Description: Homo sapiens ras homolog family member A (RHOA), mRNA. RefSeq Summary (NM_001664): This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]. Transcript (Including UTRs) Position: hg19 chr3:49,396,579-49,449,526 Size: 52,948 Total Exon Count: 5 Strand: - Coding Region Position: hg19 chr3:49,397,642-49,413,022 Size: 15,381 Coding Exon Count: 4
ID:RHOA_HUMAN DESCRIPTION: RecName: Full=Transforming protein RhoA; AltName: Full=Rho cDNA clone 12; Short=h12; Flags: Precursor; FUNCTION: Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA- DIAPH1 signaling pathway plays an important role in ERBB2- dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. COFACTOR: Magnesium. ENZYME REGULATION: GTP hydrolysis is stimulated by ARHGAP30. SUBUNIT: Interacts with ARHGEF28 (By similarity). Binds PRKCL1, ROCK1 and ROCK2. Interacts with ARHGEF2, ARHGEF3, NET1 and RTKN. Interacts with PLCE1 and AKAP13. Interacts (in the constitutively activated, GTP-bound form) with DGKQ. Interacts with human respiratory syncytial virus (HRSV) protein F; this interaction facilitates virus-induced syncytium formation. Interacts with GNB2L1/RACK1; enhances RHOA activation. Interacts with PKP4; the interaction is detected at the midbody. Interacts (GTP-bound form preferentially) with PKN2; the interaction stimulates autophosphorylation and phosphorylation of PKN2. INTERACTION: Q07960:ARHGAP1; NbExp=2; IntAct=EBI-446668, EBI-602762; P52565:ARHGDIA; NbExp=2; IntAct=EBI-446668, EBI-712693; O15085:ARHGEF11; NbExp=2; IntAct=EBI-446668, EBI-311099; Q969H4:CNKSR1; NbExp=4; IntAct=EBI-446668, EBI-741671; O08808:Diaph1 (xeno); NbExp=3; IntAct=EBI-446668, EBI-1026445; Q6PDM6:Mcf2l (xeno); NbExp=3; IntAct=EBI-446668, EBI-602149; Q9Z0S9:Rabac1 (xeno); NbExp=3; IntAct=EBI-446668, EBI-476965; Q8C6B2:Rtkn (xeno); NbExp=2; IntAct=EBI-446668, EBI-1162441; Q15796:SMAD2; NbExp=2; IntAct=EBI-446668, EBI-1040141; SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side. Cytoplasm, cytoskeleton. Cleavage furrow. Cytoplasm, cell cortex. Midbody. Note=Localized to cell-cell contacts in calcium- treated keratinocytes (By similarity). Translocates to the equatorial region before furrow formation in a ECT2-dependent manner. Localizes to the equatorial cell cortex (at the site of the presumptive furrow) in early anaphase in a activated form and in a myosin- and actin-independent manner. DOMAIN: The basic-rich region is essential for yopT recognition and cleavage. PTM: Substrate for botulinum ADP-ribosyltransferase. PTM: Cleaved by yopT protease when the cell is infected by some Yersinia pathogens. This removes the lipid attachment, and leads to its displacement from plasma membrane and to subsequent cytoskeleton cleavage. PTM: AMPylation at Tyr-34 and Thr-37 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo. PTM: Phosphorylation by PRKG1 at Ser-188 inactivates RHOA signaling. PTM: Ubiquitinated by the BCR(BACURD1) and BCR(BACURD2) E3 ubiquitin ligase complexes, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. SIMILARITY: Belongs to the small GTPase superfamily. Rho family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RHOAID42107ch3p21.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P61586
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_cardiacegfPathway - Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy h_malPathway - Role of MAL in Rho-Mediated Activation of SRF h_akap13Pathway - Rho-Selective Guanine Exchange Factor AKAP13 Mediates Stress Fiber Formation h_ecmPathway - Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia h_rhoPathway - Rho cell motility signaling pathway h_Par1Pathway - Thrombin signaling and protease-activated receptors h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition h_edg1Pathway - Phospholipids as signalling intermediaries h_integrinPathway - Integrin Signaling Pathway h_cdc42racPathway - Role of PI3K subunit p85 in regulation of Actin Organization and Cell Migration h_tffPathway - Trefoil Factors Initiate Mucosal Healing h_CCR3Pathway - CCR3 signaling in Eosinophils h_rasPathway - Ras Signaling Pathway h_ucalpainPathway - uCalpain and friends in Cell spread h_akapCentrosomePathway - Protein Kinase A at the Centrosome
Reactome (by CSHL, EBI, and GO)
Protein P61586 (Reactome details) participates in the following event(s):