P61006 · RAB8A_HUMAN
- ProteinRas-related protein Rab-8A
- GeneRAB8A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids207 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. 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. That Rab is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (PubMed:20890297).
Regulates the compacted morphology of the Golgi (PubMed:26209634).
Together with MYO5B and RAB11A participates in epithelial cell polarization (PubMed:21282656).
Also involved in membrane trafficking to the cilium and ciliogenesis (PubMed:21844891, PubMed:30398148).
Together with MICALL2, may also regulate adherens junction assembly (By similarity).
May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity).
Involved in autophagy (PubMed:27103069).
Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433).
Targeted to and stabilized on stressed lysosomes through LRRK2 phosphorylation (PubMed:30209220).
Suppresses stress-induced lysosomal enlargement through EHBP1 and EHNP1L1 effector proteins (PubMed:30209220).
Regulates the compacted morphology of the Golgi (PubMed:26209634).
Together with MYO5B and RAB11A participates in epithelial cell polarization (PubMed:21282656).
Also involved in membrane trafficking to the cilium and ciliogenesis (PubMed:21844891, PubMed:30398148).
Together with MICALL2, may also regulate adherens junction assembly (By similarity).
May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity).
Involved in autophagy (PubMed:27103069).
Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433).
Targeted to and stabilized on stressed lysosomes through LRRK2 phosphorylation (PubMed:30209220).
Suppresses stress-induced lysosomal enlargement through EHBP1 and EHNP1L1 effector proteins (PubMed:30209220).
Catalytic activity
- GTP + H2O = GDP + H+ + phosphateThis reaction proceeds in the forward direction.
Activity regulation
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase (Probable). Activated in response to insulin (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 17-22 | GTP (UniProtKB | ChEBI) | ||||
Sequence: SGVGKT | ||||||
Binding site | 34-40 | GTP (UniProtKB | ChEBI) | ||||
Sequence: NSTFIST | ||||||
Binding site | 63-67 | GTP (UniProtKB | ChEBI) | ||||
Sequence: DTAGQ | ||||||
Binding site | 121-124 | GTP (UniProtKB | ChEBI) | ||||
Sequence: NKCD | ||||||
Binding site | 152-154 | GTP (UniProtKB | ChEBI) | ||||
Sequence: AKA |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRas-related protein Rab-8A
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP61006
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Lipid-anchor
Cytoplasmic vesicle, phagosome membrane ; Lipid-anchor
Note: Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane (PubMed:15837803).
In the GDP-bound form, present in the perinuclear region (PubMed:12221131).
Shows a polarized distribution to distal regions of cell protrusions in the GTP-bound form (PubMed:12221131).
Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and RAB11A in apical membrane initiation sites (AMIS) during the generation of apical surface and lumenogenesis (PubMed:20890297).
Localizes to tubular recycling endosome (PubMed:19864458).
Recruited to phagosomes containing S.aureus or M.tuberculosis (PubMed:21255211).
Non-phosphorylated RAB8A predominantly localized to the cytoplasm whereas phosphorylated RAB8A localized to the membrane (PubMed:26824392, PubMed:29125462, PubMed:30398148).
Colocalized with MICAL1, GRAF1/ARHGAP26 and GRAF2/ARHGAP10 on endosomal tubules (PubMed:32344433).
Localizes to enlarged lysosomes through LRRK2 phosphorylation (PubMed:30209220).
In the GDP-bound form, present in the perinuclear region (PubMed:12221131).
Shows a polarized distribution to distal regions of cell protrusions in the GTP-bound form (PubMed:12221131).
Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and RAB11A in apical membrane initiation sites (AMIS) during the generation of apical surface and lumenogenesis (PubMed:20890297).
Localizes to tubular recycling endosome (PubMed:19864458).
Recruited to phagosomes containing S.aureus or M.tuberculosis (PubMed:21255211).
Non-phosphorylated RAB8A predominantly localized to the cytoplasm whereas phosphorylated RAB8A localized to the membrane (PubMed:26824392, PubMed:29125462, PubMed:30398148).
Colocalized with MICAL1, GRAF1/ARHGAP26 and GRAF2/ARHGAP10 on endosomal tubules (PubMed:32344433).
Localizes to enlarged lysosomes through LRRK2 phosphorylation (PubMed:30209220).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 22 | Loss of interaction with MICAL1. Loss of GRAF1/ARHGAP26 and GRAF2/ARHGAP10 tubular localization. Loss of E-cadherin and MMP14 export. | ||||
Sequence: T → N | ||||||
Mutagenesis | 67 | Probable constitutively active mutant locked in the active GTP-bound form. Stimulates interaction with MICALL1. Increased WDR44-positive tubulation. | ||||
Sequence: Q → L | ||||||
Mutagenesis | 72 | Loss of phosphorylation. No effect on the binding of GDP or GTP. Localizes primarily to the Golgi complex but does not affect membrane localization. Does not translocate to LRRK2-positive lysosomes and does not suppress lysosomal enlargement. | ||||
Sequence: T → A | ||||||
Mutagenesis | 72 | Phosphomimetic mutant. Suppresses interaction with GDI1. | ||||
Sequence: T → D | ||||||
Mutagenesis | 72 | Phosphomimetic mutant. No effect on the binding of GDP or GTP. Loss of GDI1, GDI2, CHM, CHML, RABGGTA, RABGGTB, RAB3IP, TBC1D15, and INPP5B binding. Increases localization to the cell membrane. | ||||
Sequence: T → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 168 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue, lipidation, propeptide.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000121130 | 1-204 | UniProt | Ras-related protein Rab-8A | |||
Sequence: MAKTYDYLFKLLLIGDSGVGKTCVLFRFSEDAFNSTFISTIGIDFKIRTIELDGKRIKLQIWDTAGQERFRTITTAYYRGAMGIMLVYDITNEKSFDNIRNWIRNIEEHASADVEKMILGNKCDVNDKRQVSKERGEKLALDYGIKFMETSAKANINVENAFFTLARDIKAKMDKKLEGNSPQGSNQGVKITPDQQKRSSFFRC | |||||||
Modified residue (large scale data) | 5 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 72 | UniProt | Phosphothreonine; by LRRK2 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 72 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 111 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 164 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 181 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 181 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 185 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 185 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 192 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 204 | UniProt | Cysteine methyl ester | ||||
Sequence: C | |||||||
Lipidation | 204 | UniProt | S-geranylgeranyl cysteine | ||||
Sequence: C | |||||||
Propeptide | PRO_0000370793 | 205-207 | UniProt | Removed in mature form | |||
Sequence: VLL |
Post-translational modification
Phosphorylation of Thr-72 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. Phosphorylation by LRRK2 is required for localization to stressed lysosomes.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts (GTP-bound form) with MICALL1; regulates RAB8A association with recycling endosomes (By similarity).
Interacts with MICALL2; competes with RAB13 and is involved in E-cadherin endocytic recycling (By similarity).
Interacts (GTP-bound form) with MICAL1, MICALCL, MICAL3, EHBP1 and EHBP1L1; at least in case of MICAL1, MICALCL, MICAL3 and EHBP1L1 two molecules of RAB8A can bind to one molecule of the effector protein; ternary complexes of RAB8A, RAB13 and either MICAL1 or EHBP1L1 are possible (PubMed:27552051, PubMed:32344433).
Interacts with EHD1 (PubMed:19864458).
Interacts with MAP4K2 and SYTL4 (By similarity).
Interacts with SGSM1 and SGSM3 (By similarity).
Interacts with RABIF, RIMS2, RPH3A and RPH3A (By similarity).
Interacts with OPTN (PubMed:15837803).
Interacts with RAB3IP (PubMed:12221131).
Interacts with MYO5B (PubMed:21282656).
Interacts with CIMAP3 (PubMed:20643351).
Interacts with BIRC6/bruce (PubMed:18329369).
Interacts with OCRL (PubMed:21378754, PubMed:22543976).
Interacts with AHI1 (By similarity).
Interacts with DCDC1 (PubMed:22159412).
Interacts with LRRK2; interaction facilitates phosphorylation of Thr-72 (PubMed:26824392).
Interacts with RAB31P, GDI1, GDI2, CHM, CHML, RABGGTA, RABGGTB, TBC1D15 and INPP5B; these interactions are dependent on Thr-72 not being phosphorylated (PubMed:26824392, PubMed:29125462).
Interacts with RILPL1 and RILPL2; these interactions are dependent on the phosphorylation of Thr-72 by LRRK2 (PubMed:29125462, PubMed:30398148).
Interacts with DZIP1; prevents inhibition by the GDP-dissociation inhibitor GDI2 (PubMed:25860027).
Interacts with MICALL2; competes with RAB13 and is involved in E-cadherin endocytic recycling (By similarity).
Interacts (GTP-bound form) with MICAL1, MICALCL, MICAL3, EHBP1 and EHBP1L1; at least in case of MICAL1, MICALCL, MICAL3 and EHBP1L1 two molecules of RAB8A can bind to one molecule of the effector protein; ternary complexes of RAB8A, RAB13 and either MICAL1 or EHBP1L1 are possible (PubMed:27552051, PubMed:32344433).
Interacts with EHD1 (PubMed:19864458).
Interacts with MAP4K2 and SYTL4 (By similarity).
Interacts with SGSM1 and SGSM3 (By similarity).
Interacts with RABIF, RIMS2, RPH3A and RPH3A (By similarity).
Interacts with OPTN (PubMed:15837803).
Interacts with RAB3IP (PubMed:12221131).
Interacts with MYO5B (PubMed:21282656).
Interacts with CIMAP3 (PubMed:20643351).
Interacts with BIRC6/bruce (PubMed:18329369).
Interacts with OCRL (PubMed:21378754, PubMed:22543976).
Interacts with AHI1 (By similarity).
Interacts with DCDC1 (PubMed:22159412).
Interacts with LRRK2; interaction facilitates phosphorylation of Thr-72 (PubMed:26824392).
Interacts with RAB31P, GDI1, GDI2, CHM, CHML, RABGGTA, RABGGTB, TBC1D15 and INPP5B; these interactions are dependent on Thr-72 not being phosphorylated (PubMed:26824392, PubMed:29125462).
Interacts with RILPL1 and RILPL2; these interactions are dependent on the phosphorylation of Thr-72 by LRRK2 (PubMed:29125462, PubMed:30398148).
Interacts with DZIP1; prevents inhibition by the GDP-dissociation inhibitor GDI2 (PubMed:25860027).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P61006 | lpg0940 Q5ZWZ3 | 3 | EBI-722293, EBI-6417967 | |
BINARY | P61006 | LRRK2 Q5S007 | 9 | EBI-722293, EBI-5323863 | |
BINARY | P61006 | OCRL Q01968 | 15 | EBI-722293, EBI-6148898 | |
BINARY | P61006 | OPTN Q96CV9 | 4 | EBI-722293, EBI-748974 | |
BINARY | P61006 | RAB3IP Q96QF0 | 5 | EBI-722293, EBI-747844 | |
BINARY | P61006 | RAB3IP Q96QF0-2 | 2 | EBI-722293, EBI-747865 | |
BINARY | P61006 | RABIF P47224 | 8 | EBI-722293, EBI-713992 | |
XENO | P61006 | rep PRO_0000449625 P0DTD1 | 3 | EBI-722293, EBI-25475871 | |
BINARY | P61006 | RILPL1 Q5EBL4 | 2 | EBI-722293, EBI-2797110 | |
BINARY | P61006 | RILPL2 Q969X0 | 8 | EBI-722293, EBI-717552 | |
BINARY | P61006 | SPAG9 O60271 | 3 | EBI-722293, EBI-1023301 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 37-45 | Effector region | ||||
Sequence: FISTIGIDF |
Sequence similarities
Belongs to the small GTPase superfamily. Rab family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
P61006-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length207
- Mass (Da)23,668
- Last updated2004-04-26 v1
- ChecksumAA52DBF54A2CD056
P61006-2
- Name2
- Differences from canonical
- 161-205: AFFTLARDIKAKMDKKLEGNSPQGSNQGVKITPDQQKRSSFFRCV → RYQSKNGQKIGRQQPPGEQPGSQNHTGPAEEEQLFPMCSSVRNTA
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056399 | 161-205 | in isoform 2 | |||
Sequence: AFFTLARDIKAKMDKKLEGNSPQGSNQGVKITPDQQKRSSFFRCV → RYQSKNGQKIGRQQPPGEQPGSQNHTGPAEEEQLFPMCSSVRNTA | ||||||
Sequence conflict | 177-183 | in Ref. 2; AAB19681 | ||||
Sequence: LEGNSPQ → WKATAP |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X56741 EMBL· GenBank· DDBJ | CAA40065.1 EMBL· GenBank· DDBJ | mRNA | ||
S53268 EMBL· GenBank· DDBJ | AAB19681.1 EMBL· GenBank· DDBJ | mRNA | ||
AF498943 EMBL· GenBank· DDBJ | AAM21091.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007184 EMBL· GenBank· DDBJ | AAP35848.1 EMBL· GenBank· DDBJ | mRNA | ||
AK293676 EMBL· GenBank· DDBJ | BAG57118.1 EMBL· GenBank· DDBJ | mRNA | ||
CR536583 EMBL· GenBank· DDBJ | CAG38820.1 EMBL· GenBank· DDBJ | mRNA | ||
AC008894 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CR542274 EMBL· GenBank· DDBJ | CAG47070.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471106 EMBL· GenBank· DDBJ | EAW84526.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002977 EMBL· GenBank· DDBJ | AAH02977.1 EMBL· GenBank· DDBJ | mRNA |