ID RALA_HUMAN Reviewed; 206 AA. AC P11233; A4D1W3; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 02-SEP-2026, entry version 241. DE RecName: Full=Ras-related protein Ral-A; DE EC=3.6.5.2 {ECO:0000269|PubMed:30500825}; DE Flags: Precursor; GN Name=RALA; Synonyms=RAL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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; DOI=10.1016/s0021-9258(19)84717-8; RA Polakis P.G., Weber R.F., Nevins B., Didsbury J.R., Evans T., Snyderman R.; RT "Identification of the ral and rac1 gene products, low molecular mass GTP- RT 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 sequenced by RT 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., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., 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., Mural R.J., RA 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., 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., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP ISOPRENYLATION AT CYS-203. RX PubMed=1903399; DOI=10.1016/s0021-9258(18)92889-9; 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., Saragosti S., RA Berger R., Tavitian A., Gacon G., Camonis J.H.; RT "Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac RT GTPase-activating protein activity."; RL J. Biol. Chem. 270:22473-22477(1995). RN [10] RP GLYCOSYLATION AT THR-46 (MICROBIAL INFECTION), AND MUTAGENESIS OF THR-46. RX PubMed=8858106; DOI=10.1006/bbrc.1996.1470; RA Hofmann F., Rex G., Aktories K., Just I.; RT "The ras-related protein Ral is monoglucosylated by Clostridium sordellii RT lethal toxin."; RL Biochem. Biophys. Res. Commun. 227:77-81(1996). RN [11] 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 nucleotide RT exchange factors for the ras-related GTPase Ral."; RL J. Biol. Chem. 275:13406-13410(2000). RN [12] 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 interactions."; RL J. Biol. Chem. 278:51743-51748(2003). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=16213214; DOI=10.1016/j.cell.2005.07.027; RA Gromley A., Yeaman C., Rosa J., Redick S., Chen C.-T., Mirabelle S., RA Guha M., Sillibourne J., Doxsey S.J.; RT "Centriolin anchoring of exocyst and SNARE complexes at the midbody is RT required for secretory-vesicle-mediated abscission."; RL Cell 123:75-87(2005). RN [14] RP SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-203, AND MUTAGENESIS OF CYS-203 RP 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 anchorage- RT dependent growth and induce apoptosis and RalA to inhibit anchorage- RT independent growth."; RL Mol. Cell. Biol. 27:8003-8014(2007). RN [15] RP FUNCTION, INTERACTION WITH EXOC2 AND EXOC8, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 1-MET--SER-11; GLY-23; GLU-38; ALA-48; ASP-49 AND GLN-72. RX PubMed=18756269; DOI=10.1038/emboj.2008.166; RA Cascone I., Selimoglu R., Ozdemir C., Del Nery E., Yeaman C., White M., RA 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 [16] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH LPAR1; RP LPAR2 AND GRK2. RX PubMed=19306925; DOI=10.1016/j.cellsig.2009.03.011; RA Aziziyeh A.I., Li T.T., Pape C., Pampillo M., Chidiac P., Possmayer F., RA Babwah A.V., Bhattacharya M.; RT "Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral RT and GRK."; RL Cell. Signal. 21:1207-1217(2009). RN [17] 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 exocytosis RT and growth signaling."; RL Curr. Biol. 20:75-79(2010). RN [18] 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., Buerckstuemmer T., RA 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 [19] RP FUNCTION, INTERACTION WITH RALBP1, PHOSPHORYLATION AT SER-194, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF SER-194. RX PubMed=21822277; DOI=10.1038/ncb2310; RA Kashatus D.F., Lim K.H., Brady D.C., Pershing N.L., Cox A.D., Counter C.M.; RT "RALA and RALBP1 regulate mitochondrial fission at mitosis."; RL Nat. Cell Biol. 13:1108-1115(2011). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [21] RP INVOLVEMENT IN HINCONS, VARIANTS HINCONS LEU-25; MET-25; ARG-128; GLY-130; RP ALA-157; ALA-158 DEL AND 176-ARG--LEU-206 DEL, CHARACTERIZATION OF VARIANTS RP HINCONS LEU-25; MET-25; GLY-130; ALA-157 AND 176-ARG--LEU-206 DEL, RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30500825; DOI=10.1371/journal.pgen.1007671; RA Hiatt S.M., Neu M.B., Ramaker R.C., Hardigan A.A., Prokop J.W., RA Hancarova M., Prchalova D., Havlovicova M., Prchal J., Stranecky V., RA Yim D.K.C., Powis Z., Keren B., Nava C., Mignot C., Rio M., RA Revah-Politi A., Hemati P., Stong N., Iglesias A.D., Suchy S.F., RA Willaert R., Wentzensen I.M., Wheeler P.G., Brick L., Kozenko M., RA Hurst A.C.E., Wheless J.W., Lacassie Y., Myers R.M., Barsh G.S., RA Sedlacek Z., Cooper G.M.; RT "De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small RT GTPase, cause intellectual disability and developmental delay."; RL PLoS Genet. 14:e1007671-e1007671(2018). RN [22] RP VARIANT HINCONS MET-25. RX PubMed=30761613; DOI=10.1111/cga.12327; RA Okamoto N., Takata A., Miyake N., Matsumoto N.; RT "RALA mutation in a patient with autism spectrum disorder and Noonan RT syndrome-like phenotype."; RL Congenit. Anom. (Kyoto) 59:195-196(2019). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 9-183 IN COMPLEX WITH EXOC8 AND RP GTP ANALOG, INTERACTION WITH EXOC2, AND MUTAGENESIS OF LYS-47; ALA-48; RP 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 RalA RT GTPase."; RL EMBO J. 24:2064-2074(2005). RN [24] 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 action RT of a bacterial exoenzyme."; RL EMBO J. 24:3670-3680(2005). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) IN COMPLEX WITH GTP AND CLOSTRIDIUM RP 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 (PubMed:18756269, PubMed:19306925, CC PubMed:20005108, PubMed:21822277, PubMed:30500825). Acts as a GTP CC sensor for GTP-dependent exocytosis of dense core vesicles. The RALA- CC exocyst complex regulates integrin-dependent membrane raft exocytosis CC and growth signaling (PubMed:20005108). Key regulator of LPAR1 CC signaling and competes with GRK2 for binding to LPAR1 thus affecting CC the signaling properties of the receptor. Required for anchorage- CC independent proliferation of transformed cells (PubMed:19306925). CC During mitosis, supports the stabilization and elongation of the CC intracellular bridge between dividing cells. Cooperates with EXOC2 to CC recruit other components of the exocyst to the early midbody CC (PubMed:18756269). During mitosis, also controls mitochondrial fission CC by recruiting to the mitochondrion RALBP1, which mediates the CC phosphorylation and activation of DNM1L by the mitotic kinase cyclin B- CC CDK1 (PubMed:21822277). {ECO:0000269|PubMed:18756269, CC ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:20005108, CC ECO:0000269|PubMed:21822277, ECO:0000269|PubMed:30500825}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2; CC Evidence={ECO:0000269|PubMed:30500825}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000269|PubMed:30500825}; CC -!- ACTIVITY REGULATION: Alternates between an inactive form bound to GDP CC and an active form bound to GTP. Activated by a guanine nucleotide- CC exchange factor (GEF) and inactivated by a GTPase-activating protein CC (GAP). CC -!- SUBUNIT: Interacts (via effector domain) with RALBP1; during mitosis, CC recruits RALBP1 to the mitochondrion where it promotes DNM1L CC phosphorylation and mitochondrial fission (PubMed:21822277, CC PubMed:7673236). Interacts with EXOC2/Sec5 and EXOC8/Exo84; binding to CC EXOC2 and EXOC8 is mutually exclusive (PubMed:14525976, CC PubMed:15920473, PubMed:18756269). Interacts with Clostridium exoenzyme CC C3 (PubMed:15809419, PubMed:16177825). Interacts with RALGPS1 CC (PubMed:10747847). Interacts with LPAR1 and LPAR2. Interacts with GRK2 CC in response to LPAR1 activation. RALA and GRK2 binding to LPAR1 is CC mutually exclusive (PubMed:19306925). Interacts with CDC42 (By CC similarity). {ECO:0000250|UniProtKB:P63322, CC ECO:0000269|PubMed:10747847, ECO:0000269|PubMed:14525976, CC ECO:0000269|PubMed:15809419, ECO:0000269|PubMed:15920473, CC ECO:0000269|PubMed:16177825, ECO:0000269|PubMed:18756269, CC ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:21822277, CC ECO:0000269|PubMed:7673236}. CC -!- INTERACTION: CC P11233; P01112: HRAS; NbExp=2; IntAct=EBI-1036803, EBI-350145; CC P11233; P30154: PPP2R1B; NbExp=6; IntAct=EBI-1036803, EBI-357094; CC P11233; Q15311: RALBP1; NbExp=6; IntAct=EBI-1036803, EBI-749285; CC P11233; O54921: Exoc2; Xeno; NbExp=2; IntAct=EBI-1036803, EBI-1036795; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17875936, CC ECO:0000269|PubMed:18756269, ECO:0000269|PubMed:19306925}; Lipid-anchor CC {ECO:0000269|PubMed:17875936}; Cytoplasmic side. Cleavage furrow CC {ECO:0000269|PubMed:18756269}. Midbody, Midbody ring CC {ECO:0000269|PubMed:16213214}. Mitochondrion CC {ECO:0000269|PubMed:21822277}. Note=Predominantly at the cell surface CC in the absence of LPA. In the presence of LPA, colocalizes with LPAR1 CC and LPAR2 in endocytic vesicles (PubMed:19306925). May colocalize with CC CNTRL/centriolin at the midbody ring (PubMed:16213214). However, CC localization at the midbody at late cytokinesis was not confirmed CC (PubMed:18756269). Relocalizes to the mitochondrion during mitosis CC where it regulates mitochondrial fission (PubMed:21822277). CC {ECO:0000269|PubMed:16213214, ECO:0000269|PubMed:18756269, CC ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:21822277}. CC -!- INDUCTION: Activated in an LPA-dependent manner by LPAR1 and in an LPA- CC independent manner by LPAR2. {ECO:0000269|PubMed:19306925}. CC -!- PTM: Phosphorylated. Phosphorylation at Ser-194 by AURKA/Aurora kinase CC A, during mitosis, induces RALA localization to the mitochondrion where CC it regulates mitochondrial fission. {ECO:0000269|PubMed:21822277}. CC -!- PTM: Prenylation is essential for membrane localization. The CC geranylgeranylated form and the farnesylated mutant do not undergo CC alternative prenylation in response to geranylgeranyltransferase I CC inhibitors (GGTIs) and farnesyltransferase I inhibitors (FTIs). CC {ECO:0000269|PubMed:17875936, ECO:0000269|PubMed:1903399}. CC -!- PTM: (Microbial infection) Glucosylated at Thr-46 by P.sordellii toxin CC TcsL from strain 6018 (PubMed:8858106). Monoglucosylation completely CC prevents the recognition of the downstream effector, blocking the CC GTPases in their inactive form (PubMed:8858106). Not glucosylated by CC TcsL from strain VPI 9048 (PubMed:8858106). CC {ECO:0000269|PubMed:8858106}. CC -!- DISEASE: Hiatt-Neu-Cooper neurodevelopmental syndrome (HINCONS) CC [MIM:619311]: An autosomal dominant neurodevelopmental disorder CC characterized by global developmental delay, delayed walking or CC inability to walk, impaired intellectual development, poor or absent CC speech, axial hypotonia, and facial dysmorphism. Additional variable CC features may include seizures, autistic or behavioral abnormalities, CC and brain abnormalities. {ECO:0000269|PubMed:30500825, CC ECO:0000269|PubMed:30761613}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family. CC {ECO:0000305}. 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; 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 CCDS; CCDS5460.1; -. DR PIR; S04596; TVHUAA. DR RefSeq; NP_005393.2; NM_005402.4. DR RefSeq; XP_047276637.1; XM_047420681.1. DR RefSeq; XP_047276638.1; XM_047420682.1. DR RefSeq; XP_054214726.1; XM_054358751.1. DR RefSeq; XP_054214727.1; XM_054358752.1. 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 PDB; 6P0I; X-ray; 1.18 A; B=1-178. DR PDB; 6P0J; X-ray; 1.31 A; B=1-178. DR PDB; 6P0K; X-ray; 1.49 A; B=1-178. DR PDB; 6P0L; X-ray; 1.30 A; B=1-178. DR PDB; 6P0M; X-ray; 1.50 A; B=1-178. DR PDB; 6P0N; X-ray; 1.63 A; B=1-178. DR PDB; 6P0O; X-ray; 1.54 A; B=1-178. DR PDB; 7NQC; NMR; -; B=187-203. DR PDB; 8FJH; X-ray; 1.54 A; B=1-178. DR PDB; 8FJI; X-ray; 1.48 A; B=1-178. DR AlphaFoldDB; P11233; -. DR SMR; P11233; -. DR BioGRID; 111834; 165. DR FunCoup; P11233; 2475. DR IntAct; P11233; 69. DR MINT; P11233; -. DR NDEx; IQUERY-CP-RALA; 14 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000005257; -. DR BindingDB; P11233; -. DR ChEMBL; CHEMBL3879855; -. DR DrugBank; DB04315; Guanosine-5'-Diphosphate. DR GlyCosmos; P11233; 1 site, No reported glycans. DR GlyGen; P11233; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; P11233; -. DR MetOSite; P11233; -. DR PhosphoSitePlus; P11233; -. DR SwissPalm; P11233; -. DR BioMuta; RALA; -. DR DMDM; 131834; -. DR jPOST; P11233; -. DR MassIVE; P11233; -. DR PaxDb; 9606-ENSP00000005257; -. DR PeptideAtlas; P11233; -. DR ProteomicsDB; 52726; -. DR Pumba; P11233; -. DR Antibodypedia; 26723; 374 antibodies from 37 providers. DR DNASU; 5898; -. DR Ensembl; ENST00000005257.7; ENSP00000005257.2; ENSG00000006451.9. DR Ensembl; ENST00000860175.1; ENSP00000530234.1; ENSG00000006451.9. DR Ensembl; ENST00000860176.1; ENSP00000530235.1; ENSG00000006451.9. DR Ensembl; ENST00000860177.1; ENSP00000530236.1; ENSG00000006451.9. DR Ensembl; ENST00000860178.1; ENSP00000530237.1; ENSG00000006451.9. DR Ensembl; ENST00000860179.1; ENSP00000530238.1; ENSG00000006451.9. DR Ensembl; ENST00000860180.1; ENSP00000530239.1; ENSG00000006451.9. DR Ensembl; ENST00000919558.1; ENSP00000589617.1; ENSG00000006451.9. DR Ensembl; ENST00000919559.1; ENSP00000589618.1; ENSG00000006451.9. DR Ensembl; ENST00000957819.1; ENSP00000627878.1; ENSG00000006451.9. DR Ensembl; ENST00000957820.1; ENSP00000627879.1; ENSG00000006451.9. DR Ensembl; ENST00000957821.1; ENSP00000627880.1; ENSG00000006451.9. DR Ensembl; ENST00000957822.1; ENSP00000627881.1; ENSG00000006451.9. DR Ensembl; ENST00000957823.1; ENSP00000627882.1; ENSG00000006451.9. DR GeneID; 5898; -. DR KEGG; hsa:5898; -. DR MANE-Select; ENST00000005257.7; ENSP00000005257.2; NM_005402.4; NP_005393.2. DR UCSC; uc003thd.4; human. DR AGR; HGNC:9839; -. DR ClinPGx; PA34197; -. DR CTD; 5898; -. DR DisGeNET; 5898; -. DR GeneCards; RALA; -. DR HGNC; HGNC:9839; RALA. DR HPA; ENSG00000006451; Low tissue specificity. DR MalaCards; RALA; -. DR MIM; 179550; gene. DR MIM; 619311; phenotype. DR OpenTargets; ENSG00000006451; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR VEuPathDB; HostDB:ENSG00000006451; -. DR eggNOG; KOG0395; Eukaryota. DR GeneTree; ENSGT00940000155142; -. DR InParanoid; P11233; -. DR OMA; LASEWHC; -. DR OrthoDB; 5976022at2759; -. DR PAN-GO; P11233; 4 GO annotations based on evolutionary models. DR PhylomeDB; P11233; -. DR PathwayCommons; P11233; -. DR Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane. DR Reactome; R-HSA-171007; p38MAPK events. DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation. DR SignaLink; P11233; -. DR SIGNOR; P11233; -. DR Agora; ENSG00000006451; -. DR BioGRID-ORCS; 5898; 20 hits in 1184 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; RALA; human. DR EvolutionaryTrace; P11233; -. DR GeneWiki; RALA; -. DR GenomeRNAi; 5898; -. DR Pharos; P11233; Tbio. DR PRO; PR:P11233; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P11233; protein. DR Bgee; ENSG00000006451; Expressed in esophagus squamous epithelium and 198 other cell types or tissues. DR ExpressionAtlas; P11233; baseline and differential. 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:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0090543; C:Flemming body; IEA:UniProtKB-SubCell. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0097060; C:synaptic membrane; IEA:Ensembl. DR GO; GO:0051117; F:ATPase binding; IPI:UniProtKB. DR GO; GO:0031755; F:Edg-2 lysophosphatidic acid receptor binding; IDA:UniProtKB. DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC. DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB. DR GO; GO:0003924; F:GTPase activity; IMP:UniProtKB. DR GO; GO:0017022; F:myosin binding; IPI:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc. DR GO; GO:0051665; P:membrane raft localization; IDA:UniProtKB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IGI:FlyBase. DR GO; GO:0051491; P:positive regulation of filopodium assembly; IDA:BHF-UCL. DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IMP:UniProtKB. DR GO; GO:0070585; P:protein localization to mitochondrion; IMP:UniProtKB. DR GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB. DR GO; GO:0031623; P:receptor internalization; IGI:FlyBase. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:BHF-UCL. DR GO; GO:0017157; P:regulation of exocytosis; IDA:UniProtKB. DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd04139; RalA_RalB; 1. DR DisProt; DP00581; -. DR FunFam; 3.40.50.300:FF:000203; Putative ras-related protein ral-a; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd. DR InterPro; IPR001806; Small_GTPase. DR InterPro; IPR020849; Small_GTPase_Ras-type. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR24070; RAS, DI-RAS, AND RHEB FAMILY MEMBERS OF SMALL GTPASE SUPERFAMILY; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00176; RAN; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51421; RAS; 1. DR PDBsum; 1UAD; -. DR PDBsum; 1ZC3; -. DR PDBsum; 1ZC4; -. DR PDBsum; 2A78; -. DR PDBsum; 2A9K; -. DR PDBsum; 2BOV; -. DR PDBsum; 6P0I; -. DR PDBsum; 6P0J; -. DR PDBsum; 6P0K; -. DR PDBsum; 6P0L; -. DR PDBsum; 6P0M; -. DR PDBsum; 6P0N; -. DR PDBsum; 6P0O; -. DR PDBsum; 7NQC; -. DR PDBsum; 8FJH; -. DR PDBsum; 8FJI; -. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Cell division; Cell membrane; Disease variant; KW Exocytosis; Glycoprotein; GTP-binding; Hydrolase; Intellectual disability; KW Lipoprotein; Membrane; Methylation; Mitochondrion; Nucleotide-binding; KW Phosphoprotein; Prenylation; Proteomics identification; Reference proteome. FT CHAIN 1..203 FT /note="Ras-related protein Ral-A" FT /id="PRO_0000082693" FT PROPEP 204..206 FT /note="Removed in mature form" FT /evidence="ECO:0000250" FT /id="PRO_0000281344" FT MOTIF 43..51 FT /note="Effector region" FT BINDING 24..29 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:15809419, FT ECO:0000269|PubMed:16177825" FT BINDING 40..46 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:15809419, FT ECO:0000269|PubMed:16177825" FT BINDING 127..130 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:15809419, FT ECO:0000269|PubMed:16177825" FT MOD_RES 194 FT /note="Phosphoserine; by AURKA" FT /evidence="ECO:0000305|PubMed:21822277" FT MOD_RES 203 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000250" FT LIPID 203 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000269|PubMed:17875936, FT ECO:0000269|PubMed:1903399" FT CARBOHYD 46 FT /note="(Microbial infection) O-linked (Glc) threonine; by FT P.sordellii toxin TcsL" FT /evidence="ECO:0000269|PubMed:8858106" FT VARIANT 25 FT /note="V -> L (in HINCONS; decreased GTPase activity; FT decreased RALA effector binding; dbSNP:rs1554297905)" FT /evidence="ECO:0000269|PubMed:30500825" FT /id="VAR_085759" FT VARIANT 25 FT /note="V -> M (in HINCONS; decreased GTPase activity; FT decreased RALA effector binding; dbSNP:rs1554297905)" FT /evidence="ECO:0000269|PubMed:30500825, FT ECO:0000269|PubMed:30761613" FT /id="VAR_085760" FT VARIANT 128 FT /note="K -> R (in HINCONS; dbSNP:rs2116098601)" FT /evidence="ECO:0000269|PubMed:30500825" FT /id="VAR_085761" FT VARIANT 130 FT /note="D -> G (in HINCONS; decreased GTPase activity; FT decreased RALA effector binding; dbSNP:rs2116098628)" FT /evidence="ECO:0000269|PubMed:30500825" FT /id="VAR_085762" FT VARIANT 157 FT /note="S -> A (in HINCONS; decreased GTPase activity; FT increased RALA effector binding; dbSNP:rs2116098885)" FT /evidence="ECO:0000269|PubMed:30500825" FT /id="VAR_085763" FT VARIANT 158 FT /note="Missing (in HINCONS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30500825" FT /id="VAR_085764" FT VARIANT 176..206 FT /note="Missing (in HINCONS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30500825" FT /id="VAR_085765" FT MUTAGEN 1..11 FT /note="Missing: Impaired cytokinesis, as shown by increased FT number of binucleate cells. Impaired cytokinesis; when FT associated with L-72." FT /evidence="ECO:0000269|PubMed:18756269" FT MUTAGEN 23 FT /note="G->V: Impaired cytokinesis, as shown by increased FT number of binucleate cells. No effect on interaction with FT EXOC2 and EXOC8. No effect on cytokinesis; when associated FT with R-38 or W-48. Decreased interaction with EXOC2 and FT EXOC8; when associated with R-38 or W-48." FT /evidence="ECO:0000269|PubMed:18756269" FT MUTAGEN 38 FT /note="E->R: Impaired cytokinesis, as shown by increased FT number of binucleate cells. No effect on cytokinesis; when FT associated with V-23. Decreased interaction with EXOC2 and FT EXOC8; when associated with V-23." FT /evidence="ECO:0000269|PubMed:18756269" FT MUTAGEN 46 FT /note="T->A: Abolished monoglucosylation by P.sordellii FT toxin TcsL." FT /evidence="ECO:0000269|PubMed:8858106" FT MUTAGEN 47 FT /note="K->E: Strongly reduces interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 47 FT /note="K->I: No effect on interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 48 FT /note="A->W: Impaired cytokinesis, as shown by increased FT number of binucleate cells. No effect on cytokinesis; when FT associated with V-23. Decreased interaction with EXOC2 and FT EXOC8; when associated with V-23." FT /evidence="ECO:0000269|PubMed:18756269" FT MUTAGEN 48 FT /note="A->W: Strongly reduces interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 49 FT /note="D->E: No effect on cytokinesis; when associated with FT L-72." FT /evidence="ECO:0000269|PubMed:18756269" FT MUTAGEN 49 FT /note="D->N: No effect on cytokinesis. Impaired FT cytokinesis, as shown by increased number of binucleate FT cells; when associated with L-72." FT /evidence="ECO:0000269|PubMed:18756269" FT MUTAGEN 50 FT /note="S->W: Strongly reduces interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 52 FT /note="R->A: Strongly reduces interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 52 FT /note="R->W: No effect on interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 72 FT /note="Q->L: Impaired cytokinesis, as shown by increased FT number of binucleate cells. Impaired cytokinesis; when FT associated with N-49 or 1-M--S-11. No effect on FT cytokinesis; when associated with E-49." FT /evidence="ECO:0000269|PubMed:18756269" FT MUTAGEN 81 FT /note="N->A: No effect on interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 81 FT /note="N->R: Strongly reduces interaction with EXOC8." FT /evidence="ECO:0000269|PubMed:15920473" FT MUTAGEN 194 FT /note="S->A: Decreased localization to mitochondrion. Loss FT of function in mitochondrial fission." FT /evidence="ECO:0000269|PubMed:21822277" FT MUTAGEN 194 FT /note="S->D: Increased localization to mitochondrion." FT /evidence="ECO:0000269|PubMed:21822277" FT MUTAGEN 203 FT /note="C->S: Loss of geranylgeranylation and membrane FT localization." FT /evidence="ECO:0000269|PubMed:17875936" FT MUTAGEN 206 FT /note="L->S: Converts geranyl-geranylation to FT farnesylation. No effect on membrane localization. Fails to FT deflect GGTI-induced apoptosis of adherent cell cultures, FT but rescues anchorage-independent cell proliferation." FT /evidence="ECO:0000269|PubMed:17875936" FT CONFLICT 1..2 FT /note="MA -> MVDYL (in Ref. 2; AAA36542 and 3; AAM12624)" FT /evidence="ECO:0000305" FT STRAND 13..20 FT /evidence="ECO:0007829|PDB:6P0I" FT HELIX 27..36 FT /evidence="ECO:0007829|PDB:6P0I" FT STRAND 49..57 FT /evidence="ECO:0007829|PDB:6P0I" FT STRAND 60..68 FT /evidence="ECO:0007829|PDB:6P0I" FT HELIX 76..85 FT /evidence="ECO:0007829|PDB:6P0I" FT STRAND 87..94 FT /evidence="ECO:0007829|PDB:6P0I" FT HELIX 98..115 FT /evidence="ECO:0007829|PDB:6P0I" FT STRAND 120..127 FT /evidence="ECO:0007829|PDB:6P0I" FT HELIX 132..134 FT /evidence="ECO:0007829|PDB:6P0I" FT HELIX 139..149 FT /evidence="ECO:0007829|PDB:6P0I" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:6P0I" FT TURN 158..160 FT /evidence="ECO:0007829|PDB:6P0I" FT HELIX 164..178 FT /evidence="ECO:0007829|PDB:6P0I" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:7NQC" FT TURN 196..200 FT /evidence="ECO:0007829|PDB:7NQC" 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 //