RALA_SAGOE
ID RALA_SAGOE Reviewed; 206 AA.
AC P63320; P05810;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 105.
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;
OS Saguinus oedipus (Cotton-top tamarin).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Callitrichinae; Saguinus.
OX NCBI_TaxID=9490;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=B-cell;
RX PubMed=3023062; DOI=10.1002/j.1460-2075.1986.tb04485.x;
RA Chardin P., Tavitian A.;
RT "The ral gene: a new ras related gene isolated by the use of a synthetic
RT probe.";
RL EMBO J. 5:2203-2208(1986).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 11-178 IN COMPLEX WITH GTP ANALOG.
RX PubMed=15530367; DOI=10.1016/j.str.2004.08.011;
RA Nicely N.I., Kosak J., de Serrano V., Mattos C.;
RT "Crystal structures of Ral-GppNHp and Ral-GDP reveal two binding sites that
RT are also present in Ras and Rap.";
RL Structure 12:2025-2036(2004).
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. The RALA-exocyst complex regulates integrin-
CC dependent membrane raft exocytosis and growth signaling. Key regulator
CC of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus
CC affecting the signaling properties of the receptor. Required for
CC anchorage-independent proliferation of transformed cells. During
CC mitosis, supports the stabilization and elongation of the intracellular
CC bridge between dividing cells. Cooperates with EXOC2 to recruit other
CC components of the exocyst to the early midbody. During mitosis, also
CC controls mitochondrial fission by recruiting to the mitochondrion
CC RALBP1, which mediates the phosphorylation and activation of DNM1L by
CC the mitotic kinase cyclin B-CDK1 (By similarity).
CC {ECO:0000250|UniProtKB:P11233}.
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; X04328; CAA27859.1; -; mRNA.
DR PDB; 1U8Y; X-ray; 1.55 A; A/B=11-178.
DR PDB; 1U8Z; X-ray; 1.50 A; A/B=11-178.
DR PDB; 1U90; X-ray; 2.00 A; A/B=11-178.
DR PDBsum; 1U8Y; -.
DR PDBsum; 1U8Z; -.
DR PDBsum; 1U90; -.
DR AlphaFoldDB; P63320; -.
DR SMR; P63320; -.
DR PRIDE; P63320; -.
DR EvolutionaryTrace; P63320; -.
DR GO; GO:0032154; C:cleavage furrow; ISS:UniProtKB.
DR GO; GO:0090543; C:Flemming body; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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:0005525; F:GTP binding; IDA:UniProtKB.
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:0090141; P:positive regulation of mitochondrial fission; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:InterPro.
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 3D-structure; Cell cycle; Cell division; Cell membrane; Exocytosis;
KW GTP-binding; Hydrolase; Lipoprotein; Membrane; Methylation; Mitochondrion;
KW Nucleotide-binding; Phosphoprotein; Prenylation.
FT CHAIN 1..203
FT /note="Ras-related protein Ral-A"
FT /id="PRO_0000082696"
FT PROPEP 204..206
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281347"
FT MOTIF 43..51
FT /note="Effector region"
FT BINDING 21..29
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 127..130
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
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 STRAND 14..20
FT /evidence="ECO:0007829|PDB:1U8Z"
FT HELIX 27..36
FT /evidence="ECO:0007829|PDB:1U8Z"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:1U8Z"
FT STRAND 60..68
FT /evidence="ECO:0007829|PDB:1U8Z"
FT HELIX 76..85
FT /evidence="ECO:0007829|PDB:1U8Z"
FT STRAND 87..94
FT /evidence="ECO:0007829|PDB:1U8Z"
FT HELIX 98..115
FT /evidence="ECO:0007829|PDB:1U8Z"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:1U8Z"
FT HELIX 129..134
FT /evidence="ECO:0007829|PDB:1U8Z"
FT HELIX 139..149
FT /evidence="ECO:0007829|PDB:1U8Z"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:1U8Z"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:1U8Z"
FT HELIX 164..176
FT /evidence="ECO:0007829|PDB:1U8Z"
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
