SMART: RBD domain annotation

RBD Raf-like Ras-binding domain

SMART accession number:	SM00455
Description:	-
Interpro abstract (IPR003116):	This is the Ras-binding domain found in proteins related to Ras. It is found in association with the PE-bind and pkinase domains.
GO process:	signal transduction (GO:0007165)
GO function:	receptor signaling protein activity (GO:0005057)
Family alignment:	View or

There are 1355 RBD domains in 1054 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing RBD domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with RBD domain is also avaliable.

Click on the protein counts, or double click on taxonomic names to display all proteins containing RBD domain in the selected taxonomic class.
Cellular role (predicted cellular role)
Cellular role: signalling
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Ponting CP
- Raf-like Ras/Rap-binding domains in RGS12- and still-life-like signalling proteins.
- J Mol Med. 1999; 77: 695-8
- Display abstract
- Ras proteins play critical roles in regulating cell growth and differentiation, and mutated Ras genes are expressed in a variety of human cancers. Consequently, much interest has centered on the binding partners of Ras, including the Ras-binding domain (RBD) of Raf kinase. Here evidence is presented that domains homologous to the Raf RBD are present in tandem in RGS12, RGS14 and LOCO, and singly in molecules similar to mouse Tiam-1. In addition, RGS12, RGS14 and LOCO are shown to contain single "LGN motifs" that are guanine nucleotide exchange factors specific for the alpha-subunit of G proteins. These findings indicate "cross-talk" interactions between signalling pathways involving Ras and Rap and pathways involving Rho, Rac and G alpha GTPases.
- Block C, Janknecht R, Herrmann C, Nassar N, Wittinghofer A
- Quantitative structure-activity analysis correlating Ras/Raf interaction in vitro to Raf activation in vivo.
- Nat Struct Biol. 1996; 3: 244-51
- Display abstract
- Binding of Ras to c-Raf-1 is a pivotal step of many mitogenic signalling pathways. Based on the recent crystal structure of the complex of Rap1A with the Ras-binding domain of Raf, mutations were introduced in c-Raf-1 and their effects on Ras/Raf binding affinity in vitro and Ras/Raf regulated gene expression in vivo were analysed. Our data reveal an empirical semilogarithmic correlation between dissociation constants and Raf-induced gene activity. The functional epitope that primarily determines binding affinity consists of residues Gln 66, Lys 84 and Arg 89 in Raf. This quantitative structure-activity investigation may provide a general approach to correlate structure-guided biochemical analysis with biological function of protein-protein interactions.
- Muslin AJ, Tanner JW, Allen PM, Shaw AS
- Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine.
- Cell. 1996; 84: 889-97
- Display abstract
- The highly conserved and ubiquitously expressed 14-3-3 family of proteins bind to a variety of proteins involved in signal transduction and cell cycle regulation. The nature and specificity of 14-3-3 binding is, however, not known. Here we show that 14-3-3 is a specific phosphoserine-binding protein. Using a panel of phosphorylated peptides based on Raf-1, we have defined the 14-3-3 binding motif and show that most of the known 14-3-3 binding proteins contain the motif. Peptides containing the motif could disrupt 14-3-3 complexes and inhibit maturation of Xenopus laevis oocytes. These results suggest that the interactions of 14-3-3 with signaling proteins are critical for the activation of signaling proteins. Our findings also suggest novel roles for serine/threonine phosphorylation in the assembly of protein-protein complexes.
- Han L, Colicelli J
- A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1.
- Mol Cell Biol. 1995; 15: 1318-23
- Display abstract
- The overexpression of some human proteins can cause interference with the Ras signal transduction pathway in the yeast Saccharomyces cerevisiae. The functional block is located at the level of the effector itself, since these proteins do not suppress activating mutations further downstream in the same pathway. We now demonstrate, with in vivo and in vitro experiments, that the protein encoded by one human cDNA (clone 99) can interact directly with yeast Ras2p and with human H-Ras protein, and we have named this gene rin1 (Ras interaction/interference). The interaction between Ras and Rin1 is enhanced when Ras is bound to GTP. Rin1 is not able to interact with either an effector mutant or a dominant negative mutant of H-Ras. Thus, Rin1 displays a human H-Ras interaction profile that is the same as that seen for Raf1 and yeast adenylyl cyclase, two known effectors of Ras. Moreover, Raf1 directly competes with Rin1 for binding to H-Ras in vitro. Unlike Raf1, however, the Rin1 protein resides primarily at the plasma membrane, where H-Ras is localized. These data are consistent with Rin1 functioning in mammalian cells as an effector or regulator of H-Ras.
- 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. 1995; 375: 554-60
- Display abstract
- The X-ray crystal structure of the complex between the Ras-related protein Rap1A in the GTP-analogue (GppNHp) form and the Ras-binding domain (RBD) of the Ras effector molecule c-Raf1, a Ser/Thr-specific protein kinase, has been solved to a resolution of 2.2 A. It shows that RBD has the ubiquitin superfold and that the structure of Rap1A is very similar to that of Ras. The interaction between the two proteins is mediated by an apparent central antiparallel beta-sheet formed by strands B1-B2 from RBD and strands beta 2-beta 3 from Rap1A. Complex formation is mediated by main-chain and side-chain interactions of the so-called effector residues in the switch I region of Rap1A.
- Sprang SR
- How Ras works: structure of a Rap-Raf complex.
- Structure. 1995; 3: 641-3
- Display abstract
- The three-dimensional structure of the complex between Rap and the 'Ras-binding domain' of Raf could be the prototype for a G protein-effector interaction.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Links (links to other resources describing this domain)
INTERPRO IPR003116

PDB code	Main view	Title
1c1y		CRYSTAL STRUCTURE OF RAP.GMPPNP IN COMPLEX WITH THE RAS-BINDING-DOMAIN OF C-RAF1 KINASE (RAFRBD).
1gua		HUMAN RAP1A, RESIDUES 1-167, DOUBLE MUTANT (E30D,K31E) COMPLEXED WITH GPPNHP AND THE RAS-BINDING-DOMAIN OF HUMAN C-RAF1, RESIDUES 51-131
1rfa		NMR SOLUTION STRUCTURE OF THE RAS-BINDING DOMAIN OF C-RAF-1
1rrb		THE RAS-BINDING DOMAIN OF RAF-1 FROM RAT, NMR, 1 STRUCTURE
1wfy		Solution structure of the Ras-binding domain of mouse RGS14
1wxm		Solution Structure of the N-terminal Ras-binding Domain (RBD) in Human a-Raf Kinase
2l05		Solution NMR Structure of the Ras-binding domain of Serine/threonine-protein kinase B-raf from Homo sapiens, Northeast Structural Genomics Consortium Target HR4694F
2mse		2MSE
3kuc		Complex of Rap1A(E30D/K31E)GDP with RafRBD(A85K/N71R)
3kud		Complex of Ras-GDP with RafRBD(A85K)
3ny5		Crystal structure of the RBD domain of serine/threonine-protein kinase B-raf from Homo sapiens. Northeast Structural Genomics Consortium Target HR4694F
4g0n		Crystal Structure of wt H-Ras-GppNHp bound to the RBD of Raf Kinase
4g3x		Crystal Structure of Q61L H-Ras-GppNHp bound to the RBD of Raf Kinase
5j17		5J17
5j18		5J18
5j2r		5J2R

RBD

Taxonomic distribution of proteins containing RBD domain.

3D Structures of RBD domains in PDB