Full text data of RALA
RALA
(RAL)
[Confidence: high (present in two of the MS resources)]
Ras-related protein Ral-A; Flags: Precursor
Ras-related protein Ral-A; Flags: Precursor
hRBCD
IPI00217519
IPI00217519 Ras-related protein Ral-A Ras-related protein Ral-A membrane n/a n/a 1 n/a 2 n/a n/a n/a 2 n/a 3 2 n/a 3 n/a 4 3 3 1 n/a cytoplasmic and membrane associated n/a found at its expected molecular weight found at molecular weight
IPI00217519 Ras-related protein Ral-A Ras-related protein Ral-A membrane n/a n/a 1 n/a 2 n/a n/a n/a 2 n/a 3 2 n/a 3 n/a 4 3 3 1 n/a cytoplasmic and membrane associated n/a found at its expected molecular weight found at molecular weight
UniProt
P11233
ID RALA_HUMAN Reviewed; 206 AA.
AC P11233; A4D1W3;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Ras-related protein Ral-A;
DE Flags: Precursor;
GN Name=RALA; Synonyms=RAL;
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=Platelet;
RX PubMed=2550440;
RA Polakis P.G., Weber R.F., Nevins B., Didsbury J.R., Evans T.,
RA Snyderman R.;
RT "Identification of the ral and rac1 gene products, low molecular mass
RT GTP-binding proteins from human platelets.";
RL J. Biol. Chem. 264:16383-16389(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [8]
RP ISOPRENYLATION AT CYS-203.
RX PubMed=1903399;
RA Kinsella B.T., Erdman R.A., Maltese W.A.;
RT "Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins
RT encoded by rac1, rac2, and ralA.";
RL J. Biol. Chem. 266:9786-9794(1991).
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 RALGPS1.
RX PubMed=10747847; DOI=10.1074/jbc.C000085200;
RA Rebhun J.F., Chen H., Quilliam L.A.;
RT "Identification and characterization of a new family of guanine
RT nucleotide exchange factors for the ras-related GTPase Ral.";
RL J. Biol. Chem. 275:13406-13410(2000).
RN [11]
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 [12]
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 [13]
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 [14]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH LPAR1;
RP LPAR2 AND ADRBK1.
RX PubMed=19306925; DOI=10.1016/j.cellsig.2009.03.011;
RA Aziziyeh A.I., Li T.T., Pape C., Pampillo M., Chidiac P.,
RA Possmayer F., Babwah A.V., Bhattacharya M.;
RT "Dual regulation of lysophosphatidic acid (LPA1) receptor signalling
RT by Ral and GRK.";
RL Cell. Signal. 21:1207-1217(2009).
RN [15]
RP FUNCTION.
RX PubMed=20005108; DOI=10.1016/j.cub.2009.11.016;
RA Balasubramanian N., Meier J.A., Scott D.W., Norambuena A., White M.A.,
RA Schwartz M.A.;
RT "RalA-exocyst complex regulates integrin-dependent membrane raft
RT exocytosis and growth signaling.";
RL Curr. Biol. 20:75-79(2010).
RN [16]
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 [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 9-183 IN COMPLEX WITH EXOC8
RP AND GTP ANALOG, INTERACTION WITH EXOC2, AND MUTAGENESIS OF LYS-47;
RP ALA-48; SER-50; ARG-52 AND ASN-81.
RX PubMed=15920473; DOI=10.1038/sj.emboj.7600699;
RA Jin R., Junutula J.R., Matern H.T., Ervin K.E., Scheller R.H.,
RA Brunger A.T.;
RT "Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the
RT RalA GTPase.";
RL EMBO J. 24:2064-2074(2005).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 9-183 IN COMPLEX WITH GTP AND
RP CLOSTRIDIUM EXOENZYME C3.
RX PubMed=16177825; DOI=10.1038/sj.emboj.7600813;
RA Pautsch A., Vogelsgesang M., Traenkle J., Herrmann C., Aktories K.;
RT "Crystal structure of the C3bot-RalA complex reveals a novel type of
RT action of a bacterial exoenzyme.";
RL EMBO J. 24:3670-3680(2005).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) IN COMPLEX WITH GTP AND
RP CLOSTRIDIUM EXOENZYME C3.
RX PubMed=15809419; DOI=10.1073/pnas.0501525102;
RA Holbourn K.P., Sutton J.M., Evans H.R., Shone C.C., Acharya K.R.;
RT "Molecular recognition of an ADP-ribosylating Clostridium botulinum C3
RT exoenzyme by RalA GTPase.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:5357-5362(2005).
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. Plays a role in the early
CC stages of cytokinesis and is required to tether the exocyst to the
CC cytokinetic furrow. The RALA-exocyst complex regulates integrin-
CC dependent membrane raft exocytosis and growth signaling. Key
CC regulator of LPAR1 signaling and competes with ADRBK1 for binding
CC to LPAR1 thus affecting the signaling properties of the receptor.
CC Required for anchorage-independent proliferation of transformed
CC cells.
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 RALBP1 via its effector domain. Interacts
CC with EXOC8 and EXOC2. EXOC2 and EXOC8 have overlapping binding
CC sites and compete for RALA binding. Interacts with Clostridium
CC exoenzyme C3. Interacts with RALGPS1. Interacts with LPAR1 and
CC LPAR2. Interacts with ADRBK1 in response to LPAR1 activation. RALA
CC and ADRBK1 mutually inhibit each other's binding to LPAR1.
CC -!- INTERACTION:
CC O54921:Exoc2 (xeno); NbExp=2; IntAct=EBI-1036803, EBI-1036795;
CC P30154:PPP2R1B; NbExp=6; IntAct=EBI-1036803, EBI-357094;
CC -!- SUBCELLULAR LOCATION: Cell surface. Cell membrane; Lipid-anchor;
CC Cytoplasmic side. Cleavage furrow. Midbody. Note=Prior to LPA
CC treatment found predominantly at the cell surface and in the
CC presence of LPA colocalizes with LPAR1 and LPAR2 in the endocytic
CC vesicles. During early cytokinesis localizes at the cleavage
CC furrow membrane. Colocalizes with EXOC2 at the early midbody ring
CC and persists there till maturation of the midbody.
CC -!- INDUCTION: Activated in an LPA-dependent manner by LPAR1 and in an
CC LPA-independent manner by LPAR2.
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.
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DR EMBL; X15014; CAA33118.1; -; mRNA.
DR EMBL; M29893; AAA36542.1; -; mRNA.
DR EMBL; AF493910; AAM12624.1; -; mRNA.
DR EMBL; AC004837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236951; EAL23994.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW94123.1; -; Genomic_DNA.
DR EMBL; BC039858; AAH39858.1; -; mRNA.
DR PIR; S04596; TVHUAA.
DR RefSeq; NP_005393.2; NM_005402.3.
DR UniGene; Hs.6906; -.
DR PDB; 1UAD; X-ray; 2.10 A; A/B=9-183.
DR PDB; 1ZC3; X-ray; 2.00 A; A/C=9-183.
DR PDB; 1ZC4; X-ray; 2.50 A; A/C=9-183.
DR PDB; 2A78; X-ray; 1.81 A; A=9-183.
DR PDB; 2A9K; X-ray; 1.73 A; A=9-183.
DR PDB; 2BOV; X-ray; 2.66 A; A=1-206.
DR PDBsum; 1UAD; -.
DR PDBsum; 1ZC3; -.
DR PDBsum; 1ZC4; -.
DR PDBsum; 2A78; -.
DR PDBsum; 2A9K; -.
DR PDBsum; 2BOV; -.
DR DisProt; DP00581; -.
DR ProteinModelPortal; P11233; -.
DR SMR; P11233; 13-182.
DR IntAct; P11233; 8.
DR MINT; MINT-238571; -.
DR STRING; 9606.ENSP00000005257; -.
DR PhosphoSite; P11233; -.
DR DMDM; 131834; -.
DR PaxDb; P11233; -.
DR PRIDE; P11233; -.
DR Ensembl; ENST00000005257; ENSP00000005257; ENSG00000006451.
DR GeneID; 5898; -.
DR KEGG; hsa:5898; -.
DR UCSC; uc003thd.3; human.
DR CTD; 5898; -.
DR GeneCards; GC07P039663; -.
DR HGNC; HGNC:9839; RALA.
DR MIM; 179550; gene.
DR neXtProt; NX_P11233; -.
DR PharmGKB; PA34197; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233973; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; P11233; -.
DR KO; K07834; -.
DR OMA; DRCKKRR; -.
DR OrthoDB; EOG7QVM41; -.
DR PhylomeDB; P11233; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_11123; Membrane Trafficking.
DR ChiTaRS; Rala; human.
DR EvolutionaryTrace; P11233; -.
DR GeneWiki; RALA; -.
DR GenomeRNAi; 5898; -.
DR NextBio; 22942; -.
DR PRO; PR:P11233; -.
DR ArrayExpress; P11233; -.
DR Bgee; P11233; -.
DR CleanEx; HS_RALA; -.
DR Genevestigator; P11233; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031755; F:Edg-2 lysophosphatidic acid receptor binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; TAS:ProtInc.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IDA:BHF-UCL.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0000910; P:cytokinesis; IDA:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0051665; P:membrane raft localization; IDA:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IDA:BHF-UCL.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
DR GO; GO:0017157; P:regulation of exocytosis; IDA: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; Cell cycle; Cell division; Cell membrane;
KW Complete proteome; Exocytosis; GTP-binding; Host-virus interaction;
KW Lipoprotein; Membrane; Methylation; Nucleotide-binding; Prenylation;
KW Reference proteome.
FT CHAIN 1 203 Ras-related protein Ral-A.
FT /FTId=PRO_0000082693.
FT PROPEP 204 206 Removed in mature form (By similarity).
FT /FTId=PRO_0000281344.
FT NP_BIND 24 29 GTP.
FT NP_BIND 40 46 GTP.
FT NP_BIND 127 130 GTP.
FT MOTIF 43 51 Effector region.
FT MOD_RES 203 203 Cysteine methyl ester.
FT LIPID 203 203 S-geranylgeranyl cysteine.
FT MUTAGEN 47 47 K->E: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 47 47 K->I: No effect on interaction with
FT EXOC8.
FT MUTAGEN 48 48 A->W: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 50 50 S->W: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 52 52 R->A: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 52 52 R->W: No effect on interaction with
FT EXOC8.
FT MUTAGEN 81 81 N->A: No effect on interaction with
FT EXOC8.
FT MUTAGEN 81 81 N->R: Strongly reduces interaction with
FT EXOC8.
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. Fails to deflect GGTI-
FT induced apoptosis of adherent cell
FT cultures, but rescues anchorage-
FT independent cell proliferation.
FT CONFLICT 1 2 MA -> MVDYL (in Ref. 2 and 3).
FT STRAND 14 20
FT HELIX 27 36
FT STRAND 49 57
FT STRAND 60 68
FT HELIX 76 85
FT STRAND 87 94
FT HELIX 98 115
FT STRAND 122 127
FT HELIX 129 134
FT HELIX 139 148
FT STRAND 152 155
FT TURN 158 160
FT HELIX 164 180
SQ SEQUENCE 206 AA; 23567 MW; 6974341EA18C1975 CRC64;
MAANKPKGQN SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS YRKKVVLDGE
EVQIDILDTA GQEDYAAIRD NYFRSGEGFL CVFSITEMES FAATADFREQ ILRVKEDENV
PFLLVGNKSD LEDKRQVSVE EAKNRAEQWN VNYVETSAKT RANVDKVFFD LMREIRARKM
EDSKEKNGKK KRKSLAKRIR ERCCIL
//
ID RALA_HUMAN Reviewed; 206 AA.
AC P11233; A4D1W3;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Ras-related protein Ral-A;
DE Flags: Precursor;
GN Name=RALA; Synonyms=RAL;
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=Platelet;
RX PubMed=2550440;
RA Polakis P.G., Weber R.F., Nevins B., Didsbury J.R., Evans T.,
RA Snyderman R.;
RT "Identification of the ral and rac1 gene products, low molecular mass
RT GTP-binding proteins from human platelets.";
RL J. Biol. Chem. 264:16383-16389(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [8]
RP ISOPRENYLATION AT CYS-203.
RX PubMed=1903399;
RA Kinsella B.T., Erdman R.A., Maltese W.A.;
RT "Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins
RT encoded by rac1, rac2, and ralA.";
RL J. Biol. Chem. 266:9786-9794(1991).
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 RALGPS1.
RX PubMed=10747847; DOI=10.1074/jbc.C000085200;
RA Rebhun J.F., Chen H., Quilliam L.A.;
RT "Identification and characterization of a new family of guanine
RT nucleotide exchange factors for the ras-related GTPase Ral.";
RL J. Biol. Chem. 275:13406-13410(2000).
RN [11]
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 [12]
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 [13]
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 [14]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH LPAR1;
RP LPAR2 AND ADRBK1.
RX PubMed=19306925; DOI=10.1016/j.cellsig.2009.03.011;
RA Aziziyeh A.I., Li T.T., Pape C., Pampillo M., Chidiac P.,
RA Possmayer F., Babwah A.V., Bhattacharya M.;
RT "Dual regulation of lysophosphatidic acid (LPA1) receptor signalling
RT by Ral and GRK.";
RL Cell. Signal. 21:1207-1217(2009).
RN [15]
RP FUNCTION.
RX PubMed=20005108; DOI=10.1016/j.cub.2009.11.016;
RA Balasubramanian N., Meier J.A., Scott D.W., Norambuena A., White M.A.,
RA Schwartz M.A.;
RT "RalA-exocyst complex regulates integrin-dependent membrane raft
RT exocytosis and growth signaling.";
RL Curr. Biol. 20:75-79(2010).
RN [16]
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 [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 9-183 IN COMPLEX WITH EXOC8
RP AND GTP ANALOG, INTERACTION WITH EXOC2, AND MUTAGENESIS OF LYS-47;
RP ALA-48; SER-50; ARG-52 AND ASN-81.
RX PubMed=15920473; DOI=10.1038/sj.emboj.7600699;
RA Jin R., Junutula J.R., Matern H.T., Ervin K.E., Scheller R.H.,
RA Brunger A.T.;
RT "Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the
RT RalA GTPase.";
RL EMBO J. 24:2064-2074(2005).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 9-183 IN COMPLEX WITH GTP AND
RP CLOSTRIDIUM EXOENZYME C3.
RX PubMed=16177825; DOI=10.1038/sj.emboj.7600813;
RA Pautsch A., Vogelsgesang M., Traenkle J., Herrmann C., Aktories K.;
RT "Crystal structure of the C3bot-RalA complex reveals a novel type of
RT action of a bacterial exoenzyme.";
RL EMBO J. 24:3670-3680(2005).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) IN COMPLEX WITH GTP AND
RP CLOSTRIDIUM EXOENZYME C3.
RX PubMed=15809419; DOI=10.1073/pnas.0501525102;
RA Holbourn K.P., Sutton J.M., Evans H.R., Shone C.C., Acharya K.R.;
RT "Molecular recognition of an ADP-ribosylating Clostridium botulinum C3
RT exoenzyme by RalA GTPase.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:5357-5362(2005).
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. Plays a role in the early
CC stages of cytokinesis and is required to tether the exocyst to the
CC cytokinetic furrow. The RALA-exocyst complex regulates integrin-
CC dependent membrane raft exocytosis and growth signaling. Key
CC regulator of LPAR1 signaling and competes with ADRBK1 for binding
CC to LPAR1 thus affecting the signaling properties of the receptor.
CC Required for anchorage-independent proliferation of transformed
CC cells.
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 RALBP1 via its effector domain. Interacts
CC with EXOC8 and EXOC2. EXOC2 and EXOC8 have overlapping binding
CC sites and compete for RALA binding. Interacts with Clostridium
CC exoenzyme C3. Interacts with RALGPS1. Interacts with LPAR1 and
CC LPAR2. Interacts with ADRBK1 in response to LPAR1 activation. RALA
CC and ADRBK1 mutually inhibit each other's binding to LPAR1.
CC -!- INTERACTION:
CC O54921:Exoc2 (xeno); NbExp=2; IntAct=EBI-1036803, EBI-1036795;
CC P30154:PPP2R1B; NbExp=6; IntAct=EBI-1036803, EBI-357094;
CC -!- SUBCELLULAR LOCATION: Cell surface. Cell membrane; Lipid-anchor;
CC Cytoplasmic side. Cleavage furrow. Midbody. Note=Prior to LPA
CC treatment found predominantly at the cell surface and in the
CC presence of LPA colocalizes with LPAR1 and LPAR2 in the endocytic
CC vesicles. During early cytokinesis localizes at the cleavage
CC furrow membrane. Colocalizes with EXOC2 at the early midbody ring
CC and persists there till maturation of the midbody.
CC -!- INDUCTION: Activated in an LPA-dependent manner by LPAR1 and in an
CC LPA-independent manner by LPAR2.
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.
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DR EMBL; X15014; CAA33118.1; -; mRNA.
DR EMBL; M29893; AAA36542.1; -; mRNA.
DR EMBL; AF493910; AAM12624.1; -; mRNA.
DR EMBL; AC004837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236951; EAL23994.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW94123.1; -; Genomic_DNA.
DR EMBL; BC039858; AAH39858.1; -; mRNA.
DR PIR; S04596; TVHUAA.
DR RefSeq; NP_005393.2; NM_005402.3.
DR UniGene; Hs.6906; -.
DR PDB; 1UAD; X-ray; 2.10 A; A/B=9-183.
DR PDB; 1ZC3; X-ray; 2.00 A; A/C=9-183.
DR PDB; 1ZC4; X-ray; 2.50 A; A/C=9-183.
DR PDB; 2A78; X-ray; 1.81 A; A=9-183.
DR PDB; 2A9K; X-ray; 1.73 A; A=9-183.
DR PDB; 2BOV; X-ray; 2.66 A; A=1-206.
DR PDBsum; 1UAD; -.
DR PDBsum; 1ZC3; -.
DR PDBsum; 1ZC4; -.
DR PDBsum; 2A78; -.
DR PDBsum; 2A9K; -.
DR PDBsum; 2BOV; -.
DR DisProt; DP00581; -.
DR ProteinModelPortal; P11233; -.
DR SMR; P11233; 13-182.
DR IntAct; P11233; 8.
DR MINT; MINT-238571; -.
DR STRING; 9606.ENSP00000005257; -.
DR PhosphoSite; P11233; -.
DR DMDM; 131834; -.
DR PaxDb; P11233; -.
DR PRIDE; P11233; -.
DR Ensembl; ENST00000005257; ENSP00000005257; ENSG00000006451.
DR GeneID; 5898; -.
DR KEGG; hsa:5898; -.
DR UCSC; uc003thd.3; human.
DR CTD; 5898; -.
DR GeneCards; GC07P039663; -.
DR HGNC; HGNC:9839; RALA.
DR MIM; 179550; gene.
DR neXtProt; NX_P11233; -.
DR PharmGKB; PA34197; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233973; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; P11233; -.
DR KO; K07834; -.
DR OMA; DRCKKRR; -.
DR OrthoDB; EOG7QVM41; -.
DR PhylomeDB; P11233; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_11123; Membrane Trafficking.
DR ChiTaRS; Rala; human.
DR EvolutionaryTrace; P11233; -.
DR GeneWiki; RALA; -.
DR GenomeRNAi; 5898; -.
DR NextBio; 22942; -.
DR PRO; PR:P11233; -.
DR ArrayExpress; P11233; -.
DR Bgee; P11233; -.
DR CleanEx; HS_RALA; -.
DR Genevestigator; P11233; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031755; F:Edg-2 lysophosphatidic acid receptor binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; TAS:ProtInc.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IDA:BHF-UCL.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0000910; P:cytokinesis; IDA:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0051665; P:membrane raft localization; IDA:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IDA:BHF-UCL.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
DR GO; GO:0017157; P:regulation of exocytosis; IDA: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; Cell cycle; Cell division; Cell membrane;
KW Complete proteome; Exocytosis; GTP-binding; Host-virus interaction;
KW Lipoprotein; Membrane; Methylation; Nucleotide-binding; Prenylation;
KW Reference proteome.
FT CHAIN 1 203 Ras-related protein Ral-A.
FT /FTId=PRO_0000082693.
FT PROPEP 204 206 Removed in mature form (By similarity).
FT /FTId=PRO_0000281344.
FT NP_BIND 24 29 GTP.
FT NP_BIND 40 46 GTP.
FT NP_BIND 127 130 GTP.
FT MOTIF 43 51 Effector region.
FT MOD_RES 203 203 Cysteine methyl ester.
FT LIPID 203 203 S-geranylgeranyl cysteine.
FT MUTAGEN 47 47 K->E: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 47 47 K->I: No effect on interaction with
FT EXOC8.
FT MUTAGEN 48 48 A->W: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 50 50 S->W: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 52 52 R->A: Strongly reduces interaction with
FT EXOC8.
FT MUTAGEN 52 52 R->W: No effect on interaction with
FT EXOC8.
FT MUTAGEN 81 81 N->A: No effect on interaction with
FT EXOC8.
FT MUTAGEN 81 81 N->R: Strongly reduces interaction with
FT EXOC8.
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. Fails to deflect GGTI-
FT induced apoptosis of adherent cell
FT cultures, but rescues anchorage-
FT independent cell proliferation.
FT CONFLICT 1 2 MA -> MVDYL (in Ref. 2 and 3).
FT STRAND 14 20
FT HELIX 27 36
FT STRAND 49 57
FT STRAND 60 68
FT HELIX 76 85
FT STRAND 87 94
FT HELIX 98 115
FT STRAND 122 127
FT HELIX 129 134
FT HELIX 139 148
FT STRAND 152 155
FT TURN 158 160
FT HELIX 164 180
SQ SEQUENCE 206 AA; 23567 MW; 6974341EA18C1975 CRC64;
MAANKPKGQN SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS YRKKVVLDGE
EVQIDILDTA GQEDYAAIRD NYFRSGEGFL CVFSITEMES FAATADFREQ ILRVKEDENV
PFLLVGNKSD LEDKRQVSVE EAKNRAEQWN VNYVETSAKT RANVDKVFFD LMREIRARKM
EDSKEKNGKK KRKSLAKRIR ERCCIL
//
MIM
179550
*RECORD*
*FIELD* NO
179550
*FIELD* TI
*179550 V-RAL SIMIAN LEUKEMIA VIRAL ONCOGENE HOMOLOG A; RALA
;;RAS-LIKE PROTEIN; RAL
read more*FIELD* TX
CLONING
Rousseau-Merck et al. (1988) stated that human cDNAs coding for RAL, a
protein that shares about 50% homology with RAS proteins (see HRAS;
190020), had been isolated.
Using a simian Rala cDNA probe and moderate hybridization stringency,
Chardin and Tavitian (1989) cloned RALA and RALB (179551) from a human
pheochromocytoma cDNA library. The deduced 206-amino acid RALA protein
shares about 85% identity with RALB.
GENE FUNCTION
Sablina et al. (2007) found that suppression of PP2A A-beta (PPP2R1B;
603113) expression allowed immortalized human cell lines to achieve a
tumorigenic state. Cancer-associated A-beta mutants failed to reverse
this tumorigenic phenotype, indicating that the mutants functioned as
null alleles. Cancer-derived A-beta mutants failed to form a complex
with the small GTPase RALA, whereas wildtype A-beta-containing complexes
dephosphorylated RALA at ser183 and ser194, inactivating RALA and
abolishing its transforming function. Sablina et al. (2007) concluded
that PP2A A-beta is a tumor suppressor that transforms immortalized
cells by regulating RALA 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
and RALB (179551), but not with any other small GTPase examined. RALA
and RALB interacted with EXO84 and with 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.
Equal distribution of mitochondria to daughter cells during mitosis
requires fission, which depends on recruitment of the large GTPase DRP1
(DNM1L; 603850) to the outer mitochondrial membrane and phosphorylation
of DRP1 by cyclin B (CCNB1; 123836)-CDK1 (116940). Using M-phase HeLa
cells, Kashatus et al. (2011) found that the mitotic kinase Aurora A
(AURKA; 603072) phosphorylated RALA at ser194, resulting in
redistribution of RALA to mitochondria, where it recruited RALBP1
(605801) and DRP1. Subsequently, RALBP1 induced cyclin B-CDK1-dependent
phosphorylation of DRP1. Knockdown of RALBP1, but not RALA, decreased
the amount of phosphorylated DRP1. Knockdown of either RALA or RALBP1
blocked mitochondrial fission, causing unequal partitioning of
mitochondria between daughter cells, reduced cellular content of ATP,
and decreased numbers of metabolically active cells. Kashatus et al.
(2011) concluded that the mitotic kinases Aurora A and cyclin B-CDK1
converge on RALA and RALBP1 to promote mitochondrial fission and
appropriate distribution of mitochondria to daughter cells.
MAPPING
Rousseau-Merck et al. (1987, 1988) used cDNAs to map the RALA gene to
chromosome 7p22-p15 by molecular hybridization to sorted chromosomes and
by in situ hybridization. Justice et al. (1990) showed that the murine
homolog of RALA is on chromosome 13.
*FIELD* RF
1. Chardin, P.; Tavitian, R.: Coding sequences of human ralA and
ralB cDNAs. Nucl. Acids Res. 17: 4380, 1989.
2. Justice, M. J.; Silan, C. M.; Ceci, J. D.; Buchberg, A. M.; Copeland,
N. G.; Jenkins, N. A.: A molecular genetic linkage map of mouse chromosome
13 anchored by the beige (bg) and satin (sa) loci. Genomics 6: 341-351,
1990.
3. Kashatus, D. F.; Lim, K.-H.; Brady, D. C.; Pershing, N. L. K.;
Cox, A. D.; Counter, C. M.: RALA and RALBP1 regulate mitochondrial
fission at mitosis. Nature Cell Biol. 13: 1108-1115, 2011.
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.
5. Rousseau-Merck, M.-F.; Bernheim, A.; Chardin, P.; Miglierina, R.;
Tavitian, A.; Berger, R.: The ras-related ral gene maps to chromosome
7p15-22. Hum. Genet. 79: 132-136, 1988.
6. Rousseau-Merck, M. F.; Bernheim, A.; Chardin, P.; Miglierina, R.;
Tavitian, A.; Berger, R.: The Ral gene maps to chromosome 7p15-22.
(Abstract) Cytogenet. Cell Genet. 46: 685 only, 1987.
7. Sablina, A. A.; Chen, W.; Arroyo, J. D.; Corral, L.; Hector, M.;
Bulmer, S. E.; DeCaprio, J. A.; Hahn, W. C.: The tumor suppressor
PP2A A-beta regulates the RalA GTPase. Cell 129: 969-982, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 10/14/2013
Patricia A. Hartz - updated: 6/21/2013
Paul J. Converse - updated: 3/5/2009
*FIELD* CD
Victor A. McKusick: 9/2/1987
*FIELD* ED
mgross: 11/08/2013
tpirozzi: 10/15/2013
tpirozzi: 10/14/2013
alopez: 7/24/2013
mgross: 6/21/2013
mgross: 3/6/2009
terry: 3/5/2009
mark: 1/11/1997
supermim: 3/16/1992
carol: 1/2/1991
carol: 12/10/1990
supermim: 3/27/1990
supermim: 3/20/1990
supermim: 2/11/1990
*RECORD*
*FIELD* NO
179550
*FIELD* TI
*179550 V-RAL SIMIAN LEUKEMIA VIRAL ONCOGENE HOMOLOG A; RALA
;;RAS-LIKE PROTEIN; RAL
read more*FIELD* TX
CLONING
Rousseau-Merck et al. (1988) stated that human cDNAs coding for RAL, a
protein that shares about 50% homology with RAS proteins (see HRAS;
190020), had been isolated.
Using a simian Rala cDNA probe and moderate hybridization stringency,
Chardin and Tavitian (1989) cloned RALA and RALB (179551) from a human
pheochromocytoma cDNA library. The deduced 206-amino acid RALA protein
shares about 85% identity with RALB.
GENE FUNCTION
Sablina et al. (2007) found that suppression of PP2A A-beta (PPP2R1B;
603113) expression allowed immortalized human cell lines to achieve a
tumorigenic state. Cancer-associated A-beta mutants failed to reverse
this tumorigenic phenotype, indicating that the mutants functioned as
null alleles. Cancer-derived A-beta mutants failed to form a complex
with the small GTPase RALA, whereas wildtype A-beta-containing complexes
dephosphorylated RALA at ser183 and ser194, inactivating RALA and
abolishing its transforming function. Sablina et al. (2007) concluded
that PP2A A-beta is a tumor suppressor that transforms immortalized
cells by regulating RALA 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
and RALB (179551), but not with any other small GTPase examined. RALA
and RALB interacted with EXO84 and with 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.
Equal distribution of mitochondria to daughter cells during mitosis
requires fission, which depends on recruitment of the large GTPase DRP1
(DNM1L; 603850) to the outer mitochondrial membrane and phosphorylation
of DRP1 by cyclin B (CCNB1; 123836)-CDK1 (116940). Using M-phase HeLa
cells, Kashatus et al. (2011) found that the mitotic kinase Aurora A
(AURKA; 603072) phosphorylated RALA at ser194, resulting in
redistribution of RALA to mitochondria, where it recruited RALBP1
(605801) and DRP1. Subsequently, RALBP1 induced cyclin B-CDK1-dependent
phosphorylation of DRP1. Knockdown of RALBP1, but not RALA, decreased
the amount of phosphorylated DRP1. Knockdown of either RALA or RALBP1
blocked mitochondrial fission, causing unequal partitioning of
mitochondria between daughter cells, reduced cellular content of ATP,
and decreased numbers of metabolically active cells. Kashatus et al.
(2011) concluded that the mitotic kinases Aurora A and cyclin B-CDK1
converge on RALA and RALBP1 to promote mitochondrial fission and
appropriate distribution of mitochondria to daughter cells.
MAPPING
Rousseau-Merck et al. (1987, 1988) used cDNAs to map the RALA gene to
chromosome 7p22-p15 by molecular hybridization to sorted chromosomes and
by in situ hybridization. Justice et al. (1990) showed that the murine
homolog of RALA is on chromosome 13.
*FIELD* RF
1. Chardin, P.; Tavitian, R.: Coding sequences of human ralA and
ralB cDNAs. Nucl. Acids Res. 17: 4380, 1989.
2. Justice, M. J.; Silan, C. M.; Ceci, J. D.; Buchberg, A. M.; Copeland,
N. G.; Jenkins, N. A.: A molecular genetic linkage map of mouse chromosome
13 anchored by the beige (bg) and satin (sa) loci. Genomics 6: 341-351,
1990.
3. Kashatus, D. F.; Lim, K.-H.; Brady, D. C.; Pershing, N. L. K.;
Cox, A. D.; Counter, C. M.: RALA and RALBP1 regulate mitochondrial
fission at mitosis. Nature Cell Biol. 13: 1108-1115, 2011.
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.
5. Rousseau-Merck, M.-F.; Bernheim, A.; Chardin, P.; Miglierina, R.;
Tavitian, A.; Berger, R.: The ras-related ral gene maps to chromosome
7p15-22. Hum. Genet. 79: 132-136, 1988.
6. Rousseau-Merck, M. F.; Bernheim, A.; Chardin, P.; Miglierina, R.;
Tavitian, A.; Berger, R.: The Ral gene maps to chromosome 7p15-22.
(Abstract) Cytogenet. Cell Genet. 46: 685 only, 1987.
7. Sablina, A. A.; Chen, W.; Arroyo, J. D.; Corral, L.; Hector, M.;
Bulmer, S. E.; DeCaprio, J. A.; Hahn, W. C.: The tumor suppressor
PP2A A-beta regulates the RalA GTPase. Cell 129: 969-982, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 10/14/2013
Patricia A. Hartz - updated: 6/21/2013
Paul J. Converse - updated: 3/5/2009
*FIELD* CD
Victor A. McKusick: 9/2/1987
*FIELD* ED
mgross: 11/08/2013
tpirozzi: 10/15/2013
tpirozzi: 10/14/2013
alopez: 7/24/2013
mgross: 6/21/2013
mgross: 3/6/2009
terry: 3/5/2009
mark: 1/11/1997
supermim: 3/16/1992
carol: 1/2/1991
carol: 12/10/1990
supermim: 3/27/1990
supermim: 3/20/1990
supermim: 2/11/1990