RHORho (Ras homology) subfamily of Ras-like small GTPases
|SMART accession number:||SM00174|
|Description:||Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.|
|Interpro abstract (IPR003578):|
Small GTPases form an independent superfamily within the larger class of regulatory GTP hydrolases. This superfamily contains proteins that control a vast number of important processes and possess a common, structurally preserved GTP-binding domain [(PUBMED:2122258), (PUBMED:1898771)]. Sequence comparisons of small G proteins from various species have revealed that they are conserved in primary structures at the level of 30-55% similarity [(PUBMED:2029511)].
Crystallographic analysis of various small G proteins revealed the presence of a 20 kDa catalytic domain that is unique for the whole superfamily [(PUBMED:1898771), (PUBMED:2196171)]. The domain is built of five alpha helices (A1-A5), six beta-strands (B1-B6) and five polypeptide loops (G1-G5). A structural comparison of the GTP- and GDP-bound form, allows one to distinguish two functional loop regions: switch I and switch II that surround the gamma-phosphate group of the nucleotide. The G1 loop (also called the P-loop) that connects the B1 strand and the A1 helix is responsible for the binding of the phosphate groups. The G3 loop provides residues for Mg(2+) and phosphate binding and is located at the N terminus of the A2 helix. The G1 and G3 loops are sequentially similar to Walker A and Walker B boxes that are found in other nucleotide binding motifs. The G2 loop connects the A1 helix and the B2 strand and contains a conserved Thr residue responsible for Mg(2+) binding. The guanine base is recognised by the G4 and G5 loops. The consensus sequence NKXD of the G4 loop contains Lys and Asp residues directly interacting with the nucleotide. Part of the G5 loop located between B6 and A5 acts as a recognition site for the guanine base [(PUBMED:11995995)].
The small GTPase superfamily can be divided into at least 8 different families, including:
This entry represents the Rho subfamily of Ras-like small GTPases. The crystal structures of a number of the members of this entry have been determined: Rnd3/RhoE [(PUBMED:12163169)], RhoA [(PUBMED:11927263)] and Cdc42 [(PUBMED:9846874)].
|GO process:||small GTPase mediated signal transduction (GO:0007264)|
|GO component:||intracellular (GO:0005622)|
|GO function:||GTP binding (GO:0005525)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing RHO domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with RHO domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing RHO domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
Binding / catalysis: GTP-hydrolysis
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Hall A
- Rho GTPases and the actin cytoskeleton.
- Science. 1998; 279: 509-14
- Display abstract
The actin cytoskeleton mediates a variety of essential biological functions in all eukaryotic cells. In addition to providing a structural framework around which cell shape and polarity are defined, its dynamic properties provide the driving force for cells to move and to divide. Understanding the biochemical mechanisms that control the organization of actin is thus a major goal of contemporary cell biology, with implications for health and disease. Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and furthermore, through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
- Ren XD, Schwartz MA
- Regulation of inositol lipid kinases by Rho and Rac.
- Curr Opin Genet Dev. 1998; 8: 63-7
- Display abstract
Rho and Rac small GTPases associate with type-I phosphatidylinositol 4-phosphate 5-kinase to regulate the production of phosphatidylinositol 4,5-bisphosphate. This lipid appears to mediate some of the effects of Rho and Rac on the actin cytoskeleton. The genes for several type-I phosphatidylinositol 4-phosphate 5-kinases have been cloned recently but it is not known which one interacts with Rho and/or Rac. Rho family GTPases also interact with phosphatidylinositol 3-kinase, though this kinase can be either upstream or downstream of the GTPases depending upon the system.
- Tanaka K, Takai Y
- Control of reorganization of the actin cytoskeleton by Rho family small GTP-binding proteins in yeast.
- Curr Opin Cell Biol. 1998; 10: 112-6
- Display abstract
Accumulating evidence indicates that Rho family small GTP-binding proteins regulate reorganization of the actin cytoskeleton. There are members of the Rho family in the budding yeast Saccharomyces cerevisiae, in which powerful molecular genetical approaches are applicable. Recent identification of regulators and targets of the Rho family members has enhanced our understanding of the regulation and modes of action of Rho family members in reorganization of the actin cytoskeleton.
- Feltham JL et al.
- Definition of the switch surface in the solution structure of Cdc42Hs.
- Biochemistry. 1997; 36: 8755-66
- Display abstract
Proteins of the rho subfamily of ras GTPases have been shown to be crucial components of pathways leading to cell growth and the establishment of cell polarity and mobility. Presented here is the solution structure of one such protein, Cdc42Hs, which provides insight into the structural basis for specificity of interactions between this protein and its effector and regulatory proteins. Standard heteronuclear NMR methods were used to assign the protein, and approximately 2100 distance and dihedral angle constraints were used to calculate a set of 20 structures using a combination of distance geometry and simulated annealing refinement. These structures show overall similarity to those of other GTP-binding proteins, with some exceptions. The regions corresponding to switch I and switch II in H-ras are disordered, and no evidence was found for an alpha-helix in switch II. The 13-residue insertion, which is only present in rho-subtype proteins and has been shown to be an important mediator of binding of regulatory and target proteins, forms a compact structure containing a short helix lying adjacent to the beta4-alpha3 loop. The insert forms one edge of a "switch surface" and, unexpectedly, does not change conformation upon activation of the protein by the exchange of GTP analogs for GDP. These studies indicate the insert region forms a stable invariant "footrest" for docking of regulatory and effector proteins.
- Hirshberg M, Stockley RW, Dodson G, Webb MR
- The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue.
- Nat Struct Biol. 1997; 4: 147-52
- Display abstract
The crystal structure of human rac1, a member of the rho family of small G-proteins, complexed with the non-hydrolysable GTP analogue, guanosine-5'-(beta gamma-imino)triphosphate (GMPPNP), has been determined by X-ray analysis at a resolution of 1.38 A. Comparison with the structure of H-ras indicates that rac1 has an extra alpha-helical domain that is characteristic of the rho G proteins, and may be involved in the signalling pathway of this family.
- Koelle MR
- A new family of G-protein regulators - the RGS proteins.
- Curr Opin Cell Biol. 1997; 9: 143-7
- Display abstract
Genetic experiments have recently been used to identify a family of 'regulator of G-protein signaling' (RGS) proteins, which downregulate signaling by heterotrimeric G proteins. The first biochemical studies of RGS proteins have shown that they accelerate the GTPase activities of G-protein alpha subunits, thus driving G proteins into their inactive GDP-bound forms. The physiological significance of the large number of different RGS proteins remains to be explored.
- Li R, Zhang B, Zheng Y
- Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190.
- J Biol Chem. 1997; 272: 32830-5
- Display abstract
The Rho family small GTP-binding proteins are subjected to regulation by Rho GTPase-activating proteins (GAPs) in the course of transmitting diverse intracellular signals. To understand the mechanism of GAP-catalyzed GTP hydrolysis of Rho GTPases, we have studied the interaction between RhoA and p190, the RasGAP binding phosphoprotein which has been implicated as a Rho-specific GAP, by delineating the structural determinants of RhoA and p190 GAP domain (p190GD) that are involved in their functional coupling. Besides the conserved residues Tyr34, Thr37, and Phe39 in the switch I region of RhoA which are required for p190GD interaction, chimeras made between RhoA and Cdc42, a close relative of RhoA with which p190GD interacts 50-fold less efficiently, revealed that residues outside the switch I and neighboring regions of RhoA, residues 85-122 in particular, contain the major p190GD-specifying determinant(s). Mutation of the unique Asp90 of RhoA in this region mostly abolished p190GD stimulation, whereas the corresponding reverse mutation of Cdc42 (S88D) was able to respond to p190GD-catalysis similarly as RhoA. Further kinetic analysis of these mutants provided evidence that Asp90 of RhoA contributes primarily to the specific binding interaction with p190GD. On the other hand, two charged residues of p190GD, Arg1283 and Lys1321, which are located in the putative G-protein binding helix pocket of GAP domain, were found to be involved in different aspects of interaction with RhoA. The R1283L mutant of p190GD lost GAP activity but retained the ability to bind to RhoA, while K1321A failed to stimulate and to bind to RhoA. These results indicate that residue Asp90 constitutes the second GAP-interactive site in RhoA which is mostly responsible for conferring p190GD-specificity, and suggest that the role of p190GD in the GTPase reaction of RhoA is in part to supply active site residue Arg1283 for efficient catalysis.
- Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ
- Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue.
- Nature. 1997; 389: 758-62
- Display abstract
Small G proteins of the Rho family, which includes Rho, Rac and Cdc42Hs, regulate phosphorylation pathways that control a range of biological functions including cytoskeleton formation and cell proliferation. They operate as molecular switches, cycling between the biologically active GTP-bound form and the inactive GDP-bound state. Their rate of hydrolysis of GTP to GDP by virtue of their intrinsic GTPase activity is slow, but can be accelerated by up to 10(5)-fold through interaction with rhoGAP, a GTPase-activating protein that stimulates Rho-family proteins. As such, rhoGAP plays a crucial role in regulating Rho-mediated signalling pathways. Here we report the crystal structure of RhoA and rhoGAP complexed with the transition-state analogue GDP.AlF4- at 1.65 A resolution. There is a rotation of 20 degrees between the Rho and rhoGAP proteins in this complex when compared with the ground-state complex Cdc42Hs.GMPPNP/rhoGAP, in which Cdc42Hs is bound to the non-hydrolysable GTP analogue GMPPNP. Consequently, in the transition state complex but not in the ground state, the rhoGAP domain contributes a residue, Arg85(GAP) directly into the active site of the G protein. We propose that this residue acts to stabilize the transition state of the GTPase reaction. RhoGAP also appears to function by stabilizing several regions of RhoA that are important in signalling the hydrolysis of GTP.
- Rittinger K et al.
- Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP.
- Nature. 1997; 388: 693-7
- Display abstract
Small G proteins transduce signals from plasma-membrane receptors to control a wide range of cellular functions. These proteins are clustered into distinct families but all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of G proteins, which includes Cdc42Hs, activate effectors involved in the regulation of cytoskeleton formation, cell proliferation and the JNK signalling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GTPase-activating proteins (GAPs) that enhance the rate of GTP hydrolysis by up to 10(5) times. We report here the crystal structure of Cdc42Hs, with the non-hydrolysable GTP analogue GMPPNP, in complex with the GAP domain of p50rhoGAP at 2.7A resolution. In the complex Cdc42Hs interacts, mainly through its switch I and II regions, with a shallow pocket on rhoGAP which is lined with conserved residues. Arg 85 of rhoGAP interacts with the P-loop of Cdc42Hs, but from biochemical data and by analogy with the G-protein subunit G(i alpha1), we propose that it adopts a different conformation during the catalytic cycle which enables it to stabilize the transition state of the GTP-hydrolysis reaction.
- Scheffzek K et al.
- The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.
- Science. 1997; 277: 333-8
- Display abstract
The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain of the human GTPase-activating protein p120GAP (GAP-334) in the presence of aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure shows the partly hydrophilic and partly hydrophobic nature of the communication between the two molecules, which explains the sensitivity of the interaction toward both salts and lipids. An arginine side chain (arginine-789) of GAP-334 is supplied into the active site of Ras to neutralize developing charges in the transition state. The switch II region of Ras is stabilized by GAP-334, thus allowing glutamine-61 of Ras, mutation of which activates the oncogenic potential, to participate in catalysis. The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state.
- Sprang SR
- G protein mechanisms: insights from structural analysis.
- Annu Rev Biochem. 1997; 66: 639-78
- Display abstract
This review is concerned with the structures and mechanisms of a superfamily of regulatory GTP hydrolases (G proteins). G proteins include Ras and its close homologs, translation elongation factors, and heterotrimeric G proteins. These proteins share a common structural core, exemplified by that of p21ras (Ras), and significant sequence identity, suggesting a common evolutionary origin. Three-dimensional structures of members of the G protein superfamily are considered in light of other biochemical findings about the function of these proteins. Relationships among G protein structures are discussed, and factors contributing to their low intrinsic rate of GTP hydrolysis are considered. Comparison of GTP- and GDP-bound conformations of G proteins reveals how specific contacts between the gamma-phosphate of GTP and the switch II region stabilize potential effector-binding sites and how GTP hydrolysis results in collapse (or reordering) of these surfaces. A GTPase-activating protein probably binds to and stabilizes the conformation of its cognate G protein that recognizes the transition state for hydrolysis, and may insert a catalytic residue into the G protein active site. Inhibitors of nucleotide release, such as the beta gamma subunit of a heterotrimeric G protein, bind selectively to and stabilize the GDP-bound state. Release factors, such as the translation elongation factor, Ts, also recognize the switch regions and destabilize the Mg(2+)-binding site, thereby promoting GDP release. G protein-coupled receptors are expected to operate by a somewhat different mechanism, given that the GDP-bound form of many G protein alpha subunits does not contain bound Mg2+.
- Sprang SR
- G proteins, effectors and GAPs: structure and mechanism.
- Curr Opin Struct Biol. 1997; 7: 849-56
- Display abstract
G proteins from a diverse family of regulatory GTPases which, in the GTP-bound state, bind to and activate downstream effectors. Structures of Ras homologs bound to effector domains have revealed mechanisms by which G proteins couple GTP binding to effector activation and achieve specificity. Complexes between structurally unrelated GTPase-activating proteins with complementary G proteins suggest common mechanisms by which GTP hydrolysis is stimulated via direct interactions with conformationally labile switch regions of the G protein.
- Tesmer JJ, Berman DM, Gilman AG, Sprang SR
- Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis.
- Cell. 1997; 89: 251-61
- Display abstract
RGS proteins are GTPase activators for heterotrimeric G proteins. We report here the 2.8 A resolution crystal structure of the RGS protein RGS4 complexed with G(i alpha1)-Mg2+-GDP-AlF4 . Only the core domain of RGS4 is visible in the crystal. The core domain binds to the three switch regions of G(i alpha1), but does not contribute catalytic residues that directly interact with either GDP or AlF4-. Therefore, RGS4 appears to catalyze rapid hydrolysis of GTP primarily by stabilizing the switch regions of G(i alpha1), although the conserved Asn-128 from RGS4 could also play a catalytic role by interacting with the hydrolytic water molecule or the side chain of Gln-204. The binding site for RGS4 on G(i alpha1) is also consistent with the activity of RGS proteins as antagonists of G(alpha) effectors.
- Narumiya S
- The small GTPase Rho: cellular functions and signal transduction.
- J Biochem (Tokyo). 1996; 120: 215-28
- Display abstract
Rho, a Ras homologue of small GTPase, is present from yeast to mammals. It shuttles between the active GTP-bound form and the inactive GDP-bound form and works as a switch in stimulus-evoked cell adhesion and motility, enhancement of contractile responses, and cytokinesis. In these actions, Rho directs the reorganization of the actin cytoskeleton at a specific time and at a specific site in the cell. It also activates serum response factor possibly via a kinase cascade and mediates a growth signal to nuclei. Two signalling processes are known to lead to Rho activation: one is activation of certain types of G-protein-coupled receptors such as lysophosphatidic acid receptor, and the other is activation of other small GTPases including Ras, CDC42, and Rac. Molecules catalyzing the GDP-GTP exchange of Rho, Rho guanine nucleotide exchange factors (Rho GEF), and those catalyzing the acceleration of GTP hydrolysis, Rho GTPase activating proteins (Rho GAP), were identified as Dbl- and Bcr-containing molecules, respectively. In addition, a molecule inhibiting guanine nucleotide exchange of Rho, Rho guanine nucleotide dissociation inhibitor (Rho-GDI), was isolated and characterized. More recently, putative Rho targets possibly mediating various Rho actions have been identified by their selective interaction with GTP-bound Rho. They include lipid kinases such as phosphatidyl-inositol-5-kinase and protein serine/threonine kinases such as PKN and p160ROCK. A model of the molecular mechanism of action of Rho constructed on the basis of these findings is presented. There are, however, still many unclarified links between cell stimulation, Rho activation and final Rho actions.
- Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A
- Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras.
- Nature. 1996; 384: 591-6
- Display abstract
Ras-related GTP-binding proteins function as molecular switches which cycle between GTP-bound 'on'- and GDP-bound 'off'-states. GTP hydrolysis is the common timing mechanism that mediates the return from the 'on' to the 'off'-state. It is usually slow but can be accelerated by orders of magnitude upon interaction with GTPase-activating proteins (GAPs). In the case of Ras, a major regulator of cellular growth, point mutations are found in approximately 30% of human tumours which render the protein unable to hydrolyse GTP, even in the presence of Ras-GAPs. The first structure determination of a GTPase-activating protein reveals the catalytically active fragment of the Ras-specific p120GAP (ref. 2), GAP-334, as an elongated, exclusively helical protein which appears to represent a novel protein fold. The molecule consists of two domains, one of which contains all the residues conserved among different GAPs for Ras. From the location of conserved residues around a shallow groove in the central domain we can identify the site of interaction with Ras x GTP. This leads to a model for the interaction between Ras and GAP that satisfies numerous biochemical and genetic data on this important regulatory process.
- Watanabe G et al.
- Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho.
- Science. 1996; 271: 645-8
- Display abstract
The Rho guanosine 5'-triphosphatase (GTPase) cycles between the active guanosine triphosphate (GTP)-bound form and the inactive guanosine diphosphate-bound form and regulates cell adhesion and cytokinesis, but how it exerts these actions is unknown. The yeast two-hybrid system was used to clone a complementary DNA for a protein (designated Rhophilin) that specifically bound to GTP-Rho. The Rho-binding domain of this protein has 40 percent identity with a putative regulatory domain of a protein kinase, PKN. PKN itself bound to GTP-Rho and was activated by this binding both in vitro and in vivo. This study indicates that a serine-threonine protein kinase is a Rho effector and presents an amino acid sequence motif for binding to GTP-Rho that may be shared by a family of Rho target proteins.
- Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ
- RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.
- Nature. 1996; 383: 172-5
- Display abstract
Signaling pathways using heterotrimeric guanine-nucleotide-binding-proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli. GTP binding activates G proteins by dissociating G alpha from G beta gamma subunits, and GTP hydrolysis by G alpha subunits deactivates G proteins by allowing heterotrimers to reform. However, deactivation of G-protein signalling pathways in vivo can occur 10- to 100-fold faster than the rate of GTP hydrolysis of G alpha subunits in vitro, suggesting that GTPase-activating proteins (GAPs) deactivate G alpha subunits. Here we report that RGS (for regulator of G-protein signalling) proteins are GAPs for G alpha subunits. RGS1, RGS4 and GAIP (for G alpha-interacting protein) bind specifically and tightly to G alphai and G alpha0 in cell membranes treated with GDP and AlF4(-), and are GAPs for G alphai, G alpha0 and transducin alpha-subunits, but not for G alphas. Thus, these RGS proteins are likely to regulate a subset of the G-protein signalling pathways in mammalian cells. Our results provide insight into the mechanisms that govern the duration and specificity of physiological responses elicited by G-protein-mediated signalling pathways.
- Zigmond SH
- Signal transduction and actin filament organization.
- Curr Opin Cell Biol. 1996; 8: 66-73
- Display abstract
Small GTP-binding proteins of the Rho family appear to integrate extracellular signals from diverse receptor types and initiate rearrangements of F-actin. Active members of the Rho family, Rho and Rac, are now joined by Cdc42 which induces filopodia. Downstream of the Rho family proteins, actin polymerization may be induced by an increase in the availability of actin filament barbed ends. Actin organization may be affected by exposure of actin-binding sites on proteins such as vinculin and ezrin.
- Scheffzek K, Klebe C, Fritz-Wolf K, Kabsch W, Wittinghofer A
- Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form.
- Nature. 1995; 374: 378-81
- Display abstract
The Ran proteins constitute a distinct branch of the superfamily of Ras-related GTP-binding proteins which function as molecular switches cycling between GTP-bound 'on' and GDP-bound 'off' states. Ran is located predominantly in the nucleus of eukaryotic cells and is involved in the nuclear import of proteins as well as in control of DNA synthesis and of cell-cycle progression. We report here the crystal structure at 2.3 A resolution of human Ran (Mr 24K) complexed with GDP and Mg2+. This structure reveals a similarity with the Ras core (G-domain) but with significant variations in regions involved in GDP and Mg2+ coordination (switch I and switch II regions in Ras), suggesting that there could be major conformational changes upon GTP binding. In addition to the G-domain, an extended chain and an alpha-helix were identified at the carboxy terminus. The amino-terminal (amino-acid residues MAAQGEP) stretch and the acidic tail (DEDDDL) appear to be flexible in the crystal structure.
- Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the RHO domain.
Protein Disease Ras-related protein Rab-27A (P51159) (SMART) OMIM:603868: Griscelli syndrome
GTPase NRas (P01111) (SMART) OMIM:164790: Colorectal cancer GTPase KRas (P01116) (SMART) OMIM:190070: Colorectal adenoma ; Colorectal cancer Isoform 2B of GTPase KRas (P01116-2) (SMART) OMIM:190070: Colorectal adenoma ; Colorectal cancer Ras-related protein R-Ras2 (P62070) (SMART) OMIM:600098: ONCOGENE TC21 GTPase HRas (P01112) (SMART) OMIM:190020: Bladder cancer
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 9.21 map04360 Axon guidance 7.77 map04670 Leukocyte transendothelial migration 7.34 map04520 Adherens junction 7.34 map04510 Focal adhesion 7.34 map04810 Regulation of actin cytoskeleton 5.76 map04370 VEGF signaling pathway 5.76 map04010 MAPK signaling pathway 5.76 map05212 Pancreatic cancer 4.46 map05210 Colorectal cancer 4.46 map04530 Tight junction 4.46 map04310 Wnt signaling pathway 4.46 map04660 T cell receptor signaling pathway 4.17 map05120 Epithelial cell signaling in Helicobacter pylori infection 4.17 map05211 Renal cell carcinoma 2.88 map04664 Fc epsilon RI signaling pathway 2.88 map04662 B cell receptor signaling pathway 2.88 map04912 GnRH signaling pathway 2.88 map04650 Natural killer cell mediated cytotoxicity 1.58 map04350 TGF-beta signaling pathway 1.29 map05030 Amyotrophic lateral sclerosis (ALS) 1.29 map04620 Toll-like receptor signaling pathway 1.01 map04120 Ubiquitin mediated proteolysis 0.86 map04910 Insulin signaling pathway
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with RHO domain which could be assigned to a KEGG orthologous group, and not all proteins containing RHO domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of RHO domains in PDB
PDB code Main view Title 1a2b HUMAN RHOA COMPLEXED WITH GTP ANALOGUE 1a4r G12V MUTANT OF HUMAN PLACENTAL CDC42 GTPASE IN THE GDP FORM 1aje CDC42 FROM HUMAN, NMR, 20 STRUCTURES 1am4 COMPLEX BETWEEN CDC42HS.GMPPNP AND P50 RHOGAP (H. SAPIENS) 1an0 CDC42HS-GDP COMPLEX 1cc0 CRYSTAL STRUCTURE OF THE RHOA.GDP-RHOGDI COMPLEX 1cee SOLUTION STRUCTURE OF CDC42 IN COMPLEX WITH THE GTPASE BINDING DOMAIN OF WASP 1cf4 CDC42/ACK GTPASE-BINDING DOMAIN COMPLEX 1cxz CRYSTAL STRUCTURE OF HUMAN RHOA COMPLEXED WITH THE EFFECTOR DOMAIN OF THE PROTEIN KINASE PKN/PRK1 1doa Structure of the rho family gtp-binding protein cdc42 in complex with the multifunctional regulator rhogdi 1dpf CRYSTAL STRUCTURE OF A MG-FREE FORM OF RHOA COMPLEXED WITH GDP 1ds6 CRYSTAL STRUCTURE OF A RAC-RHOGDI COMPLEX 1e0a Cdc42 complexed with the GTPase binding domain of p21 activated kinase 1e96 Structure of the Rac/p67phox complex 1ees SOLUTION STRUCTURE OF CDC42HS COMPLEXED WITH A PEPTIDE DERIVED FROM P-21 ACTIVATED KINASE, NMR, 20 STRUCTURES 1foe CRYSTAL STRUCTURE OF RAC1 IN COMPLEX WITH THE GUANINE NUCLEOTIDE EXCHANGE REGION OF TIAM1 1ftn CRYSTAL STRUCTURE OF THE HUMAN RHOA/GDP COMPLEX 1g4u CRYSTAL STRUCTURE OF THE SALMONELLA TYROSINE PHOSPHATASE AND GTPASE ACTIVATING PROTEIN SPTP BOUND TO RAC1 1grn CRYSTAL STRUCTURE OF THE CDC42/CDC42GAP/ALF3 COMPLEX. 1gwn The crystal structure of the core domain of RhoE/Rnd3 - a constitutively activated small G protein 1gzs CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE GEF DOMAIN OF THE SALMONELLA TYPHIMURIUM SOPE TOXIN AND HUMAN Cdc42 1he1 Crystal structure of the complex between the GAP domain of the Pseudomonas aeruginosa ExoS toxin and human Rac 1hh4 Rac1-RhoGDI complex involved in NADPH oxidase activation 1i4d CRYSTAL STRUCTURE ANALYSIS OF RAC1-GDP COMPLEXED WITH ARFAPTIN (P21) 1i4l CRYSTAL STRUCTURE ANALYSIS OF RAC1-GDP IN COMPLEX WITH ARFAPTIN (P41) 1i4t CRYSTAL STRUCTURE ANALYSIS OF RAC1-GMPPNP IN COMPLEX WITH ARFAPTIN 1ki1 Guanine Nucleotide Exchange Region of Intersectin in Complex with Cdc42 1kmq Crystal Structure of a Constitutively Activated RhoA Mutant (Q63L) 1kz7 Crystal Structure of the DH/PH Fragment of Murine Dbs in Complex with the Placental Isoform of Human Cdc42 1kzg DbsCdc42(Y889F) 1lb1 Crystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoA 1m7b Crystal structure of Rnd3/RhoE: functional implications 1mh1 SMALL G-PROTEIN 1nf3 Structure of Cdc42 in a complex with the GTPase-binding domain of the cell polarity protein, Par6 1ow3 Crystal Structure of RhoA.GDP.MgF3-in Complex with RhoGAP 1ryf Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase 1ryh Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase 1s1c Crystal structure of the complex between the human RhoA and Rho-binding domain of human ROCKI 1tx4 RHO/RHOGAP/GDP(DOT)ALF4 COMPLEX 1x86 Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF in complex with RhoA 1xcg Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF 1z2c Crystal structure of mDIA1 GBD-FH3 in complex with RhoC-GMPPNP 2ase NMR structure of the F28L mutant of Cdc42Hs 2atx Crystal Structure of the TC10 GppNHp complex 2c2h CRYSTAL STRUCTURE OF THE HUMAN RAC3 IN COMPLEX WITH GDP 2cls The crystal structure of the human RND1 GTPase in the active GTP bound state 2dfk Crystal structure of the CDC42-Collybistin II complex 2fju Activated Rac1 bound to its effector phospholipase C beta 2 2fv8 The crystal structure of RhoB in the GDP-bound state 2g0n The Crystal Structure of the Human RAC3 in complex with GDP and Chloride 2gcn Crystal structure of the human RhoC-GDP complex 2gco Crystal structure of the human RhoC-GppNHp complex 2gcp Crystal structure of the human RhoC-GSP complex 2h7v Co-crystal structure of YpkA-Rac1 2ic5 Crystal structure of human RAC3 grown in the presence of Gpp(NH)p. 2j0v The crystal structure of Arabidopsis thaliana RAC7-ROP9: the first RAS superfamily GTPase from the plant kingdom 2j1l Crystal Structure of Human Rho-related GTP-binding protein RhoD 2kb0 Cdc42(T35A) 2ngr TRANSITION STATE COMPLEX FOR GTP HYDROLYSIS BY CDC42: COMPARISONS OF THE HIGH RESOLUTION STRUCTURES FOR CDC42 BOUND TO THE ACTIVE AND CATALYTICALLY COMPROMISED FORMS OF THE CDC42-GAP. 2nty Rop4-GDP-PRONE8 2nz8 N-terminal DHPH cassette of Trio in complex with nucleotide-free Rac1 2odb The crystal structure of human cdc42 in complex with the CRIB domain of human p21-activated kinase 6 (PAK6) 2ov2 The crystal structure of the human RAC3 in complex with the CRIB domain of human p21-activated kinase 4 (PAK4) 2p2l Rac1-GDP-Zinc Complex 2q3h The crystal structure of RhouA in the GDP-bound state. 2qme Crystal structure of human RAC3 in complex with CRIB domain of human p21-activated kinase 1 (PAK1) 2qrz Cdc42 bound to GMP-PCP: Induced Fit by Effector is Required 2rex Crystal structure of the effector domain of PLXNB1 bound with Rnd1 GTPase 2rgn Crystal Structure of p63RhoGEF complex with Galpha-q and RhoA 2rmk Rac1/PRK1 Complex 2v55 Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure 2vrw Critical structural role for the PH and C1 domains of the Vav1 exchange factor 2w2t Rac2 (G12V) in complex with GDP 2w2v Rac2 (G12V) in complex with GTPgS 2w2x Complex of Rac2 and PLCg2 spPH Domain 2wbl Three-dimensional structure of a binary ROP-PRONE complex 2wkp Structure of a photoactivatable Rac1 containing Lov2 Wildtype 2wkq Structure of a photoactivatable Rac1 containing the Lov2 C450A Mutant 2wkr Structure of a photoactivatable Rac1 containing the Lov2 C450M Mutant 2wm9 Structure of the complex between DOCK9 and Cdc42. 2wmn Structure of the complex between DOCK9 and Cdc42-GDP. 2wmo Structure of the complex between DOCK9 and Cdc42. 2yin STRUCTURE OF THE COMPLEX BETWEEN Dock2 AND Rac1. 3a58 Crystal structure of Sec3p - Rho1p complex from Saccharomyces cerevisiae 3b13 Crystal structure of the DHR-2 domain of DOCK2 in complex with Rac1 (T17N mutant) 3bji Structural Basis of Promiscuous Guanine Nucleotide Exchange by the T-Cell Essential Vav1 3bwd Crystal structure of the plant Rho protein ROP5 3eg5 Crystal structure of MDIA1-TSH GBD-FH3 in complex with CDC42-GMPPNP 3gcg crystal structure of MAP and CDC42 complex 3kz1 Crystal Structure of the Complex of PDZ-RhoGEF DH/PH domains with GTP-gamma-S Activated RhoA 3lw8 Shigella IpgB2 in complex with human RhoA, GDP and Mg2+ (complex A) 3lwn Shigella IpgB2 in complex with human RhoA, GDP and Mg2+ (complex B) 3lxr Shigella IpgB2 in complex with human RhoA and GDP (complex C) 3msx Crystal structure of RhoA.GDP.MgF3 in complex with GAP domain of ArhGAP20 3q3j Crystal structure of plexin A2 RBD in complex with Rnd1 3qbv Structure of designed orthogonal interaction between CDC42 and nucleotide exchange domains of intersectin 3ref Crystal structure of EhRho1 bound to GDP and Magnesium 3reg Crystal structure of EhRho1 bound to a GTP analog and Magnesium 3ryt The Plexin A1 intracellular region in complex with Rac1 3sbd Crystal structure of RAC1 P29S mutant 3sbe Crystal structure of RAC1 P29S mutant 3su8 Crystal structure of a truncated intracellular domain of Plexin-B1 in complex with Rac1 3sua Crystal structure of the intracellular domain of Plexin-B1 in complex with Rac1 3t06 Crystal Structure of the DH/PH fragment of PDZRHOGEF with N-terminal regulatory elements in complex with Human RhoA 3th5 Crystal structure of wild-type RAC1 3tvd Crystal Structure of Mouse RhoA-GTP complex 3vhl Crystal structure of the DHR-2 domain of DOCK8 in complex with Cdc42 (T17N mutant) 4d0n AKAP13 (AKAP-Lbc) RhoGEF domain in complex with RhoA 4did Crystal structure of Salmonella effector N-terminal domain SopB in complex with Cdc42 4dvg Crystal structure of E. histolytica Formin1 bound to EhRho1-GTPgammaS 4f38 Crystal structure of geranylgeranylated RhoA in complex with RhoGDI in its active GPPNHP-bound form 4gzl Crystal structure of RAC1 Q61L mutant 4gzm Crystal structure of RAC1 F28L mutant 4itr Crystal Structure of IbpAFic2-H3717A in complex with adenylylated Cdc42 4js0 Complex of Cdc42 with the CRIB-PR domain of IRSp53
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