Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; a protein interaction module
CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. 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. CAS proteins associate with the 14-3-3 family; this interaction is regulated by integrin-mediated cell adhesion. The serine rich four helix bundle domain of BCAR1, another CAS protein, has been shown to bind 14-3-3 in a phosphorylation-dependent manner. This domain is structurally similar to other helical bundles found in cell adhesion components such as alpha-catenin, vinculin, and FAK, and may bind other proteins in addition to the 14-3-3 family.
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