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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).CATALYTIC ACTIVITY GTP + H2O = GDP + phosphate + H(+)COFACTOR 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).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, RAB3IP functions as guanine exchange factor (GEF) (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 (in GDP-bound form) with RAB3IP/Rabin8, RAB3IP functions as guanine exchange factor (GEF) towards RAB8A (PubMed:12221131). Interacts (in GDP-bound form) with RPGR, RPGR functions as GEF towards RAB8A (PubMed:20631154).INTERACTION 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).ALTERNATIVE PRODUCTS 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-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.SIMILARITY Belongs to the small GTPase superfamily. Rab family.
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