ID RHOB_HUMAN STANDARD; PRT; 196 AA. AC P62745; P01121; Q7RTN5; Q7RTR9; Q9CUV7; DT 21-JUL-1986 (Rel. 01, Created) DT 01-AUG-1988 (Rel. 08, Last sequence update) DT 10-MAY-2005 (Rel. 47, Last annotation update) DE Rho-related GTP-binding protein RhoB (H6). GN Name=RHOB; Synonyms=ARH6, ARHB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE. RX MEDLINE=88203210; PubMed=3283705; RA Chardin P., Madaule P., Tavitian A.; RT "Coding sequence of human rho cDNAs clone 6 and clone 9."; RL Nucleic Acids Res. 16:2717-2717(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction RT sequenced by the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [7] RP NUCLEOTIDE SEQUENCE OF 29-196. RX MEDLINE=85201682; PubMed=3888408; DOI=10.1016/0092-8674(85)90058-3; RA Madaule P., Axel R.; RT "A novel ras-related gene family."; RL Cell 41:31-40(1985). RN [8] RP FUNCTION, AND INTERACTION WITH PKN1. RX PubMed=9478917; DOI=10.1074/jbc.273.9.4811; RA Mellor H., Flynn P., Nobes C.D., Hall A., Parker P.J.; RT "PRK1 is targeted to endosomes by the small GTPase, RhoB."; RL J. Biol. Chem. 273:4811-4814(1998). RN [9] RP FUNCTION, AND MUTAGENESIS OF PHE-39. RX PubMed=10508588; DOI=10.1016/S0960-9822(99)80422-9; RA Gampel A., Parker P.J., Mellor H.; RT "Regulation of epidermal growth factor receptor traffic by the small RT GTPase rhoB."; RL Curr. Biol. 9:955-958(1999). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-14. RX PubMed=15226397; DOI=10.1242/jcs.01193; RA Wherlock M., Gampel A., Futter C., Mellor H.; RT "Farnesyltransferase inhibitors disrupt EGF receptor traffic through RT modulation of the RhoB GTPase."; RL J. Cell Sci. 117:3221-3231(2004). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=7537292; RA Robertson D., Paterson H.F., Adamson P., Hall A., Monaghan P.; RT "Ultrastructural localization of ras-related proteins using epitope- RT tagged plasmids."; RL J. Histochem. Cytochem. 43:471-480(1995). RN [12] RP METHYLATION, PALMITOYLATION, PRENYLATION, AND MUTAGENESIS OF CYS-189; RP CYS-192; CYS-193 AND LYS-194. RX PubMed=1400319; RA Adamson P., Marshall C.J., Hall A., Tilbrook P.A.; RT "Post-translational modifications of p21rho proteins."; RL J. Biol. Chem. 267:20033-20038(1992). RN [13] RP PRENYLATION, AND MUTAGENESIS OF CYS-192 AND CYS-193. RX PubMed=7713879; DOI=10.1074/jbc.270.14.7864; RA Armstrong S.A., Hannah V.C., Goldstein J.L., Brown M.S.; RT "CAAX geranylgeranyl transferase transfers farnesyl as efficiently as RT geranylgeranyl to RhoB."; RL J. Biol. Chem. 270:7864-7868(1995). RN [14] RP INTERACTION WITH ARHGEF3. RX PubMed=12221096; DOI=10.1074/jbc.M207401200; RA Arthur W.T., Ellerbroek S.M., Der C.J., Burridge K., Wennerberg K.; RT "XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RT RhoC."; RL J. Biol. Chem. 277:42964-42972(2002). CC -!- FUNCTION: Mediates apoptosis in neoplastically transformed cells CC after DNA damage. Not essential for development but affects cell CC adhesion and growth factor signaling in transformed cells. Plays a CC negative role in tumorigenesis as deletion causes tumor formation. CC Involved in intracellular protein trafficking of a number of CC proteins. Targets PKN1 to endosomes and is involved in trafficking CC of the EGF receptor from late endosomes to lysosomes. Also CC required for stability and nuclear trafficking of AKT1/AKT which CC promotes endothelial cell survival during vascular development. CC -!- SUBUNIT: Binds ROCK1 and ROCK2. Also binds PKN1/PRK1. Interacts CC with ARGGEF3. CC -!- SUBCELLULAR LOCATION: Late endosomal membrane (geranylgeranylated CC form) and plasma membrane (farnesylated form). Also detected at CC the nuclear margin and in the nucleus. CC -!- PTM: Prenylation specifies the subcellular location of RHOB. The CC farnesylated form is localized to the plasma membrane while the CC geranylgeranylated form is localized to the endosome. CC -!- MISCELLANEOUS: RHOB is one of the targets of farnesyltransferase CC inhibitors which are currently under investigation as cancer CC therapeutics. These elevate the levels of geranylgeranylated RHOB CC and cause mislocalization, leading to apoptosis and antineoplasic CC effects. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M12174; AAA36565.1; -; mRNA. DR EMBL; AF498971; AAM21118.1; -; mRNA. DR EMBL; BT019547; AAV38354.1; -; mRNA. DR EMBL; CR542272; CAG47068.1; -; mRNA. DR EMBL; AC023137; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC066954; AAH66954.1; -; mRNA. DR EMBL; X06820; CAA29968.1; -; mRNA. DR EMBL; BK001232; DAA01138.1; -; mRNA. DR EMBL; BK001671; DAA01912.1; -; Genomic_DNA. DR PIR; A01372; TVHURH. DR HSSP; P06749; 1CXZ. DR SMR; P62745; 1-180. DR Ensembl; ENSG00000143878; Homo sapiens. DR Genew; HGNC:668; RHOB. DR MIM; 165370; -. DR GO; GO:0010008; C:endosome membrane; IDA. DR GO; GO:0005634; C:nucleus; ISS. DR GO; GO:0005886; C:plasma membrane; IDA. DR GO; GO:0005525; F:GTP binding; TAS. DR GO; GO:0007155; P:cell adhesion; ISS. DR GO; GO:0008333; P:endosome to lysosome transport; IDA. DR GO; GO:0045786; P:negative regulation of cell cycle; ISS. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS. DR GO; GO:0006927; P:programmed cell death, transformed cells; ISS. DR InterPro; IPR003578; GTPase_Rho. DR InterPro; IPR001806; Ras_trnsfrmng. DR InterPro; IPR005225; Small_GTP. DR Pfam; PF00071; Ras; 1. DR TIGRFAMs; TIGR00231; small_GTP; 1. KW Angiogenesis; Anti-oncogene; Apoptosis; Cell adhesion; Cell cycle; KW Developmental protein; Differentiation; GTP-binding; Lipoprotein; KW Membrane; Methylation; Nuclear protein; Palmitate; Prenylation; KW Protein transport; Transport. FT CHAIN 1 193 Rho-related GTP-binding protein RhoB. FT PROPEP 194 196 Removed in mature form. FT NP_BIND 12 19 GTP (By similarity). FT NP_BIND 59 63 GTP (By similarity). FT NP_BIND 117 120 GTP (By similarity). FT MOTIF 34 42 Effector region (Potential). FT MOD_RES 193 193 Cysteine methyl ester (in mature form). FT LIPID 189 189 S-palmitoyl cysteine. FT LIPID 192 192 S-palmitoyl cysteine. FT LIPID 193 193 S-farnesyl cysteine (in plasma membrane FT form). FT LIPID 193 193 S-geranylgeranyl cysteine (in endosomal FT form). FT MUTAGEN 14 14 G->V: No effect on internalization of EGF FT receptor but decreases trafficking of FT receptor to the lysosome with associated FT accumulation in late endosomes. FT MUTAGEN 39 39 F->G: Abolishes binding to PKN1 and FT trafficking of EGF receptor. FT MUTAGEN 189 189 C->S: No effect on prenylation. Reduced FT palmitoylation. Abolishes palmitoylation; FT when associated with Ser-192. FT MUTAGEN 192 192 C->S: Reduced geranylgeranylation but no FT effect on farnesylation. Reduced FT palmitoylation. Abolishes palmitoylation; FT when associated with Ser-189. FT MUTAGEN 193 193 C->S: Abolishes methylation, FT palmitoylation and prenylation. FT MUTAGEN 194 194 K->L: No effect on palmitoylation or FT prenylation. SQ SEQUENCE 196 AA; 22123 MW; CCE6FD53AE00CD83 CRC64; MAAIRKKLVV VGDGACGKTC LLIVFSKDEF PEVYVPTVFE NYVADIEVDG KQVELALWDT AGQEDYDRLR PLSYPDTDVI LMCFSVDSPD SLENIPEKWV PEVKHFCPNV PIILVANKKD LRSDEHVRTE LARMKQEPVR TDDGRAMAVR IQAYDYLECS AKTKEGVREV FETATRAALQ KRYGSQNGCI NCCKVL //