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RHOA (ras homolog gene family, member A)

Written2007-01Teresa Gomez del Pulgar, Juan Carlos Lacal
Translational Oncology Unit, CSIC-UAM-La Paz, Madrid, Spain
Updated2014-09Rebeca Manso
Pathology Department, Fundacion Conchita Rabago, IIS Fundacion Jimenez Diaz, E-28040 Madrid, Spain

Abstract Review on RHOA, with data on DNA/RNA, on the protein encoded and where the gene is implicated.

Keywords RhoA, Small Rho GTPase

(Note : for Links provided by Atlas : click)

Identity

Alias_namesARH12
ARHA
ras homolog gene family
Alias_symbol (synonym)RhoA
Rho12
RHOH12
Other aliasH12
RHO12
HGNC (Hugo) RHOA
LocusID (NCBI) 387
Atlas_Id 42107
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 49359136 and ends at 49412097 bp from pter ( according to hg19-Feb_2009)  [Mapping RHOA.png]
Local_order From the plasmatic membrane and cytoplasm.
Fusion genes
(updated 2016)
ARIH2 (3p21.31) / RHOA (3p21.31)CEP128 (14q31.1) / RHOA (3p21.31)MAP4 (3p21.31) / RHOA (3p21.31)
RHOA (3p21.31) / AHNAK2 (14q32.33)RHOA (3p21.31) / CACNA2D2 (3p21.31)RHOA (3p21.31) / CCDC150 (2q33.1)
RHOA (3p21.31) / COL7A1 (3p21.31)RHOA (3p21.31) / CTNNB1 (3p22.1)RHOA (3p21.31) / LARP7 (4q25)
RHOA (3p21.31) / NICN1 (3p21.31)RHOA (3p21.31) / RHOA (3p21.31)RHOA (3p21.31) / SMCO1 (3q29)
SLC39A6 (18q12.2) / RHOA (3p21.31)TAL1 (1p33) / RHOA (3p21.31)USP4 (3p21.31) / RHOA (3p21.31)

DNA/RNA

Description The RhoA gene can be found on chromosome 3 at location: 49371585-49424530. This gene includes 5 exons.
Transcription This gene has 6 transcripts (splice variants): 2031 bp (variant a); 961 bp (variant b); 889 bp (variant c); 633 bp (variant d); 539 bp (variant e); 388 bp (variant f).

Protein

 
  Schematic representation of the domains of RhoA. The available functional and structural data show that RHO-GTP-binding proteins are made-up of an effector domain, four separate guanosine phosphate binding regions that span the length of the core structure, a hypervariable region and a CAAX box motif (Lartey and López Bernal, 2009).
Description The RhoA protein encodes five alternative isoforms: variant a (193 amino acids), variant b (187 amino acids), variant c (90 amino acids), variant d (129 amino acids) and variant e (86 amino acids).
- RhoA structure:
The available functional and structural data show that RHO-GTP-binding proteins are made-up of an effector domain, four separate guanosine phosphate binding regions that span the length of the core structure, a hypervariable region and a CAAX box motif (C: Cys; A: aliphatic residue; X: any residue). The effector domain (residues 26-45) changes conformation between the GTP bound and GDP bound states. All RHO proteins have conserved residues at Gly14, Thr19, Phe30 and Gln93 which are involved in binding, stabilization or regulation of GTP hydrolysis. The N-terminus region also contains switch 1 (residues 27-40) and switch 2 (residues 59-78) regions which change conformation between GTP- and GDP-bound states and may facilitate changes in effector region required for binding to downstream targets. RhoA protein is target for several bacterial toxins, which modify key conserved amino acids involved in their regulation. These include Clostridium botulinum exoenzyme C3 transferase, which modifies Asn41, and Toxin B, which acts on Thr37. The hypervariable region made-up of residues 173-189 is the region of most diversity between individual RHO family members. It may contain sites for palmitoylation and a polybasic region which can determine membrane association. The C-terminus of RhoA is essential for correct localization of the protein. RhoA is post-translationally modified by prenylation of a conserved C-terminal cysteine followed by methylation and proteolytic removal of the last three amino acids. The prenyl group (geranylgeranyl) anchors the GTPase into membranes and this modification is essential for its stability, cell growth, transformation, and cytoskeletal organization.
- RhoA activity regulation:
Rho GTPases can be activated by intrinsic or extrinsic cues, setting off a signaling cascade (Etienne-Manneville and Hall, 2002). Rho GTPases behave as molecular switches that fluctuate between inactive and active states, two conformations that depend on the binding of either GDP or GTP to the GTPases, respectively (Bustelo et al., 2007). Two types of regulatory proteins control this cycling: guanine nucleotide-exchange factors (GEFs), which activate Rho GTPases by catalyzing the exchange of GDP for GTP (Rossman et al., 2005), and GTPase-activating proteins (GAPs), which inactivate the GTPases by enhancing intrinsic GTP hydrolysis activity (Bos et al., 2007). There are over 80 GEFs and 70 GAPs for Rho GTPases, whose activity is tightly regulated and can be highly specific. RhoA can be sequestered in the cytoplasm by guanine nucleotide-dissociation inhibitors (GDIs), which bind prenylated GDP-bound Rho proteins (Garcia-Mata et al., 2011), allowing translocation of Rho GTPases between membranes and cytosol.
- RhoA effectors binding:
To date, at least 21 proteins have been identified which directly interact with RhoA (ROCK1, ROCK2, PRKcA, PKN1, PKN2, RTKN1, RTKN2, RHPN1, RHPN2, KTN1, CIT, DIAPH1, KCNA2, ITRP1, PLD, MYBPH, PIP5K, FAK, BORG, MBS, GDIA). Some of these have been shown to contribute to specific responses downstream of RhoA. Similarly to GEFs and GAPs, effectors bind to Rho both through the Switch 1 and 2 regions, but the amino acids involved in interaction with each target differ.
 
  RhoA activity regulation. Rho GTPase activity is controlled by guanine nucleotide exchange factor (GEF), GTPase-activating protein (GAP) and guanine nucleotide dissociation inhibitor (GDI). GEF activates Rho GTPases by facilitating the release of GDP and the binding of GTP. GAP inactivates Rho GTPases by promoting hydrolysis of the bound GTP molecules, resulting in their quick change from the GTP-bound form to the GDP-bound form. GDI binds to C-terminal prenyl groups on some Rho proteins, maintaining them in the inactive state. Active Rho GTPases act on their downstream effector proteins, stimulating a variety of cellular processes (Chi et al., 2013).
Expression RhoA protein is expressed in all tissues tested. RhoA expression in normal human tissues, embryonic tissues and stem cells.
Localisation RhoA localizes predominantly in the plasmatic membrane and cytoplasm. Also, it localizes to cell-cell contacts and cell projections.
Function RhoA is a protein involved in multiple cellular processes.
- Role in actin organization:
RhoA protein plays a central role in regulating cell shape, polarity and locomotion through their effects on actin polymerization, actomyosin contractility, cell adhesion, and microtubule dynamics. RhoA is believed to act primarily at the rear of migrating cells to promote detachment.
RhoA directly stimulates actin polymerization through activiation of diaphanous-related formins (DRFs, also known as Dia proteins). These stimulate addition of actin monomers to the fast-growing end of actin filaments. DRFs act together with ROCKs to mediate Rho-induced stress fiber formation. ROCK-mediated phosphorylation of LIMK and consequent inhibition of cofilin also contributes to the increase in actin filaments in response to Rho. In addition, ROCKs induce actomyosin-based contractility and phosphorylate several proteins involved in regulating myosins and other actin-binding proteins. Actomyosin contractility is important in migrating cells for detachment of the rear. Microtubules are essential for determining cell polarity as well as for vesicular locomotion and intracellular transport. The concerted action of ROCK and Dia is essential for the regulation of cell polarity and organization of microtubules. ROCK phosphorylates TAU and MAP2, proteins that regulate microtubule stability.
RhoA plays a key role in regulating the integrity of cell-extracellular matrix and cell-cell adhesions, the latter including both adherens junctions and tight junctions. Loss of cell-cell junctions is required form the migration of epithelial cells and may be regulated reciprocally by ROCKs and DRFs. Also, RhoA is localized to developing axons and growth cones, and this localization is mediated by an axonal targeting element located in the RhoA 3' untranslated region (UTR). Local RhoA translations regulates the neuronal cytoskeleton and identify a new mechanism for the regulation of RhoA signaling (Wu et al., 2005). On the other hand, increasing expression of the transcription repressor, GCF2, can silence RhoA expression, leading to actin cytoskeleton disorganization (Shen et al., 2012).
- Role in cell migration:
The inhibition of RhoA signaling by blocking the interaction with its downstream effectors Rho-associated kinase (ROCK) and mDia is required for both vaccinia morphogenesis and virus-induced cell motility (Valderrama et al., 2006).
- Role in cell protrusion:
RhoA activates focal adhesion kinase (FAK) signaling. RhoA has a role in the initial events of protrusion, whereas Rac1 and Cdc42 activate pathways implicated in reinforcement and stabilization of newly expanded protrusions (Machacek et al., 2009).
- Role in exocytosis:
RhoA is involved in Ca2+-dependent exocytosis at least partly through the reorganization of actin filaments (Komuro et al., 1996). This type of exocytosis is regulated by G12/G13 alpha through a Rho/Rho-associated kinase-dependent pathway (Yamaguchi et al., 2000).
- Role in endocytosis:
RhoA helps direct endocytosis in a variety of cell types (Lamaze et al., 1996; Khandelwal et al., 2010; Yu et al., 2010). RhoA is essential for clathrin- and caveolar- independent endocytosis (Sabharanjak et al., 2002). Treatment with the PI3K inhibitor (LY294002) or the FAK inhibitor (PF573228) suppresses compensatory endocytosis by inhibiting the activation of RhoA and then reducing the recruitment of ROCK (Khandelwal et al., 2010).
- Role in cytokinesis:
Cytokinesis requires actomyosin-based contraction. Inhibition of ROCK or citron kinase causes defects in cytokinesis resulting in multinucleate cells. Diaphanous-related formins (DRFs) are also implicated in this process, the DRF mDia1 localizes to the cleavage furrow during cytokinesis. DRFs could contribute to cytokinesis by stimulating local actin polymerization and/or by coordinating microtubules with actin filaments at the site of the contractile ring. RhoA signaling is controlled by the central spindle, a set of microtubule bundles that forms between the separating chromosomes. Thus, inactivation of Rac by centralspindlin functions in parallel with RhoA activation to drive contractile ring constriction during cytokinesis (Canman et al., 2008).
- Role in cell cycle regulation:
RhoA plays a pivotal role in G1 cell cycle progression, primarily through regulation of both cyclin D1 expression, and the levels of the cyclin-dependent kinase inhibitors p21 and p27. Multiple pathways seem to link Rho proteins to the control of cyclin D1 levels. Many of these involve the activation of protein kinases, leading to the subsequent modulation of transcription factor activity. RhoA suppresses p21 levels in multiple normal and transformed cell lines. This effect appears to occur through a transcriptional mechanism but is independent of p53, a major transcriptional regulator of p21. RhoA plays an important role in determining the levels of p27 through a pathway involving its effector, the Rho-associated kinases. RhoA facilitates entry into S phase by degradation of the cyclin-dependent kinase inhibitor p27kip1 (Hirai et al., 1997).
- Role in development:
RhoA protein is required for processes involving cell migration in development including: neurite outgrowth, dorsal closure, bone formation, and myogenesis. Rho-loss of function is embryonically lethal in mouse development by E7. This is attributed to failure in gastrulation and an inability of cells to migrate.
- Role in transcriptional control:
The relationship between many of the cellular functions mediated by RhoA with transcriptional regulation has been described. RhoA modulates the activity of SRF, NF-kappaB, c/EBPb, Stat3, Stat5, FHL-2, PAX6, GATA-4, E2F, estrogen receptor alpha, estrogen receptor beta, CREB, and transcription factors that depend on the JNK and p38 MAP kinase pathways. Substrates to these kinases include c-Jun, ELK, PEA3, ATF2, MEF2A, Max and CHOP/GADD153.
- Role in cell proliferation:
RhoA plays cell type-specific roles in the regulation of cell proliferation. RhoA plays critical roles in both early and late stages of B-cell development (Zhang et al., 2012).

Mutations

Note 48 mutations have been described in the RhoA gene, according to the Catalogue of Somatic Mutations in Cancer (COSMIC) database.
De novo mutations have been described in patients with Burkitt lymphoma: R5Q and I23R (Richter et al., 2012; Rohde et al., 2014); peripheral T-cell lymphoma: G17V, affecting the GTP-binding domain (Manso et al., 2014; Palomero et al., 2014; Sakata-Yanagimoto et al., 2014; Yoo et al., 2014); head and neck carcinoma: E40Q and Y42I, affecting the effector domain (Lawrence et al., 2014); diffuse-type gastric carcinoma: R5Q, Y42I and G17V (Kakiuchi et al., 2014).

Implicated in

Note
  
Entity Breast carcinoma
Oncogenesis RhoA protein levels were significantly increased in breast cancer compared with the corresponding normal tissue. Of particular note, protein levels of RhoA were barely detectable in normal mammary tissue, but were highly expressed in all breast tumors tested. Interestingly, RhoA protein levels correlated with increasing breast tumor grade. Moreover, decreased metastasis-free survival was predicted by RhoA and ROCK1 co-overexpression in breast cell lines and cancer tissues (Gilkes et al., 2014). On the other hand, blocking RhoA activity with the RhoA pathway specific inhibitor H-1152, or a RhoA specific siRNA, resulted in inhibition of invasive behavior in a triple-negative breast cancer cell line (Fagan-Solis et al., 2013).
  
  
Entity Ovarian carcinoma
Oncogenesis Expression of RhoA is significantly increased in advanced ovarian carcinomas and also in the peritoneal disseminated lesions (Horiuchi et al., 2008). The expression of the protein is further upregulated in tumors of stages III/IV when compared to those of stages I/II. Analysis of matched pairs of primary and metastatic lesions showed that expression of both RhoA mRNA was significantly higher in metastatic lesions of peritoneal dissemination than in the respective primary tumors.
  
  
Entity Testicular cancer
Oncogenesis RhoA is involved in testicular germinal epithelial carcinogenesis and progression in testicular germ cell tumors (GCT) (Kamai et al., 2001). Protein expression of RhoA and its two major downstream effectors ROCK1 and ROCK2, was significantly higher in tumor tissue than in nontumor tissue from 57 patients with GCT. The expression was greater in tumors of higher stages than lower stages, thus RhoA correlates with tumor stage and aggressiveness.
  
  
Entity Pelvic/ureteric cancer
Oncogenesis Both mRNA and protein level of RhoA are elevated in pelvic/ureteric cancer with an increase in lymph node metastasis. The expression levels of RhoA were related to poorly differentiated grade and muscle invasion and associated with a shorter disease-free and overall survival. These findings suggest that RhoA is involved in the invasion and metastasis of upper urinary tract cancer, indicating that RhoA may be a useful prognostic factor in this disease.
  
  
Entity Bladder cancer
Oncogenesis A similar deregulation of RhoA is observed in bladder cancer. In this sense, RhoA and ROCK protein levels are elevated in tumors, again with higher expression in less differentiated tumors and metastatic lymph nodes compared to normal bladder. Interestingly, the levels of expression of RhoA and ROCK correlated positively with one another suggesting that the GTPase and its effector synergize to promote tumor progression.
  
  
Entity Lung tumors
Oncogenesis Of the two major forms of lung cancer, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), the former has a greater metastatic potential. The expression and activation of RhoA is greater in SCLC than NSCLC cell lines. It has been observed that RhoA repress the expression of nitric oxide synthase-2 (NOS-2) in a lung cancer-derived cell line. Since NOS-2 activity is related to reduced proliferation, RhoA could be eliminating this antiproliferative signal in lung carcinogenesis. In addition, inhibition of RhoA by C3 exoenzyme or through ADP-ribosylation leads to an increase in cadherin-based adhesion and loss of motility of SCLC. RhoA overexpression and delta-catenin positive expression are consistently found in NSCLC, but not in normal lung tissue (Zhang et al., 2014).
  
  
Entity Oesophageal squamous cell carcinoma (ESCC)
Oncogenesis RhoA and RhoC proteins promote both cell proliferation and cell invasion of human ESCC cell lines in vitro and in vivo (Faried et al., 2006). There were significant correlations among RhoA overexpression and tumor-node-metastasis (TNM) clinical classification, lymphatic invasion, and blood-vessel invasion. The five-year survival rates for ESCC patients with RhoA overexpression were significantly lower than those in patients with RhoA under-expression. The expression of RhoA protein appeared to be correlated with tumour progression of ESCC. Patients with RhoA overexpression tended to have poor prognosis compared with patients with RhoA under-expression.
  
  
Entity Gastric cancer
Oncogenesis RhoA was found frequently overexpressed in gastric cancer tissues compared with normal tissues, suggesting that RhoA may play a critical role in the carcinogenesis of this type of cancer. The interference of RhoA expression and/or activity could significantly inhibit the proliferation and tumorigenicity of gastric cancer cells and enhance the chemosensitivity to therapeutic agents such as Adriamycin and 5-fluorouracil. Inhibition of RhoA/ROCK signaling pathway promotes the apoptosis of gastric cancer cells (Xu et al., 2012). Recently, recurrent gain-of-function mutations of RhoA have been described in diffuse-type gastric carcinoma (Kakiuchi et al., 2014).
  
  
Entity Hepatocellular carcinoma (HCC)
Oncogenesis Invasiveness of HCC is facilitated by the Rho/Rho-kinase pathway and likely to be relevant to tumor progression. The Rho/Rho-kinase may be useful as a prognostic indicator and in the development of novel therapeutic strategies. The high expression of RhoA protein in HCC plays an important role in intrahepatic recurrence of patients who underwent a hepatectomy for HCC, and RhoA is a useful marker for predicting early recurrence in an early-stage HCC (Fukui et al., 2006). Overexpression of RhoA is associated with poor prognosis in HCC (Li et al., 2006; Hu et al., 2013).
  
  
Entity Pancreatic tumor
Oncogenesis Although overexpression of RhoA has not been detected in any pancreatic tumor tissue to date, it might nevertheless also be involved in pancreatic tumors. The progression of pancreatic tumors is partially controlled by the balance between Tiam1-Rac1 and RhoA (Guo et al., 2013). Use of two 3-hydroxy 3methylgultaryl coenzyme A (HMG-CoA) reductase inhibitors, fluvastatin and lovastatin inhibit human pancreatic cancer cell invasion and metastasis in a Rho-dependent manner. These inhibitors prevent the synthesis of cholesterol precursors necessary for proper membrane translocation of Rho protein. Also, BART plays a role in inhibiting cell invasion by regulating the activity of RhoA in pancreatic cancer cells (Taniuchi et al., 2011).
  
  
Entity Colorectal cancer
Oncogenesis A high proportion of colon cancers overexpress RhoA and several aspects of colon tumor biology have been related to Rho GTPases. Leptin receptor and leptin-induced migration of colonic epithelial cancer cells is dependent on RhoA, since inhibition of the activity of the GTPase through introduction of dominant negative mutants completely abolishes the invasive capacity of the tumor cells. On the other hand, GCF2 plays an important role in colorectal cancer metastasis by regulating RhoA-induced cell adhesion, migration, and invasion (Ariake et al., 2012).
  
  
Entity Head and neck squamous cell carcinoma
Oncogenesis RhoA, Rac2, and other proteins involved in initiating cell motility are promising clinical molecular markers for head and neck squamous cell cancer (Abraham et al., 2001). Mutations have affecting the effector domain (ED) have been described: these include five E40Q mutations and a single Y42I mutation, which alter the seventh and ninth amino acids, respectively, of the ED (Lawrence et al., 2014).
  
  
Entity Peripheral T-cell lymphoma (PTCL)
Oncogenesis New studies identify recurrent dominant-negative mutation of the RhoA GTPase gene in these lymphomas. In T-cell lines, expression of the G17V mutant reduced the formation of stress fibers in fibroblast, increased cell proliferation and cell migration. It has an important role in the pathogenesis of angioimmunoblastic t-cell lymphoma (AITL) and other subtypes of PTCL (Manso et al., 2014; Palomero et al., 2014; Sakata-Yanagimoto et al., 2014; Yoo et al., 2014).
  
  
Entity Acute promyelocytic leukaemia (APL)
Oncogenesis RhoA modulates functional and physical interaction between ROCK1 and Erk1/Erk2 in selenite-induced apoptosis of human leukaemia cells (Li et al., 2013).
  
  
Entity Pediatric Burkitt lymphoma
Oncogenesis The mutation R5Q is detection in patients with pediatric Burkitt lymphoma. RhoA mutant induced inactivate the RhoA protein. Thus, deregulation of RhoA by mutation is a recurrent event in Burkitt lymphomagenesis in children (Rohde et al., 2014).
  
  
Entity Chronic myeloid leukemia (CML)
Oncogenesis Higher expression of RhoA in CML could be responsible for increased proliferation of polymorphonuclear leukocytes (PMNL) cells (Molli et al., 2012).
  
  
Entity Prostate cancer
Oncogenesis LPA stimulates RhoA and increased PC-3 prostate cancer cell invasion activity through an NF-kappaB-dependent pathway (Hwang et al., 2006). Inhibition of RhoA activity induced senescence-like arrest in a human prostate carcinoma cell line (Park et al., 2007).
  
  
Entity Osteosarcoma
Oncogenesis Lipophilic statins induced membrane RhoA relocalization to the cytosol and inhibited RhoA activity, which resulted in decreased phospho-p42/p44- mitogen-activated protein kinases (MAPKs) and Bcl-2 levels. Constitutively active RhoA rescued phospho-p42/p44-MAPKs and Bcl-2 and abolished statin-induced apoptosis (Fromigué et al., 2006).
  
  
Entity Glioblastoma
Oncogenesis Decreased RhoA activity occurred in correlation with increased glioma cell migration (Fortin Ensign et al., 2013).
  
  
Entity Cervical cancer
Oncogenesis Overexpression of RhoA promotes the proliferation and migration of cervical cancer cells (Liu et al., 2014).
  
  
Entity Squamous cell carcinoma of tongue (TSCC)
Oncogenesis RhoA plays a significant role in TSCC progression by regulating cell migration and invasion through Wnt/β-catenin signaling pathway and cell proliferation through cell cycle regulation, respectively (Yan et al., 2014).
  
  
Entity Neurological disorders
Oncogenesis RhoA protein was lower in the Alzheimer's disease (AD) brain hippocampus, reflecting loss of the membrane bound. Altered subcellular targeting of RhoA is related to neurodegeneration (Huesa et al., 2010). In addition, an upregulation of RhoA immunoreactivity occurs in the brains of patients with intractable epilepsy (Yuan et al., 2010). Also, the Down syndrome critical region protein TTC3 inhibits neuronal differentiation via RhoA and Citron kinase (Berto et al., 2007).
  
  
Entity Diabetic nephropathy
Oncogenesis High glucose activates RhoA/Rho-kinase in mesangial cells (MC), leading to downstream AP-1 activation and fibronectin induction. Inhibition of this pathway in vivo prevents the pathologic changes of diabetic nephropathy, supporting a potential role for inhibitors of RhoA/Rho in the treatment of diabetic renal disease (Peng et al., 2008).
  
  
Entity Pregnancy
Oncogenesis In the early stage pregnancy, up-regulation of RhoA induced by low oxygen conditions may play an important role in regulation of HIF-1α expression in trophoblast cells (Hayashi et al., 2005).
  
  
Entity Pulmonary hypertension (PH)
Oncogenesis RhoA and Rho kinase activities are increased in PH (Guilluy et al., 2009). Inhibition of this pathway is involved in the beneficial effect of sildenafil on PH (Guilluy et al., 2005).
  
  
Entity Hypertension
Oncogenesis RhoA signaling through Arhgef1 is central to the development of angiotensin II-dependent hypertension and identify Arhgef1 as a potential target for the treatment of hypertension (Guilluy et al., 2010).
  

To be noted

miR that target RHOA: RHOA is target of different microRNAs, according to the bioinformatic algorithms microRNA (microRNA.org).

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Guilluy C, Bregeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, Henrion D, Scalbert E, Bril A, Torres RM, Offermanns S, Pacaud P, Loirand G.
Nat Med. 2010 Feb;16(2):183-90. doi: 10.1038/nm.2079. Epub 2010 Jan 24.
PMID 20098430
 
RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling.
Guilluy C, Eddahibi S, Agard C, Guignabert C, Izikki M, Tu L, Savale L, Humbert M, Fadel E, Adnot S, Loirand G, Pacaud P.
Am J Respir Crit Care Med. 2009 Jun 15;179(12):1151-8. doi: 10.1164/rccm.200805-691OC. Epub 2009 Mar 19.
PMID 19299501
 
Inhibition of RhoA/Rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension.
Guilluy C, Sauzeau V, Rolli-Derkinderen M, Guerin P, Sagan C, Pacaud P, Loirand G.
Br J Pharmacol. 2005 Dec;146(7):1010-8.
PMID 16205723
 
Balanced Tiam1-rac1 and RhoA drives proliferation and invasion of pancreatic cancer cells.
Guo X, Wang M, Jiang J, Xie C, Peng F, Li X, Tian R, Qin R.
Mol Cancer Res. 2013 Mar;11(3):230-9. doi: 10.1158/1541-7786.MCR-12-0632. Epub 2013 Jan 15.
PMID 23322732
 
Hypoxia up-regulates hypoxia-inducible factor-1alpha expression through RhoA activation in trophoblast cells.
Hayashi M, Sakata M, Takeda T, Tahara M, Yamamoto T, Minekawa R, Isobe A, Tasaka K, Murata Y.
J Clin Endocrinol Metab. 2005 Mar;90(3):1712-9. Epub 2004 Dec 14.
PMID 15598682
 
Geranylgeranylated rho small GTPase(s) are essential for the degradation of p27Kip1 and facilitate the progression from G1 to S phase in growth-stimulated rat FRTL-5 cells.
Hirai A, Nakamura S, Noguchi Y, Yasuda T, Kitagawa M, Tatsuno I, Oeda T, Tahara K, Terano T, Narumiya S, Kohn LD, Saito Y.
J Biol Chem. 1997 Jan 3;272(1):13-6.
PMID 8995216
 
Overexpression of RhoA enhances peritoneal dissemination: RhoA suppression with Lovastatin may be useful for ovarian cancer.
Horiuchi A, Kikuchi N, Osada R, Wang C, Hayashi A, Nikaido T, Konishi I.
Cancer Sci. 2008 Dec;99(12):2532-9. doi: 10.1111/j.1349-7006.2008.00977.x. Epub 2008 Nov 24.
PMID 19038009
 
Loss of p57 expression and RhoA overexpression are associated with poor survival of patients with hepatocellular carcinoma.
Hu T, Guo H, Wang W, Yu S, Han L, Jiang L, Ma J, Yang C, Guo Q, Nan K.
Oncol Rep. 2013 Oct;30(4):1707-14. doi: 10.3892/or.2013.2608. Epub 2013 Jul 9.
PMID 23842948
 
Altered distribution of RhoA in Alzheimer's disease and AbetaPP overexpressing mice.
Huesa G, Baltrons MA, Gomez-Ramos P, Moran A, Garcia A, Hidalgo J, Frances S, Santpere G, Ferrer I, Galea E.
J Alzheimers Dis. 2010;19(1):37-56. doi: 10.3233/JAD-2010-1203.
PMID 20061625
 
Lysophosphatidic acid stimulates PC-3 prostate cancer cell Matrigel invasion through activation of RhoA and NF-kappaB activity.
Hwang YS, Hodge JC, Sivapurapu N, Lindholm PF.
Mol Carcinog. 2006 Jul;45(7):518-29.
PMID 16402387
 
Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma.
Kakiuchi M, Nishizawa T, Ueda H, Gotoh K, Tanaka A, Hayashi A, Yamamoto S, Tatsuno K, Katoh H, Watanabe Y, Ichimura T, Ushiku T, Funahashi S, Tateishi K, Wada I, Shimizu N, Nomura S, Koike K, Seto Y, Fukayama M, Aburatani H, Ishikawa S.
Nat Genet. 2014 Jun;46(6):583-7. doi: 10.1038/ng.2984. Epub 2014 May 11.
PMID 24816255
 
Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour.
Kamai T, Arai K, Tsujii T, Honda M, Yoshida K.
BJU Int. 2001 Feb;87(3):227-31.
PMID 11167647
 
RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer.
Kamai T, Kawakami S, Koga F, Arai G, Takagi K, Arai K, Tsujii T, Yoshida KI.
BJU Int. 2003 Feb;91(3):234-8.
PMID 12581011
 
Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer.
Kamai T, Yamanishi T, Shirataki H, Takagi K, Asami H, Ito Y, Yoshida K.
Clin Cancer Res. 2004 Jul 15;10(14):4799-805.
PMID 15269155
 
Compensatory endocytosis in bladder umbrella cells occurs through an integrin-regulated and RhoA- and dynamin-dependent pathway.
Khandelwal P, Ruiz WG, Apodaca G.
EMBO J. 2010 Jun 16;29(12):1961-75. doi: 10.1038/emboj.2010.91. Epub 2010 May 11.
PMID 20461056
 
Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells.
Kitajo H, Shibata T, Nagayasu H, Kawano T, Hamada J, Yamashita T, Arisue M.
Oncol Rep. 2003 Sep-Oct;10(5):1351-6.
PMID 12883706
 
Involvement of Rho and Rac small G proteins and Rho GDI in Ca2+-dependent exocytosis from PC12 cells.
Komuro R, Sasaki T, Takaishi K, Orita S, Takai Y.
Genes Cells. 1996 Oct;1(10):943-51.
PMID 9077452
 
3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis.
Kusama T, Mukai M, Iwasaki T, Tatsuta M, Matsumoto Y, Akedo H, Inoue M, Nakamura H.
Gastroenterology. 2002 Feb;122(2):308-17.
PMID 11832446
 
Regulation of receptor-mediated endocytosis by Rho and Rac.
Lamaze C, Chuang TH, Terlecky LJ, Bokoch GM, Schmid SL.
Nature. 1996 Jul 11;382(6587):177-9.
PMID 8700210
 
RHO protein regulation of contraction in the human uterus.
Lartey J, Lopez Bernal A.
Reproduction. 2009 Sep;138(3):407-24. doi: 10.1530/REP-09-0160. Epub 2009 Jul 9. (REVIEW)
PMID 19589855
 
Discovery and saturation analysis of cancer genes across 21 tumour types.
Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G.
Nature. 2014 Jan 23;505(7484):495-501. doi: 10.1038/nature12912. Epub 2014 Jan 5.
PMID 24390350
 
RhoA modulates functional and physical interaction between ROCK1 and Erk1/2 in selenite-induced apoptosis of leukaemia cells.
Li F, Jiang Q, Shi KJ, Luo H, Yang Y, Xu CM.
Cell Death Dis. 2013 Jul 4;4:e708. doi: 10.1038/cddis.2013.243.
PMID 23828571
 
Overexpression of RhoA is associated with poor prognosis in hepatocellular carcinoma.
Li XR, Ji F, Ouyang J, Wu W, Qian LY, Yang KY.
Eur J Surg Oncol. 2006 Dec;32(10):1130-4. Epub 2006 Jun 27.
PMID 16806792
 
Overexpression of RhoA promotes the proliferation and migration of cervical cancer cells.
Liu X, Chen D, Liu G.
Biosci Biotechnol Biochem. 2014 Nov;78(11):1895-901. doi: 10.1080/09168451.2014.943650. Epub 2014 Aug 7.
PMID 25104222
 
Coordination of Rho GTPase activities during cell protrusion.
Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, Abell A, Johnson GL, Hahn KM, Danuser G.
Nature. 2009 Sep 3;461(7260):99-103. doi: 10.1038/nature08242. Epub 2009 Aug 19.
PMID 19693013
 
The RHOA G17V gene mutation occurs frequently in peripheral T-cell lymphoma and is associated with a characteristic molecular signature.
Manso R, Sanchez-Beato M, Monsalvo S, Gomez S, Cereceda L, Llamas P, Rojo F, Mollejo M, Menarguez J, Alves J, Garcia-Cosio M, Piris MA, Rodriguez-Pinilla SM.
Blood. 2014 May 1;123(18):2893-4. doi: 10.1182/blood-2014-02-555946.
PMID 24786457
 
RhoA: a therapeutic target for chronic myeloid leukemia.
Molli PR, Pradhan MB, Advani SH, Naik NR.
Mol Cancer. 2012 Mar 25;11:16. doi: 10.1186/1476-4598-11-16.
PMID 22443473
 
Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas.
Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, Carpenter Z, Abate F, Allegretta M, Haydu JE, Jiang X, Lossos IS, Nicolas C, Balbin M, Bastard C, Bhagat G, Piris MA, Campo E, Bernard OA, Rabadan R, Ferrando AA.
Nat Genet. 2014 Feb;46(2):166-70. doi: 10.1038/ng.2873. Epub 2014 Jan 12.
PMID 24413734
 
Inhibitory role of RhoA on senescence-like growth arrest by a mechanism involving modulation of phosphatase activity.
Park C, Lee I, Jang JH, Kang WK.
FEBS Lett. 2007 Aug 7;581(20):3800-4. Epub 2007 Jul 16.
PMID 17658517
 
RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease.
Peng F, Wu D, Gao B, Ingram AJ, Zhang B, Chorneyko K, McKenzie R, Krepinsky JC.
Diabetes. 2008 Jun;57(6):1683-92. doi: 10.2337/db07-1149. Epub 2008 Mar 20.
PMID 18356410
 
Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing.
Richter J, Schlesner M, Hoffmann S, Kreuz M, Leich E, Burkhardt B, Rosolowski M, Ammerpohl O, Wagener R, Bernhart SH, Lenze D, Szczepanowski M, Paulsen M, Lipinski S, Russell RB, Adam-Klages S, Apic G, Claviez A, Hasenclever D, Hovestadt V, Hornig N, Korbel JO, Kube D, Langenberger D, Lawerenz C, Lisfeld J, Meyer K, Picelli S, Pischimarov J, Radlwimmer B, Rausch T, Rohde M, Schilhabel M, Scholtysik R, Spang R, Trautmann H, Zenz T, Borkhardt A, Drexler HG, Moller P, MacLeod RA, Pott C, Schreiber S, Trumper L, Loeffler M, Stadler PF, Lichter P, Eils R, Kuppers R, Hummel M, Klapper W, Rosenstiel P, Rosenwald A, Brors B, Siebert R; ICGC MMML-Seq Project.
Nat Genet. 2012 Dec;44(12):1316-20. doi: 10.1038/ng.2469. Epub 2012 Nov 11.
PMID 23143595
 
Cell migration: integrating signals from front to back.
Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR.
Science. 2003 Dec 5;302(5651):1704-9. (REVIEW)
PMID 14657486
 
Recurrent RHOA mutations in pediatric Burkitt lymphoma treated according to the NHL-BFM protocols.
Rohde M, Richter J, Schlesner M, Betts MJ, Claviez A, Bonn BR, Zimmermann M, Damm-Welk C, Russell RB, Borkhardt A, Eils R, Hoell JI, Szczepanowski M, Oschlies I, Klapper W, Burkhardt B, Siebert R; German ICGC MMML-Seq-Project; NHL-BFM Study Group.
Genes Chromosomes Cancer. 2014 Nov;53(11):911-6. doi: 10.1002/gcc.22202. Epub 2014 Jul 8.
PMID 25044415
 
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.
Rossman KL, Der CJ, Sondek J.
Nat Rev Mol Cell Biol. 2005 Feb;6(2):167-80. (REVIEW)
PMID 15688002
 
GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway.
Sabharanjak S, Sharma P, Parton RG, Mayor S.
Dev Cell. 2002 Apr;2(4):411-23.
PMID 11970892
 
Somatic RHOA mutation in angioimmunoblastic T cell lymphoma.
Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, Muto H, Tsuyama N, Sato-Otsubo A, Okuno Y, Sakata S, Kamada Y, Nakamoto-Matsubara R, Tran NB, Izutsu K, Sato Y, Ohta Y, Furuta J, Shimizu S, Komeno T, Sato Y, Ito T, Noguchi M, Noguchi E, Sanada M, Chiba K, Tanaka H, Suzukawa K, Nanmoku T, Hasegawa Y, Nureki O, Miyano S, Nakamura N, Takeuchi K, Ogawa S, Chiba S.
Nat Genet. 2014 Feb;46(2):171-5. doi: 10.1038/ng.2872. Epub 2014 Jan 12.
PMID 24413737
 
The transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin.
Shen DW, Pouliot LM, Gillet JP, Ma W, Johnson AC, Hall MD, Gottesman MM.
Mol Pharm. 2012 Jun 4;9(6):1822-33. doi: 10.1021/mp300153z. Epub 2012 May 17.
PMID 22571463
 
BART inhibits pancreatic cancer cell invasion by inhibiting ARL2-mediated RhoA inactivation.
Taniuchi K, Iwasaki S, Saibara T.
Int J Oncol. 2011 Nov;39(5):1243-52. doi: 10.3892/ijo.2011.1156. Epub 2011 Aug 10.
PMID 21833473
 
Vaccinia virus-induced cell motility requires F11L-mediated inhibition of RhoA signaling.
Valderrama F, Cordeiro JV, Schleich S, Frischknecht F, Way M.
Science. 2006 Jan 20;311(5759):377-81.
PMID 16424340
 
The small GTPase RhoA has greater expression in small cell lung carcinoma than in non-small cell lung carcinoma and contributes to their unique morphologies.
Varker KA, Phelps SH, King MM, Williams CL.
Int J Oncol. 2003 Mar;22(3):671-81.
PMID 12579323
 
Rho-family GTPases: it's not only Rac and Rho (and I like it).
Wennerberg K, Der CJ.
J Cell Sci. 2004 Mar 15;117(Pt 8):1301-12. (REVIEW)
PMID 15020670
 
Local translation of RhoA regulates growth cone collapse.
Wu KY, Hengst U, Cox LJ, Macosko EZ, Jeromin A, Urquhart ER, Jaffrey SR.
Nature. 2005 Aug 18;436(7053):1020-4.
PMID 16107849
 
Inhibition of RhoA/ROCK signaling pathway promotes the apoptosis of gastric cancer cells.
Xu XT, Song QB, Yao Y, Ruan P, Tao ZZ.
Hepatogastroenterology. 2012 Nov-Dec;59(120):2523-6.
PMID 22584506
 
Galpha(12) and galpha(13) inhibit Ca(2+)-dependent exocytosis through Rho/Rho-associated kinase-dependent pathway.
Yamaguchi Y, Katoh H, Yasui H, Aoki J, Nakamura K, Negishi M.
J Neurochem. 2000 Aug;75(2):708-17.
PMID 10899946
 
Silencing RhoA inhibits migration and invasion through Wnt/?-catenin pathway and growth through cell cycle regulation in human tongue cancer.
Yan G, Zou R, Chen Z, Fan B, Wang Z, Wang Y, Yin X, Zhang D, Tong L, Yang F, Jiang W, Fu W, Zheng J, Bergo MO, Dalin M, Zheng J, Chen S, Zhou J.
Acta Biochim Biophys Sin (Shanghai). 2014 Aug;46(8):682-90. doi: 10.1093/abbs/gmu051.
PMID 25001480
 
A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma.
Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, Kim SC, Lee B, Rho K, Lee JE, Cho KH, Kim W, Ju H, Kim J, Kim SJ, Kim WS, Lee S, Ko YH.
Nat Genet. 2014 Apr;46(4):371-5. doi: 10.1038/ng.2916. Epub 2014 Mar 2.
PMID 24584070
 
Endocytic pathways mediating oligomeric Abeta42 neurotoxicity.
Yu C, Nwabuisi-Heath E, Laxton K, Ladu MJ.
Mol Neurodegener. 2010 May 17;5:19. doi: 10.1186/1750-1326-5-19.
PMID 20478062
 
Altered expression of the small guanosine triphosphatase RhoA in human temporal lobe epilepsy.
Yuan J, Wang LY, Li JM, Cao NJ, Wang L, Feng GB, Xue T, Lu Y, Wang XF.
J Mol Neurosci. 2010 Sep;42(1):53-8. doi: 10.1007/s12031-010-9330-4. Epub 2010 Feb 6.
PMID 20140537
 
Co-expression of delta-catenin and RhoA is significantly associated with a malignant lung cancer phenotype.
Zhang D, Zhang JY, Dai SD, Liu SL, Liu Y, Tang N, Wang EH.
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PMID 25120748
 
RhoA of the Rho family small GTPases is essential for B lymphocyte development.
Zhang S, Zhou X, Lang RA, Guo F.
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PMID 22438996
 

Citation

This paper should be referenced as such :
Manso R
RHOA (ras homolog gene family, member A);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/RHOAID42107ch3p21.html
History of this paper:
Gomez, del Pulgar T ; Lacal, JC. RHOA (ras homolog gene family, member A). Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):124-127.
http://documents.irevues.inist.fr/bitstream/handle/2042/38415/01-2007-RHOAID42107ch3p21.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(4;11)(q23;p15) NUP98/RAP1GDS1


External links

Nomenclature
HGNC (Hugo)RHOA   667
LRG (Locus Reference Genomic)LRG_1085
Cards
AtlasRHOAID42107ch3p21
Entrez_Gene (NCBI)RHOA  387  ras homolog family member A
AliasesARH12; ARHA; RHO12; RHOH12
GeneCards (Weizmann)RHOA
Ensembl hg19 (Hinxton)ENSG00000067560 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000067560 [Gene_View]  chr3:49359136-49412097 [Contig_View]  RHOA [Vega]
ICGC DataPortalENSG00000067560
TCGA cBioPortalRHOA
AceView (NCBI)RHOA
Genatlas (Paris)RHOA
WikiGenes387
SOURCE (Princeton)RHOA
Genetics Home Reference (NIH)RHOA
Genomic and cartography
GoldenPath hg38 (UCSC)RHOA  -     chr3:49359136-49412097 -  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RHOA  -     3p21.31   [Description]    (hg19-Feb_2009)
EnsemblRHOA - 3p21.31 [CytoView hg19]  RHOA - 3p21.31 [CytoView hg38]
Mapping of homologs : NCBIRHOA [Mapview hg19]  RHOA [Mapview hg38]
OMIM165390   
Gene and transcription
Genbank (Entrez)AA542841 AF498970 AI269293 AK130066 AK130808
RefSeq transcript (Entrez)NM_001313941 NM_001313943 NM_001313944 NM_001313945 NM_001313946 NM_001313947 NM_001664
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RHOA
Cluster EST : UnigeneHs.247077 [ NCBI ]
CGAP (NCI)Hs.247077
Alternative Splicing GalleryENSG00000067560
Gene ExpressionRHOA [ NCBI-GEO ]   RHOA [ EBI - ARRAY_EXPRESS ]   RHOA [ SEEK ]   RHOA [ MEM ]
Gene Expression Viewer (FireBrowse)RHOA [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)387
GTEX Portal (Tissue expression)RHOA
Protein : pattern, domain, 3D structure
UniProt/SwissProtP61586   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP61586  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP61586
Splice isoforms : SwissVarP61586
PhosPhoSitePlusP61586
Domaine pattern : Prosite (Expaxy)RHO (PS51420)   
Domains : Interpro (EBI)P-loop_NTPase    Small_GTP-bd_dom    Small_GTPase   
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Conserved Domain (NCBI)RHOA
DMDM Disease mutations387
Blocks (Seattle)RHOA
PDB (SRS)1A2B    1CC0    1CXZ    1DPF    1FTN    1KMQ    1LB1    1OW3    1S1C    1TX4    1X86    1XCG    2RGN    3KZ1    3LW8    3LWN    3LXR    3MSX    3T06    4D0N    4XH9    4XOI    4XSG    4XSH    5A0F    5BWM    5C2K    5C4M    5EZ6    5FR1    5FR2    5HPY    5IRC    5JCP   
PDB (PDBSum)1A2B    1CC0    1CXZ    1DPF    1FTN    1KMQ    1LB1    1OW3    1S1C    1TX4    1X86    1XCG    2RGN    3KZ1    3LW8    3LWN    3LXR    3MSX    3T06    4D0N    4XH9    4XOI    4XSG    4XSH    5A0F    5BWM    5C2K    5C4M    5EZ6    5FR1    5FR2    5HPY    5IRC    5JCP   
PDB (IMB)1A2B    1CC0    1CXZ    1DPF    1FTN    1KMQ    1LB1    1OW3    1S1C    1TX4    1X86    1XCG    2RGN    3KZ1    3LW8    3LWN    3LXR    3MSX    3T06    4D0N    4XH9    4XOI    4XSG    4XSH    5A0F    5BWM    5C2K    5C4M    5EZ6    5FR1    5FR2    5HPY    5IRC    5JCP   
PDB (RSDB)1A2B    1CC0    1CXZ    1DPF    1FTN    1KMQ    1LB1    1OW3    1S1C    1TX4    1X86    1XCG    2RGN    3KZ1    3LW8    3LWN    3LXR    3MSX    3T06    4D0N    4XH9    4XOI    4XSG    4XSH    5A0F    5BWM    5C2K    5C4M    5EZ6    5FR1    5FR2    5HPY    5IRC    5JCP   
Structural Biology KnowledgeBase1A2B    1CC0    1CXZ    1DPF    1FTN    1KMQ    1LB1    1OW3    1S1C    1TX4    1X86    1XCG    2RGN    3KZ1    3LW8    3LWN    3LXR    3MSX    3T06    4D0N    4XH9    4XOI    4XSG    4XSH    5A0F    5BWM    5C2K    5C4M    5EZ6    5FR1    5FR2    5HPY    5IRC    5JCP   
SCOP (Structural Classification of Proteins)1A2B    1CC0    1CXZ    1DPF    1FTN    1KMQ    1LB1    1OW3    1S1C    1TX4    1X86    1XCG    2RGN    3KZ1    3LW8    3LWN    3LXR    3MSX    3T06    4D0N    4XH9    4XOI    4XSG    4XSH    5A0F    5BWM    5C2K    5C4M    5EZ6    5FR1    5FR2    5HPY    5IRC    5JCP   
CATH (Classification of proteins structures)1A2B    1CC0    1CXZ    1DPF    1FTN    1KMQ    1LB1    1OW3    1S1C    1TX4    1X86    1XCG    2RGN    3KZ1    3LW8    3LWN    3LXR    3MSX    3T06    4D0N    4XH9    4XOI    4XSG    4XSH    5A0F    5BWM    5C2K    5C4M    5EZ6    5FR1    5FR2    5HPY    5IRC    5JCP   
SuperfamilyP61586
Human Protein AtlasENSG00000067560
Peptide AtlasP61586
HPRD01323
IPIIPI00478231   IPI00927114   IPI00926881   IPI00926710   IPI00926466   
Protein Interaction databases
DIP (DOE-UCLA)P61586
IntAct (EBI)P61586
FunCoupENSG00000067560
BioGRIDRHOA
STRING (EMBL)RHOA
ZODIACRHOA
Ontologies - Pathways
QuickGOP61586
Ontology : AmiGOGTPase activity  GTPase activity  GTPase activity  protein binding  GTP binding  endosome  endoplasmic reticulum membrane  cytosol  cytosol  cytoskeleton  plasma membrane  focal adhesion  cell cortex  transforming growth factor beta receptor signaling pathway  Rho protein signal transduction  Rho protein signal transduction  Rho protein signal transduction  viral process  cell migration  cell migration  protein deubiquitination  myosin binding  substantia nigra development  lamellipodium  actin cytoskeleton organization  cell junction  platelet activation  regulation of cell migration  midbody  secretory granule membrane  extrinsic component of cytoplasmic side of plasma membrane  actin cytoskeleton reorganization  vesicle  cleavage furrow  positive regulation of cytokinesis  regulation of actin cytoskeleton organization  regulation of osteoblast proliferation  Roundabout signaling pathway  cleavage furrow formation  apolipoprotein A-I-mediated signaling pathway  positive regulation of NF-kappaB import into nucleus  positive regulation of I-kappaB kinase/NF-kappaB signaling  stress fiber assembly  dendritic spine  apical junction complex  apical junction assembly  neutrophil degranulation  endothelial cell migration  ossification involved in bone maturation  wound healing, spreading of cells  positive regulation of neuron differentiation  negative regulation of cell size  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  phosphatidylinositol-mediated signaling  negative regulation of axonogenesis  positive regulation of axonogenesis  negative chemotaxis  regulation of small GTPase mediated signal transduction  positive regulation of stress fiber assembly  positive regulation of stress fiber assembly  Wnt signaling pathway, planar cell polarity pathway  Wnt signaling pathway, planar cell polarity pathway  positive regulation of lipase activity  positive regulation of lipase activity  trabecula morphogenesis  extracellular exosome  positive regulation of protein serine/threonine kinase activity  cell periphery  negative regulation of cell migration involved in sprouting angiogenesis  mitotic spindle assembly  endothelial tube lumen extension  ficolin-1-rich granule membrane  skeletal muscle satellite cell migration  mitotic cleavage furrow formation  cellular response to chemokine  regulation of cell motility  positive regulation of T cell migration  
Ontology : EGO-EBIGTPase activity  GTPase activity  GTPase activity  protein binding  GTP binding  endosome  endoplasmic reticulum membrane  cytosol  cytosol  cytoskeleton  plasma membrane  focal adhesion  cell cortex  transforming growth factor beta receptor signaling pathway  Rho protein signal transduction  Rho protein signal transduction  Rho protein signal transduction  viral process  cell migration  cell migration  protein deubiquitination  myosin binding  substantia nigra development  lamellipodium  actin cytoskeleton organization  cell junction  platelet activation  regulation of cell migration  midbody  secretory granule membrane  extrinsic component of cytoplasmic side of plasma membrane  actin cytoskeleton reorganization  vesicle  cleavage furrow  positive regulation of cytokinesis  regulation of actin cytoskeleton organization  regulation of osteoblast proliferation  Roundabout signaling pathway  cleavage furrow formation  apolipoprotein A-I-mediated signaling pathway  positive regulation of NF-kappaB import into nucleus  positive regulation of I-kappaB kinase/NF-kappaB signaling  stress fiber assembly  dendritic spine  apical junction complex  apical junction assembly  neutrophil degranulation  endothelial cell migration  ossification involved in bone maturation  wound healing, spreading of cells  positive regulation of neuron differentiation  negative regulation of cell size  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  phosphatidylinositol-mediated signaling  negative regulation of axonogenesis  positive regulation of axonogenesis  negative chemotaxis  regulation of small GTPase mediated signal transduction  positive regulation of stress fiber assembly  positive regulation of stress fiber assembly  Wnt signaling pathway, planar cell polarity pathway  Wnt signaling pathway, planar cell polarity pathway  positive regulation of lipase activity  positive regulation of lipase activity  trabecula morphogenesis  extracellular exosome  positive regulation of protein serine/threonine kinase activity  cell periphery  negative regulation of cell migration involved in sprouting angiogenesis  mitotic spindle assembly  endothelial tube lumen extension  ficolin-1-rich granule membrane  skeletal muscle satellite cell migration  mitotic cleavage furrow formation  cellular response to chemokine  regulation of cell motility  positive regulation of T cell migration  
Pathways : BIOCARTA [Genes]   
Pathways : KEGG   
REACTOMEP61586 [protein]
REACTOME PathwaysR-HSA-8849471 [pathway]   
NDEx NetworkRHOA
Atlas of Cancer Signalling NetworkRHOA
Wikipedia pathwaysRHOA
Orthology - Evolution
OrthoDB387
GeneTree (enSembl)ENSG00000067560
Phylogenetic Trees/Animal Genes : TreeFamRHOA
HOVERGENP61586
HOGENOMP61586
Homologs : HomoloGeneRHOA
Homology/Alignments : Family Browser (UCSC)RHOA
Gene fusions - Rearrangements
Fusion : MitelmanARIH2/RHOA [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanMAP4/RHOA [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanRHOA/CACNA2D2 [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanRHOA/COL7A1 [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanRHOA/NICN1 [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanRHOA/SMCO1 [3p21.31/3q29]  [t(3;3)(p21;q29)]  
Fusion: TCGAARIH2 3p21.31 RHOA 3p21.31 BLCA
Fusion: TCGAMAP4 3p21.31 RHOA 3p21.31 BRCA
Fusion: TCGARHOA 3p21.31 C3orf43 BRCA
Fusion: TCGARHOA 3p21.31 CACNA2D2 3p21.31 BLCA
Fusion: TCGARHOA 3p21.31 NICN1 3p21.31 KIRC
Fusion : TICdbTAL1 [1p33]  -  RHOA [3p21.31]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRHOA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RHOA
dbVarRHOA
ClinVarRHOA
1000_GenomesRHOA 
Exome Variant ServerRHOA
ExAC (Exome Aggregation Consortium)RHOA (select the gene name)
Genetic variants : HAPMAP387
Genomic Variants (DGV)RHOA [DGVbeta]
DECIPHERRHOA [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRHOA 
Mutations
ICGC Data PortalRHOA 
TCGA Data PortalRHOA 
Broad Tumor PortalRHOA
OASIS PortalRHOA [ Somatic mutations - Copy number]
Cancer Gene: CensusRHOA 
Somatic Mutations in Cancer : COSMICRHOA  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRHOA
intOGen PortalRHOA
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch RHOA
DgiDB (Drug Gene Interaction Database)RHOA
DoCM (Curated mutations)RHOA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RHOA (select a term)
intoGenRHOA
NCG5 (London)RHOA
Cancer3DRHOA(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM165390   
Orphanet
MedgenRHOA
Genetic Testing Registry RHOA
NextProtP61586 [Medical]
TSGene387
GENETestsRHOA
Target ValidationRHOA
Huge Navigator RHOA [HugePedia]
snp3D : Map Gene to Disease387
BioCentury BCIQRHOA
ClinGenRHOA
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD387
Chemical/Pharm GKB GenePA134865095
Clinical trialRHOA
Miscellaneous
canSAR (ICR)RHOA (select the gene name)
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRHOA
EVEXRHOA
GoPubMedRHOA
iHOPRHOA
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jun 7 12:13:26 CEST 2017

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