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FERM domain C-lobe of Janus kinase (JAK) 2 JAK2 has been implicated in signaling by members of the type II cytokine receptor family, the GM-CSF receptor family, the gp130 receptor family, and the single chain receptors. JAK2 orthologs have been identified in all mammals. Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, myelofibrosis as well as other myeloproliferative disorders. JAK2 gene fusions with the PCM1 and TEL(ETV6) (TEL-JAK2) genes have been found in leukemia patients. Researcher are targetting JAK2 inhibitors in the treatment of patients with prostate cancer. JAK2 has been shown to interact with a variety of proteins including growth hormone receptor, STAT5A, STAT5B, interleukin 5 receptor alpha subunit, interleukin 12 receptor, SOCS3, PTPN6,PTPN11, Grb2, VAV1, and YES1. 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.",