RhoC (ras homolog gene family, member C)

Identity

Other names	ARH9
	ARHC
	H9
	MGC1448
	MGC61427
	RhoH9
Hugo	RHOC
Location	1p13.1

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

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.

External links

	Nomenclature
Hugo	RHOC
GDB	RHOC
Entrez_Gene	RHOC  389  ras homolog gene family, member C
	Cards
Atlas	RHOCID42110ch1p13
GeneCards	RHOC
Ensembl	RHOC [Search_View]   ENSG00000155366 [Gene_View]
Genatlas	RHOC
GeneLynx	RHOC
eGenome	RHOC
euGene	389
	Genomic and cartography
GoldenPath	RHOC  -  1p13.1   chr1:113045272-113051201 -  1p13.1   [Description]    (hg18-Mar_2006)
Ensembl	RHOC - 1p13.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	RHOC
	Gene and transcription
Genbank	AF085893 [ ENTREZ ]
Genbank	AF498972 [ ENTREZ ]
Genbank	AK094474 [ ENTREZ ]
Genbank	BC007245 [ ENTREZ ]
Genbank	BC009177 [ ENTREZ ]
RefSeq	NM_001042678 [ SRS ]    NM_001042678 [ ENTREZ ]
RefSeq	NM_001042679 [ SRS ]    NM_001042679 [ ENTREZ ]
RefSeq	NM_175744 [ SRS ]    NM_175744 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NT_019273 [ SRS ]    NT_019273 [ ENTREZ ]
RefSeq	NW_001838594 [ SRS ]    NW_001838594 [ ENTREZ ]
RefSeq	NW_922462 [ SRS ]    NW_922462 [ ENTREZ ]
AceView	RHOC AceView - NCBI
Unigene	Hs.658289 [ SRS ]    Hs.658289 [ NCBI ]     HS658289 [ spliceNest ]
Fast-db	17098 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P08134 [ SRS]    P08134 [ EXPASY ]     P08134 [ INTERPRO ]
Interpro	IPR003578 GTPase_Rho [ SRS ]    IPR003578 GTPase_Rho [ EBI ]
Interpro	IPR013753 Ras [ SRS ]    IPR013753 Ras [ EBI ]
Interpro	IPR001806 Ras_trnsfrmng [ SRS ]    IPR001806 Ras_trnsfrmng [ EBI ]
Interpro	IPR005225 Small_GTP_bd [ SRS ]    IPR005225 Small_GTP_bd [ EBI ]
CluSTr	P08134
Pfam	PF00071 Ras [ SRS ]    PF00071 Ras [ Sanger ]    pfam00071 [ NCBI-CDD ]
Smart	SM00174 RHO [EMBL]
Blocks	P08134
PDB	RHOC [ SRS ]    RHOC [ PdbSum ],   RHOC [ IMB ]   RHOC [ RSDB ]
HPRD	01322
	Protein Interaction databases
DIP	P08134
IntAct	P08134
	Polymorphism : SNP, mutations, diseases
OMIM	165380    [ map ]
GENECLINICS	165380
SNP	RHOC [dbSNP-NCBI]
SNP	NM_001042678 [SNP-NCI]
SNP	NM_001042679 [SNP-NCI]
SNP	NM_175744 [SNP-NCI]
SNP	RHOC [GeneSNPs - Utah]  RHOC] [HGBASE - SRS]
HAPMAP	RHOC [HAPMAP]
COSMIC	RHOC [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	RHOC
	General knowledge
Family Browser	RHOC [UCSC Family Browser]
SOURCE	NM_001042678
SOURCE	NM_001042679
SOURCE	NM_175744
SMD	Hs.658289
SAGE	Hs.658289
GO	nucleotide binding [Amigo]  nucleotide binding
GO	GTPase activity [Amigo]  GTPase activity
GO	signal transducer activity [Amigo]  signal transducer activity
GO	protein binding [Amigo]  protein binding
GO	GTP binding [Amigo]  GTP binding
GO	intracellular [Amigo]  intracellular
GO	plasma membrane [Amigo]  plasma membrane
GO	small GTPase mediated signal transduction [Amigo]  small GTPase mediated signal transduction
GO	positive regulation of I-kappaB kinase/NF-kappaB cascade [Amigo]  positive regulation of I-kappaB kinase/NF-kappaB cascade
PubGene	RHOC
TreeFam	RHOC
CTD	389 [Comparative ToxicoGenomics Database]
	Other databases
Other database	at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=homologene
	Probes
Probe	RHOC Related clones (RZPD - Berlin)
	PubMed
PubMed	47 Pubmed reference(s) in LocusLink

Bibliography

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RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype.

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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.

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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.

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Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer.

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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.

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PMID 15501444

Rho GTPases: biochemistry and biology.

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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

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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

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Contributor(s)

Written	06-2007	Ahmad Faried, Leri S. Faried
		Department of General Surgical Science, Graduate School of Medicine, Gunma University, Japan

Citation

This paper should be referenced as such :

Faried A, Faried LS . RhoC (ras homolog gene family, member C). Atlas Genet Cytogenet Oncol Haematol. June 2007 . URL : http://AtlasGeneticsOncology.org/Genes/RHOCID42110ch1p13.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 17:49:44 2008