{PDOC50898} {PS50898; RBD} {BEGIN} ************************************ * Ras-binding domain (RBD) profile * ************************************ Ras and heterotrimeric G proteins' alpha subunits are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms. The activities of these GTPases are regulated in part by GTPase-activating protein (GAPs) that stimulate hydrolysis of GTP, and guanine nucleotide exchange factors (GEFs) that stimulate GDP release. Ras and G alpha GTPases are prolific signalling molecules interacting with a spectrum of effector molecules and acting through more than one signalling pathway. The Ras-binding domain (RBD) is an independent domain of about 75 residues, which is sufficient for GTP-dependent binding of Ras and other G alpha GTPases. The RBD domain can be present singly or in tandem and it can be found associated with many other domains, such as PDZ (see ), RGS (see ), PID (see ), PH (see ), C1 (see ), DH (see ), or protein kinase (see ) [1]. Structurally, the RBD domain of Raf-1 consists of a five-stranded mixed beta- sheet with an interrupted alpha-helix and two additional small alpha-helices (see ). The structure of the RBD domain belongs to the ubiquitin alpha/beta roll superfold and is similar to that of the RA domain (see ) despite the lack of significant sequence identity. The major interaction between Ras and Raf-1 RBD domain occurs between two antiparallel beta-strands: beta 2 of Ras and beta 2 of RBD [2]. Some proteins known to contain a RBD domain are listed below: - Vertebrate Raf proto-oncogene serine/threonine-protein kinase. - Mammalian regulator of G-protein signalling 12 (RGS12) and 14 (RGS14). - Mammalian T-lymphoma invasion and metastasis inducing protein 1 (TIAM1). TIAM1 modulates the activity of Rho-like proteins and connects extracellular signals to cytoskeletal activities. - Mouse Sif and Tiam1-like exchange factor (STEF). - Drosophila LOCO-c1 and LOCO-c2, two proteins required for glial cell differentiation. - Drosophila Still life proteins (SIF) type 1 and 2. They regulate synaptic differentiation through the organization of actin cytoskeleton possibly by activating Rho-like GTPases. The profile we developed covers the entire RBD domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: February 2003 / First entry. [ 1] Ponting C.P. "Raf-like Ras/Rap-binding domains in RGS12- and still-life-like signalling proteins." J. Mol. Med. 77:695-698(1999). PubMed=10606204 [ 2] Nassar N., Horn G., Herrmann C., Scherer A., McCormick F., Wittinghofer A. "The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue." Nature 375:554-560(1995). PubMed=7791872; DOI=10.1038/375554a0 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}