RHOB (ras homolog gene family, member B)

2007-02-01   Minzhou Huang , Lisa D Laury-Kleintop , George Prendergast 

Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood PA 19096, USA

Identity

HGNC
LOCATION
2p24.1
LOCUSID
ALIAS
ARH6,ARHB,MST081,MSTP081,RHOH6
FUSION GENES

DNA/RNA

Atlas Image

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.

Proteins

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 name
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 name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
14003191992Post-translational modifications of p21rho proteins.Adamson P et al
145976662003RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development.Adini I et al
121144242002Suppression of rho B expression in invasive carcinoma from head and neck cancer patients.Adnane J et al
77138791995CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB.Armstrong SA et al
24076421990Chromosome localization of human ARH genes, a ras-related gene family.Cannizzaro LA et al
32837051988Coding sequence of human rho cDNAs clone 6 and clone 9.Chardin P et al
105085881999Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB.Gampel A et al
162474492006RhoB facilitates c-Myc turnover by supporting efficient nuclear accumulation of GSK-3.Huang M et al
163290462006RhoB in cancer suppression.Huang M et al
146474152004EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation.Jiang K et al
151699152004Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis.Jiang K et al
109131922000RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors.Liu Ax et al
113538462001RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage.Liu Ax et al
38884081985A novel ras-related gene family.Madaule P et al
151026792004Loss of RhoB expression in human lung cancer progression.Mazieres J et al
119058082001Actin' up: RhoB in cancer and apoptosis.Prendergast GC et al
155721282004RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane.Sandilands E et al
170963272007RhoB 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 et al
152263972004Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase.Wherlock M et al

Other Information

Locus ID:

NCBI: 388
MIM: 165370
HGNC: 668
Ensembl: ENSG00000143878

Variants:

dbSNP: 388
ClinVar: 388
TCGA: ENSG00000143878
COSMIC: RHOB

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000143878ENST00000272233P62745

Expression (GTEx)

0
500
1000
1500
2000
2500
3000
3500

Pathways

PathwaySourceExternal ID
HemostasisREACTOMER-HSA-109582
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
GPVI-mediated activation cascadeREACTOMER-HSA-114604
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
Rho GTPase cycleREACTOMER-HSA-194840
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate ROCKsREACTOMER-HSA-5627117
RHO GTPases activate PKNsREACTOMER-HSA-5625740
RHO GTPases activate CITREACTOMER-HSA-5625900
RHO GTPases Activate ForminsREACTOMER-HSA-5663220
RHO GTPases Activate Rhotekin and RhophilinsREACTOMER-HSA-5666185
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (12/13) signalling eventsREACTOMER-HSA-416482
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
Semaphorin interactionsREACTOMER-HSA-373755
Sema4D in semaphorin signalingREACTOMER-HSA-400685
Sema4D induced cell migration and growth-cone collapseREACTOMER-HSA-416572

References

Pubmed IDYearTitleCitations
213473322011MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.85
119058082001Actin' up: RhoB in cancer and apoptosis.63
151026792004Loss of RhoB expression in human lung cancer progression.59
122210962002XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC.54
159443962005RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1.53
234889322013RhoA, RhoB and RhoC have different roles in cancer cell migration.52
171987022007RhoB and the mammalian Diaphanous-related formin mDia2 in endosome trafficking.45
184642902008Alphavbeta3 and alphavbeta5 integrins control glioma cell response to ionising radiation through ILK and RhoB.41
235834112013Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB.40
208105682010Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell lines and their use for verification of RhoB as a molecular therapeutic target.39

Citation

Minzhou Huang ; Lisa D Laury-Kleintop ; George Prendergast

RHOB (ras homolog gene family, member B)

Atlas Genet Cytogenet Oncol Haematol. 2007-02-01

Online version: http://atlasgeneticsoncology.org/gene/42108/rhob