ZAP-70 Antibody – Mouse Monoclonal

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]

Function: Plays a role in T-cell development and lymphocyte activation. Essential for TCR-mediated IL-2 production. Isoform 1 induces TCR-mediated signal transduction, isoform 2 does not. Ref.1 Ref.5

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure: Interacts with SLA2 when it is phosphorylated. Interacts with CD3Z and with phosphorylated NFAM1. Interacts with CBLB

By similarity. Interacts with CBL and SLA when it is phosphorylated. The association with SLA (or SLA2) and CBL probably leads to its destruction. Interacts with SHB. Interacts with DEF6. Interacts (via SH2 domains) with RHOH

By similarity. Interacts with FCRL3. Ref.1 Ref.8 Ref.9 Ref.10

Subcellular location: Cytoplasm

By similarity. Cell membrane

By similarity. Note: After antigen stimulation, isoform 1 concentrates at the immunological synapse and isoform 2 remains cytoplasmic. Co-localizes together with RHOH in the immunological synapse. RHOH is required for its proper localization to the cell membrane and cytoskeleton fractions in the thymocytes

Tissue specificity: Expressed in T- and natural killer cells. Ref.1

Domain: The SH2 domains bind to the phosphorylated tyrosine-based activation motif (TAM) of CD3Z and the non-canonical phosphorylated tyrosine-based activation motif (TAM) of RHOH

Post-translational modification: Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Tyr-319 phosphorylation is essential for full activity. Ref.1 Ref.7 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16

Involvement in disease: Defects in ZAP70 are the cause of selective T-cell defect (STD) [

MIM:176947]. STD is an autosomal recessive form of severe combined immunodeficiency characterized by a selective absence of CD8-type T-cells. Ref.5 Ref.19 Ref.20

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.Contains 1 protein kinase domain.Contains 2 SH2 domains.