RALA_MOUSE
ID RALA_MOUSE Reviewed; 206 AA.
AC P63321; P05810;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Ras-related protein Ral-A;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P11233};
DE Flags: Precursor;
GN Name=Rala; Synonyms=Ral, Ral-a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RA Roger T.T.;
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11025226; DOI=10.1016/s0925-4773(00)00427-5;
RA Zhao Z., Rivkees S.A.;
RT "Tissue-specific expression of GTPas RalA and RalB during embryogenesis and
RT regulation by epithelial-mesenchymal interaction.";
RL Mech. Dev. 97:201-204(2000).
RN [3]
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 [4]
RP PROTEIN SEQUENCE OF 8-16; 28-47; 114-128 AND 167-173, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP INTERACTION WITH RALBP1.
RX PubMed=8570186;
RA Park S.-H., Weinberg R.A.;
RT "A putative effector of Ral has homology to Rho/Rac GTPase activating
RT proteins.";
RL Oncogene 11:2349-2355(1995).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
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).
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 exocytosis
CC of dense core vesicles. Key regulator of LPAR1 signaling and competes
CC with GRK2 for binding to LPAR1 thus affecting the signaling properties
CC of the receptor. Required for anchorage-independent proliferation of
CC transformed cells (By similarity). The RALA-exocyst complex regulates
CC integrin-dependent membrane raft exocytosis and growth signaling
CC (PubMed:20005108). During mitosis, supports the stabilization and
CC elongation of the intracellular bridge between dividing cells.
CC Cooperates with EXOC2 to recruit other components of the exocyst to the
CC early midbody (By similarity). During mitosis, also controls
CC mitochondrial fission by recruiting to the mitochondrion RALBP1, which
CC mediates the phosphorylation and activation of DNM1L by the mitotic
CC kinase cyclin B-CDK1 (By similarity). {ECO:0000250|UniProtKB:P11233,
CC ECO:0000269|PubMed:20005108}.
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:0000250|UniProtKB:P11233};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P11233};
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 (By similarity). Interacts
CC with EXOC2/Sec5 and EXOC8/Exo84; binding to EXOC2 and EXOC8 is mutually
CC exclusive. Interacts with Clostridium exoenzyme C3. Interacts with
CC RALGPS1. Interacts with LPAR1 and LPAR2. Interacts with GRK2 in
CC response to LPAR1 activation. RALA and GRK2 binding to LPAR1 is
CC mutually exclusive (By similarity). Interacts with CDC42 (By
CC similarity). {ECO:0000250|UniProtKB:P11233,
CC ECO:0000250|UniProtKB:P63322}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P11233};
CC Lipid-anchor {ECO:0000250|UniProtKB:P11233}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P11233}. Cleavage furrow
CC {ECO:0000250|UniProtKB:P11233}. Midbody, Midbody ring
CC {ECO:0000250|UniProtKB:P11233}. Mitochondrion
CC {ECO:0000250|UniProtKB:P11233}. 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. May colocalize with CNTRL/centriolin
CC at the midbody ring. However, localization at the midbody at late
CC cytokinesis was not confirmed. Relocalizes to the mitochondrion during
CC mitosis where it regulates mitochondrial fission.
CC {ECO:0000250|UniProtKB:P11233}.
CC -!- PTM: Prenylation is essential for membrane localization.
CC {ECO:0000250|UniProtKB:P11233}.
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:0000250|UniProtKB:P11233}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
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DR EMBL; Z48587; CAA88488.1; -; mRNA.
DR EMBL; AF244951; AAG23136.1; -; mRNA.
DR EMBL; BC031741; AAH31741.1; -; mRNA.
DR CCDS; CCDS26255.1; -.
DR RefSeq; NP_062364.3; NM_019491.5.
DR AlphaFoldDB; P63321; -.
DR SMR; P63321; -.
DR BioGRID; 207790; 7.
DR IntAct; P63321; 1.
DR STRING; 10090.ENSMUSP00000009003; -.
DR iPTMnet; P63321; -.
DR PhosphoSitePlus; P63321; -.
DR SwissPalm; P63321; -.
DR EPD; P63321; -.
DR jPOST; P63321; -.
DR MaxQB; P63321; -.
DR PaxDb; P63321; -.
DR PeptideAtlas; P63321; -.
DR PRIDE; P63321; -.
DR ProteomicsDB; 253169; -.
DR Antibodypedia; 26723; 375 antibodies from 35 providers.
DR DNASU; 56044; -.
DR Ensembl; ENSMUST00000009003; ENSMUSP00000009003; ENSMUSG00000008859.
DR GeneID; 56044; -.
DR KEGG; mmu:56044; -.
DR UCSC; uc007pof.1; mouse.
DR CTD; 5898; -.
DR MGI; MGI:1927243; Rala.
DR VEuPathDB; HostDB:ENSMUSG00000008859; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000155142; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P63321; -.
DR OMA; QSRAQQW; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; P63321; -.
DR TreeFam; TF312796; -.
DR BioGRID-ORCS; 56044; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Rala; mouse.
DR PRO; PR:P63321; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P63321; protein.
DR Bgee; ENSMUSG00000008859; Expressed in otic placode and 275 other tissues.
DR ExpressionAtlas; P63321; baseline and differential.
DR Genevisible; P63321; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0032154; C:cleavage furrow; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; ISO:MGI.
DR GO; GO:0090543; C:Flemming body; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0031755; F:Edg-2 lysophosphatidic acid receptor binding; ISS:UniProtKB.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; EXP:Reactome.
DR GO; GO:0017022; F:myosin binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; ISS: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; IMP:CACAO.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISO:MGI.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; ISO:MGI.
DR GO; GO:0017157; P:regulation of exocytosis; IDA:UniProtKB.
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 Cell cycle; Cell division; Cell membrane; Direct protein sequencing;
KW Exocytosis; GTP-binding; Hydrolase; Lipoprotein; Membrane; Methylation;
KW Mitochondrion; Nucleotide-binding; Phosphoprotein; Prenylation;
KW Reference proteome.
FT CHAIN 1..203
FT /note="Ras-related protein Ral-A"
FT /id="PRO_0000082694"
FT PROPEP 204..206
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281345"
FT MOTIF 43..51
FT /note="Effector region"
FT BINDING 21..28
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 68..72
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 127..130
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11233"
FT MOD_RES 203
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 203
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 206 AA; 23553 MW; 6974341FA08C1874 CRC64;
MAANKPKGQN SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS YRKKVVLDGE
EVQIDILDTA GQEDYAAIRD NYFRSGEGFL CVFSITEMES FAATADFREQ ILRVKEDENV
PFLLVGNKSD LEDKRQVSVE EAKNRADQWN VNYVETSAKT RANVDKVFFD LMREIRARKM
EDSKEKNGKK KRKSLAKRIR ERCCIL
