Zap-70 tyrosine kinase; zeta-associated protein 70 kD; Syk-related tyrosine kinase (ZAP70, SRK)

Function

• plays a role in T-cell development & lymphocyte activation
• essential for TCR-mediated IL-2 production
• isoform 1 induces TCR-mediated signal transduction; isoform 2 does not
• In activated T-cells, Zap-70 binds to TCR-delta, gamma, epsilon or zeta subunits that associate with TCR-alpha/beta
• binding is mediated through N-terminal SH2-domains in Zap-70 & tyrosine phosphates in the TCR-associated subunit
• in turn, Zap-70 phosphorylates & activates PLC-gamma1 leading to the rise in intracellular Ca+2 that accompanies T-cell activation
• interacts with SLA2 when it is phosphorylated
• interacts with CD3Z & with phosphorylated NFAM1
• interacts with CBLB
• interacts with CBL & SLA when it is phosphorylated
• association with SLA (or SLA2) & CBL probably leads to its destruction
• interacts with SHB
• interacts with DEF6
• interacts with FCRL3
• phosphorylated on Tyr upon T-cell antigen receptor (TCR) stimulation
• Tyr-319 phosphorylation is essential for full activity

Structure

• the SH2 domain binds to the phosphorylated tyrosine-based activation motif (TAM) of CD3Z
• belongs to the protein kinase superfamily, Tyr protein kinase family, SYK/ZAP-70 subfamily
• contains 1 protein kinase domain
• contains 2 SH2 domains

Compartment

• cytoplasm
• after antigen stimulation, isoform 1 concentrates at the immunological synapse & isoform 2 remains cytoplasmic (putative)

Alternative splicing

named isoforms=3

Expression

expressed in T-cells & natural killer cells

Pathology

• defects in ZAP70 are the cause of selective T-cell defect
• defects in ZAP70 are assocatied with CLL

More general terms

• tyrosine kinase (protein tyrosine kinase, PTK)

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7535
• OMIM: https://mirror.omim.org/entry/176947
• UniProt: http://www.uniprot.org/uniprot/P43403.html