Ras-associating (RA) domain found in Ral guanine nucleotide dissociation stimulator-like 2 (RalGDS-like 2) and similar proteins
RalGDS-like 2 (RGL2), also termed RalGDS-like factor (RLF), or Ras-associated protein RAB2L, is a novel Ras and Rap 1A-associating protein that belongs to RalGDS family, whose members are involved in Ras and Ral signaling pathways as downstream effector proteins. RGL2 exhibits guanine nucleotide exchange activity towards the small GTPase Ral. Members in this family have similar domain structure: a central CDC25 homology domain with an upstream Ras Exchange motif (REM), and a C-terminal Ras-associating (RA) domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. The RA domain of RGL2 is phosphorylated by protein kinase A and the phosphorylation affects the ability of RGL2 to bind both Ras and Rap1.
Feature 1:putative RA-Ras interaction site [polypeptide binding site]
Evidence:
Comment:Based on the structural evidence that Rattus norvegicus RA domain of RalGDS (1LFD) in complex with Ras, contacts at 4A.
Comment:All RA domains have the common ubiquitin fold but not all of them bind to Ras proteins
Comment:Computational and manual sequence and structure analysis of RA domains show the positively charged sequence epitopes of its ubiquitin fold (beta1, beta2 and alpha1) which are located at similar positions are the hot spots of the binding interface to Ras.
Comment:The Ras protein signals to a number of distinct pathways by interacting with diverse downstream effectors. In the case of the Ras-RA_RalGDs complex a second RA_RalGDS molecule also interacts with a different part of the Ras molecule.
Jiyao W et al.(2023). "The conserved domain database in 2023.",