RAB3A_RAT
ID RAB3A_RAT Reviewed; 220 AA.
AC P63012; P05713;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Ras-related protein Rab-3A;
GN Name=Rab3a;
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].
RC TISSUE=Brain;
RX PubMed=3317403; DOI=10.1073/pnas.84.23.8210;
RA Touchot N., Chardin P., Tavitian A.;
RT "Four additional members of the ras gene superfamily isolated by an
RT oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat
RT brain library.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8210-8214(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=3344209; DOI=10.1093/nar/16.3.1204;
RA Zahraoui A., Touchot N., Chardin P., Tavitian A.;
RT "Complete coding sequences of the ras related rab 3 and 4 cDNAs.";
RL Nucleic Acids Res. 16:1204-1204(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18407218; DOI=10.1016/1043-2760(94)p3201-h;
RA Macara I.G.;
RT "Role of the Rab3A GTPase in regulated secretion from neuroendocrine
RT cells.";
RL Trends Endocrinol. Metab. 5:267-271(1994).
RN [5]
RP INTERACTION WITH RAB3IP, AND MUTAGENESIS OF THR-36; PHE-51; VAL-52; VAL-55
RP AND GLY-56.
RX PubMed=7532276; DOI=10.1128/mcb.15.3.1137;
RA Brondyk W.H., McKiernan C.J., Fortner K.A., Stabila P., Holz R.W.,
RA Macara I.G.;
RT "Interaction cloning of Rabin3, a novel protein that associates with the
RT Ras-like GTPase Rab3A.";
RL Mol. Cell. Biol. 15:1137-1143(1995).
RN [6]
RP INTERACTION WITH RIMS2.
RX PubMed=10748113; DOI=10.1074/jbc.m909008199;
RA Wang Y., Sugita S., Suedhof T.C.;
RT "The RIM/NIM family of neuronal C2 domain proteins. Interactions with Rab3
RT and a new class of Src homology 3 domain proteins.";
RL J. Biol. Chem. 275:20033-20044(2000).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=17311845; DOI=10.1242/jcs.03406;
RA Handley M.T., Haynes L.P., Burgoyne R.D.;
RT "Differential dynamics of Rab3A and Rab27A on secretory granules.";
RL J. Cell Sci. 120:973-984(2007).
RN [8]
RP FUNCTION.
RX PubMed=17149709; DOI=10.1002/jcp.20938;
RA Lin C.C., Huang C.C., Lin K.H., Cheng K.H., Yang D.M., Tsai Y.S., Ong R.Y.,
RA Huang Y.N., Kao L.S.;
RT "Visualization of Rab3A dissociation during exocytosis: a study by total
RT internal reflection microscopy.";
RL J. Cell. Physiol. 211:316-326(2007).
RN [9]
RP FUNCTION, AND INTERACTION WITH STXBP1.
RX PubMed=21689256; DOI=10.1111/j.1600-0854.2011.01237.x;
RA Huang C.C., Yang D.M., Lin C.C., Kao L.S.;
RT "Involvement of Rab3A in vesicle priming during exocytosis: interaction
RT with Munc13-1 and Munc18-1.";
RL Traffic 12:1356-1370(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188 AND SER-190, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [11]
RP FUNCTION, AND INTERACTION WITH SYT1.
RX PubMed=28057568; DOI=10.1016/j.ijbiomac.2016.12.074;
RA Tang X., Xie C., Wang Y., Wang X.;
RT "Localization of Rab3A-binding site on C2A domain of synaptotagmin I to
RT reveal its regulatory mechanism.";
RL Int. J. Biol. Macromol. 96:736-742(2017).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 19-217 IN COMPLEX WITH GTP AND
RP RPH3A, AND INTERACTION WITH RPH3A.
RX PubMed=10025402; DOI=10.1016/s0092-8674(00)80549-8;
RA Ostermeier C., Brunger A.T.;
RT "Structural basis of Rab effector specificity: crystal structure of the
RT small G protein Rab3A complexed with the effector domain of rabphilin-3A.";
RL Cell 96:363-374(1999).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 18-186 IN COMPLEX WITH GTP ANALOG.
RX PubMed=10196122; DOI=10.1016/s0969-2126(99)80054-9;
RA Dumas J.J., Zhu Z., Connolly J.L., Lambright D.G.;
RT "Structural basis of activation and GTP hydrolysis in rab proteins.";
RL Structure 7:413-423(1999).
CC -!- FUNCTION: Small GTP-binding protein that plays a central role in
CC regulated exocytosis and secretion. Controls the recruitment, tethering
CC and docking of secretory vesicles to the plasma membrane
CC (PubMed:21689256). Upon stimulation, switches to its active GTP-bound
CC form, cycles to vesicles and recruits effectors such as RIMS1, RIMS2,
CC Rabphilin-3A/RPH3A, RPH3AL or SYTL4 to help the docking of vesicules
CC onto the plasma membrane (PubMed:18407218). Upon GTP hydrolysis by
CC GTPase-activating protein, dissociates from the vesicle membrane
CC allowing the exocytosis to proceed (PubMed:17149709). Stimulates
CC insulin secretion through interaction with RIMS2 and RPH3AL effectors
CC in pancreatic beta cells (By similarity). Regulates calcium-dependent
CC lysosome exocytosis and plasma membrane repair (PMR) via the
CC interaction with 2 effectors, SYTL4 and myosin-9/MYH9 (By similarity).
CC Acts as a positive regulator of acrosome content secretion in sperm
CC cells by interacting with RIMS1 (By similarity). Plays a role in the
CC regulation of dopamine release by interacting with synaptotagmin I/SYT
CC (PubMed:28057568). Interacts with MADD (via uDENN domain); the GTP-
CC bound form is preferred for interaction (By similarity).
CC {ECO:0000250|UniProtKB:P20336, ECO:0000250|UniProtKB:P63011,
CC ECO:0000269|PubMed:17149709, ECO:0000269|PubMed:18407218,
CC ECO:0000269|PubMed:21689256, ECO:0000269|PubMed:28057568}.
CC -!- SUBUNIT: Interacts with RIMS1 and RIMS2 (PubMed:10748113) (By
CC similarity). Interacts with Rabphilin-3A/RPH3A and Rab effector
CC Noc2/RPH3AL (PubMed:10025402) (By similarity). Interacts with SYTL4 (By
CC similarity). Interacts with RAB3IP (PubMed:7532276). Interacts with
CC SGSM1 and SGSM3 (By similarity). Interacts with SYT1 (PubMed:28057568).
CC Interacts with MYH9; this interaction is essential for lysosome
CC exocytosis and plasma membrane repair (By similarity). Interacts with
CC STXBP1; this interaction promotes RAB3A dissociation from the vesicle
CC membrane (PubMed:21689256). Interacts with SNCA (By similarity).
CC Interacts with GDI1, GDI2 and CHM; phosphorylation at Thr-86 disrupts
CC these interactions (By similarity). {ECO:0000250|UniProtKB:P20336,
CC ECO:0000250|UniProtKB:P63011, ECO:0000269|PubMed:10025402,
CC ECO:0000269|PubMed:10748113, ECO:0000269|PubMed:21689256,
CC ECO:0000269|PubMed:28057568, ECO:0000269|PubMed:7532276}.
CC -!- INTERACTION:
CC P63012; P47709: Rph3a; NbExp=2; IntAct=EBI-440126, EBI-1027524;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17311845,
CC ECO:0000269|PubMed:18407218}. Lysosome {ECO:0000250|UniProtKB:P20336}.
CC Cytoplasmic vesicle, secretory vesicle {ECO:0000269|PubMed:17311845,
CC ECO:0000269|PubMed:18407218}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P63011}. Cell membrane {ECO:0000305}; Lipid-
CC anchor {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Presynapse
CC {ECO:0000250|UniProtKB:P63011}. Postsynapse
CC {ECO:0000250|UniProtKB:P63011}. Note=Cycles between a vesicle-
CC associated GTP-bound form and a cytosolic GDP-bound form.
CC {ECO:0000269|PubMed:18407218}.
CC -!- TISSUE SPECIFICITY: Detected in brain.
CC -!- PTM: Phosphorylation of Thr-86 in the switch II region by LRRK2
CC prevents the association of RAB regulatory proteins, including CHM and
CC RAB GDP dissociation inhibitors GDI1 and GDI2.
CC {ECO:0000250|UniProtKB:P20336}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; X06889; CAA30005.1; -; mRNA.
DR EMBL; BC087580; AAH87580.1; -; mRNA.
DR PIR; S01765; S01765.
DR RefSeq; NP_037150.2; NM_013018.2.
DR PDB; 1ZBD; X-ray; 2.60 A; A=19-217.
DR PDB; 3RAB; X-ray; 2.00 A; A=18-186.
DR PDBsum; 1ZBD; -.
DR PDBsum; 3RAB; -.
DR AlphaFoldDB; P63012; -.
DR SMR; P63012; -.
DR BioGRID; 247563; 6.
DR CORUM; P63012; -.
DR IntAct; P63012; 6.
DR MINT; P63012; -.
DR STRING; 10116.ENSRNOP00000026392; -.
DR iPTMnet; P63012; -.
DR PhosphoSitePlus; P63012; -.
DR SwissPalm; P63012; -.
DR jPOST; P63012; -.
DR PaxDb; P63012; -.
DR PRIDE; P63012; -.
DR GeneID; 25531; -.
DR KEGG; rno:25531; -.
DR UCSC; RGD:3528; rat.
DR CTD; 5864; -.
DR RGD; 3528; Rab3a.
DR VEuPathDB; HostDB:ENSRNOG00000019433; -.
DR eggNOG; KOG0093; Eukaryota.
DR HOGENOM; CLU_041217_10_1_1; -.
DR InParanoid; P63012; -.
DR OMA; MERYCED; -.
DR OrthoDB; 1426655at2759; -.
DR PhylomeDB; P63012; -.
DR TreeFam; TF313199; -.
DR Reactome; R-RNO-181429; Serotonin Neurotransmitter Release Cycle.
DR Reactome; R-RNO-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-RNO-212676; Dopamine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-264642; Acetylcholine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8873719; RAB geranylgeranylation.
DR Reactome; R-RNO-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-RNO-888590; GABA synthesis, release, reuptake and degradation.
DR EvolutionaryTrace; P63012; -.
DR PRO; PR:P63012; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000019433; Expressed in frontal cortex and 20 other tissues.
DR Genevisible; P63012; RN.
DR GO; GO:0001669; C:acrosomal vesicle; ISO:RGD.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0043229; C:intracellular organelle; IDA:RGD.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098794; C:postsynapse; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISO:RGD.
DR GO; GO:0048786; C:presynaptic active zone; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB.
DR GO; GO:0043195; C:terminal bouton; IDA:ParkinsonsUK-UCL.
DR GO; GO:0001671; F:ATPase activator activity; IDA:RGD.
DR GO; GO:0051117; F:ATPase binding; IPI:RGD.
DR GO; GO:0051021; F:GDP-dissociation inhibitor binding; IPI:RGD.
DR GO; GO:0005525; F:GTP binding; IDA:RGD.
DR GO; GO:0030742; F:GTP-dependent protein binding; ISO:RGD.
DR GO; GO:0003924; F:GTPase activity; ISO:RGD.
DR GO; GO:0031489; F:myosin V binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0060478; P:acrosomal vesicle exocytosis; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISO:RGD.
DR GO; GO:0061670; P:evoked neurotransmitter secretion; ISO:RGD.
DR GO; GO:0006887; P:exocytosis; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0032418; P:lysosome localization; ISO:RGD.
DR GO; GO:0048790; P:maintenance of presynaptic active zone structure; ISO:RGD.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; ISO:RGD.
DR GO; GO:0001778; P:plasma membrane repair; ISO:RGD.
DR GO; GO:1903307; P:positive regulation of regulated secretory pathway; ISO:RGD.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0009306; P:protein secretion; IBA:GO_Central.
DR GO; GO:0032482; P:Rab protein signal transduction; IC:RGD.
DR GO; GO:0045055; P:regulated exocytosis; ISO:RGD.
DR GO; GO:0014059; P:regulation of dopamine secretion; IDA:CACAO.
DR GO; GO:0017157; P:regulation of exocytosis; ISO:RGD.
DR GO; GO:1905684; P:regulation of plasma membrane repair; ISO:RGD.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; ISS:ParkinsonsUK-UCL.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:UniProtKB.
DR GO; GO:0031630; P:regulation of synaptic vesicle fusion to presynaptic active zone membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010807; P:regulation of synaptic vesicle priming; IDA:UniProtKB.
DR GO; GO:0003016; P:respiratory system process; ISO:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; ISO:RGD.
DR GO; GO:0050975; P:sensory perception of touch; ISO:RGD.
DR GO; GO:0097091; P:synaptic vesicle clustering; ISO:RGD.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016188; P:synaptic vesicle maturation; ISO:RGD.
DR GO; GO:0036465; P:synaptic vesicle recycling; IMP:ParkinsonsUK-UCL.
DR GO; GO:0048489; P:synaptic vesicle transport; ISO:RGD.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IBA:GO_Central.
DR CDD; cd01865; Rab3; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR037872; Rab3.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Exocytosis; GTP-binding; Lipoprotein; Lysosome;
KW Membrane; Methylation; Nucleotide-binding; Phosphoprotein; Prenylation;
KW Protein transport; Reference proteome; Synapse; Transport.
FT CHAIN 1..220
FT /note="Ras-related protein Rab-3A"
FT /id="PRO_0000121079"
FT REGION 194..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 51..59
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 29..37
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:10025402"
FT BINDING 48..54
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:10025402"
FT BINDING 77..81
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:10025402"
FT BINDING 135..138
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:10025402"
FT BINDING 165..167
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:O95716"
FT MOD_RES 86
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P20336"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 220
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 218
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 220
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 36
FT /note="T->N: No significant effect on interaction with
FT RAB3IP."
FT /evidence="ECO:0000269|PubMed:7532276"
FT MUTAGEN 51
FT /note="F->L: Disrupts the interaction with RAB3IP."
FT /evidence="ECO:0000269|PubMed:7532276"
FT MUTAGEN 52
FT /note="V->A: No significant effect on interaction with
FT RAB3IP."
FT /evidence="ECO:0000269|PubMed:7532276"
FT MUTAGEN 55
FT /note="V->E: Disrupts the interaction with RAB3IP."
FT /evidence="ECO:0000269|PubMed:7532276"
FT MUTAGEN 56
FT /note="G->D: Disrupts the interaction with RAB3IP."
FT /evidence="ECO:0000269|PubMed:7532276"
FT CONFLICT 196
FT /note="P -> L (in Ref. 2; CAA30005)"
FT /evidence="ECO:0000305"
FT STRAND 20..28
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 35..44
FT /evidence="ECO:0007829|PDB:3RAB"
FT STRAND 56..66
FT /evidence="ECO:0007829|PDB:3RAB"
FT STRAND 69..78
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 85..89
FT /evidence="ECO:0007829|PDB:3RAB"
FT TURN 90..94
FT /evidence="ECO:0007829|PDB:3RAB"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 107..111
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 113..123
FT /evidence="ECO:0007829|PDB:3RAB"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:3RAB"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:3RAB"
FT TURN 166..169
FT /evidence="ECO:0007829|PDB:3RAB"
FT HELIX 172..184
FT /evidence="ECO:0007829|PDB:3RAB"
SQ SEQUENCE 220 AA; 24970 MW; 1A3E9F8C9D09EB40 CRC64;
MASATDSRYG QKESSDQNFD YMFKILIIGN SSVGKTSFLF RYADDSFTPA FVSTVGIDFK
VKTIYRNDKR IKLQIWDTAG QERYRTITTA YYRGAMGFIL MYDITNEESF NAVQDWSTQI
KTYSWDNAQV LLVGNKCDME DERVVSSERG RQLADHLGFE FFEASAKDNI NVKQTFERLV
DVICEKMSES LDTADPAVTG AKQGPQLTDQ QAPPHQDCAC
