| Primary Identifier | IPR041791 | Type | Domain |
| Short Name | KRIT1_FERM_C |
| description | KRIT1, also known as CCM1, a Rap1-binding protein, is expressed in endothelial cells where it is present in cell-cell junctions and associated with junctional proteins []. Together with CCM2/MGC4607 and CCM3/PDCD10, KRIT1 constitutes a set of proteins, mutations of which are found in cerebral cavernous malformations which are characterized by cerebral hemorrhages and vascular malformations in the central nervous system. KRIT-1 possesses four ankyrin repeats, a FERM domain, and multiple NPXY sequences, one of which is essential for integrin cytoplasmic domain-associated protein-1alpha (ICAP1alpha) binding and all of which mediate binding of CCM2. KRIT-1 localization is mediated by its FERM domain [].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. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain 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 [, ]. |
