Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot P62745 (RHOB_HUMAN)

Last modified November 25, 2008. Version 62. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Rho-related GTP-binding protein RhoB
Alternative name(s):
    H6
Gene names
Name: RHOB
Synonyms: ARH6, ARHB
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length196 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development.

Subunit structure

Binds ROCK1 and ROCK2. Also binds PKN1/PRK1. Interacts with ARGGEF3, RTKN and AKAP13.

Subcellular location

Late endosome membrane; Lipid-anchor. Cell membrane; Lipid-anchor. Nucleus. Note= Late endosomal membrane (geranylgeranylated form). Plasma membrane (farnesylated form). Also detected at the nuclear margin and in the nucleus.

Post-translational modification

Prenylation specifies the subcellular location of RHOB. The farnesylated form is localized to the plasma membrane while the geranylgeranylated form is localized to the endosome.

Miscellaneous

RHOB is one of the targets of farnesyltransferase inhibitors which are currently under investigation as cancer therapeutics. These elevate the levels of geranylgeranylated RHOB and cause mislocalization, leading to apoptosis and antineoplastic effects.

Sequence similarities

Belongs to the small GTPase superfamily. Rho family.

Ontologies

Keywords

   Biological processAngiogenesis
Apoptosis
Cell adhesion
Cell cycle
Differentiation
Protein transport
Transport
   Cellular componentCell membrane
Endosome
Membrane
Nucleus
   LigandGTP-binding
Nucleotide-binding
   Molecular functionAnti-oncogene
Developmental protein
   PTMADP-ribosylation
Lipoprotein
Methylation
Palmitate
Phosphoprotein
Prenylation
   Technical term3D-structure

Gene Ontology (GO)

   Biological processRho protein signal transduction Ref.7

Traceable author statement. Source: UniProtKB

cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

endosome to lysosome transport Ref.9

Inferred from direct assay. Source: UniProtKB

negative regulation of cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

transformed cell apoptosis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular componentlate endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane Ref.10

Inferred from direct assay. Source: UniProtKB

   Molecular functionGTP binding Ref.12

Traceable author statement. Source: UniProtKB

GTPase activity Ref.7

Traceable author statement. Source: UniProtKB

protein binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 193193Rho-related GTP-binding protein RhoB
PRO_0000030417
Propeptide194 – 1963Removed in mature form
PRO_0000030418

Regions

Nucleotide binding12 – 198GTP By similarity
Nucleotide binding59 – 635GTP By similarity
Nucleotide binding117 – 1204GTP By similarity
Motif34 – 429Effector region Potential

Amino acid modifications

Modified residue411ADP-ribosylasparagine; by botulinum toxin By similarity
Modified residue1541Phosphotyrosine By similarity
Modified residue1931Cysteine methyl ester
Lipidation1891S-palmitoyl cysteine
Lipidation1921S-palmitoyl cysteine
Lipidation1931S-farnesyl cysteine; in plasma membrane form
Lipidation1931S-geranylgeranyl cysteine; in endosomal form

Experimental info

Mutagenesis141G → V: No effect on internalization of EGF receptor but decreases trafficking of receptor to the lysosome with associated accumulation in late endosomes
Mutagenesis391F → G: Abolishes binding to PKN1 and trafficking of EGF receptor
Mutagenesis1891C → S: No effect on prenylation. Reduced palmitoylation. Abolishes palmitoylation; when associated with S-192
Mutagenesis1921C → S: Reduced geranylgeranylation but no effect on farnesylation. Reduced palmitoylation. Abolishes palmitoylation; when associated with S-189
Mutagenesis1931C → S: Abolishes methylation, palmitoylation and prenylation
Mutagenesis1941K → L: No effect on palmitoylation or prenylation

Secondary structure

................................ 196
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P62745-1 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: CCE6FD53AE00CD83

FASTA19622,123
        10         20         30         40         50         60 
MAAIRKKLVV VGDGACGKTC LLIVFSKDEF PEVYVPTVFE NYVADIEVDG KQVELALWDT 

        70         80         90        100        110        120 
AGQEDYDRLR PLSYPDTDVI LMCFSVDSPD SLENIPEKWV PEVKHFCPNV PIILVANKKD 

       130        140        150        160        170        180 
LRSDEHVRTE LARMKQEPVR TDDGRAMAVR IQAYDYLECS AKTKEGVREV FETATRAALQ 

       190 
KRYGSQNGCI NCCKVL 

« Hide

References

« Hide 'large scale' references
[1]"Coding sequence of human rho cDNAs clone 6 and clone 9."
Chardin P., Madaule P., Tavitian A.
Nucleic Acids Res. 16:2717-2717(1988) [PubMed: 3283705] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed: 15815621] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"A novel ras-related gene family."
Madaule P., Axel R.
Cell 41:31-40(1985) [PubMed: 3888408] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 29-196.
[8]"PRK1 is targeted to endosomes by the small GTPase, RhoB."
Mellor H., Flynn P., Nobes C.D., Hall A., Parker P.J.
J. Biol. Chem. 273:4811-4814(1998) [PubMed: 9478917] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PKN1.
[9]"Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB."
Gampel A., Parker P.J., Mellor H.
Curr. Biol. 9:955-958(1999) [PubMed: 10508588] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF PHE-39.
[10]"Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase."
Wherlock M., Gampel A., Futter C., Mellor H.
J. Cell Sci. 117:3221-3231(2004) [PubMed: 15226397] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-14.
[11]"Ultrastructural localization of ras-related proteins using epitope-tagged plasmids."
Robertson D., Paterson H.F., Adamson P., Hall A., Monaghan P.
J. Histochem. Cytochem. 43:471-480(1995) [PubMed: 7537292] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[12]"Post-translational modifications of p21rho proteins."
Adamson P., Marshall C.J., Hall A., Tilbrook P.A.
J. Biol. Chem. 267:20033-20038(1992) [PubMed: 1400319] [Abstract]
Cited for: PALMITOYLATION AT CYS-189 AND CYS-192, ISOPRENYLATION AT CYS-193, METHYLATION AT CYS-193, MUTAGENESIS OF CYS-189; CYS-192; CYS-193 AND LYS-194.
[13]"CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB."
Armstrong S.A., Hannah V.C., Goldstein J.L., Brown M.S.
J. Biol. Chem. 270:7864-7868(1995) [PubMed: 7713879] [Abstract]
Cited for: ISOPRENYLATION AT CYS-193, MUTAGENESIS OF CYS-192 AND CYS-193.
[14]"AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation."
Diviani D., Soderling J., Scott J.D.
J. Biol. Chem. 276:44247-44257(2001) [PubMed: 11546812] [Abstract]
Cited for: INTERACTION WITH AKAP13.
[15]"XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC."
Arthur W.T., Ellerbroek S.M., Der C.J., Burridge K., Wennerberg K.
J. Biol. Chem. 277:42964-42972(2002) [PubMed: 12221096] [Abstract]
Cited for: INTERACTION WITH ARHGEF3.
+Additional computationally mapped references.

Cross-references

Sequence databases

X06820 mRNA. Translation: CAA29968.1.
AF498971 mRNA. Translation: AAM21118.1.
CR542272 mRNA. Translation: CAG47068.1.
BT019546 mRNA. Translation: AAV38353.1.
BT019547 mRNA. Translation: AAV38354.1.
AC023137 Genomic DNA. Translation: AAY24345.1.
BC066954 mRNA. Translation: AAH66954.1.
M12174 mRNA. Translation: AAA36565.1.
BK001232 mRNA. Translation: DAA01138.1.
BK001671 Genomic DNA. Translation: DAA01912.1.
PIRTVHURH. A01372.
RefSeqNP_004031.1.
UniGeneHs.502876

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2FV8X-ray1.90A4-187[»]
ModBaseSearch...

PTM databases

PhosphoSiteP62745.

Proteomic databases

PeptideAtlasP62745.

Genome annotation databases

EnsemblENSG00000143878. Homo sapiens. [Contig view]
GeneID388.
KEGGhsa:388.

Organism-specific databases

H-InvDBHIX0023937.
HGNCHGNC:668. RHOB.
HPACAB004560.
MIM165370. gene.
PharmGKBPA24950.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP62745.
HOVERGENP62745.

Enzyme and pathway databases

ReactomeREACT_11044. Signaling by Rho GTPases.

Gene expression databases

ArrayExpressP62745.
CleanExHS_RHOB.
GermOnlineENSG00000143878. Homo sapiens.

Family and domain databases

InterProIPR003578. GTPase_Rho.
IPR013753. Ras.
IPR001806. Ras_trnsfrmng.
IPR005225. Small_GTP_bd.
[Graphical view]
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00174. RHO. 1 hit.
[Graphical view]
TIGRFAMsTIGR00231. small_GTP. 1 hit.
ProtoNetSearch...

Other Resources

NextBio1615.
SOURCESearch...

Entry information

Entry nameRHOB_HUMAN
AccessionPrimary (citable) accession number: P62745
Secondary accession number(s): P01121 expand/collapse secondary AC list , Q5U0H6, Q7RTN5, Q7RTR9, Q9CUV7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 1, 1988
Last modified: November 25, 2008
This is version 62 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents