Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

RHOB (ras homolog gene family, member B)

Written2007-02Minzhou Huang, Lisa D Laury-Kleintop, George Prendergast
Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood PA 19096, USA

(Note : for Links provided by Atlas : click)

Identity

Other namesARH6
ARHB
H6
RHOH6
HGNC (Hugo) RHOB
LocusID (NCBI) 388
Atlas_Id 42108
Location 2p24.1  [Link to chromosome band 2p24]
Location_base_pair Starts at 20646832 and ends at 20649204 bp from pter ( according to hg19-Feb_2009)  [Mapping RHOB.png]
Fusion genes
(updated 2016)
CACNA1C (12p13.33) / RHOB (2p24.1)NCOA2 (8q13.3) / RHOB (2p24.1)RHOB (2p24.1) / CLPTM1 (19q13.32)
RHOB (2p24.1) / GATA3 (10p14)RHOB (2p24.1) / SYN3 (22q12.3)RHOB (2p24.1) / UBE2D3 (4q24)

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

Note
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.
  

Bibliography

Post-translational modifications of p21rho proteins.
Adamson P, Marshall CJ, Hall A, Tilbrook PA
The Journal of biological chemistry. 1992 ; 267 (28) : 20033-20038.
PMID 1400319
 
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
 
Suppression of rho B expression in invasive carcinoma from head and neck cancer patients.
Adnane J, Muro-Cacho C, Mathews L, Sebti SM, Muñoz-Antonia T
Clinical cancer research : an official journal of the American Association for Cancer Research. 2002 ; 8 (7) : 2225-2232.
PMID 12114424
 
CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB.
Armstrong SA, Hannah VC, Goldstein JL, Brown MS
The Journal of biological chemistry. 1995 ; 270 (14) : 7864-7868.
PMID 7713879
 
Chromosome localization of human ARH genes, a ras-related gene family.
Cannizzaro LA, Madaule P, Hecht F, Axel R, Croce CM, Huebner K
Genomics. 1990 ; 6 (2) : 197-203.
PMID 2407642
 
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
 
Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB.
Gampel A, Parker PJ, Mellor H
Current biology : CB. 1999 ; 9 (17) : 955-958.
PMID 10508588
 
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
 
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
 
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
 
A novel ras-related gene family.
Madaule P, Axel R
Cell. 1985 ; 41 (1) : 31-40.
PMID 3888408
 
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
 
Actin' up: RhoB in cancer and apoptosis.
Prendergast GC
Nature reviews. Cancer. 2001 ; 1 (2) : 162-168.
PMID 11905808
 
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 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
 
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
 

Citation

This paper should be referenced as such :
Prendergast, G ; Laury-Kleintop, LD ; Huang, M
RHOB (ras homolog gene family, member B)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):217-218.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RHOBID42108ch2p24.html


External links

Nomenclature
HGNC (Hugo)RHOB   668
Cards
AtlasRHOBID42108ch2p24
Entrez_Gene (NCBI)RHOB  388  ras homolog family member B
AliasesARH6; ARHB; MST081; MSTP081; 
RHOH6
GeneCards (Weizmann)RHOB
Ensembl hg19 (Hinxton)ENSG00000143878 [Gene_View]  chr2:20646832-20649204 [Contig_View]  RHOB [Vega]
Ensembl hg38 (Hinxton)ENSG00000143878 [Gene_View]  chr2:20646832-20649204 [Contig_View]  RHOB [Vega]
ICGC DataPortalENSG00000143878
TCGA cBioPortalRHOB
AceView (NCBI)RHOB
Genatlas (Paris)RHOB
WikiGenes388
SOURCE (Princeton)RHOB
Genomic and cartography
GoldenPath hg19 (UCSC)RHOB  -     chr2:20646832-20649204 +  2p24   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RHOB  -     2p24   [Description]    (hg38-Dec_2013)
EnsemblRHOB - 2p24 [CytoView hg19]  RHOB - 2p24 [CytoView hg38]
Mapping of homologs : NCBIRHOB [Mapview hg19]  RHOB [Mapview hg38]
OMIM165370   
Gene and transcription
Genbank (Entrez)AF171089 AF498971 AK124398 AK309991 AK310813
RefSeq transcript (Entrez)NM_004040
RefSeq genomic (Entrez)NC_000002 NC_018913 NT_022184 NW_004929299
Consensus coding sequences : CCDS (NCBI)RHOB
Cluster EST : UnigeneHs.502876 [ NCBI ]
CGAP (NCI)Hs.502876
Alternative Splicing GalleryENSG00000143878
Gene ExpressionRHOB [ NCBI-GEO ]   RHOB [ EBI - ARRAY_EXPRESS ]   RHOB [ SEEK ]   RHOB [ MEM ]
Gene Expression Viewer (FireBrowse)RHOB [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)388
GTEX Portal (Tissue expression)RHOB
Protein : pattern, domain, 3D structure
UniProt/SwissProtP62745 (Uniprot)
NextProtP62745  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP62745
Splice isoforms : SwissVarP62745 (Swissvar)
PhosPhoSitePlusP62745
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 mutations388
Blocks (Seattle)RHOB
PDB (SRS)2FV8   
PDB (PDBSum)2FV8   
PDB (IMB)2FV8   
PDB (RSDB)2FV8   
Structural Biology KnowledgeBase2FV8   
SCOP (Structural Classification of Proteins)2FV8   
CATH (Classification of proteins structures)2FV8   
SuperfamilyP62745
Human Protein AtlasENSG00000143878
Peptide AtlasP62745
HPRD01321
IPIIPI00000041   IPI00385100   
Protein Interaction databases
DIP (DOE-UCLA)P62745
IntAct (EBI)P62745
FunCoupENSG00000143878
BioGRIDRHOB
STRING (EMBL)RHOB
ZODIACRHOB
Ontologies - Pathways
QuickGOP62745
Ontology : AmiGOcytokinesis  angiogenesis  GTPase activity  protein binding  GTP binding  nucleus  early endosome  cytosol  plasma membrane  plasma membrane  focal adhesion  intracellular protein transport  apoptotic process  transformed cell apoptotic process  cell adhesion  Rho protein signal transduction  endosome to lysosome transport  endosome membrane  endosome membrane  positive regulation of endothelial cell migration  GDP binding  cell differentiation  platelet activation  regulation of cell migration  negative regulation of cell migration  late endosome membrane  cleavage furrow  positive regulation of apoptotic process  positive regulation of angiogenesis  negative regulation of cell cycle  regulation of small GTPase mediated signal transduction  endothelial tube morphogenesis  extracellular exosome  cellular response to hydrogen peroxide  cellular response to ionizing radiation  
Ontology : EGO-EBIcytokinesis  angiogenesis  GTPase activity  protein binding  GTP binding  nucleus  early endosome  cytosol  plasma membrane  plasma membrane  focal adhesion  intracellular protein transport  apoptotic process  transformed cell apoptotic process  cell adhesion  Rho protein signal transduction  endosome to lysosome transport  endosome membrane  endosome membrane  positive regulation of endothelial cell migration  GDP binding  cell differentiation  platelet activation  regulation of cell migration  negative regulation of cell migration  late endosome membrane  cleavage furrow  positive regulation of apoptotic process  positive regulation of angiogenesis  negative regulation of cell cycle  regulation of small GTPase mediated signal transduction  endothelial tube morphogenesis  extracellular exosome  cellular response to hydrogen peroxide  cellular response to ionizing radiation  
REACTOMEP62745 [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-114604 GPVI-mediated activation cascade [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 NetworkRHOB
Wikipedia pathwaysRHOB
Orthology - Evolution
OrthoDB388
GeneTree (enSembl)ENSG00000143878
Phylogenetic Trees/Animal Genes : TreeFamRHOB
Homologs : HomoloGeneRHOB
Homology/Alignments : Family Browser (UCSC)RHOB
Gene fusions - Rearrangements
Fusion : MitelmanRHOB/GATA3 [2p24.1/10p14]  
Polymorphisms : SNP, variants
NCBI Variation ViewerRHOB [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RHOB
dbVarRHOB
ClinVarRHOB
1000_GenomesRHOB 
Exome Variant ServerRHOB
ExAC (Exome Aggregation Consortium)RHOB (select the gene name)
Genetic variants : HAPMAP388
Genomic Variants (DGV)RHOB [DGVbeta]
Mutations
ICGC Data PortalRHOB 
TCGA Data PortalRHOB 
Broad Tumor PortalRHOB
OASIS PortalRHOB [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRHOB 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RHOB
DgiDB (Drug Gene Interaction Database)RHOB
DoCM (Curated mutations)RHOB (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RHOB (select a term)
intoGenRHOB
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)2:20646832-20649204  ENSG00000143878
CONAN: Copy Number AnalysisRHOB 
Mutations and Diseases : HGMDRHOB
OMIM165370   
MedgenRHOB
Genetic Testing Registry RHOB
NextProtP62745 [Medical]
TSGene388
GENETestsRHOB
Huge Navigator RHOB [HugePedia]
snp3D : Map Gene to Disease388
BioCentury BCIQRHOB
ClinGenRHOB
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD388
Chemical/Pharm GKB GenePA24950
Clinical trialRHOB
Miscellaneous
canSAR (ICR)RHOB (select the gene name)
Probes
Litterature
PubMed115 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRHOB
EVEXRHOB
GoPubMedRHOB
iHOPRHOB
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Aug 10 18:46:58 CEST 2016

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.