RAB8A
entrez
4218
canonical
uniprot
P61006
canonical
ensembl
ENSG00000167461
resolver
ensp
ENSP00000300935
resolver
genesymbol
RAB8A
resolver
genesymbol_syn
MEL
resolver
genesymbol_syn
RAB8
resolver
hgnc
HGNC:7007
resolver
uniprot
B4DEK7
resolver
uniprot
P24407
resolver
uniprot
Q6FHV5
resolver
uniprot_entry
RAB8A_HUMAN
resolver
uniprot_sec
B4DEK7
resolver
uniprot_sec
P24407
resolver
uniprot_sec
Q6FHV5
resolver
activity_regulation
ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors (GEFs) such as RAB3IP/Rabin8 and RPGR which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors (GDIs) which inhibit the dissociation of the nucleotide from the GTPase (PubMed:12221131, PubMed:20631154). Activated in response to insulin (By similarity). {ECO:0000250|UniProtKB:P35280, ECO:0000269|PubMed:12221131, ECO:0000305}.
uniprot
proteins
amino_acid_sequence
MAKTYDYLFKLLLIGDSGVGKTCVLFRFSEDAFNSTFISTIGIDFKIRTIELDGKRIKLQIWDTAGQERFRTITTAYYRGAMGIMLVYDITNEKSFDNIRNWIRNIEEHASADVEKMILGNKCDVNDKRQVSKERGEKLALDYGIKFMETSAKANINVENAFFTLARDIKAKMDKKLEGNSPQGSNQGVKITPDQQKRSSFFRCVLL
uniprot
proteins
ec_number
3.6.5.2
uniprot
proteins
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. RAB8A 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, PubMed:20631154). 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). {ECO:0000250|UniProtKB:P35280, ECO:0000250|UniProtKB:P55258, ECO:0000269|PubMed:20631154, ECO:0000269|PubMed:20890297, ECO:0000269|PubMed:21282656, ECO:0000269|PubMed:21844891, ECO:0000269|PubMed:26209634, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:32344433}.
uniprot
proteins
mass_dalton
23668
uniprot
proteins
mutagenesis
MUTAGEN 22; /note="T->N: Loss of interaction with MICAL1. Loss of GRAF1/ARHGAP26 and GRAF2/ARHGAP10 tubular localization. Loss of E-cadherin and MMP14 export. Stimulates interaction with RPGR."; /evidence="ECO:0000269|PubMed:19864458, ECO:0000269|PubMed:20631154"; MUTAGEN 67; /note="Q->L: Probable constitutively active mutant locked in the active GTP-bound form. Stimulates interaction with MICALL1. Increased WDR44-positive tubulation. No change in interaction with RPGR, compared to wild-type."; /evidence="ECO:0000269|PubMed:19864458, ECO:0000269|PubMed:20631154, ECO:0000269|PubMed:32344433"; MUTAGEN 72; /note="T->A: 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."; /evidence="ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148"; MUTAGEN 72; /note="T->D: Phosphomimetic mutant. Suppresses interaction with GDI1."; /evidence="ECO:0000269|PubMed:30209220"; MUTAGEN 72; /note="T->E: 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."; /evidence="ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:30209220}.
uniprot
proteins
protein_family
Rab family
uniprot
proteins
protein_family
Small GTPase superfamily
uniprot
proteins
pubmed
12221131
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15837803
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18329369
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
1886711
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19864458
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20631154
uniprot
proteins
pubmed
20643351
uniprot
proteins
pubmed
20890297
uniprot
proteins
pubmed
21255211
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21282656
uniprot
proteins
pubmed
21378754
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21844891
uniprot
proteins
pubmed
22159412
uniprot
proteins
pubmed
22543976
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25860027
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26209634
uniprot
proteins
pubmed
26824392
uniprot
proteins
pubmed
27103069
uniprot
proteins
pubmed
27552051
uniprot
proteins
pubmed
29125462
uniprot
proteins
pubmed
30209220
uniprot
proteins
pubmed
30398148
uniprot
proteins
pubmed
32344433
uniprot
proteins
pubmed
8294494
uniprot
proteins
pubmed
8375503
uniprot
proteins
sequence_length
207
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26824392, ECO:0000305|PubMed:12221131}; Lipid-anchor {ECO:0000305|PubMed:12221131}; Cytoplasmic side {ECO:0000305|PubMed:12221131}. Golgi apparatus {ECO:0000269|PubMed:15837803}. Endosome membrane {ECO:0000269|PubMed:32344433}. Recycling endosome membrane {ECO:0000269|PubMed:19864458}. Cell projection, cilium {ECO:0000269|PubMed:21844891, ECO:0000269|PubMed:29125462}. Cytoplasmic vesicle, phagosome {ECO:0000269|PubMed:21255211}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:Q92930}; Lipid-anchor {ECO:0000250|UniProtKB:Q92930}; Cytoplasmic side {ECO:0000250|UniProtKB:Q92930}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000250|UniProtKB:P55258}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:30398148}. Midbody {ECO:0000269|PubMed:22159412}. Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000269|PubMed:30398148}. Cytoplasm {ECO:0000269|PubMed:26824392}. Lysosome {ECO:0000269|PubMed:30209220}. 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). Colocalizes with RPGR at the primary cilia of epithelial cells (By similarity). {ECO:0000250|UniProtKB:P61007, ECO:0000269|PubMed:12221131, ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:19864458, ECO:0000269|PubMed:20890297, ECO:0000269|PubMed:21255211, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:32344433}.
uniprot
proteins