InterPro : IPR020776

Name  Tyrosine-protein kinase, non-receptor Jak1 Short Name  Tyr_kinase_non-rcpt_Jak1
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, 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 represents the non-receptor tyrosine kinase JAK1, which is involved in the IFN-alpha/beta/gamma signal pathway. Jak1 acts as the kinase partner for the interleukin (IL)-2 receptor.JAK1 was initially cloned using a PCR-based strategy utilising degenerateprimers corresponding to conserved motifs within the catalytic domain of protein-tyrosine kinases []. In common with JAK2 and TYK2, and by contrastwith JAK3, JAK1 appears to be ubiquitously expressed.
 Feedback

Sequence Features

GO Displayer

Proteins

InterPro protein domain ID --> Contigs

 

Other

0 Child Features

9 Contains

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

0 Found In

1 Parent Features

Id Name Short Name Type
IPR016251 Tyrosine-protein kinase, non-receptor Jak/Tyk2 Tyr_kinase_non-rcpt_Jak/Tyk2 Family

10 Publications

First Author Title Year Journal Volume Pages
Hanks SK The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. 1988 Science 241 42-52
Manning G Evolution of protein kinase signaling from yeast to man. 2002 Trends Biochem Sci 27 514-20
Manning G The protein kinase complement of the human genome. 2002 Science 298 1912-34
Stout TJ High-throughput structural biology in drug discovery: protein kinases. 2004 Curr Pharm Des 10 1069-82
Li B Creating chemical diversity to target protein kinases. 2004 Comb Chem High Throughput Screen 7 453-72
Sharma PS Receptor tyrosine kinase inhibitors as potent weapons in war against cancers. 2009 Curr Pharm Des 15 758-76
Li E Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. 2006 Biochemistry 45 6241-51
Roskoski R Jr Src kinase regulation by phosphorylation and dephosphorylation. 2005 Biochem Biophys Res Commun 331 1-14
Ghoreschi K Janus kinases in immune cell signaling. 2009 Immunol Rev 228 273-87
Wilks AF Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. 1991 Mol Cell Biol 11 2057-65



To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)