PROSITE documentation PDOC50898 [for PROSITE entry PS50898]

Ras-binding domain (RBD) profile

Ras and heterotrimeric G proteins' α 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 α 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 α 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 <PDOC50106>), RGS (see <PDOC50132>), PID (see <PDOC00907>), PH (see <PDOC50003>), C1 (see <PDOC00379>), DH (see <PDOC00605>), or protein kinase (see <PDOC00100>) [1].

Structurally, the RBD domain of Raf-1 consists of a five-stranded mixed β-sheet with an interrupted α-helix and two additional small α-helices (see <PDB:1GUA>). The structure of the RBD domain belongs to the ubiquitin α/β roll superfold and is similar to that of the RA domain (see <PDOC50200>) despite the lack of significant sequence identity. The major interaction between Ras and Raf-1 RBD domain occurs between two antiparallel β-strands: β 2 of Ras and β 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.