cd05038: PTKc_Jak_rpt2 (this model, PSSM-Id:173628 is obsolete and has been replaced by 270634)
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases
Protein Tyrosine Kinase (PTK) family; Janus kinase (Jak) subfamily; catalytic (c) domain (repeat 2). The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. 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. Jak subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis.
Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structures of human Jak2 bound with a pan-Jak inhibitor , and human Jak3 tyr kinase bound with an analog of the inhibitor, staurosporine (1YVJ_A and 2B7A_B respectively).