RHOA

5BWM, 1A2B, 1CC0, 1CXZ, 1DPF, 1FTN, 1KMQ, 1LB1, 1OW3, 1S1C, 1TX4, 1X86, 1XCG, 2RGN, 3KZ1, 3LW8, 3LWN, 3LXR, 3MSX, 3T06, 4D0N, 4XH9, 4XSG, 4XSH, 4XOI, 5A0F, 5FR2, 5FR1, 5JCP, 5C2K, 5C4M, 5HPY38711848ENSG00000067560ENSMUSG00000007815P61586Q9QUI0NM_001313947NM_001664NM_016802NM_001313961NM_001313962NP_001300876NP_001655NP_001300870.1NP_001655.1NP_001300890NP_001300891NP_058082Ras homolog gene family, member A (RhoA) is a small GTPase protein in the Rho family. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. In humans, it is encoded by the gene RHOA. It acts upon several effectors. Among them, ROCK1 (Rho-associated, coiled-coil containing protein kinase 1) and DIAPH1 (Diaphanous Homologue 1, a.k.a. hDia1, homologue to mDia1 in mouse, diaphanous in Drosophila) are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billions years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.1a2b: HUMAN RHOA COMPLEXED WITH GTP ANALOGUE1cc0: CRYSTAL STRUCTURE OF THE RHOA.GDP-RHOGDI COMPLEX1cxz: CRYSTAL STRUCTURE OF HUMAN RHOA COMPLEXED WITH THE EFFECTOR DOMAIN OF THE PROTEIN KINASE PKN/PRK11dpf: CRYSTAL STRUCTURE OF A MG-FREE FORM OF RHOA COMPLEXED WITH GDP1ftn: CRYSTAL STRUCTURE OF THE HUMAN RHOA/GDP COMPLEX1kmq: Crystal Structure of a Constitutively Activated RhoA Mutant (Q63L)1lb1: Crystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoA1ow3: Crystal Structure of RhoA.GDP.MgF3-in Complex with RhoGAP1s1c: Crystal structure of the complex between the human RhoA and Rho-binding domain of human ROCKI1tx4: RHO/RHOGAP/GDP(DOT)ALF4 COMPLEX1x86: Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF in complex with RhoA1xcg: Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF1z2c: Crystal structure of mDIA1 GBD-FH3 in complex with RhoC-GMPPNP2gcn: Crystal structure of the human RhoC-GDP complex2gco: Crystal structure of the human RhoC-GppNHp complex2gcp: Crystal structure of the human RhoC-GSP complex Ras homolog gene family, member A (RhoA) is a small GTPase protein in the Rho family. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. In humans, it is encoded by the gene RHOA. It acts upon several effectors. Among them, ROCK1 (Rho-associated, coiled-coil containing protein kinase 1) and DIAPH1 (Diaphanous Homologue 1, a.k.a. hDia1, homologue to mDia1 in mouse, diaphanous in Drosophila) are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billions years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation. The specific gene that encodes RhoA, RHOA, is located on chromosome 3 and consists of four exons, which has also been linked as a possible risk factor for atherothrombolic stroke. Similar to other GTPases, RhoA presents a Rho insert in its primary sequence in the GTPase domain. RhoA contains also four insertion or deletion sites with an extra helical subdomain; these sites are characteristic of many GTPases in the Rho family. Most importantly, RhoA contains two switch region, Switch I and Switch II whose conformational states are modified following the activation or inactivation of the protein. Both of these switches have characteristic folding, correspond to specific regions on the RhoA coil and are uniformly stabilized via hydrogen bonds. The conformations of the Switch domains are modified depending on the binding of either GDP or GTP to RhoA. The nature of the bound nucleotide and the ensuing conformational modification of the Switch domains dictates the ability of RhoA to bind or not to partner proteins (see below). The primary protein sequences of members of the Rho family are mostly identical, with the N-terminal containing most of the protein coding for GTP binding and hydrolysis. The C-terminal of RhoA is modified via prenylation, anchoring the GTPase into membranes, which is essential for its role in cell growth and cytoskeleton organization. Key amino acids that are involved in the stabilization and regulation of GTP hydrolysis are conserved in RhoA as Gly14, Thr19, Phe30 and Gln63. Correct localization of the RhoA proteins is heavily dependent on the C-terminus; during prenylation, the anchoring of the prenyl group is essential for the stability, inhibition of and the synthesis of enzymes and proliferation. RhoA is sequestered by dissociation inhibitors (RhoGDIs) which remove the protein from the membrane while preventing its further interaction with other downstream effectors. RhoA acquires both inactive GDP-bound and active GTP-bound conformational states; these states alternate between the active and inactive states via the exchange of GDP to GTP (conducted simultaneously via guanine nucleotide exchange factors and GTPase activating factor). RhoA is activated primarily by guanine nucleotide exchange factors (GEFs) via phosphorylation; due to large network of overlapping phosphorylation, a multitude of GEFs are utilized to enable specific signaling pathways. These structural arrangements provide interaction sites that can interact with effectors and guanine factors in order to stabilize and signal the hydrolysis of GTP.