Afadin, also termed ALL1-fused gene from chromosome 6 protein (AF-6), or canoe, is involved in many fundamental signaling cascades in cells. In addition, it is involved in oncogenesis and metastasis. Afadin has multiple domains: from the N-terminus to the C-terminus it has two Ras-associated (RA) domains, a forkhead-associated domain, a dilute domain, a PDZ domain, three proline-rich domains, and an F-actin binding domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. Afadin is abundant at cadherin-based adherens junctions in epithelial cells, endothelial cells, and fibroblasts. This family corresponds to the second RA domain of afadin.
Feature 1: key conserved lysine K33, 1 residue position
Conserved feature residue pattern:[KR]
Evidence:
Comment:K33/R (Ub numbering) is one of 7 lysines involved in chain linkage in ubiquitin (K6, K11, K27, K29, K33, K48, or K63, Ub numbering), the other 6 lysines are not conserved in this subfamily; may have other functions
Jiyao W et al.(2023). "The conserved domain database in 2023.",