Seroatlas · Human Serome Atlas

ZAP70

Tyrosine-protein kinase ZAP-70

Also known as: SRK, STD, ZAP-70, ZAP70_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P43403
Gene
ZAP70
Ensembl
ENSG00000115085
Chromosome
2
Canonical length
619 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, RAS pathway related proteins

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

619 residues, UniProt reviewed canonical sequence.

>P43403|ZAP70
     1  MPDPAAHLPF FYGSISRAEA EEHLKLAGMA DGLFLLRQCL RSLGGYVLSL VHDVRFHHFP
    61  IERQLNGTYA IAGGKAHCGP AELCEFYSRD PDGLPCNLRK PCNRPSGLEP QPGVFDCLRD
   121  AMVRDYVRQT WKLEGEALEQ AIISQAPQVE KLIATTAHER MPWYHSSLTR EEAERKLYSG
   181  AQTDGKFLLR PRKEQGTYAL SLIYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK
   241  LKADGLIYCL KEACPNSSAS NASGAAAPTL PAHPSTLTHP QRRIDTLNSD GYTPEPARIT
   301  SPDKPRPMPM DTSVYESPYS DPEELKDKKL FLKRDNLLIA DIELGCGNFG SVRQGVYRMR
   361  KKQIDVAIKV LKQGTEKADT EEMMREAQIM HQLDNPYIVR LIGVCQAEAL MLVMEMAGGG
   421  PLHKFLVGKR EEIPVSNVAE LLHQVSMGMK YLEEKNFVHR DLAARNVLLV NRHYAKISDF
   481  GLSKALGADD SYYTARSAGK WPLKWYAPEC INFRKFSSRS DVWSYGVTMW EALSYGQKPY
   541  KKMKGPEVMA FIEQGKRMEC PPECPPELYA LMSDCWIYKW EDRPDFLTVE QRMRACYYSL
   601  ASKVEGPPGS TQKAEAACA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZAP70 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.28
Highest tissue expression
74 nTPM

Expression across tissuesHPA

Tissue

  • thymus: 74 nTPM
  • lymph node: 50 nTPM
  • spleen: 35 nTPM
  • appendix: 25 nTPM
  • bone marrow: 23 nTPM
  • small intestine: 18 nTPM

Single-cell type

  • nk-cells: 127 nCPM
  • t-cells: 87 nCPM
  • thymocytes: 41 nCPM
  • innate lymphoid cells: 30 nCPM
  • neutrophil progenitors: 10 nCPM
  • myosatellite cells: 9.7 nCPM

Immune cell

  • gdT-cell: 138 nTPM
  • NK-cell: 113 nTPM
  • memory CD8 T-cell: 108 nTPM
  • MAIT T-cell: 94 nTPM
  • T-reg: 80 nTPM
  • naive CD8 T-cell: 80 nTPM

Brain region

  • thalamus: 2.3 nTPM
  • midbrain: 2.1 nTPM
  • medulla oblongata: 1.2 nTPM
  • hypothalamus: 1.1 nTPM
  • pons: 1 nTPM
  • cerebral cortex: 0.8 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZAP70.

Disease | AllUniProt

Conditions ZAP70 is implicated in, by any mechanism.

  • Immunodeficiency 48 (IMD48) MIM:269840
  • Autoimmune disease, multisystem, infantile-onset, 2 (ADMIO2) MIM:617006

Disease | GeneticClinVar

38 pathogenic / likely-pathogenic of 573 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.36
gnomAD pLI
0.88
gnomAD missense Z
2.76
DepMap mean gene effect
-0.02
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ZAP70 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ZAP70 as an antibody target. Whether an autoantibody or antibody against ZAP70 could matter depends on whether native ZAP70 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZAP70 is annotated at the cell surface, where native ZAP70 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label ZAP70 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ZAP70. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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