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FLASH GENE
Symbol ZAP70 contributors: mct/npt - updated : 23-06-2016
HGNC name zeta-chain (TCR) associated protein kinase 70kDa
HGNC id 12858
Corresponding disease
ADMIO2 Autoimmune disease, multisystem, infantile-onset, 2
IMD48 immunodeficiency, severe, combined
Location 2q11.2      Physical location : 98.330.030 - 98.356.323
Synonym name
  • srk-related tyrosine kinase
  • truncated ZAP kinase
  • syk-related tyrosine kinase
  • Synonym symbol(s) SRK, STD, TZK, ZAP-70, FLJ17670, FLJ17679
    EC.number 2.7.10.2
    DNA
    TYPE functioning gene
    STRUCTURE 26.29 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC93082 2q11.2 hypothetical protein BC012317 MRF-1 FLJ10081 2p12-p11.2 hypothetical protein FLJ10081 LOC391408 2 similar to myoferlin isoform b; fer-1-like 3 LOC90342 2q11.2 similar to fer-1 like protein 3 LMAN2L 2q11.1 lectin, mannose-binding 2-like CNNM4 2p12-p11.2 cyclin M4 LOC130643 2q11.2 hypothetical LOC130643 CNNM3 2p12-p11.2 cyclin M3 DARP MGC41816 2q11.2 hypothetical protein MGC41816 SEMA4C 2q11.1 sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4C LOC51252 2q11.2 hypothetical protein LOC51252 LOC391409 2 hypothetical gene supported by NM_138800 LOC375247 2q11.2 hypothetical LOC375247 DKFZp434N062 2q11.2 hypothetical protein DKFZp434N062 UNQ2430 2q11.2 ankyrin-related KIAA1641 2q11.2 KIAA1641 protein UBE3AP1 2q11.1 ubiquitin protein ligase E3A pseudogene 1 LOC389008 2 similar to KIAA1641 protein LOC151320 2q11.2 similar to autoantigen NOR-90 COX5B 2cen-q13 cytochrome c oxidase subunit Vb ACTR1B 2q11.1-q11.2 ARP1 actin-related protein 1 homolog B, centractin beta (yeast) RNU4P2 2q11.2 RNA, U4 small nuclear pseudogene 2 (U4/14) LOC130639 2q11.2 hypothetical LOC130639 ZAP70 2q12 zeta-chain (TCR) associated protein kinase 70kDa RW1 2q11.2 RW1 protein MGC26733 2q11.2 hypothetical protein MGC26733 CNGA3 2q11.2 cyclic nucleotide gated channel alpha 3 INPP4A 2q11.2 inositol polyphosphate-4-phosphatase, type I, 107kDa GMH1 MGAT4A 2q12 mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isoenzyme A LOC343990 2q11.2 hypothetical LOC343990
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 2450 - 619 accumulated at the immune synapse 2004 14985102
    6 - 1468 - 312 - 2004 14985102
    - - 1085 - 312 thymus, spleen, and lymph nodes, pre-T-cell receptor-minus thymocytes 2004 14985102
  • also called TZK
  • lacking the SH2 domain and a part of interdomain B
  • functioning as a kinase not associated with T-cell receptor
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Blood / hematopoieticplasma    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/HematopoieticNK cell Homo sapiens
    Lymphoid/ImmuneB cell Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two SH2 domains
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • SYK/ZAP-70 subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • non myristoylated cytoplasmic tyrosine kinase, playing a role in lymphocyte activation
  • nonredundant role for ZAP70 in signals induced by the T cell antigen receptor (TCR)
  • is a tyrosine kinase that plays a role in signal transduction from the T-cell receptor
  • ZAP70 inhibits SYK-mediated osteoclast function
  • critical role of ZAP70 in T-cell receptor (TCR) signalling
  • distinct roles for ZAP70 as a structural protein regulating integrin-mediated control of actin vs its catalytic activity that regulates TCR-mediated control of actin and membrane remodelling during formation of the immunological synapse
  • kinase activity of ZAP70 stimulates negative feedback pathways that target LCK and thereby modulate the phosphorylation patterns of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3 and zeta chain components of the TCR
  • potential role for ZAP70 dependent signaling in CD27 induction, implicating CD27 in cell-cell interactions with the lymphoid tissue microenvironment
  • differential requirements of ZAP70 and SYK during thymic development, peripheral homeostasis as well as effector functions of CD4 and CD8 T cells (PMUID: 26187144)
  • OTUD7B is a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating ZAP70 function
  • LAT, like CD247 and ZAP70, plays likely a role in neurogenesis and that perturbation of this pathway may lead to neurodevelopmental phenotypes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • ITGB2/LCK/ZAP70 complex is in position to initiate the rapid adhesion strengthening and migration necessary for T-lymphocyte responses when stimulated vasculature is encountered at sites of infection or injury
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding LAT (linker adaptor protein) linking T cell receptor to cellular activation
  • interacting with DBNL
  • ITGB2 is constitutively associated with the protein tyrosine kinases LCK and ZAP70
  • UBASH3A regulates the level of tyrosine phosphorylation on targets within T cells, among them the critical T cell tyrosine kinase ZAP70
  • GNAI2 and ZAP70 mediate RASGRP1 membrane localization and activation of CXCL12-induced T cell functions
  • NCK1 recruitment to the TCR required for ZAP70 activation during thymic development
  • ZAP70 acts directly as an amplifier of NFKB1 signalling in Chronic lymphocytic leukaemia (CLL) cells which could be an underlying mechanism for its association with poor prognosis and which may represent a therapeutic target
  • upon TCR ligation, OTUD7B is rapidly recruited to the tyrosine kinase ZAP70, a central mediator of TCR-proximal signaling
  • USP9X functions as a positive regulatory switch during T lymphocyte priming through removal of inhibitory monoubiquitination from ZAP70
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD48 , ADMIO2
    related resource ZAP70base: Mutation registry for autosomal recessive ZAP70 immunodeficiency
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
          --over  
    wth CD38 in chronic lymphocytic leukemia with poor prognosis (el-Sharnouby 2006)
    tumoral       loss of function
    results in a severe immunodeficiency, characterized by a lack of mature CD8(+) T cells and non-functional CD4(+) T cells (Picard 2009)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • expression of this protein provides an ideal prognostic marker for chronic lymphocytic leukaemia
  • Therapy target
    ANIMAL & CELL MODELS