{PDOC50238} {PS50238; RHOGAP} {BEGIN} ************************************************* * Rho GTPase-activating proteins domain profile * ************************************************* Small G proteins of the Rho family, which includes Rho, Rac and Cdc42, regulate phosphorylation pathways that control a range of biological functions including cytoskeleton formation and cell proliferation. Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. The inactive GDP bound form is promoted by GTPase-activating proteins (GAPs). GAP proteins specific for Rho contain a conserved region of around 200 amino-acid residues, the Rho-GAP domain. This domain can accelerate the GTP hydrolysis activity of Rho by five orders of magnitude [1]. RhoGAP domains are usually associated with other signaling modules like SH2 (see ), SH3 (see ) or PH (see ). Like other GAP domains Rho-GAP is exclusively helical (nine helices) (see ) [2]. The core of the domain forms a four-helix bundle. The most conserved residues across the family are located on the bundle face that interacts with the G protein [3]. Rho-GAP domain like Ras-GAP supplies an arginine residue in trans into the active site of the G protein which confers a self-stimulatory GAP activity through homophilic interaction [4]. Some of the proteins containing a RhoGAP domain are listed below: - Mammalian ARAP 1,2 and 3 proteins, a family of GTPase activating proteins that contains both a RhoGAP and a ARFGAP domains (see ). They can regulate Rho or ARF G proteins according to their localization in the cell. - Vertebrate Beta-chimaerin protein, a GTPase activating protein for the Rho- like GTPase Rac. - Mammalian Nadrin protein, a neuron-specific GTPase-activating protein involved in regulated exocytosis. - Mammalian unconventional myosin-9b. - Mammalian breakpoint cluster region protein (BCR) and Drosophila Rotund protein, GTPase-activating proteins for Rac and Cdc42. - Mammalian Rho-GAP hematopoietic protein C1. - Mammalian Rho-GTPase-activating protein 6. It promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology. - Mammalian phosphatidylinositol 3-kinase regulatory alpha subunit, an adapter subunit of the phosphatidylinositol 3-kinase (PI3K). It has a critical role in signal transduction pathways originating from a variety of membrane-bound receptors. - Mammalian Inositol polyphosphate 5-phosphatase OCRL-1 (EC 3.1.3.-). It may function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes. - Mammalian type II inositol-1,4,5-trisphosphate 5-phosphatase involved in signal-terminating reaction (EC 3.1.3.56.). - Yeast LRG1 and SAC7 proteins, the two major Rho GTPase-activating proteins. The SAC7 protein is involved in assembly of actin. - Yeast BEM2 protein, a GTPase activating protein involved in the control of cellular morphogenesis. The profile we developed covers the whole domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: January 2003 / First entry. [ 1] Gamblin S.J., Smerdon S.J. "GTPase-activating proteins and their complexes." Curr. Opin. Struct. Biol. 8:195-201(1998). PubMed=9631293 [ 2] Barrett T., Xiao B., Dodson E.J., Dodson G., Ludbrook S.B., Nurmahomed K., Gamblin S.J., Musacchio A., Smerdon S.J., Eccleston J.F. "The structure of the GTPase-activating domain from p50rhoGAP." Nature 385:458-461(1997). PubMed=9009196 [ 3] Rittinger K., Walker P.A., Eccleston J.F., Nurmahomed K., Owen D., Laue E., Gamblin S.J., Smerdon S.J. "Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP." Nature 388:693-697(1997). PubMed=9262406; DOI=10.1038/41805 [ 4] Rittinger K., Walker P.A., Eccleston J.F., Smerdon S.J., Gamblin S.J. "Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue." Nature 389:758-762(1997). PubMed=9338791; DOI=10.1038/39651 -------------------------------------------------------------------------------- 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}