cd05073: PTKc_Hck (this model, PSSM-Id:133204 is obsolete and has been replaced by 270658)
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase
Protein Tyrosine Kinase (PTK) family; Hematopoietic cell kinase (Hck); 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. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) tyr kinases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of granulocyte colony-stimulating factor (G-CSF)-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes (PMNs). Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD).
Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structures of human Hck bound with various inhibitors and ATP analogs (2HK5_A, 2C0T_A and 1AD5_A ).
Jiyao W et al.(2023). "The conserved domain database in 2023.",