non-germinal center cells   

    See ZAP70 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for ZAP70

    SOURCE GeneReport for Unigene cluster: Hs.234569

    UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403
    Tissue specificity: Expressed in T- and natural killer cells. Also present in early thymocytes and pro/pre B-cells

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for ZAP70 gene from 4/12 species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Zap701 , 5 zeta-chain (TCR) associated protein kinase1, 5 87.88(n)1
    94.16(a)1
      1 (15.41 cM)5
    226371  NM_009539.21  NP_033565.21 
     367618615 
    chicken
    (Gallus gallus)
    Aves ZAP701 zeta-chain (TCR) associated protein kinase 70kDa 73.63(n)
    77.61(a)
      420086  XM_418206.3  XP_418206.3 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.142142 Transcribed sequence with moderate similarity to protein more 77.19(n)    BI846328.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta shark6
    hop6
    hopscotch
    21(a)
    11(a)
    possible ortholog
    possible ortholog
    2R(12086931-12090388)
    X(11254932-11262130)


    ENSEMBL Gene Tree for ZAP70 (if available)
    TreeFam Gene Tree for ZAP70 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for ZAP70 gene
    SYK2  TNK12  JAK32  JAK22  TNK22  TYK22  ERBB42  JAK12  
    ERBB32  PTK22  ERBB22  EGFR2  PTK2B2  
    4 SIMAP similar genes for ZAP70 using alignment to 1 protein entry:     ZAP70_HUMAN:
    SYK    EPHA2    DKFZp434L0319    urf-ret

    ZAP70 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/862 SNPs in ZAP70 are shown (see all 862)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0656234
    Selective T-cell defect (STCD)4--see VAR_0656232 L R mis40--------
    VAR_0155384
    Selective T-cell defect (STCD)4--see VAR_0155382 R H mis40--------
    VAR_0063514
    Selective T-cell defect (STCD)4--see VAR_0063512 S R mis40--------
    VAR_0418484
    Neck squamous cell carcinoma sample4--see VAR_0418482 G E mis40--------
    VAR_0656254
    Selective T-cell defect (STCD)4--see VAR_0656252 A V mis40--------
    VAR_0656264
    Selective T-cell defect (STCD)4--see VAR_0656262 C R mis40--------
    VAR_0656244
    Selective T-cell defect (STCD)4--see VAR_0656242 R C mis40--------
    rs1048936741,2
    Cpathogenic198011309(+) TCCAGA/CCGCAG 4 R S mis10--------
    rs1939226331,2
    Cprobable-non-pathogenic198008803(+) ATGCGC/TGAGGC 4 R syn10--------
    rs560670091,2
    C--92121301(+) CACCC-/CAGAGTC 2 -- int10--------

    HapMap Linkage Disequilibrium report for ZAP70 (98330023 - 98356325 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for ZAP70:    About this table     
    Variant IDTypeSubtypePubMed ID
    nsv2837CNV Insertion18451855
    nsv874696CNV Loss21882294
    esv33510CNV Gain17666407
    nsv10104CNV Gain18304495
    esv718CNV CNV17122850
    essv18990CNV CNV17122850


    Human Gene Mutation Database (HGMD): ZAP70

    Locus Specific Mutation Databases (LSDB): ZAP70
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 176947    OMIM disorders: --

    UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403
  • Selective T-cell defect (STCD) [MIM:269840]: A form of severe combined immunodeficiency characterized by
    a selective absence of CD8+ T cells. Note=The disease is caused by mutations affecting the gene represented in
    this entry

  • 20/46 diseases for ZAP70 (see all 46):    About MalaCards
    zap-70 deficiency    cll/sll    zap70-related severe combined immunodeficiency    juvenile nasopharyngeal angiofibroma
    b-cell chronic lymphocytic leukemia    prolymphocytic leukemia    t-cell prolymphocytic leukemia    b cell prolymphocytic leukemia
    waldenstrom macroglobulinemia    macroglobulinemia    severe combined immunodeficiency    malt lymphoma
    lymphopenia    refractive error    chronic lymphocytic leukemia    essential thrombocythemia
    wiskott-aldrich syndrome    acute lymphoblastic leukemia    cblc    lymphoblastic leukemia


    ZAP70 for disorders           About GeneDecksing

    10/42 Novoseek inferred disease relationships for ZAP70 gene (see all 42)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    leukemia lymphocytic chronic 92 104 15972449 (2), 16418492 (2), 16321853 (2), 17948236 (2) (see all 78)
    lymphocytic leukemia chronic b-cell 88.3 45 18223290 (4), 15759031 (2), 17476690 (2), 16906587 (2) (see all 32)
    leukaemia lymphocytic 78.8 34 16932341 (2), 17456058 (2), 19144411 (2), 17625948 (2) (see all 24)
    lymphoma small lymphocytic 57.1 8 19575876 (2), 15133473 (1), 20029467 (1), 16280661 (1) (see all 7)
    severe combined immunodeficiency 56 10 8202712 (2), 9801260 (1), 12149205 (1), 8920891 (1) (see all 9)
    leukemia b-cell 55.2 4 14523469 (1), 20135127 (1), 12393534 (1), 17051411 (1)
    trisomy 51.8 6 16434371 (1), 18223290 (1), 18689273 (1), 19717645 (1) (see all 6)
    lymphocytosis 49.9 1 18689273 (1)
    leukemia t-cell 41.4 7 17178387 (2), 7524094 (1), 16369048 (1), 18687687 (1)
    leukemia prolymphocytic 38.4 2 15133473 (1), 16642047 (1)

    Genatlas disease: ZAP70
    immunodeficiency,severe,combined with selective absence of peripheral CD8+ cells,and presence of CD4+ T cells,not
    responding to TCR mediated stimuli in vitro

    Genetic Association Database (GAD): ZAP70
    Human Genome Epidemiology (HuGE) Navigator: ZAP70 (4 documents)
    Tumor Gene Database (TGDB): ZAP70

    Export disorders for ZAP70 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for ZAP70 gene, integrated from 9 sources (see all 709):
    (articles sorted by number of sources associating them with ZAP70)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. (PubMed id 1423621)1, 2, 3, 9 Chan A.C....Weiss A. (1992)
    2. Identification of a novel isoform of ZAP-70, truncated ZAP kinase. (PubMed id 14985102)1, 2, 9 Kuroyama H.... Hirokawa K. (2004)
    3. ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. (PubMed id 7528772)1, 2, 9 Isakov N....Samelson L.E. (1995)
    4. T cell activation-induced CrkII binding to the Zap70 protein tyrosine kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine 315. (PubMed id 16339550)1, 2, 9 Gelkop S....Isakov N. (2005)
    5. In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. (PubMed id 9378960)1, 2, 9 Gary-Gouy H....Bismuth G. (1997)
    6. Structural basis for the inhibition of tyrosine kinase activity of ZAP-70. (PubMed id 17512407)1, 2, 9 Deindl S....Kuriyan J. (2007)
    7. Identification of substrates of human protein-tyrosine phosphatase PTPN22. (PubMed id 16461343)1, 2, 9 Wu J....Clark J.M. (2006)
    8. Cbl promotes ubiquitination of the T cell receptor zeta through an adaptor function of Zap-70. (PubMed id 11353765)1, 2, 9 Wang H.Y....Liu Y.C. (2001)
    9. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. (PubMed id 8702662)1, 2, 9 Bubeck Wardenburg J....Findell P.R. (1996)
    10. Polymorphisms in innate immunity genes and patients r esponse to dendritic cell-based HIV immuno-treatment. (PubMed id 20056178)1, 4 Segat L....Crovella S. (2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 7535 HGNC: 12858 AceView: ZAP70 Ensembl:ENSG00000115085 euGenes: HUgn7535
    ECgene: ZAP70 Kegg: 7535 H-InvDB: ZAP70

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for ZAP70 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ZAP70 Genetics and Cytogenetics in Oncology and Haematology
    ZAP70basehttp://bioinf.uta.fi/ZAP70base/
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ZAP70

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for ZAP70 gene:
    Search GeneIP for patents involving ZAP70

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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    About This Section

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