RALA_RAT
ID RALA_RAT Reviewed; 206 AA.
AC P63322; P05810;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 146.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7687439; DOI=10.1006/bbrc.1993.1855;
RA Wildey G.M., Viggeswarapu M., Rim S., Denker J.K.;
RT "Isolation of cDNA clones and tissue expression of rat ral A and ral B GTP-
RT binding proteins.";
RL Biochem. Biophys. Res. Commun. 194:552-559(1993).
RN [2]
RP INTERACTION WITH RALBP1 AND CDC42, AND MUTAGENESIS OF ASP-49.
RX PubMed=7623849; DOI=10.1128/mcb.15.8.4578;
RA Cantor S.B., Urano T., Feig L.A.;
RT "Identification and characterization of Ral-binding protein 1, a potential
RT downstream target of Ral GTPases.";
RL Mol. Cell. Biol. 15:4578-4584(1995).
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 (By
CC similarity). During mitosis, supports the stabilization and elongation
CC of the intracellular bridge between dividing cells. Cooperates with
CC EXOC2 to recruit other components of the exocyst to the early midbody
CC (By similarity). During mitosis, also controls mitochondrial fission by
CC recruiting to the mitochondrion RALBP1, which mediates the
CC phosphorylation and activation of DNM1L by the mitotic kinase cyclin B-
CC CDK1 (By similarity). {ECO:0000250|UniProtKB:P11233,
CC ECO:0000250|UniProtKB:P63321}.
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 (PubMed:7623849). 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
CC (PubMed:7623849). {ECO:0000250|UniProtKB:P11233,
CC ECO:0000269|PubMed:7623849}.
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 -!- TISSUE SPECIFICITY: Higher levels where found in testes followed by
CC brain, adrenal gland, pituitary gland, ovary, liver and kidney. Low
CC expression was found in muscle. {ECO:0000269|PubMed:7687439}.
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; L19698; AAA42003.1; -; mRNA.
DR PIR; JN0622; JN0622.
DR RefSeq; NP_112355.1; NM_031093.2.
DR RefSeq; XP_006254055.1; XM_006253993.3.
DR RefSeq; XP_017456153.1; XM_017600664.1.
DR RefSeq; XP_017456154.1; XM_017600665.1.
DR AlphaFoldDB; P63322; -.
DR SMR; P63322; -.
DR BioGRID; 249629; 5.
DR IntAct; P63322; 1.
DR STRING; 10116.ENSRNOP00000018190; -.
DR iPTMnet; P63322; -.
DR PhosphoSitePlus; P63322; -.
DR SwissPalm; P63322; -.
DR PaxDb; P63322; -.
DR PRIDE; P63322; -.
DR Ensembl; ENSRNOT00000102020; ENSRNOP00000090376; ENSRNOG00000013454.
DR GeneID; 81757; -.
DR KEGG; rno:81757; -.
DR UCSC; RGD:619851; rat.
DR CTD; 5898; -.
DR RGD; 619851; Rala.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000155142; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P63322; -.
DR OMA; QSRAQQW; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; P63322; -.
DR TreeFam; TF312796; -.
DR PRO; PR:P63322; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000013454; Expressed in heart and 20 other tissues.
DR Genevisible; P63322; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0032154; C:cleavage furrow; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl.
DR GO; GO:0090543; C:Flemming body; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
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:RGD.
DR GO; GO:0005525; F:GTP binding; ISO:RGD.
DR GO; GO:0003924; F:GTPase activity; ISO:RGD.
DR GO; GO:0017022; F:myosin binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISO:RGD.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; ISO:RGD.
DR GO; GO:0017157; P:regulation of exocytosis; ISS: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; Exocytosis; GTP-binding;
KW Hydrolase; Lipoprotein; Membrane; Methylation; Mitochondrion;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1..203
FT /note="Ras-related protein Ral-A"
FT /id="PRO_0000082695"
FT PROPEP 204..206
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281346"
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"
FT MUTAGEN 49
FT /note="D->N: Loss of RALBP1 binding."
FT /evidence="ECO:0000269|PubMed:7623849"
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
