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 24-JAN-2024, entry version 171. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 7. 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; 10116-ENSRNOP00000026392; -. DR GeneID; 25531; -. DR KEGG; rno:25531; -. DR UCSC; RGD:3528; rat. DR AGR; RGD:3528; -. 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 OrthoDB; 8685at2759; -. 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 cell types or tissues. DR GO; GO:0001669; C:acrosomal vesicle; ISO:RGD. DR GO; GO:0030424; C:axon; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; ISO:RGD. DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell. 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:0030672; C:synaptic vesicle membrane; IDA:SynGO. 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:0030674; F:protein-macromolecule adaptor activity; ISO: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:0051649; P:establishment of localization in cell; ISO:RGD. DR GO; GO:0061670; P:evoked neurotransmitter secretion; ISO:RGD. DR GO; GO:0006887; P:exocytosis; ISO:RGD. DR GO; GO:0030073; P:insulin secretion; 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:0099161; P:regulation of presynaptic dense core granule exocytosis; 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; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR037872; Rab3. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR001806; Small_GTPase. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR47980; LD44762P; 1. DR PANTHER; PTHR47980:SF9; RAS-RELATED PROTEIN RAB-3A; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00176; RAN; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51419; RAB; 1. DR Genevisible; P63012; RN. 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 //