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Aliases for ZAP70 Gene

Aliases for ZAP70 Gene

  • Zeta-Chain (TCR) Associated Protein Kinase 70kDa 2 3
  • SRK 3 4 6
  • 70 KDa Zeta-Chain Associated Protein 3 4
  • Syk-Related Tyrosine Kinase 3 4
  • EC 2.7.10.2 4 63
  • STCD 3 6
  • STD 3 6
  • Zeta-Chain (TCR) Associated Protein Kinase (70 KD) 2
  • Zeta-Chain Associated Protein Kinase, 70kD 3
  • 70 KDa Zeta-Associated Protein 3
  • Tyrosine-Protein Kinase ZAP-70 3
  • EC 2.7.10 63
  • ZAP-70 3
  • TZK 3

External Ids for ZAP70 Gene

Previous Symbols for ZAP70 Gene

  • SRK

Summaries for ZAP70 Gene

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 selective t-cell defect and zap70-related severe combined immunodeficiency. Among its related pathways are Ras signaling pathway and Class I MHC mediated antigen processing and presentation. GO annotations related to this gene include protein tyrosine kinase activity and phosphotyrosine binding. An important paralog of this gene is TNK1.

UniProtKB/Swiss-Prot for ZAP70 Gene

  • 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ZAP70 Gene

Genomics for ZAP70 Gene

Genomic Location for ZAP70 Gene

Start:
97,713,560 bp from pter
End:
97,739,862 bp from pter
Size:
26,303 bases
Orientation:
Plus strand

Genomic View for ZAP70 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ZAP70 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ZAP70 Gene

Regulatory Elements for ZAP70 Gene

Proteins for ZAP70 Gene

  • Protein details for ZAP70 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P43403-ZAP70_HUMAN
    Recommended name:
    Tyrosine-protein kinase ZAP-70
    Protein Accession:
    P43403
    Secondary Accessions:
    • A6NFP4
    • Q6PIA4
    • Q8IXD6
    • Q9UBS6

    Protein attributes for ZAP70 Gene

    Size:
    619 amino acids
    Molecular mass:
    69872 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for ZAP70 Gene

    Alternative splice isoforms for ZAP70 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ZAP70 Gene

Proteomics data for ZAP70 Gene at MOPED

Post-translational modifications for ZAP70 Gene

  • 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.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys25, Lys75, Lys100, Lys132, Lys151, Lys176, Lys193, Lys217, Lys361, Lys362, Lys377, Lys455, Lys484, Lys556, Lys603, and Lys613

Other Protein References for ZAP70 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for ZAP70 Gene

Gene Families for ZAP70 Gene

HGNC:
  • SH2D :SH2 domain containing
IUPHAR :

Suggested Antigen Peptide Sequences for ZAP70 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P43403

UniProtKB/Swiss-Prot:

ZAP70_HUMAN
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.:
    • P43403
  • Contains 1 protein kinase domain.:
    • P43403
  • Contains 2 SH2 domains.:
    • P43403
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.:
    • P43403
genes like me logo Genes that share domains with ZAP70: view

Function for ZAP70 Gene

Molecular function for ZAP70 Gene

GENATLAS Biochemistry: CD3 zeta associated tyrosine kinase,SYK (non SRC) family,expressed in T and NK cells,involved in signal transduction
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation: Activated by phosphorylation at Tyr-493 in the activation loop. Inhibited by staurosporine.
UniProtKB/Swiss-Prot 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).

Enzyme Numbers (IUBMB) for ZAP70 Gene

Gene Ontology (GO) - Molecular Function for ZAP70 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine binding IEA --
GO:0004672 protein kinase activity --
GO:0004713 protein tyrosine kinase activity TAS --
GO:0004715 non-membrane spanning protein tyrosine kinase activity TAS 20135127
GO:0005102 receptor binding IBA --
genes like me logo Genes that share ontologies with ZAP70: view
genes like me logo Genes that share phenotypes with ZAP70: view

Animal Models for ZAP70 Gene

MGI Knock Outs for ZAP70:

miRNA for ZAP70 Gene

miRTarBase miRNAs that target ZAP70

No data available for Transcription Factor Targeting and HOMER Transcription for ZAP70 Gene

Localization for ZAP70 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ZAP70 Gene

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). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ZAP70 Gene COMPARTMENTS Subcellular localization image for ZAP70 gene
Compartment Confidence
plasma membrane 5
cytosol 4
nucleus 2
peroxisome 2
extracellular 1

Gene Ontology (GO) - Cellular Components for ZAP70 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001772 immunological synapse IBA --
GO:0005737 cytoplasm TAS 12359715
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS 20135127
GO:0005911 cell-cell junction IEA --
genes like me logo Genes that share ontologies with ZAP70: view

Pathways for ZAP70 Gene

genes like me logo Genes that share pathways with ZAP70: view

Gene Ontology (GO) - Biological Process for ZAP70 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002250 adaptive immune response TAS 20135127
GO:0006468 protein phosphorylation NAS 1423621
GO:0006955 immune response IDA 1423621
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway IBA --
GO:0016477 cell migration IBA --
genes like me logo Genes that share ontologies with ZAP70: view

Compounds for ZAP70 Gene

(2) HMDB Compounds for ZAP70 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(1) Drugbank Compounds for ZAP70 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Staurosporine
62996-74-1 target

(38) Novoseek inferred chemical compound relationships for ZAP70 Gene

Compound -log(P) Hits PubMed IDs
tyrosine 84.3 229
fludarabine 68.3 6
phosphotyrosine 63.4 7
piceatannol 49.6 2
rituximab 48.9 1
genes like me logo Genes that share compounds with ZAP70: view

Transcripts for ZAP70 Gene

Unigene Clusters for ZAP70 Gene

Zeta-chain (TCR) associated protein kinase 70kDa:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ZAP70 Gene

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: - -
SP6:
SP7:
SP8:
SP9:

ExUns: 17b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for ZAP70 Gene

GeneLoc Exon Structure for
ZAP70
ECgene alternative splicing isoforms for
ZAP70

Expression for ZAP70 Gene

mRNA expression in normal human tissues for ZAP70 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ZAP70 Gene

This gene is overexpressed in Whole Blood (23.7), Spleen (7.2), and Small Intestine - Terminal Ileum (4.4).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for ZAP70 Gene

SOURCE GeneReport for Unigene cluster for ZAP70 Gene Hs.234569

mRNA Expression by UniProt/SwissProt for ZAP70 Gene

P43403-ZAP70_HUMAN
Tissue specificity: Expressed in T- and natural killer cells. Also present in early thymocytes and pro/pre B-cells.
genes like me logo Genes that share expressions with ZAP70: view

Orthologs for ZAP70 Gene

This gene was present in the common ancestor of animals.

Orthologs for ZAP70 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ZAP70 35
  • 99.57 (n)
  • 99.84 (a)
ZAP70 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ZAP70 35
  • 89.77 (n)
  • 93.67 (a)
ZAP70 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ZAP70 35
  • 88.78 (n)
  • 90.2 (a)
ZAP70 36
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Zap70 35
  • 87.63 (n)
  • 93.84 (a)
Zap70 16
Zap70 36
  • 94 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ZAP70 36
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 75 (a)
OneToMany
-- 36
  • 80 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Zap70 35
  • 87.89 (n)
  • 93.32 (a)
chicken
(Gallus gallus)
Aves ZAP70 35
  • 73.26 (n)
  • 76.61 (a)
ZAP70 36
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia zap70 35
  • 67.05 (n)
  • 74.3 (a)
zebrafish
(Danio rerio)
Actinopterygii Dr.14214 35
zap70 35
  • 65.65 (n)
  • 67.18 (a)
zap70 36
  • 66 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta hop 36
  • 13 (a)
ManyToMany
PR2 36
  • 9 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea kin-24 37
  • 33 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2657 36
  • 28 (a)
OneToMany
Species with no ortholog for ZAP70:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ZAP70 Gene

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

Paralogs for ZAP70 Gene

Paralogs for ZAP70 Gene

Selected SIMAP similar genes for ZAP70 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with ZAP70: view

Variants for ZAP70 Gene

Sequence variations from dbSNP and Humsavar for ZAP70 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs895437 -- 97,733,883(+) GGTCA(C/T)TGTGT intron-variant, upstream-variant-2KB
rs895439 -- 97,739,257(-) TCAGC(A/G)GGGCT intron-variant, utr-variant-3-prime
rs1020396 -- 97,714,363(+) AGGGC(C/T)GTGAG intron-variant
rs2167008 -- 97,719,310(-) AGCTG(C/T)ACATG intron-variant
rs2276644 -- 97,713,755(-) GTTCA(C/T)CCTCT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for ZAP70 Gene

Variant ID Type Subtype PubMed ID
esv718 CNV CNV 17122850
essv18990 CNV CNV 17122850
nsv874696 CNV Loss 21882294
nsv2837 CNV Insertion 18451855
esv33510 CNV Gain 17666407
nsv10104 CNV Gain 18304495

Relevant External Links for ZAP70 Gene

HapMap Linkage Disequilibrium report
ZAP70
Human Gene Mutation Database (HGMD)
ZAP70
Locus Specific Mutation Databases (LSDB)
ZAP70

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ZAP70 Gene

Disorders for ZAP70 Gene

(1) OMIM Diseases for ZAP70 Gene (176947)

UniProtKB/Swiss-Prot

ZAP70_HUMAN
  • Selective T-cell defect (STCD) [MIM:269840]: A form of severe combined immunodeficiency characterized by a selective absence of CD8+ T-cells. {ECO:0000269 PubMed:11123350, ECO:0000269 PubMed:11412303, ECO:0000269 PubMed:18509675, ECO:0000269 PubMed:8124727, ECO:0000269 PubMed:8202713}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(42) Novoseek inferred disease relationships for ZAP70 Gene

Disease -log(P) Hits PubMed IDs
leukemia lymphocytic chronic 92 100
lymphocytic leukemia chronic b-cell 88.3 40
leukaemia lymphocytic 78.8 28
lymphoma small lymphocytic 57.1 8
severe combined immunodeficiency 56 10

Genatlas disease for ZAP70 Gene

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

Relevant External Links for ZAP70

Genetic Association Database (GAD)
ZAP70
Human Genome Epidemiology (HuGE) Navigator
ZAP70
Tumor Gene Database (TGDB):
ZAP70
genes like me logo Genes that share disorders with ZAP70: view

Publications for ZAP70 Gene

  1. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. (PMID: 1423621) Chan A.C. … Weiss A. (Cell 1992) 2 3 4 23
  2. 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. (PMID: 7528772) Isakov N. … Samelson L.E. (J. Exp. Med. 1995) 3 4 23
  3. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. (PMID: 8702662) Bubeck Wardenburg J. … Findell P.R. (J. Biol. Chem. 1996) 3 4 23
  4. In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. (PMID: 9378960) Gary-Gouy H. … Bismuth G. (J. Immunol. 1997) 3 4 23
  5. Identification of a novel isoform of ZAP-70, truncated ZAP kinase. (PMID: 14985102) Kuroyama H. … Hirokawa K. (Biochem. Biophys. Res. Commun. 2004) 3 4 23

Products for ZAP70 Gene

  • Addgene plasmids for ZAP70

Sources for ZAP70 Gene

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