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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)
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Aliases
Zeta-Chain (TCR) Associated Protein Kinase 70kDa1 2     Zeta-Chain (TCR) Associated Protein Kinase (70 KD)1
SRK1 2 3 5     70 KDa Zeta-Associated Protein2
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
STCD2 5     Zeta-Chain Associated Protein Kinase, 70kD2
STD2 5     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, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 zap70-related severe combined immunodeficiency, and cll/sll. 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000002.12  NT_005403.18  NC_018913.2  
Regulatory elements:
   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 Chromatin IP Primers for ZAP70

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing 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 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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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
Selected PDB 3D structures from and Proteopedia for ZAP70 (see all 11):
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: 

  • 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 PTN221
  • Ubiquitination2 at Lys25, Lys75, Lys100, Lys132, Lys151, Lys176, Lys193, Lys217, Lys361, Lys362,
                                 Lys377, Lys455, Lys484, Lys556, Lys603, Lys613
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for ZAP70 (P43403) (see all 12)
     FVHRDLA  AARNVLL  RDLAARN  SYGQKPY 


    See ZAP70 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

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

    ENSEMBL proteins: 
     ENSP00000264972   ENSP00000400475   ENSP00000411141  
    Reactome Protein details: P43403

    ZAP70 Human Recombinant Protein Products:

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    Novus Biologicals ZAP70 Proteins
    Novus Biologicals ZAP70 Lysates
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    Browse Proteins at Cloud-Clone Corp.

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    ZAP70 Assay Products:

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    Browse CLIAs at Cloud-Clone Corp.


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

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

    Selected InterPro protein domains (see all 9):
     IPR012234 Tyr_kinase_non-rcpt_SYK/ZAP70
     IPR017441 Protein_kinase_ATP_BS
     IPR011009 Kinase-like_dom
     IPR000719 Prot_kinase_dom
     IPR001245 Ser-Thr/Tyr_kinase_cat_dom

    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,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    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): Selected molecular function terms (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 

         6 MGI mutant phenotypes (inferred from 12 alleles(MGI details for Zap70):
     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: Let us create your new Knockout/Knockin mouse model for ZAP70
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models 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-5p (MIRT005760), hsa-mir-34c-5p (MIRT005762), hsa-mir-34b-3p (MIRT005761)

    Block miRNA regulation of human, mouse, rat ZAP70 using miScript Target Protectors
    Search for qRT-PCR Assays for microRNAs that regulate ZAP70
    SwitchGear 3'UTR luciferase reporter plasmidZAP70 3' UTR sequence
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for ZAP70
    Predesigned siRNA for gene silencing in human, mouse, rat ZAP70

    Gene Editing
    Products:
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    Clone
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    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)
    Sino Biological Human cDNA Clone for ZAP70
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ZAP70
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ZAP70

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ZAP70_HUMAN, P43403: 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.
    Colocalizes 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)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytosol4
    nucleus2
    peroxisome2
    extracellular1

    Gene Ontology (GO): Selected cellular component terms (see all 6):    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


    (SuperPaths according to PathCards, Pathways according to 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 QIAGEN, 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 Apr 2014 via Entrez Gene).
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    SuperPaths for ZAP70 About   (see all 32)  
    See pathways by source

    SuperPathContained pathways About
    1Immune response Role of DAP12 receptors in NK cells
    Immune response Role of DAP12 receptors in NK cells0.33
    Natural killer cell mediated cytotoxicity0.31
    Immune response CD16 signaling in NK cells0.33
    2B cell receptor signaling pathway (KEGG)
    T cell receptor signaling pathway0.38
    TCR Signaling Pathway0.36
    3Immune response NFAT in immune response
    Immune response NFAT in immune response0.55
    Immune response T cell receptor signaling pathway0.50
    Immune response ICOS pathway in T helper cell0.55
    Immune response CD28 signaling0.49
    4TCR Signaling (Qiagen)
    PKC-Theta Pathway0.68
    ITK and TCR Signaling0.54
    TCR Signaling0.68
    5Translocation of ZAP-70 to Immunological synapse
    Translocation of ZAP-70 to Immunological synapse0.83
    Generation of second messenger molecules0.62

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe 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

    Selected 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

    Selected BioSystems Pathways for ZAP70 (see all 7)
        Interferon type I
    B Cell Receptor Signaling Pathway
    TCR Signaling Pathway
    Prolactin Signaling Pathway
    TCR signaling in naive CD4+ T cells


    2 Reactome Pathways for ZAP70
        Translocation of ZAP-70 to Immunological synapse
    Generation of second messenger molecules


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


    ZAP70 for pathways           About GeneDecksing

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for ZAP70
    Interactions:

        GeneGlobe Interaction Network for ZAP70

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

    Selected Interacting proteins for ZAP70 (P434031, 2, 3 ENSP000002649724) via UniProtKB, MINT, STRING, and/or I2D (see all 141)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CD247P209631, 2, 3, ENSP000003547824EBI-1211276,EBI-1165705 MINT-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
    CD3EP077661, 2, 3, ENSP000003545664EBI-1211276,EBI-1211297 MINT-8031576 MINT-8031519 MINT-8035855 I2D: score=4 STRING: ENSP00000354566
    LCKP062391, 2, 3, ENSP000003378254EBI-1211276,EBI-1348 MINT-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): Selected biological process terms (see all 20):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002250adaptive immune response TAS--
    GO:0006468protein phosphorylation NAS1423621
    GO:0006955immune response IDA1423621
    GO:0018108peptidyl-tyrosine phosphorylation IDA--
    GO:0030217T cell differentiation NAS8613493

    ZAP70 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    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

    Selected 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)



    ZAP70 for compounds           About GeneDecksing



    (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,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    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 

    Selected AceView cDNA sequences (see all 54):

    BC053878 BM916976 BQ054223 BC039039 BE254072 AB083211 NM_207519 L05148 
    AA353108 AI473901 AJ346204 BX092836 AL832287 BQ051966 AI382267 NM_001079 
    BX426017 AJ573211 AI817942 BX421713 T28969 BM917637 AW136108 AW590195 

    GeneLoc Exon Structure

    Selected 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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ZAP70 expression in normal human tissues (normalized intensities)
    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
     selected tissues (see all 4) fully expand
     
     NULL (Uncategorized)    fully expand to see all 2 entries
             Mesoderm-like cells
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Thymus (Hematopoietic System)
     
     Spleen (Hematopoietic System)
    ZAP70 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ZAP70 Protein Expression

    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)
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    This gene was present in the common ancestor of animals.

    Orthologs for ZAP70 gene from Selected species (see all 13)    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 87.63(n)1
    93.84(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 73.26(n)
    76.61(a)
      420086  XM_418206.4  XP_418206.4 
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia zap701 zeta-chain (TCR) associated protein kinase 70kDa 67.05(n)
    74.3(a)
      448557  NM_001006824.1  NP_001006825.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.142142 Transcribed sequence with moderate similarity to protein more 77.19(n)    BI846328.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta PR26
    hop6
    hopscotch
    9(a)
    13(a)
    many ↔ many
    many ↔ many
    2R(9030339-9040182)
    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)
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    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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ZAP70 (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, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 176947   
    OMIM disorders: 269840  
    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

  • Selected diseases for ZAP70 (see all 51):    
    About MalaCards
    zap70-related severe combined immunodeficiency    cll/sll    zap-70 deficiency    juvenile nasopharyngeal angiofibroma
    prolymphocytic leukemia    t-cell prolymphocytic leukemia    b cell prolymphocytic leukemia    waldenstrom macroglobulinemia
    pre-b-cell acute lymphoblastic leukemia    chronic lymphocytic leukemia    macroglobulinemia    severe combined immunodeficiency
    b-cell chronic lymphocytic leukemia    lymphopenia    malt lymphoma    refractive error
    lymphoid leukemia    wiskott-aldrich syndrome    essential thrombocythemia    anaplastic large cell lymphoma


    ZAP70 for disorders           About GeneDecksing

    Selected 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)
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    PubMed articles for ZAP70 gene, integrated from 10 sources (see all 718):
    (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. (Cell 1992)
    2. Identification of a novel isoform of ZAP-70, truncated ZAP kinase. (PubMed id 14985102)1, 2, 9 Kuroyama H.... Hirokawa K. (Biochem. Biophys. Res. Commun. 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. (J. Exp. Med. 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. (J. Immunol. 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. (J. Immunol. 1997)
    6. Structural basis for the inhibition of tyrosine kinase activity of ZAP-70. (PubMed id 17512407)1, 2, 9 Deindl S.... Kuriyan J. (Cell 2007)
    7. Identification of substrates of human protein-tyrosine phosphatase PTPN22. (PubMed id 16461343)1, 2, 9 Wu J....Clark J.M. (J. Biol. Chem. 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. (J. Biol. Chem. 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. (J. Biol. Chem. 1996)
    10. Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment. (PubMed id 20056178)1, 4 Segat L....Crovella S. (Vaccine 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     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)
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    Entrez Gene: 7535 HGNC: 12858 AceView: ZAP70 Ensembl:ENSG00000115085 euGenes: HUgn7535
    ECgene: ZAP70 Kegg: 7535 H-InvDB: ZAP70

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    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/books/NBK1116/?term=ZAP70[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    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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