Rho-related GTP-binding protein RhoB precursor

Protein attributes

Sequence length	196 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Angiogenesis Apoptosis Cell adhesion Cell cycle Differentiation Protein transport Transport
Cellular component	Cell membrane Endosome Membrane Nucleus
Ligand	GTP-binding Nucleotide-binding
Molecular function	Anti-oncogene Developmental protein
PTM	ADP-ribosylation Lipoprotein Methylation Palmitate Phosphoprotein Prenylation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Rho 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 component	late 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 function	GTP 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 193

193

Rho-related GTP-binding protein RhoB

PRO_0000030417

Propeptide

194 – 196

3

Removed in mature form

PRO_0000030418

Regions

Nucleotide binding

12 – 19

8

GTP By similarity

Nucleotide binding

59 – 63

5

GTP By similarity

Nucleotide binding

117 – 120

4

GTP By similarity

Motif

34 – 42

9

Effector region Potential

Amino acid modifications

Modified residue

41

1

ADP-ribosylasparagine; by botulinum toxin By similarity

Modified residue

154

1

Phosphotyrosine By similarity

Modified residue

1

Cysteine methyl ester

Lipidation

189

1

S-palmitoyl cysteine

Lipidation

192

1

S-palmitoyl cysteine

Lipidation

1

S-farnesyl cysteine; in plasma membrane form

Lipidation

1

S-geranylgeranyl cysteine; in endosomal form

Experimental info

Mutagenesis

14

1

G → V: No effect on internalization of EGF receptor but decreases trafficking of receptor to the lysosome with associated accumulation in late endosomes

Mutagenesis

39

1

F → G: Abolishes binding to PKN1 and trafficking of EGF receptor

Mutagenesis

189

1

C → S: No effect on prenylation. Reduced palmitoylation. Abolishes palmitoylation; when associated with S-192

Mutagenesis

192

1

C → S: Reduced geranylgeranylation but no effect on farnesylation. Reduced palmitoylation. Abolishes palmitoylation; when associated with S-189

Mutagenesis

1

C → S: Abolishes methylation, palmitoylation and prenylation

Mutagenesis

194

1

K → L: No effect on palmitoylation or prenylation

Secondary structure

1

.

196

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P62745-1 [UniParc].

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

FASTA

196

22,123

        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' referencesShow '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. 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.

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Web resources

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.

PIR

TVHURH. A01372.

RefSeq

NP_004031.1.

UniGene

Hs.502876

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FV8	X-ray	1.90	A	4-187	[»]

ModBase

PTM databases

PhosphoSite

P62745.

Proteomic databases

PeptideAtlas

P62745.

Genome annotation databases

Ensembl

ENSG00000143878. Homo sapiens. [Contig view]

GeneID

388.

KEGG

hsa:388.

Organism-specific databases

H-InvDB

HIX0023937.

HGNC

HGNC:668. RHOB.

HPA

CAB004560.

MIM

165370. gene.

PharmGKB

PA24950.

GenAtlas

GeneCards

Phylogenomic databases

HOGENOM

P62745.

HOVERGEN

P62745.

Enzyme and pathway databases

Reactome

REACT_11044. Signaling by Rho GTPases.

Gene expression databases

ArrayExpress

P62745.

CleanEx

HS_RHOB.

GermOnline

ENSG00000143878. Homo sapiens.

Family and domain databases

InterPro

IPR003578. GTPase_Rho.
IPR013753. Ras.
IPR001806. Ras_trnsfrmng.
IPR005225. Small_GTP_bd.
[Graphical view]

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00174. RHO. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

ProtoNet

Other Resources

NextBio

1615.

SOURCE

Entry information

Entry name

RHOB_HUMAN

Accession

Primary (citable) accession number: P62745
Secondary accession number(s): P01121

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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)