P20336 · RAB3A_HUMAN
- ProteinRas-related protein Rab-3A
- GeneRAB3A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids220 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Small GTP-binding protein that plays a central role in regulated exocytosis and secretion. Controls the recruitment, tethering and docking of secretory vesicles to the plasma membrane (By similarity).
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).
Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction (By similarity).
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).
Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 29-37 | GTP (UniProtKB | ChEBI) | ||||
Sequence: GNSSVGKTS | ||||||
Binding site | 48-54 | GTP (UniProtKB | ChEBI) | ||||
Sequence: TPAFVST | ||||||
Binding site | 77-81 | GTP (UniProtKB | ChEBI) | ||||
Sequence: DTAGQ | ||||||
Binding site | 135-138 | GTP (UniProtKB | ChEBI) | ||||
Sequence: NKCD | ||||||
Binding site | 165-167 | GTP (UniProtKB | ChEBI) | ||||
Sequence: SAK |
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRas-related protein Rab-3A
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP20336
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Lipid-anchor
Note: Cycles between a vesicle-associated GTP-bound form and a cytosolic GDP-bound form.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 86 | Loss of phosphorylation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 86 | Phosphomimetic mutant. Loss of GDI1, GDI2, CHM and CHML binding. | ||||
Sequence: T → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 165 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data), lipidation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000121076 | 1-220 | UniProt | Ras-related protein Rab-3A | |||
Sequence: MASATDSRYGQKESSDQNFDYMFKILIIGNSSVGKTSFLFRYADDSFTPAFVSTVGIDFKVKTIYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILMYDITNEESFNAVQDWSTQIKTYSWDNAQVLLVGNKCDMEDERVVSSERGRQLADHLGFEFFEASAKDNINVKQTFERLVDVICEKMSESLDTADPAVTGAKQGPQLSDQQVPPHQDCAC | |||||||
Modified residue | 86 | UniProt | Phosphothreonine; by LRRK2 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 86 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 188 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 188 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 190 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 190 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Lipidation | 218 | UniProt | S-geranylgeranyl cysteine | ||||
Sequence: C | |||||||
Modified residue | 220 | UniProt | Cysteine methyl ester | ||||
Sequence: C | |||||||
Lipidation | 220 | UniProt | S-geranylgeranyl cysteine | ||||
Sequence: C |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Specifically expressed in brain.
Gene expression databases
Organism-specific databases
Interaction
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).
Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-86 disrupts these interactions (PubMed:29125462).
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).
Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-86 disrupts these interactions (PubMed:29125462).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P20336 | KRTAP10-8 P60410 | 3 | EBI-1045943, EBI-10171774 | |
BINARY | P20336 | RAB3IL1 Q8TBN0 | 3 | EBI-1045943, EBI-743796 | |
BINARY | P20336 | RAB3IP Q96QF0 | 3 | EBI-1045943, EBI-747844 | |
BINARY | P20336 | RAB3IP Q96QF0-7 | 3 | EBI-1045943, EBI-11984839 | |
BINARY | P20336 | RABIF P47224 | 11 | EBI-1045943, EBI-713992 | |
BINARY | P20336 | VRTN Q9H8Y1 | 5 | EBI-1045943, EBI-12894399 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 51-59 | Effector region | ||||
Sequence: FVSTVGIDF | ||||||
Region | 194-220 | Disordered | ||||
Sequence: ADPAVTGAKQGPQLSDQQVPPHQDCAC |
Sequence similarities
Belongs to the small GTPase superfamily. Rab family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length220
- Mass (Da)24,984
- Last updated1991-02-01 v1
- Checksum08B59F8C9BD2EB40
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 70 | in Ref. 2; AAF67748 | ||||
Sequence: R → K | ||||||
Sequence conflict | 180 | in Ref. 2; AAF67748 | ||||
Sequence: V → E |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M28210 EMBL· GenBank· DDBJ | AAA60242.1 EMBL· GenBank· DDBJ | mRNA | ||
AF157809 EMBL· GenBank· DDBJ | AAD46811.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF157806 EMBL· GenBank· DDBJ | AAD46811.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF157807 EMBL· GenBank· DDBJ | AAD46811.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF157808 EMBL· GenBank· DDBJ | AAD46811.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF254795 EMBL· GenBank· DDBJ | AAF67748.1 EMBL· GenBank· DDBJ | mRNA | ||
AF498931 EMBL· GenBank· DDBJ | AAM21079.1 EMBL· GenBank· DDBJ | mRNA | ||
AK289559 EMBL· GenBank· DDBJ | BAF82248.1 EMBL· GenBank· DDBJ | mRNA | ||
AC068499 EMBL· GenBank· DDBJ | AAF67385.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471106 EMBL· GenBank· DDBJ | EAW84672.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC011782 EMBL· GenBank· DDBJ | AAH11782.1 EMBL· GenBank· DDBJ | mRNA |