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FLASH GENE
Symbol RHOA contributors: mct/shn - updated : 17-11-2016
HGNC name ras homolog gene family, member A
HGNC id 667
Location 3p21.31      Physical location : 49.396.580 - 49.449.526
Synonym name
  • transforming protein RhoA
  • rho cDNA clone 12
  • aplysia ras-related homolog 12
  • oncogene RHO H12
  • small GTP binding protein RhoA
  • Synonym symbol(s) ARH12, ARHA, RHOH12, H12, Rho12
    DNA
    TYPE functioning gene
    STRUCTURE 52.95 kb     5 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map pter - D3S3560 - D3S1581 - RHOA - D3S3629 - D3S2456 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1926 - 193 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymus   highly
    Reproductivefemale systemuteruscervix highly
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone   
    Nervousperipherous   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • C-terminal polybasic region (PBR)
  • conjugated LipoP
    HOMOLOGY
    interspecies ortholog to Rhoa, Mus musculus
    ortholog to Rhoa, Rattus norvegicus
    ortholog to RHOA, Pan troglodytes
    Homologene
    FAMILY
  • small GTPase superfamily
  • RHO family
  • CATEGORY regulatory , protooncogene , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton
    basic FUNCTION
  • coordinated assembly of focal adhesions and stress fibers
  • linking growth factor receptors to the activation of actin polymerization
  • playing a critical role in muscle differentiation
  • mediating the distinct actin cytoskeleton changes required for both cellular motility and cell-cell adhesion
  • CYTH1 and RHOA are both required for the induction of chemokine-dependent conformational changes of ITGB2 subunit of Dendritic cells during adhesion under physiological flow conditions
  • with RHOC, are essential for tumor invasion and/or metastasis in breast carcinomas
  • with RAC1, and RHOB, are involved in the establishment of the migratory and invasive phenotype of tumour cells that have CDH1 mutation
  • major regulator of CDH1-mediated cell–cell adhesion and are involved in the induction, propagation and expansion of cell–cell contacts
  • in the spinal cord neuroepithelium, RhoA is essential to localize N-cadherin and beta-catenin to adherens junctions and maintain apical-basal polarity of neural progenitor cells
  • necessary for adherens junctions regulation and for the maintenance of mammalian neuroepithelium organization preventing precocious cell-cycle exit and differentiation
  • IQGAP1 acts both upstream of RHOA/C, regulating their activation state, and downstream of RHOA/C, mediating their effects on breast cancer cell proliferation and migration, respectively
  • is a gene contributing to variation in LDL-cholesterol response to statin
  • RHOA, RHOB and RHOC all have the potential to interact with the same downstream effectors, yet they have substantially different effects on cell shape and migratory properties
  • important role for RHOA-ROCK2 signaling to maintain apico-basal polarity in retinal progenitor cells, which is essential for subsequent cellular differentiation, morphology and eventually organ function
  • new role of GEM/GMIP/RHOA signaling in cortical actin regulation during early mitotic stages
  • RHOA and RAC1 function as master regulators of cytokinesis by controlling the actomyosin cytoskeleton
  • CELLULAR PROCESS cell life, differentiation
    cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • TTC3-RHOA-CIT-K pathway that could be a crucial determinant of neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program
  • MEMO1-RHOA-DIAPH1 signaling coordinates the organization of the lamellipodial actin network, adhesion site formation, and microtubules outgrowth within the cell leading edge to sustain cell motility
  • RHOA-PLD1-phosphatidic acid (PA) may represent a novel signaling pathway in the restriction of dendritic branching
  • CDH1-ANAPC/SMURF1/RHOA pathway that mediates axonal growth suppression in the developing mammalian brain
  • RHOA GTPase is an important effector of GEM/GMIP signaling
  • TNS1-DLC1-RhoA signaling axis is critical in regulating cellular functions that lead to angiogenesis
  • a component
  • RAP1GDS1-RHOA complexes accumulate in the cytoplasm
  • PI 3-kinase/RHOA/DIAPH1 axis is a critical pathway for coupling thrombin signaling to actin cytoskeletal remodeling during platelet spreading
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • GTP binding
  • Mg2+
  • protein
  • putative regulator of myogenin and MEF25 genes
  • rhotekin (
  • GDP/GTP exchange factor, RhoGEF (
  • p190 (
  • protein-kinase C-related kinase 1, PRK1 (
  • Kinectin, mDia2, the guanine nucleotide exchange factor mNET1, beta2 and Skn7 (
  • caveolin-1, CAV1 (
  • DGKtheta (
  • trio guanine nucleotide exchange factor (
  • phospholipase D1, PLD1 (
  • RhoA-associated kinase-2, ROCK-2 (
  • small G-protein dissociation stimulator, smgGDS (
  • G-protein betagamma, Gbetagamma and phospholipase C-gamma1, PLC-gamma1 (
  • Rhophilin-2, RHPN2 (
  • exchange factor found in platelets and leukemic and neuronal tissues, XPLN (
  • heat shock protein HSP72 (
  • inositol 1,4,5-trisphosphate receptor, type 3, IP3R and transient receptor potential channel-1, TRPC1 (
  • Myosin phosphatase-Rho interacting protein, M-RIP (
  • transiently-expressed axonal glycoprotein, TAX (
  • differentially expressed in FDCP 6 homolog (mouse), DEF6 (
  • MYH9 and PLEKHG6
  • full activation of RHOA required ECT2 as well as PKP4 indicating that these two proteins act in conjunction to regulate RHOA during cytokinesis
  • ANLN is a scaffold protein that links RHOA, actin, and myosin during cytokinesis
  • CGNL1 is a regulator of the activity of two small GTPases, RAC1 and RHOA, through the functional interaction with their respective activators, TIAM1 and ARHGEF2
  • ARHGEF10
  • RHOA and RHOC are both required for the ROCK2-dependent promotion of centrosome duplication
  • interacting with SMURF1 (C2 domain of SMURF1 is necessary and sufficient for binding RHOA, and therefore is crucial for targeting RhHOA for ubiquitination)
  • ARHGEF3 is a regulator of transferrin uptake in erythroid cells, through activation of RHOA
  • ARHGAP18 is one of the crucial factors for the regulation of RHOA for the control of cell shape, spreading, and migration
  • CIT maintains correct RHOA localization at the cleavage site, which is necessary for proper RHOA activity and contractile ring dynamics in cytokinesis
  • novel role of RPKD1, PRKD2 as a regulator of RHOA activity and actin stress fiber formation through phosphorylation of rhotekin
  • OPHN1 exhibits strong GTPase-stimulating activity towards RHOA, CDC42, and RAC1 and regulates cell adhesion and spreading
  • SLIT2 regulates the dispersal of oligodendrocyte precursor cells through FYN and RHOA signaling
  • RHOA activity polarizes around SYTL1-containing secretory granules, suggesting that it may control directionality of granule movement
  • AGAP1 and AGAP2 can bind to RHOA
  • INPPL1 interacts with RHOA in a GTP-dependent manner (RHOA associates with INPPL1 to regulate cell polarization and migration)
  • involvement of RHOA and ROCK1 in F11R relocalization
  • RYK is required for Wnt/planar cell polarity signaling during mammalian development and signals via VANGL2 and RHOA
  • IQGAP1 interacts directly with GTP-bound, prenylated RHOA and RHOC, but not with RHOB
  • direct binding of RHOA and C to the C-terminal half of IQGAP1, which contains the GAP-related domain required for CDC42 and RAC1 binding
  • ARHGEF3 activates RHOA and RHOB, but not RHOC, although their GTPase sequences are highly conserved
  • ARHGAP21 presented GAP activity for RHOA and RHOC and induced changes in cell morphology
  • deregulation of RHOA activation in the absence of SLC3A2 is also a result of impaired SLC3A2-dependent amino acid transports
  • stimulates the production of FN1 by podocytes, specifically testing the role of nuclear factor of activated T cells (NFATC1)
  • NFATC1 mediates RHOA-induced FN1 upregulation in glomerular podocytes
  • CES1 had a clear impact not only on the methylation status of RHOA but also RHOA activation and cell morphology
  • function of PLEKHG5 is mediated by the selective activation of the RHOA downstream effector DIAPH1 (PMID
  • ARHGEF18 is a key regulator of RHOA-ROCK2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium
  • XIAP and, to a lesser extent, BIRC2 were found to directly interact with RHOA independently of the RHOA activation status
  • STARD13 is a RHO-GAP that specifically inhibits the function of RHOA and CDC42
  • regulation of desmosomal adhesion by RHOA- and PRKC-mediated ADD1 phosphorylation in keratinocytes
  • CGN and CGNL1 control RHOA activation in epithelial cells by interacting with RHOA guanidine exchange factors
  • RACGAP1 promoted the activations of RHOA, PTK2, PXN and triggered focal adhesion formation and cytoskeletal rearrangement
  • is a GTPase-activating protein (GAP) that inactivates ARF6 and RHOA small GTPases
  • GPR56 regulates oligodendrocyte development via interactions with GNA12/GNA13 and RHOA
  • interplay between ARHGEF40 and KRT8/KRT18 filaments plays a crucial role in tensile force-induced RHOA activation and consequent actin cytoskeletal reinforcement
  • regulation of RHOA activation through ARHGEF18 is important for tissue morphogenesis and migration and in the assembly and maintenance of cell-cell junction
  • cell & other
    REGULATION
    activated by PLEKHG6
    differentially expressed in FDCP 6 homolog (mouse), DEF6 (
    Leukemia-associated Rho guanine nucleotide exchange factor, LARG (
    leukotriene D4, LTD4 (
    trio guanine nucleotide exchange factor (
    Other ARHA (Rho-A) induced neuronal morphology modulated by the complex p80-ROK alpha/DPYSL2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    leads to an upregulation of SNAI1 and a reduction in the transcription of E-cadherin
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS