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Protein Domain : IPR016251

Name  Tyrosine-protein kinase, non-receptor Jak/Tyk2 Short Name  Tyr_kinase_non-rcpt_Jak/Tyk2
Type  Family 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, andan 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 tyrosinekinase-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 [].

Publication Counts Displayer

3 Child Features

DB identifier Name Short Name Type
IPR020693 Tyrosine-protein kinase, non-receptor Jak2 Tyr_kinase_non-rcpt_Jak2 Family
IPR020775 Tyrosine-protein kinase, non-receptor Jak3 Tyr_kinase_non-rcpt_Jak3 Family
IPR020776 Tyrosine-protein kinase, non-receptor Jak1 Tyr_kinase_non-rcpt_Jak1 Family

10 Contains

DB identifier Name Short Name Type
IPR011009 Protein kinase-like domain Kinase-like_dom Domain
IPR000719 Protein kinase domain Prot_kinase_dom Domain
IPR017441 Protein kinase, ATP binding site Protein_kinase_ATP_BS Binding_site
IPR000980 SH2 domain SH2 Domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain Ser-Thr/Tyr_kinase_cat_dom Domain
IPR019749 Band 4.1 domain Band_41_domain Domain
IPR000299 FERM domain FERM_domain Domain
IPR020635 Tyrosine-protein kinase, catalytic domain Tyr_kinase_cat_dom Domain
IPR008266 Tyrosine-protein kinase, active site Tyr_kinase_AS Active_site
IPR016045 Tyrosine-protein kinase, non-receptor, TYK2, N-terminal Tyr_kinase_non-rcpt_TYK2_N Domain

2 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PIRSF000636 PIRSF IPR016251
PR01823 PRINTS IPR016251

2 Data Sets

Name URL
InterPro data set  
InterPro GO Annotation data set  

0 Found In

5 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0004715 non-membrane spanning protein tyrosine kinase activity
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0005524 ATP binding
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0006468 protein phosphorylation
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0035556 intracellular signal transduction
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0016020 membrane

5 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0004715 non-membrane spanning protein tyrosine kinase activity
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0005524 ATP binding
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0006468 protein phosphorylation
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0035556 intracellular signal transduction
Tyrosine-protein kinase, non-receptor Jak/Tyk2   GO:0016020 membrane

0 Parent Features

0 Proteins