This domain is the binding/interacting region of several protein kinases, such as the Schizosaccharomyces pombe Byr2. Byr2 is a Ser/Thr-specific protein kinase acting as mediator of signals for sexual differentiation in S. pombe by initiating a MAPK module, which is a highly conserved element in eukaryotes. Byr2 is activated by interacting with Ras, which then translocates the molecule to the plasma membrane. Ras proteins are key elements in intracellular signaling and are involved in a variety of vital processes such as DNA transcription, growth control, and differentiation. They function like molecular switches cycling between GTP-bound on and GDP-bound off states PMID:11709168.
This entry represents the Ras binding/interacting domain of the Byr2 protein from Schizosaccharomyces pombe. The Ras binding domain (RBD) of Byr2 is necessary and sufficient for the protein to be translocated by Ras to the plasma membrane [ (PUBMED:11709168) ]. This domain can also be found in Ste11 protein from Saccharomyces cerevisiae.
Byr2 is mitogen-activated protein/ERK kinase kinase (MEKK) that responds to pheromone signalling and controls mating through a mitogen-activated protein kinase (MAPK) pathway [ (PUBMED:16754851) ]. The small GTP binding protein Ras binds and activates Byr2 [ (PUBMED:11709168) ].
Ste11 is a mitogen activated protein kinase kinase kinase (MAPKKK) involved in the MAPK pathways governing mating, osmosensing, and filamentous growth [ (PUBMED:15567849) ].
Family alignment:
There are 375 Ras_bdg_2 domains in 375 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 Ras_bdg_2 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with Ras_bdg_2 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing Ras_bdg_2 domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast.
Structure. 2001; 9: 1043-50
Display abstract
BACKGROUND: The small GTP binding protein Ras has important roles in cellulargrowth and differentiation. Mutant Ras is permanently active and contributes tocancer development. In its activated form, Ras interacts with effector proteins, frequently initiating a kinase cascade. In the lower eukaryoticSchizosaccharomyces pombe, Byr2 kinase represents a Ras target that in terms ofsignal-transduction hierarchy can be considered a homolog of mammalianRaf-kinase. The activation mechanism of protein kinases by Ras is not understood,and there is no detailed structural information about Ras binding domains (RBDs) in nonmammalian organisms. RESULTS: The crystal structure of the Ras-Byr2RBDcomplex at 3 A resolution shows a complex architecture similar to that observedin mammalian homologous systems, with an interprotein beta sheet stabilized bypredominantly polar interactions between the interacting components. TheC-terminal half of the Ras switch I region contains most of the contact anchors, while on the Byr2 side, a number of residues from topologically distinct regions are involved in complex stabilization. A C-terminal helical segment, which is notpresent in the known mammalian homologous systems and which is part of theauto-inhibitory region, has an additional binding site outside the switch Iregion. CONCLUSIONS: The structure of the Ras-Byr2 complex confirms the Rasbinding module as a communication element mediating Ras-effector interactions;the Ras-Byr2 complex is also conserved in a lower eukaryotic system like yeast,which is in contrast to other small GTPase families. The extra helical segmentmight be involved in kinase activation.
