Protein: Ras-related protein Rab-8A (EC 3.6.5.2) (P35280)
Organism: Rattus norvegicus (Rat)
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 (By similarity). Regulates the compacted morphology of the Golgi (By similarity). Together with MYO5B and RAB11A participates in epithelial cell polarization (By similarity). Also involved in membrane trafficking to the cilium and ciliogenesis (By similarity). 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. Involved in autophagy (By similarity).
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P55258}; Lipid-anchor {ECO:0000250|UniProtKB:P55258}; Cytoplasmic side {ECO:0000250|UniProtKB:P55258}. Golgi apparatus {ECO:0000250|UniProtKB:P61006}. Endosome membrane {ECO:0000250|UniProtKB:P61006}. Recycling endosome membrane {ECO:0000250|UniProtKB:P61006}. Cell projection, cilium {ECO:0000250|UniProtKB:P61006}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:P61006, 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:0000250|UniProtKB:P55258}. Midbody {ECO:0000250|UniProtKB:P61006}. Cytoplasm {ECO:0000250|UniProtKB:P61006}. Lysosome {ECO:0000250|UniProtKB:P61006}. Note=Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane. In the GDP-bound form, present in the perinuclear region. Shows a polarized distribution to distal regions of cell protrusions in the GTP-bound form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and RAB11A in apical membrane initiation sites (AMIS) during the generation of apical surface and lumenogenesis. Localizes to tubular recycling endosome. Recruited to phagosomes containing S.aureus or Mycobacterium (By similarity). Non-phosphorylated RAB8A predominantly localizes to the cytoplasm whereas phosphorylated RAB8A localizes to the membrane (By similarity). Localizes to enlarged lysosomes through LRRK2 phosphorylation (By similarity). Colocalizes with RPGR at the primary cilia of epithelial cells (By similarity). {ECO:0000250|UniProtKB:P61006, ECO:0000250|UniProtKB:P61007}.
Sequence: MAKTYDYLFKLLLIGDSGVGKTCVLFRFSEDAFNSTFISTIGIDFKIRTIELDGKRIKLQIWDTAGQERFRTITTAYYRGAMGIMLVYDITNEKSFDNIRNWIRNIEEHASADVEKMILGNKCDVNDKRQVSKERGEKLALDYGIKFMETSAKANINVENAFFTLARDIKAKMDKKLEGNSPQGSSHGVKITVEQQKRTSFFRCSLL
InterPro domains: - IPR001806: Small GTPase (family) [1-207]
- IPR005225: Small GTP-binding domain (domain) [7-162]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [1-204]
- IPR050305: Small GTPase superfamily, Rab (family) [2-192]
Interaction partners: - Rab-3A-interacting protein
- RILP-like protein 2
- Unconventional myosin-Vb
- SMCR8-C9orf72 complex subunit
- MICAL-like protein 2
- Ras-related protein Rab-8B
- WD repeat-containing protein 41
- TBC1 domain family member 1
- Solute carrier family 2, facilitated glucose transporter member 4
- Optineurin
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019904 (protein domain specific binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0065008 (regulation of biological quality), GO:0051641 (cellular localization), GO:0031503 (protein-containing complex localization), GO:0032879 (regulation of localization), GO:0050794 (regulation of cellular process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0140352 (export from cell), GO:0033036 (macromolecule localization), GO:1903530 (regulation of secretion by cell), GO:0051049 (regulation of transport), GO:0046907 (intracellular transport), GO:0060341 (regulation of cellular localization), GO:0006810 (transport), GO:0070727 (cellular macromolecule localization), GO:0051649 (establishment of localization in cell), GO:0032940 (secretion by cell), GO:0016043 (cellular component organization), GO:0060627 (regulation of vesicle-mediated transport), GO:0099072 (regulation of postsynaptic membrane neurotransmitter receptor levels), GO:0051668 (localization within membrane), GO:0045184 (establishment of protein localization), GO:0097120 (receptor localization to synapse), GO:0098969 (neurotransmitter receptor transport to postsynaptic membrane), GO:0006887 (exocytosis), GO:0071705 (nitrogen compound transport), GO:0016197 (endosomal transport), GO:0098876 (vesicle-mediated transport to the plasma membrane), GO:0015031 (protein transport), GO:0070201 (regulation of establishment of protein localization), GO:0017157 (regulation of exocytosis), GO:0071702 (organic substance transport), GO:0046903 (secretion), GO:0051046 (regulation of secretion), GO:0016192 (vesicle-mediated transport), GO:0008104 (protein localization), GO:0034330 (cell junction organization), GO:0098877 (neurotransmitter receptor transport to plasma membrane), GO:0090150 (establishment of protein localization to membrane), GO:0072657 (protein localization to membrane), GO:0048169 (regulation of long-term neuronal synaptic plasticity), GO:0099638 (endosome to plasma membrane protein transport), GO:1902414 (protein localization to cell junction), GO:0099003 (vesicle-mediated transport in synapse), GO:0072659 (protein localization to plasma membrane), GO:0032456 (endocytic recycling), GO:1903539 (protein localization to postsynaptic membrane), GO:1990778 (protein localization to cell periphery), GO:0045055 (regulated exocytosis), GO:1990778 (protein localization to cell periphery), GO:1903540 (establishment of protein localization to postsynaptic membrane), GO:0061951 (establishment of protein localization to plasma membrane), GO:0035418 (protein localization to synapse), GO:0062237 (protein localization to postsynapse)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0098793 (presynapse), GO:0030054 (cell junction), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0008021 (synaptic vesicle), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0030133 (transport vesicle), GO:0043227 (membrane-bounded organelle), GO:0030658 (transport vesicle membrane), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0070382 (exocytic vesicle), GO:0030672 (synaptic vesicle membrane), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0097708 (intracellular vesicle), GO:0099501 (exocytic vesicle membrane)