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RHOC (ras homolog gene family, member C)

Written2007-06Ahmad Faried, Leri S. Faried
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Japan

(Note : for Links provided by Atlas : click)

Identity

Other namesRhoC
ARH9
ARHC
H9
MGC1448
MGC61427
RhoH9
HGNC (Hugo) RHOC
LocusID (NCBI) 389
Atlas_Id 42110
Location 1p13.2
Location_base_pair Starts at 113243749 and ends at 113250025 bp from pter ( according to hg19-Feb_2009)  [Mapping RHOC.png]
Fusion genes
(updated 2016)
RHOC (1p13.2) / SPIDR (8q11.21)UQCRHL (1p36.21) / RHOC (1p13.2)

DNA/RNA

Description The RhoC gene contains 6 exons and 5 introns. It was predicted to span over approximately 6.3 kb of the genomic DNA with mRNA size approximately 1116 bp. This gene is related to a gene originally identified in the marine snail, Aplysia. After the original cloning of Rho gene in Aplysia californica, then several genes in mammal been identified and divided into several subfamily, among them is (RhoA, RhoB and RhoC isoforms). In 1993, human ARH9 (RhoC), was reexamined and showed that it was present in choromosome 1. Human cDNA of RhoC proteins were isolated from the complete H9Rho (clone 9) coding sequence. Other group isolated RhoC from adult retina library.
Transcription Three alternative transcripts encoding the same protein have been identified for RhoC gene.

Protein

Description The primary protein sequences of Rho-subfamily (RhoA, B and C) are about 85% identical, with most divergence close to the C-terminus. The sequence divergence among RhoA, B and C is found in the insert loop, a helix between amino acids 123 and 137. The RhoC consists of 193 amino acids corresponding to a molecular weight of 22 kDa. RhoC protein consists of GTPase binding domain in the N-terminal. In C-terminal consists of geranylgeranyl group and carboxyl methylation extension. RhoC contains the sequence motif of GTP-binding proteins, bind to GDP and GTP with high affinity and are involved in cycle between in-active, GDP-bound and active, GTP-bound states. RhoC displays about 30% amino acids identity with Ras proteins which mainly clustered in four highly homologues internal region corresponding to the GTP binding site.
Expression The RhoC proteins are over-expressed in bladder carcinoma, breast carcinoma, and in the squamous cell carcinoma of the head and neck. At mRNA level, RhoC are over-expressed in adenocarcinoma of the ovary, pancreatic cancer and hepatocellular carcinoma.
Localisation Mainly in the cytoplasm, there is a small fraction localized in the plasma membrane of the Rat-2 fibroblast cells and associated with undefined perinuclear structures.
Function The Rho proteins are involved in multiple processes, such as organization of the cytoskeletal components, cell division or intracellular trafficking. Role of RhoC also been observed in limb development. The RhoC protein has been connected to cancer development. It is up-regulated in malignant pancreatic ductal carcinoma, inflammatory breast cancer tumors and highly metastatic melanoma. Ectopic over-expression of this gene increases the tumorigenic and metastasis properties of tumor progenitor cell. RhoC also induces the expression of angiogenic factors in human mammary epithelial cells, by facilitating the vascularization of tumors in which it is expressed.
Homology At least there are five homologues of RhoC sequences with pair-wise similarity from 80-100% at the amino acids level. Among them in dog (Canis lupus familiaris), rat (Rattus norvergicus), mouse (Mus musculus), zebrafish (Danio rerio), and chicken (Gallus gallus).

Mutations

Germinal Not found in Homo sapiens
Somatic Not found in Homo sapiens

Implicated in

Note
Entity Morphogenesis
Note The RhoC exhibits specific expression domain in regions undergoing major cell rearrangement process in the developing limb autopod, including the prechondrogeneic aggregates, the developing interphalangeal joints and tendons. Functional experiments indicate that RhoC is a regulator of mesenchymal cell shape and adhesiveness, acting as a modulator of digit morphogenesis and joint formation.
  
Entity Malignancy
Disease The RhoC reported to be over-expressed in many human cancers (see above).
Prognosis The RhoC over-expression is a predictor of poor prognosis in malignancy.
Oncogenesis The RhoC and RhoA are 94% identical, only 11 amino acids are different. RhoC plays a major role in cell locomotion compare with RhoA. Over-expression of RhoC is closely related with tumor cell invasion and metastasis.
  

Bibliography

A novel ras-related gene family.
Madaule P, Axel R
Cell. 1985 ; 41 (1) : 31-40.
PMID 3888408
 
Coding sequence of human rho cDNAs clone 6 and clone 9.
Chardin P, Madaule P, Tavitian A
Nucleic acids research. 1988 ; 16 (6) : page 2717.
PMID 3283705
 
Intracellular localization of the P21rho proteins.
Adamson P, Paterson HF, Hall A
The Journal of cell biology. 1992 ; 119 (3) : 617-627.
PMID 1383236
 
Reassignment of the human ARH9 RAS-related gene to chromosome 1p13-p21.
Morris SW, Valentine MB, Kirstein MN, Huebner K
Genomics. 1993 ; 15 (3) : 677-679.
PMID 8468062
 
Sequence of rho small GTP-binding protein cDNAs from human retina and identification of novel 5' end cloning artifacts.
Fagan KP, Oliveira L, Pittler SJ
Experimental eye research. 1994 ; 59 (2) : 235-237.
PMID 7835413
 
Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue.
Ihara K, Muraguchi S, Kato M, Shimizu T, Shirakawa M, Kuroda S, Kaibuchi K, Hakoshima T
The Journal of biological chemistry. 1998 ; 273 (16) : 9656-9666.
PMID 9545299
 
Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas.
Suwa H, Ohshio G, Imamura T, Watanabe G, Arii S, Imamura M, Narumiya S, Hiai H, Fukumoto M
British journal of cancer. 1998 ; 77 (1) : 147-152.
PMID 9459160
 
Genomic analysis of metastasis reveals an essential role for RhoC.
Clark EA, Golub TR, Lander ES, Hynes RO
Nature. 2000 ; 406 (6795) : 532-535.
PMID 10952316
 
RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype.
van Golen KL, Wu ZF, Qiao XT, Bao LW, Merajver SD
Cancer research. 2000 ; 60 (20) : 5832-5838.
PMID 11059780
 
RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells.
van Golen KL, Wu ZF, Qiao XT, Bao L, Merajver SD
Neoplasia (New York, N.Y.). 2000 ; 2 (5) : 418-425.
PMID 11191108
 
Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding.
Michaelson D, Silletti J, Murphy G, D'Eustachio P, Rush M, Philips MR
The Journal of cell biology. 2001 ; 152 (1) : 111-126.
PMID 11149925
 
Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability.
Kleer CG, van Golen KL, Zhang Y, Wu ZF, Rubin MA, Merajver SD
The American journal of pathology. 2002 ; 160 (2) : 579-584.
PMID 11839578
 
Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma.
Horiuchi A, Imai T, Wang C, Ohira S, Feng Y, Nikaido T, Konishi I
Laboratory investigation; a journal of technical methods and pathology. 2003 ; 83 (6) : 861-870.
PMID 12808121
 
Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer.
Kamai T, Tsujii T, Arai K, Takagi K, Asami H, Ito Y, Oshima H
Clinical cancer research : an official journal of the American Association for Cancer Research. 2003 ; 9 (7) : 2632-2641.
PMID 12855641
 
A novel strategy for specifically down-regulating individual Rho GTPase activity in tumor cells.
Wang L, Yang L, Luo Y, Zheng Y
The Journal of biological chemistry. 2003 ; 278 (45) : 44617-44625.
PMID 12939257
 
Actin and microtubules in cell motility: which one is in control?
Etienne-Manneville S
Traffic (Copenhagen, Denmark). 2004 ; 5 (7) : 470-477.
PMID 15180824
 
A definitive role of RhoC in metastasis of orthotopic lung cancer in mice.
Ikoma T, Takahashi T, Nagano S, Li YM, Ohno Y, Ando K, Fujiwara T, Fujiwara H, Kosai K
Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (3) : 1192-1200.
PMID 14871999
 
Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis.
Wang W, Yang LY, Huang GW, Lu WQ, Yang ZL, Yang JQ, Liu HL
British journal of cancer. 2004 ; 90 (12) : 2349-2355.
PMID 15150600
 
Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility.
Wheeler AP, Ridley AJ
Experimental cell research. 2004 ; 301 (1) : 43-49.
PMID 15501444
 
Rho GTPases: biochemistry and biology.
Jaffe AB, Hall A
Annual review of cell and developmental biology. 2005 ; 21 : 247-269.
PMID 16212495
 
RhoA and RhoC proteins promote both cell proliferation and cell invasion of human oesophageal squamous cell carcinoma cell lines in vitro and in vivo.
Faried A, Faried LS, Kimura H, Nakajima M, Sohda M, Miyazaki T, Kato H, Usman N, Kuwano H
European journal of cancer (Oxford, England : 1990). 2006 ; 42 (10) : 1455-1465.
PMID 16750623
 
RhoC GTPase expression as a potential marker of lymph node metastasis in squamous cell carcinomas of the head and neck.
Kleer CG, Teknos TN, Islam M, Marcus B, Lee JS, Pan Q, Merajver SD
Clinical cancer research : an official journal of the American Association for Cancer Research. 2006 ; 12 (15) : 4485-4490.
PMID 16899593
 
Role of RhoC in digit morphogenesis during limb development.
Montero JA, Zuzarte-Luis V, Garcia-Martinez V, Hurle JM
Developmental biology. 2007 ; 303 (1) : 325-335.
PMID 17208217
 

Citation

This paper should be referenced as such :
Faried, A ; Faried, LS
RHOC (ras homolog gene family, member C)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):8-9.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RHOCID42110ch1p13.html


External links

Nomenclature
HGNC (Hugo)RHOC   669
Cards
AtlasRHOCID42110ch1p13
Entrez_Gene (NCBI)RHOC  389  ras homolog family member C
AliasesARH9; ARHC; H9; RHOH9
GeneCards (Weizmann)RHOC
Ensembl hg19 (Hinxton)ENSG00000155366 [Gene_View]  chr1:113243749-113250025 [Contig_View]  RHOC [Vega]
Ensembl hg38 (Hinxton)ENSG00000155366 [Gene_View]  chr1:113243749-113250025 [Contig_View]  RHOC [Vega]
ICGC DataPortalENSG00000155366
TCGA cBioPortalRHOC
AceView (NCBI)RHOC
Genatlas (Paris)RHOC
WikiGenes389
SOURCE (Princeton)RHOC
Genomic and cartography
GoldenPath hg19 (UCSC)RHOC  -     chr1:113243749-113250025 -  1p13.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RHOC  -     1p13.1   [Description]    (hg38-Dec_2013)
EnsemblRHOC - 1p13.1 [CytoView hg19]  RHOC - 1p13.1 [CytoView hg38]
Mapping of homologs : NCBIRHOC [Mapview hg19]  RHOC [Mapview hg38]
OMIM165380   
Gene and transcription
Genbank (Entrez)AF085893 AF498972 AK094474 BC007245 BC009177
RefSeq transcript (Entrez)NM_001042678 NM_001042679 NM_175744
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_032977 NW_004929290
Consensus coding sequences : CCDS (NCBI)RHOC
Cluster EST : UnigeneHs.658289 [ NCBI ]
CGAP (NCI)Hs.658289
Alternative Splicing GalleryENSG00000155366
Gene ExpressionRHOC [ NCBI-GEO ]   RHOC [ EBI - ARRAY_EXPRESS ]   RHOC [ SEEK ]   RHOC [ MEM ]
Gene Expression Viewer (FireBrowse)RHOC [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)389
GTEX Portal (Tissue expression)RHOC
Protein : pattern, domain, 3D structure
UniProt/SwissProtP08134 (Uniprot)
NextProtP08134  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP08134
Splice isoforms : SwissVarP08134 (Swissvar)
PhosPhoSitePlusP08134
Domaine pattern : Prosite (Expaxy)RHO (PS51420)   
Domains : Interpro (EBI)P-loop_NTPase    Small_GTP-bd_dom    Small_GTPase    Small_GTPase_Rho   
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Domain families : Smart (EMBL)RHO (SM00174)  
DMDM Disease mutations389
Blocks (Seattle)RHOC
PDB (SRS)1Z2C    2GCN    2GCO    2GCP   
PDB (PDBSum)1Z2C    2GCN    2GCO    2GCP   
PDB (IMB)1Z2C    2GCN    2GCO    2GCP   
PDB (RSDB)1Z2C    2GCN    2GCO    2GCP   
Structural Biology KnowledgeBase1Z2C    2GCN    2GCO    2GCP   
SCOP (Structural Classification of Proteins)1Z2C    2GCN    2GCO    2GCP   
CATH (Classification of proteins structures)1Z2C    2GCN    2GCO    2GCP   
SuperfamilyP08134
Human Protein AtlasENSG00000155366
Peptide AtlasP08134
HPRD01322
IPIIPI00027434   IPI00552834   IPI00647268   IPI00643368   IPI00644425   IPI00982162   IPI00980853   IPI01009702   
Protein Interaction databases
DIP (DOE-UCLA)P08134
IntAct (EBI)P08134
FunCoupENSG00000155366
BioGRIDRHOC
STRING (EMBL)RHOC
ZODIACRHOC
Ontologies - Pathways
QuickGOP08134
Ontology : AmiGOcytokinesis  signal transducer activity  protein binding  GTP binding  nucleus  cytosol  plasma membrane  small GTPase mediated signal transduction  protein transport  cleavage furrow  positive regulation of I-kappaB kinase/NF-kappaB signaling  apical junction assembly  wound healing, spreading of cells  regulation of small GTPase mediated signal transduction  positive regulation of lipase activity  extracellular exosome  skeletal muscle satellite cell migration  
Ontology : EGO-EBIcytokinesis  signal transducer activity  protein binding  GTP binding  nucleus  cytosol  plasma membrane  small GTPase mediated signal transduction  protein transport  cleavage furrow  positive regulation of I-kappaB kinase/NF-kappaB signaling  apical junction assembly  wound healing, spreading of cells  regulation of small GTPase mediated signal transduction  positive regulation of lipase activity  extracellular exosome  skeletal muscle satellite cell migration  
REACTOMEP08134 [protein]
REACTOME PathwaysR-HSA-194840 Rho GTPase cycle [pathway]
REACTOME PathwaysR-HSA-5666185 RHO GTPases Activate Rhotekin and Rhophilins [pathway]
REACTOME PathwaysR-HSA-5627117 RHO GTPases Activate ROCKs [pathway]
REACTOME PathwaysR-HSA-5625900 RHO GTPases activate CIT [pathway]
REACTOME PathwaysR-HSA-5663220 RHO GTPases Activate Formins [pathway]
REACTOME PathwaysR-HSA-5625740 RHO GTPases activate PKNs [pathway]
REACTOME PathwaysR-HSA-416482 G alpha (12/13) signalling events [pathway]
REACTOME PathwaysR-HSA-416572 Sema4D induced cell migration and growth-cone collapse [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkRHOC
Wikipedia pathwaysRHOC
Orthology - Evolution
OrthoDB389
GeneTree (enSembl)ENSG00000155366
Phylogenetic Trees/Animal Genes : TreeFamRHOC
Homologs : HomoloGeneRHOC
Homology/Alignments : Family Browser (UCSC)RHOC
Gene fusions - Rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerRHOC [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RHOC
dbVarRHOC
ClinVarRHOC
1000_GenomesRHOC 
Exome Variant ServerRHOC
ExAC (Exome Aggregation Consortium)RHOC (select the gene name)
Genetic variants : HAPMAP389
Genomic Variants (DGV)RHOC [DGVbeta]
Mutations
ICGC Data PortalRHOC 
TCGA Data PortalRHOC 
Broad Tumor PortalRHOC
OASIS PortalRHOC [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRHOC 
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
BioMutasearch RHOC
DgiDB (Drug Gene Interaction Database)RHOC
DoCM (Curated mutations)RHOC (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RHOC (select a term)
intoGenRHOC
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)1:113243749-113250025  ENSG00000155366
CONAN: Copy Number AnalysisRHOC 
Mutations and Diseases : HGMDRHOC
OMIM165380   
MedgenRHOC
Genetic Testing Registry RHOC
NextProtP08134 [Medical]
TSGene389
GENETestsRHOC
Huge Navigator RHOC [HugePedia]
snp3D : Map Gene to Disease389
BioCentury BCIQRHOC
ClinGenRHOC
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD389
Chemical/Pharm GKB GenePA24951
Clinical trialRHOC
Miscellaneous
canSAR (ICR)RHOC (select the gene name)
Other databaseat http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=homologene
Probes
Litterature
PubMed134 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRHOC
EVEXRHOC
GoPubMedRHOC
iHOPRHOC
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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