?
FERM domain C-lobe of Janus kinase (JAK) 3 JAK3 functions in signal transduction and interacts with members of the STAT (signal transduction and activators of transcription) family. It is required for signaling of the type I receptors that use the common gamma chain: IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. Cytokine binding induces the association of separate cytokine receptor subunits and the activation of the receptor-associated JAKs. In the absence of cytokine, JAKs lack protein tyrosine kinase activity. Once activated, the JAKs create docking sites for the STAT transcription factors by phosphorylation of specific tyrosine residues on the cytokine receptor subunits. Unlike the ubiquitous expression of JAK1, JAK2 and Tyk2, JAK3 is predominantly expressed in hematopoietic cells, such as NK cells, T cells and B cells. Mutations of JAK3 result in severe combined immunodeficiency (SCID). In addition to its well-known roles in T cells and NK cells, JAK3 has recently been found to inhibits IL-8-mediated chemotaxis. JAK3 interacts with CD247, TIAF1, and IL2RG. JAK (also called Just Another Kinase) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. The JAK family in mammals consists of 4 members: JAK1, JAK2, JAK3 and TYK2. JAKs are composed of seven JAK homology (JH) domains (JH1-JH7) . The C-terminal JH1 domain is the main catalytic domain, followed by JH2, which is often referred to as a pseudokinase domain, followed by JH3-JH4 which is homologous to the SH2 domain, and lastly JH5-JH7 which is a FERM domain. Named after Janus, the two-faced Roman god of doorways, JAKs possess two near-identical phosphate-transferring domains; one which displays the kinase activity (JH1), while the other negatively regulates the kinase activity of the first (JH2). The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",