Full text data of RALB
RALB
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ras-related protein Ral-B; Flags: Precursor
Ras-related protein Ral-B; Flags: Precursor
UniProt
P11234
ID RALB_HUMAN Reviewed; 206 AA.
AC P11234; Q53T32;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Ras-related protein Ral-B;
DE Flags: Precursor;
GN Name=RALB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2662142; DOI=10.1093/nar/17.11.4380;
RA Chardin P., Tavitian A.;
RT "Coding sequences of human ralA and ralB cDNAs.";
RL Nucleic Acids Res. 17:4380-4380(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=2120779; DOI=10.1007/BF01232469;
RA Hsieh C.-L., Swaroop A., Francke U.;
RT "Chromosomal localization and cDNA sequence of human ralB, a GTP
RT binding protein.";
RL Somat. Cell Mol. Genet. 16:407-410(1990).
RN [3]
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 (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH RALBP1.
RX PubMed=7673236; DOI=10.1074/jbc.270.38.22473;
RA Jullien-Flores V., Dorseuil O., Romero F., Letourneur F.,
RA Saragosti S., Berger R., Tavitian A., Gacon G., Camonis J.H.;
RT "Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with
RT CDC42/Rac GTPase-activating protein activity.";
RL J. Biol. Chem. 270:22473-22477(1995).
RN [10]
RP INTERACTION WITH EXOC8.
RX PubMed=14525976; DOI=10.1074/jbc.M308702200;
RA Moskalenko S., Tong C., Rosse C., Mirey G., Formstecher E., Daviet L.,
RA Camonis J., White M.A.;
RT "Ral GTPases regulate exocyst assembly through dual subunit
RT interactions.";
RL J. Biol. Chem. 278:51743-51748(2003).
RN [11]
RP SUBCELLULAR LOCATION, ISOPRENYLATION, ISOPRENYLATION AT CYS-203, AND
RP MUTAGENESIS OF CYS-203 AND LEU-206.
RX PubMed=17875936; DOI=10.1128/MCB.00057-07;
RA Falsetti S.C., Wang D.A., Peng H., Carrico D., Cox A.D., Der C.J.,
RA Hamilton A.D., Sebti S.M.;
RT "Geranylgeranyltransferase I inhibitors target RalB to inhibit
RT anchorage-dependent growth and induce apoptosis and RalA to inhibit
RT anchorage-independent growth.";
RL Mol. Cell. Biol. 27:8003-8014(2007).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18756269; DOI=10.1038/emboj.2008.166;
RA Cascone I., Selimoglu R., Ozdemir C., Del Nery E., Yeaman C.,
RA White M., Camonis J.;
RT "Distinct roles of RalA and RalB in the progression of cytokinesis are
RT supported by distinct RalGEFs.";
RL EMBO J. 27:2375-2387(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP STRUCTURE BY NMR OF 12-185 IN COMPLEX WITH GTP ANALOG, INTERACTION
RP WITH EXOC2, AND MUTAGENESIS OF THR-46 AND GLN-72.
RX PubMed=19166349; DOI=10.1021/bi802129d;
RA Fenwick R.B., Prasannan S., Campbell L.J., Nietlispach D.,
RA Evetts K.A., Camonis J., Mott H.R., Owen D.;
RT "Solution structure and dynamics of the small GTPase RalB in its
RT active conformation: significance for effector protein binding.";
RL Biochemistry 48:2192-2206(2009).
RN [15]
RP STRUCTURE BY NMR OF 8-185 IN COMPLEX WITH RALBP1, AND INTERACTION WITH
RP RALBP1.
RX PubMed=20696399; DOI=10.1016/j.str.2010.05.013;
RA Fenwick R.B., Campbell L.J., Rajasekar K., Prasannan S.,
RA Nietlispach D., Camonis J., Owen D., Mott H.R.;
RT "The RalB-RLIP76 complex reveals a novel mode of ral-effector
RT interaction.";
RL Structure 18:985-995(2010).
CC -!- FUNCTION: Multifunctional GTPase involved in a variety of cellular
CC processes including gene expression, cell migration, cell
CC proliferation, oncogenic transformation and membrane trafficking.
CC Accomplishes its multiple functions by interacting with distinct
CC downstream effectors. Acts as a GTP sensor for GTP-dependent
CC exocytosis of dense core vesicles. Required both to stabilize the
CC assembly of the exocyst complex and to localize functional exocyst
CC complexes to the leading edge of migrating cells. Plays a role in
CC the late stages of cytokinesis and is required for the abscission
CC of the bridge joining the sister cells emerging from mitosis.
CC Required for suppression of apoptosis.
CC -!- ENZYME REGULATION: Alternates between an inactive form bound to
CC GDP and an active form bound to GTP. Activated by a guanine
CC nucleotide-exchange factor (GEF) and inactivated by a GTPase-
CC activating protein (GAP).
CC -!- SUBUNIT: Interacts with EXOC2 and EXOC8. Interacts with RALBP1 via
CC its effector domain.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side. Note=During late cytokinesis localizes at the midbody.
CC -!- PTM: Prenylation is essential for membrane localization. The
CC geranylgeranylated form and the farnesylated mutant does not
CC undergo alternative prenylation in response to
CC geranylgeranyltransferase I inhibitors (GGTIs) and
CC farnesyltransferase I inhibitors (FTIs).
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X15015; CAA33119.1; -; mRNA.
DR EMBL; M35416; AAA60250.1; -; mRNA.
DR EMBL; AF493911; AAM12625.1; -; mRNA.
DR EMBL; BT006953; AAP35599.1; -; mRNA.
DR EMBL; AK312453; BAG35360.1; -; mRNA.
DR EMBL; AC012363; AAY14800.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95240.1; -; Genomic_DNA.
DR EMBL; BC018163; AAH18163.1; -; mRNA.
DR PIR; S04597; TVHUAB.
DR RefSeq; NP_002872.1; NM_002881.2.
DR RefSeq; XP_005263784.1; XM_005263727.1.
DR RefSeq; XP_005263785.1; XM_005263728.1.
DR RefSeq; XP_005263786.1; XM_005263729.1.
DR UniGene; Hs.469820; -.
DR PDB; 2KE5; NMR; -; A=12-185.
DR PDB; 2KWI; NMR; -; A=8-185.
DR PDBsum; 2KE5; -.
DR PDBsum; 2KWI; -.
DR ProteinModelPortal; P11234; -.
DR SMR; P11234; 8-185.
DR IntAct; P11234; 12.
DR MINT; MINT-5000915; -.
DR STRING; 9606.ENSP00000272519; -.
DR PhosphoSite; P11234; -.
DR DMDM; 131835; -.
DR PaxDb; P11234; -.
DR PRIDE; P11234; -.
DR DNASU; 5899; -.
DR Ensembl; ENST00000272519; ENSP00000272519; ENSG00000144118.
DR Ensembl; ENST00000420510; ENSP00000414224; ENSG00000144118.
DR GeneID; 5899; -.
DR KEGG; hsa:5899; -.
DR UCSC; uc002tmk.3; human.
DR CTD; 5899; -.
DR GeneCards; GC02P120997; -.
DR HGNC; HGNC:9840; RALB.
DR HPA; CAB026010; -.
DR MIM; 179551; gene.
DR neXtProt; NX_P11234; -.
DR PharmGKB; PA34198; -.
DR eggNOG; COG1100; -.
DR HOVERGEN; HBG009351; -.
DR KO; K07835; -.
DR PhylomeDB; P11234; -.
DR Reactome; REACT_111102; Signal Transduction.
DR ChiTaRS; RALB; human.
DR EvolutionaryTrace; P11234; -.
DR GeneWiki; RALB; -.
DR GenomeRNAi; 5899; -.
DR NextBio; 22946; -.
DR PRO; PR:P11234; -.
DR ArrayExpress; P11234; -.
DR Bgee; P11234; -.
DR CleanEx; HS_RALB; -.
DR Genevestigator; P11234; -.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0000910; P:cytokinesis; IDA:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
DR GO; GO:0001928; P:regulation of exocyst assembly; ISS:UniProtKB.
DR GO; GO:0060178; P:regulation of exocyst localization; ISS:UniProtKB.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR028412; Ral.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR PANTHER; PTHR24070:SF3; PTHR24070:SF3; 1.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00173; RAS; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cell cycle; Cell division; Cell membrane;
KW Complete proteome; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Prenylation; Reference proteome.
FT CHAIN 1 203 Ras-related protein Ral-B.
FT /FTId=PRO_0000082698.
FT PROPEP 204 206 Removed in mature form (By similarity).
FT /FTId=PRO_0000281349.
FT NP_BIND 21 29 GTP.
FT NP_BIND 68 72 GTP.
FT NP_BIND 128 131 GTP.
FT NP_BIND 158 160 GTP.
FT MOTIF 43 51 Effector region.
FT MOD_RES 203 203 Cysteine methyl ester.
FT LIPID 203 203 S-geranylgeranyl cysteine.
FT MUTAGEN 46 46 T->A: Reduces the binding affinity to
FT EXOC2 effector.
FT MUTAGEN 46 46 T->S: Reduces the binding affinity to
FT EXOC2 effector.
FT MUTAGEN 72 72 Q->L: Loss of GTPase activity.
FT MUTAGEN 203 203 C->S: Loss of geranylgeranylation and
FT membrane localization.
FT MUTAGEN 206 206 L->S: Converts geranyl-geranylation to
FT farnesylation. No effect on membrane
FT localization. Confers resistance to GGTI-
FT induced pancreatic cancer cell apoptosis,
FT but not to GGTI-dependent inhibition of
FT anchorage-independent proliferation.
FT TURN 10 12
FT STRAND 14 25
FT HELIX 27 36
FT STRAND 51 56
FT STRAND 61 68
FT STRAND 74 77
FT HELIX 78 84
FT STRAND 87 96
FT HELIX 98 114
FT STRAND 117 119
FT STRAND 123 128
FT HELIX 140 148
FT TURN 149 151
FT STRAND 154 156
FT TURN 159 161
FT HELIX 165 179
FT TURN 180 182
SQ SEQUENCE 206 AA; 23409 MW; E0AC95130FB6452C CRC64;
MAANKSKGQS SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS YRKKVVLDGE
EVQIDILDTA GQEDYAAIRD NYFRSGEGFL LVFSITEHES FTATAEFREQ ILRVKAEEDK
IPLLVVGNKS DLEERRQVPV EEARSKAEEW GVQYVETSAK TRANVDKVFF DLMREIRTKK
MSENKDKNGK KSSKNKKSFK ERCCLL
//
ID RALB_HUMAN Reviewed; 206 AA.
AC P11234; Q53T32;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Ras-related protein Ral-B;
DE Flags: Precursor;
GN Name=RALB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2662142; DOI=10.1093/nar/17.11.4380;
RA Chardin P., Tavitian A.;
RT "Coding sequences of human ralA and ralB cDNAs.";
RL Nucleic Acids Res. 17:4380-4380(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=2120779; DOI=10.1007/BF01232469;
RA Hsieh C.-L., Swaroop A., Francke U.;
RT "Chromosomal localization and cDNA sequence of human ralB, a GTP
RT binding protein.";
RL Somat. Cell Mol. Genet. 16:407-410(1990).
RN [3]
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 (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH RALBP1.
RX PubMed=7673236; DOI=10.1074/jbc.270.38.22473;
RA Jullien-Flores V., Dorseuil O., Romero F., Letourneur F.,
RA Saragosti S., Berger R., Tavitian A., Gacon G., Camonis J.H.;
RT "Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with
RT CDC42/Rac GTPase-activating protein activity.";
RL J. Biol. Chem. 270:22473-22477(1995).
RN [10]
RP INTERACTION WITH EXOC8.
RX PubMed=14525976; DOI=10.1074/jbc.M308702200;
RA Moskalenko S., Tong C., Rosse C., Mirey G., Formstecher E., Daviet L.,
RA Camonis J., White M.A.;
RT "Ral GTPases regulate exocyst assembly through dual subunit
RT interactions.";
RL J. Biol. Chem. 278:51743-51748(2003).
RN [11]
RP SUBCELLULAR LOCATION, ISOPRENYLATION, ISOPRENYLATION AT CYS-203, AND
RP MUTAGENESIS OF CYS-203 AND LEU-206.
RX PubMed=17875936; DOI=10.1128/MCB.00057-07;
RA Falsetti S.C., Wang D.A., Peng H., Carrico D., Cox A.D., Der C.J.,
RA Hamilton A.D., Sebti S.M.;
RT "Geranylgeranyltransferase I inhibitors target RalB to inhibit
RT anchorage-dependent growth and induce apoptosis and RalA to inhibit
RT anchorage-independent growth.";
RL Mol. Cell. Biol. 27:8003-8014(2007).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18756269; DOI=10.1038/emboj.2008.166;
RA Cascone I., Selimoglu R., Ozdemir C., Del Nery E., Yeaman C.,
RA White M., Camonis J.;
RT "Distinct roles of RalA and RalB in the progression of cytokinesis are
RT supported by distinct RalGEFs.";
RL EMBO J. 27:2375-2387(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP STRUCTURE BY NMR OF 12-185 IN COMPLEX WITH GTP ANALOG, INTERACTION
RP WITH EXOC2, AND MUTAGENESIS OF THR-46 AND GLN-72.
RX PubMed=19166349; DOI=10.1021/bi802129d;
RA Fenwick R.B., Prasannan S., Campbell L.J., Nietlispach D.,
RA Evetts K.A., Camonis J., Mott H.R., Owen D.;
RT "Solution structure and dynamics of the small GTPase RalB in its
RT active conformation: significance for effector protein binding.";
RL Biochemistry 48:2192-2206(2009).
RN [15]
RP STRUCTURE BY NMR OF 8-185 IN COMPLEX WITH RALBP1, AND INTERACTION WITH
RP RALBP1.
RX PubMed=20696399; DOI=10.1016/j.str.2010.05.013;
RA Fenwick R.B., Campbell L.J., Rajasekar K., Prasannan S.,
RA Nietlispach D., Camonis J., Owen D., Mott H.R.;
RT "The RalB-RLIP76 complex reveals a novel mode of ral-effector
RT interaction.";
RL Structure 18:985-995(2010).
CC -!- FUNCTION: Multifunctional GTPase involved in a variety of cellular
CC processes including gene expression, cell migration, cell
CC proliferation, oncogenic transformation and membrane trafficking.
CC Accomplishes its multiple functions by interacting with distinct
CC downstream effectors. Acts as a GTP sensor for GTP-dependent
CC exocytosis of dense core vesicles. Required both to stabilize the
CC assembly of the exocyst complex and to localize functional exocyst
CC complexes to the leading edge of migrating cells. Plays a role in
CC the late stages of cytokinesis and is required for the abscission
CC of the bridge joining the sister cells emerging from mitosis.
CC Required for suppression of apoptosis.
CC -!- ENZYME REGULATION: Alternates between an inactive form bound to
CC GDP and an active form bound to GTP. Activated by a guanine
CC nucleotide-exchange factor (GEF) and inactivated by a GTPase-
CC activating protein (GAP).
CC -!- SUBUNIT: Interacts with EXOC2 and EXOC8. Interacts with RALBP1 via
CC its effector domain.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side. Note=During late cytokinesis localizes at the midbody.
CC -!- PTM: Prenylation is essential for membrane localization. The
CC geranylgeranylated form and the farnesylated mutant does not
CC undergo alternative prenylation in response to
CC geranylgeranyltransferase I inhibitors (GGTIs) and
CC farnesyltransferase I inhibitors (FTIs).
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X15015; CAA33119.1; -; mRNA.
DR EMBL; M35416; AAA60250.1; -; mRNA.
DR EMBL; AF493911; AAM12625.1; -; mRNA.
DR EMBL; BT006953; AAP35599.1; -; mRNA.
DR EMBL; AK312453; BAG35360.1; -; mRNA.
DR EMBL; AC012363; AAY14800.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95240.1; -; Genomic_DNA.
DR EMBL; BC018163; AAH18163.1; -; mRNA.
DR PIR; S04597; TVHUAB.
DR RefSeq; NP_002872.1; NM_002881.2.
DR RefSeq; XP_005263784.1; XM_005263727.1.
DR RefSeq; XP_005263785.1; XM_005263728.1.
DR RefSeq; XP_005263786.1; XM_005263729.1.
DR UniGene; Hs.469820; -.
DR PDB; 2KE5; NMR; -; A=12-185.
DR PDB; 2KWI; NMR; -; A=8-185.
DR PDBsum; 2KE5; -.
DR PDBsum; 2KWI; -.
DR ProteinModelPortal; P11234; -.
DR SMR; P11234; 8-185.
DR IntAct; P11234; 12.
DR MINT; MINT-5000915; -.
DR STRING; 9606.ENSP00000272519; -.
DR PhosphoSite; P11234; -.
DR DMDM; 131835; -.
DR PaxDb; P11234; -.
DR PRIDE; P11234; -.
DR DNASU; 5899; -.
DR Ensembl; ENST00000272519; ENSP00000272519; ENSG00000144118.
DR Ensembl; ENST00000420510; ENSP00000414224; ENSG00000144118.
DR GeneID; 5899; -.
DR KEGG; hsa:5899; -.
DR UCSC; uc002tmk.3; human.
DR CTD; 5899; -.
DR GeneCards; GC02P120997; -.
DR HGNC; HGNC:9840; RALB.
DR HPA; CAB026010; -.
DR MIM; 179551; gene.
DR neXtProt; NX_P11234; -.
DR PharmGKB; PA34198; -.
DR eggNOG; COG1100; -.
DR HOVERGEN; HBG009351; -.
DR KO; K07835; -.
DR PhylomeDB; P11234; -.
DR Reactome; REACT_111102; Signal Transduction.
DR ChiTaRS; RALB; human.
DR EvolutionaryTrace; P11234; -.
DR GeneWiki; RALB; -.
DR GenomeRNAi; 5899; -.
DR NextBio; 22946; -.
DR PRO; PR:P11234; -.
DR ArrayExpress; P11234; -.
DR Bgee; P11234; -.
DR CleanEx; HS_RALB; -.
DR Genevestigator; P11234; -.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0000910; P:cytokinesis; IDA:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
DR GO; GO:0001928; P:regulation of exocyst assembly; ISS:UniProtKB.
DR GO; GO:0060178; P:regulation of exocyst localization; ISS:UniProtKB.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR028412; Ral.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR PANTHER; PTHR24070:SF3; PTHR24070:SF3; 1.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00173; RAS; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cell cycle; Cell division; Cell membrane;
KW Complete proteome; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Prenylation; Reference proteome.
FT CHAIN 1 203 Ras-related protein Ral-B.
FT /FTId=PRO_0000082698.
FT PROPEP 204 206 Removed in mature form (By similarity).
FT /FTId=PRO_0000281349.
FT NP_BIND 21 29 GTP.
FT NP_BIND 68 72 GTP.
FT NP_BIND 128 131 GTP.
FT NP_BIND 158 160 GTP.
FT MOTIF 43 51 Effector region.
FT MOD_RES 203 203 Cysteine methyl ester.
FT LIPID 203 203 S-geranylgeranyl cysteine.
FT MUTAGEN 46 46 T->A: Reduces the binding affinity to
FT EXOC2 effector.
FT MUTAGEN 46 46 T->S: Reduces the binding affinity to
FT EXOC2 effector.
FT MUTAGEN 72 72 Q->L: Loss of GTPase activity.
FT MUTAGEN 203 203 C->S: Loss of geranylgeranylation and
FT membrane localization.
FT MUTAGEN 206 206 L->S: Converts geranyl-geranylation to
FT farnesylation. No effect on membrane
FT localization. Confers resistance to GGTI-
FT induced pancreatic cancer cell apoptosis,
FT but not to GGTI-dependent inhibition of
FT anchorage-independent proliferation.
FT TURN 10 12
FT STRAND 14 25
FT HELIX 27 36
FT STRAND 51 56
FT STRAND 61 68
FT STRAND 74 77
FT HELIX 78 84
FT STRAND 87 96
FT HELIX 98 114
FT STRAND 117 119
FT STRAND 123 128
FT HELIX 140 148
FT TURN 149 151
FT STRAND 154 156
FT TURN 159 161
FT HELIX 165 179
FT TURN 180 182
SQ SEQUENCE 206 AA; 23409 MW; E0AC95130FB6452C CRC64;
MAANKSKGQS SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS YRKKVVLDGE
EVQIDILDTA GQEDYAAIRD NYFRSGEGFL LVFSITEHES FTATAEFREQ ILRVKAEEDK
IPLLVVGNKS DLEERRQVPV EEARSKAEEW GVQYVETSAK TRANVDKVFF DLMREIRTKK
MSENKDKNGK KSSKNKKSFK ERCCLL
//
MIM
179551
*RECORD*
*FIELD* NO
179551
*FIELD* TI
*179551 V-RAL SIMIAN LEUKEMIA VIRAL ONCOGENE HOMOLOG B; RALB
;;RAS-LIKE PROTEIN B
*FIELD* TX
read more
CLONING
The human RAL proteins share more than 50% homology and some properties
with the RAS proteins. Hsieh et al. (1990) isolated a member of the RAL
family, RALB, a GTP-binding protein.
Using a simian Rala (179550) cDNA probe and moderate hybridization
stringency, Chardin and Tavitian (1989) cloned RALA and RALB from a
human pheochromocytoma library. The deduced 206-amino acid RALB protein
shares about 85% identity with RALA.
GENE FUNCTION
The exocyst is an evolutionarily conserved octameric complex involved in
post-Golgi targeting of secretory vesicles. Moskalenko et al. (2003)
noted that RAL GTPases regulate exocyst-dependent trafficking and are
required for exocyst assembly. Using yeast 2-hybrid analysis of HEK293T
cells, they showed that human EXO84 (EXOC8; 615283) interacted with RALA
(179550) and RALB, but not with any other small GTPase examined. RALA
and RALB interacted with EXO84 and SEC5 (EXOC2; 615329), but not with
any other exocyst component examined. In vitro binding assays revealed
that EXO84 interacted with GTP-bound RALA, and truncation analysis
revealed that the pleckstrin (PLEK; 173570) homology (PH) domain of
EXO84 was required for the interaction. Membrane depolarization resulted
in recruitment of the isolated RAL-binding domain of EXO84 to membranes,
and this recruitment required lipid-binding prenylated RALB. RAL-GTP
competed with phosphatidylinositol 3,4,5-trisphosphate for EXO84
binding. In rat PC12 cells, Exo84 appeared to fractionate with a
subcomplex of vesicles that included Sec10 (EXOC5; 604469), but not
Sec5. Moskalenko et al. (2003) proposed that RAL GTPases regulate
assembly of the full exocyst complex through interaction with EXO84 and
SEC5.
Using normal and tumorigenic human epithelial cell lines, Chien et al.
(2006) found that a RALB/SEC5 effector complex specifically supported
tumor cell survival by directly recruiting and activating TBK1 (604834).
In cancer cell lines, constitutive engagement of this pathway, via
chronic RALB activation, restricted initiation of apoptotic programs
typically engaged in the context of oncogenic stress. Although
dispensable for survival of nontumorigenic human epithelial cells in
culture, this pathway helped mount an innate immune response to
double-stranded RNA or Sendai virus exposure. Chien et al. (2006)
concluded that the RALB/SEC5 effector complex is a component of
TBK1-dependent innate immune signaling and that this pathway is required
to support pathologic survival in the context of a tumorigenic
regulatory environment.
MAPPING
By study of human/Chinese hamster hybrids, Hsieh et al. (1990) concluded
that the RALB gene maps to chromosome 2cen-q13.
*FIELD* RF
1. Chardin, P.; Tavitian, R.: Coding sequences of human ralA and
ralB cDNAs. Nucl. Acids Res. 17: 4380, 1989.
2. Chien, Y.; Kim, S.; Bumeister, R.; Loo, Y.-M.; Kwon, S. W.; Johnson,
C. L.; Balakireva, M. G.; Romeo, Y.; Kopelovich, L.; Gale, M., Jr.;
Yeaman, C.; Camonis, J. H.; Zhao, Y.; White, M. A.: RalB GTPase-mediated
activation of the I-kappa-B family kinase TBK1 couples innate immune
signaling to tumor cell survival. Cell 127: 157-170, 2006.
3. Hsieh, C.-L.; Swaroop, A.; Francke, U.: Chromosomal localization
and cDNA sequence of human RALB, a GTP binding protein. Somat. Cell
Molec. Genet. 16: 407-410, 1990.
4. Moskalenko, S.; Tong, C.; Rosse, C.; Mirey, G.; Formstecher, E.;
Daviet, L.; Camonis, J.; White, M. A.: Ral GTPases regulate exocyst
assembly through dual subunit interactions. J. Biol. Chem. 278:
51743-51748, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 10/14/2013
Patricia A. Hartz - updated: 6/21/2013
Matthew B. Gross - updated: 5/7/2009
*FIELD* CD
Victor A. McKusick: 12/10/1990
*FIELD* ED
mgross: 11/08/2013
mgross: 11/8/2013
tpirozzi: 10/14/2013
alopez: 7/24/2013
mgross: 6/21/2013
wwang: 5/12/2009
mgross: 5/7/2009
mark: 1/11/1997
supermim: 3/16/1992
carol: 12/10/1990
*RECORD*
*FIELD* NO
179551
*FIELD* TI
*179551 V-RAL SIMIAN LEUKEMIA VIRAL ONCOGENE HOMOLOG B; RALB
;;RAS-LIKE PROTEIN B
*FIELD* TX
read more
CLONING
The human RAL proteins share more than 50% homology and some properties
with the RAS proteins. Hsieh et al. (1990) isolated a member of the RAL
family, RALB, a GTP-binding protein.
Using a simian Rala (179550) cDNA probe and moderate hybridization
stringency, Chardin and Tavitian (1989) cloned RALA and RALB from a
human pheochromocytoma library. The deduced 206-amino acid RALB protein
shares about 85% identity with RALA.
GENE FUNCTION
The exocyst is an evolutionarily conserved octameric complex involved in
post-Golgi targeting of secretory vesicles. Moskalenko et al. (2003)
noted that RAL GTPases regulate exocyst-dependent trafficking and are
required for exocyst assembly. Using yeast 2-hybrid analysis of HEK293T
cells, they showed that human EXO84 (EXOC8; 615283) interacted with RALA
(179550) and RALB, but not with any other small GTPase examined. RALA
and RALB interacted with EXO84 and SEC5 (EXOC2; 615329), but not with
any other exocyst component examined. In vitro binding assays revealed
that EXO84 interacted with GTP-bound RALA, and truncation analysis
revealed that the pleckstrin (PLEK; 173570) homology (PH) domain of
EXO84 was required for the interaction. Membrane depolarization resulted
in recruitment of the isolated RAL-binding domain of EXO84 to membranes,
and this recruitment required lipid-binding prenylated RALB. RAL-GTP
competed with phosphatidylinositol 3,4,5-trisphosphate for EXO84
binding. In rat PC12 cells, Exo84 appeared to fractionate with a
subcomplex of vesicles that included Sec10 (EXOC5; 604469), but not
Sec5. Moskalenko et al. (2003) proposed that RAL GTPases regulate
assembly of the full exocyst complex through interaction with EXO84 and
SEC5.
Using normal and tumorigenic human epithelial cell lines, Chien et al.
(2006) found that a RALB/SEC5 effector complex specifically supported
tumor cell survival by directly recruiting and activating TBK1 (604834).
In cancer cell lines, constitutive engagement of this pathway, via
chronic RALB activation, restricted initiation of apoptotic programs
typically engaged in the context of oncogenic stress. Although
dispensable for survival of nontumorigenic human epithelial cells in
culture, this pathway helped mount an innate immune response to
double-stranded RNA or Sendai virus exposure. Chien et al. (2006)
concluded that the RALB/SEC5 effector complex is a component of
TBK1-dependent innate immune signaling and that this pathway is required
to support pathologic survival in the context of a tumorigenic
regulatory environment.
MAPPING
By study of human/Chinese hamster hybrids, Hsieh et al. (1990) concluded
that the RALB gene maps to chromosome 2cen-q13.
*FIELD* RF
1. Chardin, P.; Tavitian, R.: Coding sequences of human ralA and
ralB cDNAs. Nucl. Acids Res. 17: 4380, 1989.
2. Chien, Y.; Kim, S.; Bumeister, R.; Loo, Y.-M.; Kwon, S. W.; Johnson,
C. L.; Balakireva, M. G.; Romeo, Y.; Kopelovich, L.; Gale, M., Jr.;
Yeaman, C.; Camonis, J. H.; Zhao, Y.; White, M. A.: RalB GTPase-mediated
activation of the I-kappa-B family kinase TBK1 couples innate immune
signaling to tumor cell survival. Cell 127: 157-170, 2006.
3. Hsieh, C.-L.; Swaroop, A.; Francke, U.: Chromosomal localization
and cDNA sequence of human RALB, a GTP binding protein. Somat. Cell
Molec. Genet. 16: 407-410, 1990.
4. Moskalenko, S.; Tong, C.; Rosse, C.; Mirey, G.; Formstecher, E.;
Daviet, L.; Camonis, J.; White, M. A.: Ral GTPases regulate exocyst
assembly through dual subunit interactions. J. Biol. Chem. 278:
51743-51748, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 10/14/2013
Patricia A. Hartz - updated: 6/21/2013
Matthew B. Gross - updated: 5/7/2009
*FIELD* CD
Victor A. McKusick: 12/10/1990
*FIELD* ED
mgross: 11/08/2013
mgross: 11/8/2013
tpirozzi: 10/14/2013
alopez: 7/24/2013
mgross: 6/21/2013
wwang: 5/12/2009
mgross: 5/7/2009
mark: 1/11/1997
supermim: 3/16/1992
carol: 12/10/1990