RALA_HUMAN
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 03-AUG-2022, entry version 222.
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 + H(+) + phosphate; 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:7673236,
CC PubMed:21822277). Interacts with EXOC2/Sec5 and EXOC8/Exo84; binding to
CC EXOC2 and EXOC8 is mutually exclusive (PubMed:14525976,
CC PubMed:18756269, PubMed:15920473). Interacts with Clostridium exoenzyme
CC C3 (PubMed:16177825, PubMed:15809419). 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}.
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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 CCDS; CCDS5460.1; -.
DR PIR; S04596; TVHUAA.
DR RefSeq; NP_005393.2; NM_005402.3.
DR RefSeq; XP_006715825.1; XM_006715762.2.
DR RefSeq; XP_011513768.1; XM_011515466.1.
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 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 AlphaFoldDB; P11233; -.
DR SMR; P11233; -.
DR BioGRID; 111834; 118.
DR IntAct; P11233; 48.
DR MINT; P11233; -.
DR STRING; 9606.ENSP00000005257; -.
DR ChEMBL; CHEMBL3879855; -.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR iPTMnet; P11233; -.
DR MetOSite; P11233; -.
DR PhosphoSitePlus; P11233; -.
DR SwissPalm; P11233; -.
DR BioMuta; RALA; -.
DR DMDM; 131834; -.
DR EPD; P11233; -.
DR jPOST; P11233; -.
DR MassIVE; P11233; -.
DR MaxQB; P11233; -.
DR PaxDb; P11233; -.
DR PeptideAtlas; P11233; -.
DR PRIDE; P11233; -.
DR ProteomicsDB; 52726; -.
DR Antibodypedia; 26723; 375 antibodies from 35 providers.
DR DNASU; 5898; -.
DR Ensembl; ENST00000005257.7; ENSP00000005257.2; ENSG00000006451.8.
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 CTD; 5898; -.
DR DisGeNET; 5898; -.
DR GeneCards; RALA; -.
DR HGNC; HGNC:9839; RALA.
DR HPA; ENSG00000006451; Low tissue specificity.
DR MIM; 179550; gene.
DR MIM; 619311; phenotype.
DR neXtProt; NX_P11233; -.
DR OpenTargets; ENSG00000006451; -.
DR PharmGKB; PA34197; -.
DR VEuPathDB; HostDB:ENSG00000006451; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000155142; -.
DR InParanoid; P11233; -.
DR OMA; QSRAQQW; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; P11233; -.
DR TreeFam; TF312796; -.
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 BioGRID-ORCS; 5898; 16 hits in 1092 CRISPR screens.
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 196 other tissues.
DR ExpressionAtlas; P11233; baseline and differential.
DR Genevisible; P11233; HS.
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; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0031532; P:actin cytoskeleton reorganization; IDA:BHF-UCL.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; IMP:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0051665; P:membrane raft localization; IDA:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
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:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0017157; P:regulation of exocytosis; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR DisProt; DP00581; -.
DR Gene3D; 3.40.50.300; -; 1.
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-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR PANTHER; PTHR24070:SF174; PTHR24070:SF174; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 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; Disease variant;
KW Exocytosis; Glycoprotein; GTP-binding; Hydrolase; Intellectual disability;
KW Lipoprotein; Membrane; Methylation; Mitochondrion; Nucleotide-binding;
KW Phosphoprotein; Prenylation; 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)"
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)"
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)"
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)"
FT /evidence="ECO:0000269|PubMed:30500825"
FT /id="VAR_085763"
FT VARIANT 158
FT /note="Missing (in HINCONS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30500825"
FT /id="VAR_085764"
FT VARIANT 176..206
FT /note="Missing (in HINCONS; unknown pathological
FT 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"
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
