Zap70 zeta-chain (TCR) associated protein kinase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Zap70provided by MGI
Official Full Name: zeta-chain (TCR) associated protein kinaseprovided by MGI
Primary source: MGI:MGI:99613
See related: Ensembl:ENSMUSG00000026117 AllianceGenome:MGI:99613
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Srk; mur; mrtle; ZAP-70
Summary: This gene encodes a member of the protein tyrosine kinase family. The encoded protein is essential for development of T lymphocytes and thymocytes, and functions in the initial step of T lymphocyte receptor-mediated signal transduction. A mutation in this gene causes chronic autoimmune arthritis, similar to rheumatoid arthritis in humans. Mice lacking this gene are deficient in alpha-beta T lymphocytes in the thymus. In humans, mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T lymphocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Expression: Biased expression in thymus adult (RPKM 70.4), spleen adult (RPKM 17.5) and 3 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 B; 1 15.41 cM

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (36800912..36821899)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (36761798..36782821)

Chromosome 1 - NC_000067.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.
Title: Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.
mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.
Title: mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.
basal ZAP70 activation in resting T cell lines reduced the threshold ("primed") TCR-stimulated activation of the classical p38 pathway
Title: Alternative ZAP70-p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation.
These findings demonstrate that PKCtheta; plays an important role in a positive feedback regulatory loop that modulates TCR-proximal signaling and, moreover, provide a mechanistic explanation for earlier reports that documented an important role for PKCtheta; in T cell Ca(2+) signaling. This PKCtheta;-Zap70 interaction could potentially serve as a promising and highly selective immunosuppressive drug target in autoimmu...
Title: Phosphotyrosine-dependent interaction between the kinases PKCθ and Zap70 promotes proximal TCR signaling.
Rasal1 binds to the kinase domain of ZAP-70 in T cells.
Title: GTPase-activating protein Rasal1 associates with ZAP-70 of the TCR and negatively regulates T-cell tumor immunity.
These results demonstrated the importance of ZAP-70 in the regulation of T cell receptor-dependent activation and apoptosis signaling pathways in autoimmune arthritis.
Title: ZAP-70 Regulates Autoimmune Arthritis via Alterations in T Cell Activation and Apoptosis.
hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing invariant natural killer T cells.
Title: Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70.
RanBP2 expression was regulated by Zap70.
Title: Zap70 and downstream RanBP2 are required for the exact timing of the meiotic cell cycle in oocytes.
disruption of normal Zap70 autoinhibition engaged negative feedback mechanisms by which negative selection and inhibitory receptors restrain TCR signaling to enforce both central and peripheral tolerance.
Title: Destabilizing the autoinhibitory conformation of Zap70 induces up-regulation of inhibitory receptors and T cell unresponsiveness.
in this study, authors discovered a cycle of recruitment, activation and release for Zap70 kinases at phosphorylated T-cell antigen receptors, which turned them into a 'catalytic unit' that amplified antigenic stimuli
Title: A cycle of Zap70 kinase activation and release from the TCR amplifies and disperses antigenic stimuli.

Submit: New GeneRIF Correction See all GeneRIFs (48)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (12) 1 citation
Endonuclease-mediated (6)
Spontaneous (2) 1 citation
Targeted (7) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine kinase activity	ISO Inferred from Sequence Orthology more info
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphotyrosine residue binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein tyrosine kinase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of T cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within T cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in T cell receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
acts_upstream_of alpha-beta T cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of alpha-beta T cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within beta selection	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in immune response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within intracellular signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative thymic T cell selection	IMP Inferred from Mutant Phenotype more info	PubMed
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 peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info	PubMed
acts_upstream_of_or_within positive regulation of T cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of T cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of alpha-beta T cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of alpha-beta T cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of alpha-beta T cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive thymic T cell selection	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive thymic T cell selection	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within thymic T cell selection	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of T cell receptor complex	ISO Inferred from Sequence Orthology more info	PubMed
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in immunological synapse	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	IEA Inferred from Electronic Annotation more info
colocalizes_with membrane raft	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: tyrosine-protein kinase ZAP-70

Names: 70 kDa zeta-chain associated protein; syk-related tyrosine kinase

NP_001276541.1

EC 2.7.10.2

NP_001276694.1

EC 2.7.10.2

NP_001276695.1

EC 2.7.10.2

NP_001407579.1

EC 2.7.10.2

NP_033565.2

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.

mRNA and Protein(s)

NM_001289612.2 → NP_001276541.1 tyrosine-protein kinase ZAP-70 isoform TZK

See identical proteins and their annotated locations for NP_001276541.1

Status: REVIEWED

Source sequence(s)

AC084389

UniProtKB/Swiss-Prot

P43404

Related

ENSMUST00000190128.2

Conserved Domains (2) summary

pfam07714
Location:36 → 286

Pkinase_Tyr; Protein tyrosine kinase

cl21453
Location:26 → 294

PKc_like; Protein Kinases, catalytic domain
NM_001289765.2 → NP_001276694.1 tyrosine-protein kinase ZAP-70 isoform a

See identical proteins and their annotated locations for NP_001276694.1

Status: REVIEWED

Source sequence(s)

AC084389

Consensus CDS

CCDS14888.1

UniProtKB/Swiss-Prot

P43404, P97455, Q80VV2, Q8CHJ3

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

cd05115
Location:332 → 600

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

cl15255
Location:152 → 256

SH2; Src homology 2 (SH2) domain
NM_001289766.2 → NP_001276695.1 tyrosine-protein kinase ZAP-70 isoform b

Status: REVIEWED

Source sequence(s)

AC084389

Conserved Domains (4) summary

cd09938
Location:32 → 135

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

cd05115
Location:356 → 624

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

pfam07714
Location:366 → 616

Pkinase_Tyr; Protein tyrosine kinase

cl15255
Location:176 → 280

SH2; Src homology 2 (SH2) domain
NM_001420650.1 → NP_001407579.1 tyrosine-protein kinase ZAP-70 isoform a

Status: REVIEWED

Source sequence(s)

AC084389

UniProtKB/Swiss-Prot

P43404, P97455, Q80VV2, Q8CHJ3
NM_009539.4 → NP_033565.2 tyrosine-protein kinase ZAP-70 isoform a

See identical proteins and their annotated locations for NP_033565.2

Status: REVIEWED

Source sequence(s)

AC084389

Consensus CDS

CCDS14888.1

UniProtKB/Swiss-Prot

P43404, P97455, Q80VV2, Q8CHJ3

Related

ENSMUSP00000027291.5, ENSMUST00000027291.7

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

cd05115
Location:332 → 600

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

cl15255
Location:152 → 256

SH2; Src homology 2 (SH2) domain