Tyrosine-protein kinase, non-receptor Jak2 (IPR020693)
Short name: Tyr_kinase_non-rcpt_Jak2
Overlapping homologous superfamilies
- Protein kinase-like domain superfamily (IPR011009)
- Tyrosine-protein kinase, non-receptor Jak/Tyk2 (IPR016251)
- Tyrosine-protein kinase, non-receptor Jak2 (IPR020693)
Janus kinases (JAKs) are tyrosine kinases that function in membrane-proximal signalling events initiated by a variety of extracellular factors binding to cell surface receptors [PMID: 19290934]. Many type I and II cytokine receptors lack a protein tyrosine kinase domain and rely on JAKs to initiate the cytoplasmic signal transduction cascade. Ligand binding induces oligomerisation of the receptors, which then activates the cytoplasmic receptor-associated JAKs. These subsequently phosphorylate tyrosine residues along the receptor chains with which they are associated. The phosphotyrosine residues are a target for a variety of SH2 domain-containing transducer proteins. Amongst these are the signal transducers and activators of transcription (STAT) proteins, which, after binding to the receptor chains, are phosphorylated by the JAK proteins. Phosphorylation enables the STAT proteins to dimerise and translocate into the nucleus, where they alter the expression of cytokine-regulated genes. This system is known as the JAK-STAT pathway.
Four mammalian JAK family members have been identified: JAK1, JAK2, JAK3, and TYK2. They are relatively large kinases of approximately 1150 amino acids, with molecular weights of ~120-130kDa. Their amino acid sequences are characterised by the presence of 7 highly conserved domains, termed JAK homology (JH) domains. The C-terminal domain (JH1) is responsible for the tyrosine kinase function. The next domain in the sequence (JH2) is known as the tyrosine kinase-like domain, as its sequence shows high similarity to functional kinases but does not possess any catalytic activity. Although the function of this domain is not well established, there is some evidence for a regulatory role on the JH1 domain, thus modulating catalytic activity. The N-terminal portion of the JAKs (spanning JH7 to JH3) is important for receptor association and non-catalytic activity, and consists of JH3-JH4, which is homologous to the SH2 domain, and lastly JH5-JH7, which is a FERM domain.
This entry represents the non-receptor tyrosine kinase JAK2 [PMID: 19290934]. JAK2 was initially cloned using a PCR-based strategy utilising primers corresponding to conserved motifs within the catalytic domain of protein-tyrosine kinases [PMID: 1848670]. In common with JAK1 and TYK2, and by contrast with JAK3, JAK2 appears to be ubiquitously expressed.
- PR01825 (JANUSKINASE2)