ZAP70 zeta chain of T cell receptor associated protein kinase 70 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ZAP70provided by HGNC
Official Full Name: zeta chain of T cell receptor associated protein kinase 70provided by HGNC
Primary source: HGNC:HGNC:12858
See related: Ensembl:ENSG00000115085 MIM:176947; AllianceGenome:HGNC:12858
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SRK; STD; TZK; STCD; IMD48; ADMIO2; ZAP-70
Summary: This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Biased expression in lymph node (RPKM 11.2), spleen (RPKM 7.9) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q11.2

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (97713576..97756364)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (98171200..98202543)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (98330039..98356323)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?
Title: Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?
Decoding the deactivation mechanism of R192W mutation of ZAP-70 using molecular dynamics simulations and binding free energy calculations.
Title: Decoding the deactivation mechanism of R192W mutation of ZAP-70 using molecular dynamics simulations and binding free energy calculations.
Combined immunodeficiency caused by pathogenic variants in the ZAP70 C-terminal SH2 domain.
Title: Combined immunodeficiency caused by pathogenic variants in the ZAP70 C-terminal SH2 domain.
Cyclophilin A associates with and regulates the activity of ZAP70 in TCR/CD3-stimulated T cells.
Title: Cyclophilin A associates with and regulates the activity of ZAP70 in TCR/CD3-stimulated T cells.
Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.
Title: Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.
A Cysteine Residue within the Kinase Domain of Zap70 Regulates Lck Activity and Proximal TCR Signaling.
Title: A Cysteine Residue within the Kinase Domain of Zap70 Regulates Lck Activity and Proximal TCR Signaling.
AQP9 and ZAP70 as immune-related prognostic biomarkers suppress proliferation, migration and invasion of laryngeal cancer cells.
Title: AQP9 and ZAP70 as immune-related prognostic biomarkers suppress proliferation, migration and invasion of laryngeal cancer cells.
SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies.
Title: SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies.
Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.
Title: Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.
The steroidal lactone withaferin A impedes T-cell motility by inhibiting the kinase ZAP70 and subsequent kinome signaling.
Title: The steroidal lactone withaferin A impedes T-cell motility by inhibiting the kinase ZAP70 and subsequent kinome signaling.

Submit: New GeneRIF Correction See all GeneRIFs (218)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autoimmune disease, multisystem, infantile-onset, 2 MedGen: C4310768 OMIM: 617006 GeneReviews: Not available	Compare labs
Combined immunodeficiency due to ZAP70 deficiency MedGen: C5575025 OMIM: 269840 GeneReviews: ZAP70-Related Combined Immunodeficiency	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Binding of HIV-1 gp120 to CD4 induces p56lck activation and zeta-chain (TCR) associated protein kinase 70kDa desensitization independent of TCR tyrosine phosphorylation	PubMed
	env	Lck is recuited to a virological synapse (VS) interface and is highly colocalized with gp120 when cells interact with gp120+ICAM-1 bilayers, leading to activation of ZAP70, LAT, SLP76, and PLCgamma	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 alone or CD4/gp160 cross-linking induces tyrosine phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also leads to ras activation	PubMed
Nef	nef	Diaminoquinoxaline benzenesulfonamide (DQBS) treatment reduces the amount of both HCK and the p85 regulatory subunit of PI3K associated with HIV-1 Nef and completely blocks Nef-dependent activation of ZAP-70	PubMed
	nef	HIV-1 Nef inhibits colocalization of activated ZAP70 with SLP76 in microclusters (MCs)	PubMed
	nef	Nef/Hck complex recruits and phosphorylates the tyrosine kinase ZAP-70, which binds class I PI3K to trigger MHC-I downregulation in primary CD4+ T cells	PubMed
Pr55(Gag)	gag	Intracellular Gag localization is regulated by the presence of ZAP70 in lymphocytes	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	NAS Non-traceable Author Statement more info	PubMed
enables non-membrane spanning protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables non-membrane spanning protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables non-membrane spanning protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed
enables phosphotyrosine residue binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	NAS Non-traceable Author Statement more info	PubMed
enables protein tyrosine kinase activity	TAS Traceable Author Statement more info
enables signaling receptor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in B cell activation	TAS Traceable Author Statement more info	PubMed
involved_in T cell activation	TAS Traceable Author Statement more info	PubMed
involved_in T cell aggregation	TAS Traceable Author Statement more info	PubMed
involved_in T cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in T cell migration	TAS Traceable Author Statement more info	PubMed
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in adaptive immune response	TAS Traceable Author Statement more info	PubMed
involved_in beta selection	IEA Inferred from Electronic Annotation more info
involved_in calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in negative thymic T cell selection	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within peptidyl-tyrosine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of alpha-beta T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive thymic T cell selection	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of T cell receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
is_active_in extrinsic component of cytoplasmic side of plasma membrane	IC Inferred by Curator more info	PubMed
located_in immunological synapse	IEA Inferred from Electronic Annotation more info
colocalizes_with membrane raft	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: tyrosine-protein kinase ZAP-70

Names: 70 kDa zeta-associated protein; 70 kDa zeta-chain associated protein; syk-related tyrosine kinase; zeta chain of T cell receptor associated protein kinase 70kDa; zeta-chain (TCR) associated protein kinase 70kDa; zeta-chain associated protein kinase, 70kD

NP_001070.2

EC 2.7.10.2

NP_001365523.1

EC 2.7.10.2

NP_997402.1

EC 2.7.10.2

XP_047301730.1

EC 2.7.10.2

XP_047301731.1

EC 2.7.10.2

XP_047301732.1

EC 2.7.10.2

XP_054188971.1

EC 2.7.10.2

XP_054188972.1

EC 2.7.10.2

XP_054188973.1

EC 2.7.10.2

XP_054188974.1

EC 2.7.10.2

XP_054188975.1

EC 2.7.10.2

XP_054199771.1

EC 2.7.10.2

XP_054199772.1

EC 2.7.10.2

XP_054199773.1

EC 2.7.10.2

XP_054199774.1

EC 2.7.10.2

XP_054199775.1

EC 2.7.10.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007727.1 RefSeqGene

Range

5001..31293

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_126

mRNA and Protein(s)

NM_001079.4 → NP_001070.2 tyrosine-protein kinase ZAP-70 isoform 1

See identical proteins and their annotated locations for NP_001070.2

Status: REVIEWED

Source sequence(s)

AC016699, AC017099

Consensus CDS

CCDS33254.1

UniProtKB/Swiss-Prot

A6NFP4, P43403, Q6PIA4, Q8IXD6, Q9UBS6

Related

ENSP00000264972.5, ENST00000264972.10

Conserved Domains (3) summary

cd09938
Location:8 → 111

SH2_N-SH2_Zap70_Syk_like; N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins

cd10402
Location:152 → 255

SH2_C-SH2_Zap70; C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70)

cd05115
Location:333 → 601

PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
NM_001378594.1 → NP_001365523.1 tyrosine-protein kinase ZAP-70 isoform 1

Status: REVIEWED

Source sequence(s)

AC016699, AC017099

Consensus CDS

CCDS33254.1

UniProtKB/Swiss-Prot

A6NFP4, P43403, Q6PIA4, Q8IXD6, Q9UBS6

Related

ENSP00000513759.1, ENST00000698508.1

Conserved Domains (3) summary

cd09938
Location:8 → 111

SH2_N-SH2_Zap70_Syk_like; N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins

cd10402
Location:152 → 255

SH2_C-SH2_Zap70; C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70)

cd05115
Location:333 → 601

PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
NM_207519.2 → NP_997402.1 tyrosine-protein kinase ZAP-70 isoform 2

See identical proteins and their annotated locations for NP_997402.1

Status: REVIEWED

Source sequence(s)

AC016699

Consensus CDS

CCDS33255.1

UniProtKB/Swiss-Prot

P43403

Related

ENSP00000400475.2, ENST00000451498.2

Conserved Domains (1) summary

cd05115
Location:26 → 294

PTKc_Zap-70; Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa