cd05115: PTKc_Zap-70 (this model, PSSM-Id:133246 is obsolete and has been replaced by 270686)
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
Protein Tyrosine Kinase (PTK) family; Zeta-chain-associated protein of 70kDa (Zap-70); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a member of the Syk subfamily of kinases, which are cytoplasmic (or nonreceptor) tyr kinases containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease.
Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structure of human Zap-70 tyr kinase bound with the inhibitor, staurosporine (1U59_A).