Protein: ADP-ribosylation factor-like protein 8B (EC 3.6.5.2) (ADP-ribosylation factor-like protein 10C) (Novel small G protein indispensable for equal chromosome segregation 1) (Q9NVJ2)
Organism: Homo sapiens (Human)
Function: Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of lysosomal positioning which is important for nutrient sensing, natural killer cell-mediated cytotoxicity and antigen presentation. Along with its effectors, orchestrates lysosomal transport and fusion. Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility by recruiting PLEKHM2, which in turn recruits the motor protein kinesin-1 on lysosomes. Required for lysosomal and cytolytic granule exocytosis. Critical factor involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function (By similarity). Also acts as a regulator of endosome to lysosome trafficking pathways of special significance for host defense. Regulates cargo trafficking to lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting in functional assembly of the HOPS complex on lysosomal membranes. Plays an important role in cargo delivery to lysosomes for antigen presentation and microbial killing. Directs the intersection of CD1d with lipid antigens in lysosomes, and plays a role in intersecting phagosomes with lysosomes to generate phagolysosomes that kill microbes. Involved in the process of MHC II presentation. Regulates the delivery of antigens to lysosomes and the formation of MHC II-peptide complexes through the recruitment of the HOPS complex to lysosomes allowing the fusion of late endosomes to lysosomes (By similarity). May play a role in chromosome segregation.
Subcellular location: Late endosome membrane {ECO:0000269|PubMed:16537643}. Lysosome membrane {ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:22172677, ECO:0000269|PubMed:25898167, ECO:0000269|PubMed:27808481, ECO:0000269|PubMed:28325809, ECO:0000269|PubMed:29592961}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:15331635}. Cell projection, axon {ECO:0000250|UniProtKB:Q9CQW2}. Synapse {ECO:0000250|UniProtKB:Q9CQW2}. Cytolytic granule membrane {ECO:0000269|PubMed:24088571}. Early endosome membrane {ECO:0000269|PubMed:36282215}. Note=GTP-bound form resides on lysosomal membranes, whereas GDP-bound form is likely associated with microtubular structures (PubMed:16650381). Localizes with microtubules at the spindle mid-zone during mitosis. In dendritic cells, localizes to MHC II+ compartments (By similarity). {ECO:0000250|UniProtKB:Q9CQW2, ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:16650381}.
Interaction partners:
- Pleckstrin homology domain-containing family M member 1
- Pleckstrin homology domain-containing family M member 2
- Kinesin-1 heavy chain
- Ras-related protein Rab-7a
- Lysosome-associated membrane glycoprotein 1
- Ras-related protein Rab-2A
Sequence:
MLALISRLLDWFRSLFWKEEMELTLVGLQYSGKTTFVNVIASGQFSEDMIPTVGFNMRKVTKGNVTIKIWDIGGQPRFRSMWERYCRGVNAIVYMIDAADREKIEASRNELHNLLDKPQLQGIPVLVLGNKRDLPNALDEKQLIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQHSKSRRS