Protein Domain : IPR016251

Type:  Family Name:  Tyrosine-protein kinase, non-receptor Jak/Tyk2
Description:  Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human []. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups []:Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis []. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction []. Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [].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 []. 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.This entry represents the non-receptor tyrosine kinases Jak and Tyk2:Jak1 appears to be required in early development for specific cell migrations (epiboly), for the expression of the homeobox protein goosecoid and for the formation of anterior structures [].Jak2 plays a role in leptin signalling and in the control of body weight. It is involved in interleukin-3, and probably interleukin-23, signal transduction [].Jak3 is involved in the interleukin-2 and interleukin-4 signalling pathway. It phosphorylates STAT6, IRS1, IRS2 and PI3K [].Tyk2 is probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signalling. It phosphorylates the interferon-alpha/beta receptor alpha chain []. Short Name:  Tyr_kinase_non-rcpt_Jak/Tyk2

3 Child Features

DB identifier Type Name
IPR020775 Family Tyrosine-protein kinase, non-receptor Jak3
IPR020693 Family Tyrosine-protein kinase, non-receptor Jak2
IPR020776 Family Tyrosine-protein kinase, non-receptor Jak1

10 Contains

DB identifier Type Name
IPR000719 Domain Protein kinase domain
IPR011009 Domain Protein kinase-like domain
IPR020635 Domain Tyrosine-protein kinase, catalytic domain
IPR001245 Domain Serine-threonine/tyrosine-protein kinase catalytic domain
IPR000980 Domain SH2 domain
IPR000299 Domain FERM domain
IPR019749 Domain Band 4.1 domain
IPR017441 Binding_site Protein kinase, ATP binding site
IPR008266 Active_site Tyrosine-protein kinase, active site
IPR016045 Domain Tyrosine-protein kinase, non-receptor, TYK2, N-terminal

2 Cross Referencess

Identifier
PIRSF000636
PR01823

0 Found In

5 GO Annotations

GO Term Gene Name Organism
GO:0004715 IPR016251
GO:0005524 IPR016251
GO:0006468 IPR016251
GO:0035556 IPR016251
GO:0016020 IPR016251

0 Parent Features

0 Proteins

13 Publications

First Author Title Year Journal Volume Pages PubMed ID
            3291115
            12368087
            12471243
            15078142
            15320712
            19275641
            16700535
            15845350
            19290934
            9096349
            19660986
            19596999
            7526154