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C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated Substrate) scaffolding proteins; a protein interaction module CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The FAT-like C-terminal domain of CAS proteins binds to the C-terminal domain of NSPs (novel SH2-containing proteins) to form multidomain signaling modules that mediate cell migration and invasion. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",