?
 
FERM domain C-lobe of Focal Adhesion Kinase 1 and 2 FAK1 (also called FRNK/Focal adhesion kinase-related nonkinase; p125FAK/pp125FAK;PTK2/Protein-tyrosine kinase 2 protein tyrosine kinase 2 (PTK2) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. It has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell survival. The N-terminal region of FAK1 contains a FERM domain, a linker, a kinase domain, and a C-terminal FRNK (FAK-related-non-kinase) domain. Three subdomains of FERM: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3), form a cloverleaf fold, similar to those of known FERM structures despite the low sequence conservation. The C-lobe/F3 within the FERM domain is part of the PH domain family. The phosphoinositide-binding site found in ERM family proteins is not present in the FERM domain of FAK1. The adjacent Src SH3 and SH2 binding sites in the linker of FAK1 associates with the F3 and F1 lobes and are thought to be involved in regulation. The FERM domain of FAK1 can inhibit enzymatic activity and repress FAK signaling. In an inactive state of FAK1, the FERM domain is thought to interact with the catalytic domain of FAK1 to repress its activity. Upon activation this interaction is disrupted and its kinase activity restored. The FRNK domain is thought to function as a negative regulator of kinase activity. The C-lobe/F3 is the third structural domain within the FERM domain. 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.",