RHOB (ras homolog gene family, member B)

Identity

Other names	ARH6
	ARHB
	H6
	RHOH6
HGNC	RHOB
Location	2p24.1

DNA/RNA

Description	The gene encompasses 2,366 bps (chr2:20,510,316-20,512,681); 1 exon.
Transcription	The coding sequence (CDS) region is 395.983bp (588 bp) encoding a protein of 196 aa long.

Protein

Description	Length 196 aa, molecular weight 22123 Da (unprocessed precursor). RhoB protein exists in different geranylgeranylated (RhoB-GG) or farnesylated (RhoB-F) isoforms in cells.
Expression	Widely expressed.
Localisation	Endosome; Late endosome; late endosomal membrane; cell membrane; Also detected at the nuclear margin and in the nucleus. Prenylation specifies the subcellular location of RHOB. In general, the farnesylated form is localized to the plasma membrane while the geranylgeranylated form is localized to the endosome.
Function	Regulator of protein signaling and trafficking: Plays a pivotal role in the dynamic regulation of the actin cytoskeleton. Involved in intracellular protein trafficking of a number of proteins. Targets PRK1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of Akt which promotes endothelial cell survival during vascular development. Identified as a component of outside-in signaling pathways that coordinate Src activation with its translocation to transmembrane receptors. Negative modifier of cancer progression: Affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as RhoB deletion increases tumor formation initiated by Ras mutation. Limits the proliferation of transformed cells by facilitating turnover of oncogene c-Myc. Expression levels are dramatically decreased in lung, head and neck, and brain cancer, when tumors become more aggressive. Modulator of cancer cell apoptosis: Promotes proapoptotic signaling of regulators involved in cell cycle checkpoints, cell adhesion, vesicle trafficking, MAPK signaling, transcription, and immunity. Mediates apoptosis in neoplastically transformed cells after DNA damage. Is essential for apoptosis and antineoplastic activity of farnesyltransferase inhibitors in a mouse model. Is one of the targets of farnesyltransferase inhibitors which are currently under investigation as cancer therapeutics.
Homology	Member of the ras gene superfamily; rho family; GTP-binding proteins. The RhoA, RhoB, and RhoC proteins form a closely related subgroup that are about 90% identical in amino acid sequence. The sequences of RHOB are highly-conserved between species (from human to fly). Amino acid sequences of human, mouse and rat are 100% identical while sequence homology between human and chicken is 97% identical.

Implicated in

Entity	Lung cancer
Note	RhoB expression is frequently downregulated in lung cancer by multiple mechanisms. Low or no expression of RhoB is more frequently observed in poorly- or moderately-differentiated adenocarcinomas, and indicative of poor patient prognosis.
Entity	Head and neck cancer
Note	RhoB expression decreases to undetectable level as tumors become more invasive and poorly differentiated. In contrast, Ki67 (proliferation marker) and RhoA protein levels increase with tumor progression.

External links

	Nomenclature
HGNC	RHOB   668
Entrez_Gene	RHOB  388  ras homolog gene family, member B
	Cards
Atlas	RHOBID42108ch2p24
GeneCards	RHOB
Ensembl	RHOB [Search_View]   ENSG00000143878 [Gene_View]
Genatlas	RHOB
GeneLynx	RHOB
eGenome	RHOB
euGene	388
	Genomic and cartography
GoldenPath	RHOB  -  2p24.1   chr2:20510316-20512682 +  2p24   [Description]    (hg18-Mar_2006)
Ensembl	RHOB - 2p24 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	RHOB
	Gene and transcription
Genbank	AF171089 [ ENTREZ ]
Genbank	AF498971 [ ENTREZ ]
Genbank	AK124398 [ ENTREZ ]
Genbank	AK312487 [ ENTREZ ]
Genbank	BC062781 [ ENTREZ ]
RefSeq	NM_004040 [ SRS ]    NM_004040 [ ENTREZ ]
RefSeq	AC_000045 [ SRS ]    AC_000045 [ ENTREZ ]
RefSeq	AC_000134 [ SRS ]    AC_000134 [ ENTREZ ]
RefSeq	NC_000002 [ SRS ]    NC_000002 [ ENTREZ ]
RefSeq	NT_015926 [ SRS ]    NT_015926 [ ENTREZ ]
RefSeq	NW_001838767 [ SRS ]    NW_001838767 [ ENTREZ ]
RefSeq	NW_927719 [ SRS ]    NW_927719 [ ENTREZ ]
AceView	RHOB AceView - NCBI
Unigene	Hs.502876 [ SRS ]    Hs.502876 [ NCBI ]     HS502876 [ spliceNest ]
Fast-db	1816 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P62745 [ SRS]    P62745 [ EXPASY ]     P62745 [ INTERPRO ]     P62745 [ UNIPROT ]
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	P62745
Pfam	PF00071 Ras [ SRS ]    PF00071 Ras [ Sanger ]    pfam00071 [ NCBI-CDD ]
Smart	SM00174 RHO [EMBL]
Blocks	P62745
PDB	2FV8 [ SRS ]    2FV8 [ PdbSum ],   2FV8 [ IMB ]   2FV8 [ RSDB ]
HPRD	01321
	Protein Interaction databases
DIP	P62745
IntAct	P62745
	Polymorphism : SNP, mutations, diseases
OMIM	165370    [ map ]
GENECLINICS	165370
SNP	RHOB [dbSNP-NCBI]
SNP	NM_004040 [SNP-NCI]
SNP	RHOB [GeneSNPs - Utah]  RHOB] [HGBASE - SRS]
HAPMAP	RHOB [HAPMAP]
COSMIC	RHOB [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	RHOB
	General knowledge
Family Browser	RHOB [UCSC Family Browser]
SOURCE	NM_004040
SMD	Hs.502876
SAGE	Hs.502876
GO	nucleotide binding [Amigo]  nucleotide binding
GO	GTPase activity [Amigo]  GTPase activity
GO	protein binding [Amigo]  protein binding
GO	GTP binding [Amigo]  GTP binding
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	endosome [Amigo]  endosome
GO	plasma membrane [Amigo]  plasma membrane
GO	transformed cell apoptosis [Amigo]  transformed cell apoptosis
GO	cell adhesion [Amigo]  cell adhesion
GO	small GTPase mediated signal transduction [Amigo]  small GTPase mediated signal transduction
GO	Rho protein signal transduction [Amigo]  Rho protein signal transduction
GO	multicellular organismal development [Amigo]  multicellular organismal development
GO	endosome to lysosome transport [Amigo]  endosome to lysosome transport
GO	protein transport [Amigo]  protein transport
GO	cell differentiation [Amigo]  cell differentiation
GO	late endosome membrane [Amigo]  late endosome membrane
GO	positive regulation of angiogenesis [Amigo]  positive regulation of angiogenesis
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
PubGene	RHOB
TreeFam	RHOB
CTD	388 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	RHOB Related clones (RZPD - Berlin)
	PubMed
PubMed	54 Pubmed reference(s) in LocusLink

Bibliography

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PMID 3888408

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PMID 1400319

CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB.

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PMID 7713879

Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB.

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PMID 10508588

RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors.

Liu A, Du W, Liu JP, Jessell TM, Prendergast GC

Molecular and cellular biology. 2000 ; 20 (16) : 6105-6113.

PMID 10913192

RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage.

Liu Ax, Cerniglia GJ, Bernhard EJ, Prendergast GC

Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (11) : 6192-6197.

PMID 11353846

Actin' up: RhoB in cancer and apoptosis.

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Nature reviews. Cancer. 2001 ; 1 (2) : 162-168.

PMID 11905808

Suppression of rho B expression in invasive carcinoma from head and neck cancer patients.

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PMID 12114424

RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development.

Adini I, Rabinovitz I, Sun JF, Prendergast GC, Benjamin LE

Genes & development. 2003 ; 17 (21) : 2721-2732.

PMID 14597666

EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation.

Jiang K, Delarue FL, Sebti SM

Oncogene. 2004 ; 23 (5) : 1136-1145.

PMID 14647415

Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis.

Jiang K, Sun J, Cheng J, Djeu JY, Wei S, Sebti S

Molecular and cellular biology. 2004 ; 24 (12) : 5565-5576.

PMID 15169915

Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase.

Wherlock M, Gampel A, Futter C, Mellor H

Journal of cell science. 2004 ; 117 (Pt 15) : 3221-3231.

PMID 15226397

Loss of RhoB expression in human lung cancer progression.

Mazieres J, Antonia T, Daste G, Muro-Cacho C, Berchery D, Tillement V, Pradines A, Sebti S, Favre G

Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (8) : 2742-2750.

PMID 15102679

RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane.

Sandilands E, Cans C, Fincham VJ, Brunton VG, Mellor H, Prendergast GC, Norman JC, Superti-Furga G, Frame MC

Developmental cell. 2004 ; 7 (6) : 855-869.

PMID 15572128

RhoB facilitates c-Myc turnover by supporting efficient nuclear accumulation of GSK-3.

Huang M, Kamasani U, Prendergast GC

Oncogene. 2006 ; 25 (9) : 1281-1289.

PMID 16247449

RhoB in cancer suppression.

Huang M, Prendergast GC

Histology and histopathology. 2006 ; 21 (2) : 213-218.

PMID 16329046

RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line.

Sato N, Fukui T, Taniguchi T, Yokoyama T, Kondo M, Nagasaka T, Goto Y, Gao W, Ueda Y, Yokoi K, Minna JD, Osada H, Kondo Y, Sekido Y

International journal of cancer. Journal international du cancer. 2007 ; 120 (3) : 543-551.

PMID 17096327

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	02-2007	Minzhou Huang, Lisa D Laury-Kleintop, George Prendergast

Citation

This paper should be referenced as such :

Huang M, Laury-Kleintop LD, Prendergast G . RHOB (ras homolog gene family, member B). Atlas Genet Cytogenet Oncol Haematol. February 2007 . URL : http://AtlasGeneticsOncology.org/Genes/RHOBID42108ch2p24.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:17:12 2008