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Details on Person UniProt:P20336 RAB3A
| Class:Id | ReferenceGeneProduct:210477 |
|---|---|
| _chainChangeLog | chain:1-220 added on Sat February 7 2015 |
| _displayName | UniProt:P20336 RAB3A |
| _timestamp | 2025-08-15 22:11:14 |
| chain | chain:1-220 |
| checksum | 08B59F8C9BD2EB40 |
| comment | FUNCTION The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:2501306). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:2501306). RAB3A plays a central role in regulated exocytosis and secretion. Controls the recruitment, tethering and docking of secretory vesicles to the plasma membrane (PubMed:2501306). Upon stimulation, switches to its active GTP-bound form, cycles to vesicles and recruits effectors such as RIMS1, RIMS2, Rabphilin-3A/RPH3A, RPH3AL or SYTL4 to help the docking of vesicules onto the plasma membrane (By similarity). Upon GTP hydrolysis by GTPase-activating protein, dissociates from the vesicle membrane allowing the exocytosis to proceed (By similarity). Stimulates insulin secretion through interaction with RIMS2 or RPH3AL effectors in pancreatic beta cells (By similarity). Regulates calcium-dependent lysosome exocytosis and plasma membrane repair (PMR) via the interaction with 2 effectors, SYTL4 and myosin-9/MYH9 (PubMed:27325790). Acts as a positive regulator of acrosome content secretion in sperm cells by interacting with RIMS1 (PubMed:22248876, PubMed:30599141). Also plays a role in the regulation of dopamine release by interacting with synaptotagmin I/SYT (By similarity).CATALYTIC ACTIVITY GTP + H2O = GDP + phosphate + H(+)COFACTOR Regulated by guanine nucleotide exchange factors (GEFs) including RAB3IL1 and MADD which promote the exchange of bound GDP for free GTP (PubMed:20937701). Regulated by GTPase activating proteins (GAPs) including RAB3GAP1 and TBC1D10B which increase the GTP hydrolysis activity (PubMed:10859313, PubMed:19077034). Inhibited by GDP dissociation inhibitors (GDIs) which prevent Rab-GDP dissociation (Probable).SUBUNIT Interacts with RIMS1 and RIMS2 (By similarity). Interacts with Rabphilin-3A/RPH3A and Rab effector Noc2/RPH3AL (By similarity). Interacts with SYTL4 (By similarity). Interacts with RAB3IP (By similarity). Interacts with SGSM1 and SGSM3 (By similarity). Interacts with SYT1 (By similarity). Interacts with MYH9; this interaction is essential for lysosome exocytosis and plasma membrane repair (PubMed:27325790). Interacts with STXBP1; this interaction promotes RAB3A dissociation from the vesicle membrane (By similarity). Interacts with SNCA (PubMed:15207266). The GTP-bound form interacts with REP15 (PubMed:35871249). Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-86 disrupts these interactions (PubMed:29125462). Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction (By similarity).INTERACTION Cycles between a vesicle-associated GTP-bound form and a cytosolic GDP-bound form.TISSUE SPECIFICITY Specifically expressed in brain.DOMAIN Switch 1, switch 2 and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drives interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.PTM Phosphorylation of Thr-86 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.SIMILARITY Belongs to the small GTPase superfamily. Rab family. |
| created | [InstanceEdit:210485] 2008-01-14 10:59:03 |
| description | recommendedName: Ras-related protein Rab-3A ecNumber evidence="10"3.6.5.2 |
| geneName | RAB3A |
| identifier | P20336 |
| isSequenceChanged | FALSE |
| keyword | Cell membrane Cell projection Cytoplasm Cytoplasmic vesicle Exocytosis GTP-binding Hydrolase Lipoprotein Lysosome Magnesium Membrane Metal-binding Methylation Nucleotide-binding Phosphoprotein Prenylation Protein transport Proteomics identification Reference proteome Synapse Transport |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | RAB3A |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990353] ENSEMBL:ENSG00000105649 RAB3A [Homo sapiens] |
| secondaryIdentifier | RAB3A_HUMAN A8K0J4 Q9NYE1 |
| sequenceLength | 220 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:210461] RAB3A [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:210466] RAB3A [clathrin-sculpted glutamate transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:372512] RAB3A [clathrin-sculpted monoamine transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:379365] RAB3A [clathrin-sculpted acetylcholine transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:917743] RAB3A [clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:6804968] RAB3A [secretory granule membrane] [Homo sapiens] [EntityWithAccessionedSequence:8870410] RAB3A [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8870429] GGC-RAB3A [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8875319] GGC-RAB3A [secretory granule membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:8870401] S-geranylgeranyl-L-cysteine at 218 [ModifiedResidue:8870405] S-geranylgeranyl-L-cysteine at 220 |
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No pathways have been reviewed or authored by UniProt:P20336 RAB3A (210477)
