ARL8B is a conserved Arf-like small GTPase that associates with lysosomal and endolysosomal membranes in its active GTP-bound state. Through effector interactions with BORC, PLEKHM2/SKIP-kinesin, PLEKHM1/HOPS, VPS41, and RUFY proteins, it coordinates lysosome positioning, endolysosomal cargo delivery, and lysosome fusion or exocytosis in contexts including autophagic cargo degradation, phagosome maturation, antigen presentation, cytolytic granule polarization, plasma membrane repair, and beta-coronavirus egress.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005765 lysosomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0008089 anterograde axonal transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: anterograde axonal transport is supported mainly by conserved neuronal ARL8 biology and automated/by-similarity transfer. Reason: The annotation is plausible for neuronal endolysosomal or presynaptic-vesicle trafficking, but human ARL8B direct evidence in this review is stronger for general lysosome positioning and cargo delivery. Supporting Evidence: file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GTPase activity annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | MARK AS OVER ANNOTATED | Summary: ARL8B is a monomeric Arf-like small GTPase, so the heterotrimeric G protein activity term is not the best molecular-function annotation. Reason: The cited evidence supports small-GTPase biology captured by GO:0003924 GTPase activity, which is already present and accepted; GO:0003925 is over-broad or semantically imprecise for ARL8B. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GTP binding annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: spindle comes from the early GIE/ARL8B microtubule and mitosis study. Reason: This appears experimentally supported but peripheral to the dominant lysosomal small-GTPase role established by later work. Supporting Evidence: PMID:15331635 Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Cytosol is a generic automated localization and is less informative than ARL8B lysosomal membrane/endolysosomal localization. Reason: ARL8B cycles between soluble and membrane-associated states, but the curated functional signal is the active lysosomal/endolysosomal membrane pool; generic cytosol is over-annotated for this review. Supporting Evidence: file:human/ARL8B/ARL8B-uniprot.txt Small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes |
| GO:0015031 protein transport | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: The broad protein transport IEA captures the general trafficking theme but is too nonspecific for ARL8B. Reason: ARL8B evidence supports lysosome positioning and specific late-endosome/phagosome/autophagosome-to-lysosome traffic rather than generic protein transport; the more specific lysosome localization and late endosome-to-lysosome transport annotations are already present and accepted. Supporting Evidence: PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:28325809 Arl8b, along with its effectors, orchestrates lysosomal transport and fusion. |
| GO:0030424 axon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: axon is supported mainly by conserved neuronal ARL8 biology and automated/by-similarity transfer. Reason: The annotation is plausible for neuronal endolysosomal or presynaptic-vesicle trafficking, but human ARL8B direct evidence in this review is stronger for general lysosome positioning and cargo delivery. Supporting Evidence: file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: early endosome membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:36282215 Arl8b determines RUFY1 endosomal localization through regulating its interaction with Rab14. PMID:36282215 RUFY1 depletion led to a delay in CI-M6PR retrieval from endosomes to the TGN, resulting in impaired delivery of newly synthesized hydrolases to lysosomes. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: late endosome membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0045202 synapse | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: synapse is supported mainly by conserved neuronal ARL8 biology and automated/by-similarity transfer. Reason: The annotation is plausible for neuronal endolysosomal or presynaptic-vesicle trafficking, but human ARL8B direct evidence in this review is stronger for general lysosome positioning and cargo delivery. Supporting Evidence: file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0051233 spindle midzone | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: spindle midzone comes from the early GIE/ARL8B microtubule and mitosis study. Reason: This appears experimentally supported but peripheral to the dominant lysosomal small-GTPase role established by later work. Supporting Evidence: PMID:15331635 Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. |
| GO:0101004 cytolytic granule membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: cytolytic granule membrane is supported for NK cells, where ARL8B localizes to lytic granules and promotes polarization toward the immune synapse. Reason: This is a well-supported lysosome-related organelle function in a specialized immune-cell context, not the general core function of ARL8B. Supporting Evidence: PMID:24088571 Arl8b colocalizes with perforin, granzyme B, and LAMP-1, markers of lytic granules. |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: axon cytoplasm is supported mainly by conserved neuronal ARL8 biology and automated/by-similarity transfer. Reason: The annotation is plausible for neuronal endolysosomal or presynaptic-vesicle trafficking, but human ARL8B direct evidence in this review is stronger for general lysosome positioning and cargo delivery. Supporting Evidence: file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0005515 protein binding | IPI PMID:28325809 The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traff... | MARK AS OVER ANNOTATED | Summary: PLEKHM1 binding is real and biologically important for HOPS-linked lysosomal fusion, but generic protein binding is not an informative GO molecular function for ARL8B. Reason: ARL8B functions as a regulated small GTPase that recruits specific effectors to endolysosomal membranes; a generic protein binding annotation obscures that biology and is therefore over-annotated. Supporting Evidence: PMID:28325809 Arl8b mediates recruitment of HOPS complex to PLEKHM1-positive vesicle contact sites. PMID:28325809 Arl8b binding is crucial for PLEKHM1 to promote lysosomal degradation of endocytic and autophagic cargo. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: The HuRI protein interaction is a broad interactome finding and does not define a specific ARL8B molecular function beyond generic binding. Reason: ARL8B functions as a regulated small GTPase that recruits specific effectors to endolysosomal membranes; a generic protein binding annotation obscures that biology and is therefore over-annotated. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0002505 antigen processing and presentation of polysaccharide antigen via MHC class II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: antigen processing and presentation of polysaccharide antigen via MHC class II is supported by immune-cell lysosomal trafficking studies but is context-specific. Reason: ARL8B controls delivery of antigen-containing cargo to lysosomal compartments; antigen presentation is a downstream immune-cell outcome rather than the core molecular role. Supporting Evidence: PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. |
| GO:0005764 lysosome | IEA GO_REF:0000107 | ACCEPT | Summary: lysosome is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0008089 anterograde axonal transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: anterograde axonal transport is supported mainly by conserved neuronal ARL8 biology and automated/by-similarity transfer. Reason: The annotation is plausible for neuronal endolysosomal or presynaptic-vesicle trafficking, but human ARL8B direct evidence in this review is stronger for general lysosome positioning and cargo delivery. Supporting Evidence: file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0046754 viral exocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ARL8B-dependent lysosomal exocytosis is exploited by beta-coronaviruses for viral egress. Reason: The process annotation is supported for infection biology, but it represents pathogen exploitation of ARL8B-dependent lysosomal exocytosis rather than a core host function. Supporting Evidence: PMID:33157038 these viruses use a lysosomal, Arl8b-dependent exocytic pathway for release into the extracellular environment. |
| GO:1902774 late endosome to lysosome transport | IEA GO_REF:0000107 | ACCEPT | Summary: late endosome to lysosome transport is supported by ARL8B loss-of-function cargo-delivery assays and HOPS recruitment evidence. Reason: This captures ARL8B-dependent delivery of endocytic cargo to lysosomes, a core part of its endolysosomal trafficking role. Supporting Evidence: PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. PMID:21802320 Arl8b was found to bind and recruit the VPS41 subunit of the HOPS (homotypic fusion and protein sorting) complex to lysosomes. PMID:28325809 Arl8b, along with its effectors, orchestrates lysosomal transport and fusion. |
| GO:0005765 lysosomal membrane | EXP PMID:16650381 The Arf-family protein, Arl8b, is involved in the spatial di... | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0005765 lysosomal membrane | EXP PMID:21802320 Lysosomal trafficking, antigen presentation, and microbial k... | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0005765 lysosomal membrane | EXP PMID:28325809 The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traff... | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0005765 lysosomal membrane | EXP PMID:29592961 Lysosome-Mediated Plasma Membrane Repair Is Dependent on the... | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0031902 late endosome membrane | EXP PMID:16537643 An N-terminally acetylated Arf-like GTPase is localised to l... | ACCEPT | Summary: late endosome membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0045202 synapse | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: synapse is supported mainly by conserved neuronal ARL8 biology and automated/by-similarity transfer. Reason: The annotation is plausible for neuronal endolysosomal or presynaptic-vesicle trafficking, but human ARL8B direct evidence in this review is stronger for general lysosome positioning and cargo delivery. Supporting Evidence: file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0005515 protein binding | IPI PMID:35314674 RUFY3 and RUFY4 are ARL8 effectors that promote coupling of ... | MARK AS OVER ANNOTATED | Summary: RUFY3/RUFY4 interactions support ARL8B-dependent endolysosome motor coupling, but generic protein binding does not capture the specific small-GTPase effector relationship. Reason: ARL8B functions as a regulated small GTPase that recruits specific effectors to endolysosomal membranes; a generic protein binding annotation obscures that biology and is therefore over-annotated. Supporting Evidence: PMID:35314674 RUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin PMID:35314674 ARL8 can thus regulate both anterograde and retrograde endolysosome transport through interactions with kinesin and dynein-dynactin motors |
| GO:0003924 GTPase activity | IDA PMID:16537643 An N-terminally acetylated Arf-like GTPase is localised to l... | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GTPase activity annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0031901 early endosome membrane | IDA PMID:36282215 RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retri... | ACCEPT | Summary: early endosome membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:36282215 Arl8b determines RUFY1 endosomal localization through regulating its interaction with Rab14. PMID:36282215 RUFY1 depletion led to a delay in CI-M6PR retrieval from endosomes to the TGN, resulting in impaired delivery of newly synthesized hydrolases to lysosomes. |
| GO:0034498 early endosome to Golgi transport | IDA PMID:36282215 RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retri... | KEEP AS NON CORE | Summary: early endosome to Golgi transport is supported by RUFY1-dependent CI-M6PR retrieval work. Reason: This is a specific cargo-sorting branch of ARL8B biology and supports lysosomal hydrolase delivery, but it is secondary to the major lysosome positioning/fusion role. Supporting Evidence: PMID:36282215 RUFY1 depletion led to a delay in CI-M6PR retrieval from endosomes to the TGN, resulting in impaired delivery of newly synthesized hydrolases to lysosomes. |
| GO:1902946 protein localization to early endosome | IDA PMID:36282215 RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retri... | KEEP AS NON CORE | Summary: protein localization to early endosome is supported by RUFY1-dependent CI-M6PR retrieval work. Reason: This is a specific cargo-sorting branch of ARL8B biology and supports lysosomal hydrolase delivery, but it is secondary to the major lysosome positioning/fusion role. Supporting Evidence: PMID:36282215 Arl8b determines RUFY1 endosomal localization through regulating its interaction with Rab14. |
| GO:0046754 viral exocytosis | IMP PMID:33157038 Ξ²-Coronaviruses Use Lysosomes for Egress Instead of the Bios... | KEEP AS NON CORE | Summary: ARL8B-dependent lysosomal exocytosis is exploited by beta-coronaviruses for viral egress. Reason: The process annotation is supported for infection biology, but it represents pathogen exploitation of ARL8B-dependent lysosomal exocytosis rather than a core host function. Supporting Evidence: PMID:33157038 these viruses use a lysosomal, Arl8b-dependent exocytic pathway for release into the extracellular environment. |
| GO:0003925 G protein activity | IDA PMID:16537643 An N-terminally acetylated Arf-like GTPase is localised to l... | MARK AS OVER ANNOTATED | Summary: ARL8B is a monomeric Arf-like small GTPase, so the heterotrimeric G protein activity term is not the best molecular-function annotation. Reason: The cited evidence supports small-GTPase biology captured by GO:0003924 GTPase activity, which is already present and accepted; GO:0003925 is over-broad or semantically imprecise for ARL8B. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0005765 lysosomal membrane | IDA PMID:27808481 RNF167 targets Arl8B for degradation to regulate lysosome po... | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0032418 lysosome localization | IDA PMID:16537643 An N-terminally acetylated Arf-like GTPase is localised to l... | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0032418 lysosome localization | IDA PMID:27808481 RNF167 targets Arl8B for degradation to regulate lysosome po... | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0042267 natural killer cell mediated cytotoxicity | IMP PMID:24088571 Arf-like GTPase Arl8b regulates lytic granule polarization a... | KEEP AS NON CORE | Summary: natural killer cell mediated cytotoxicity is supported for NK cells, where ARL8B localizes to lytic granules and promotes polarization toward the immune synapse. Reason: This is a well-supported lysosome-related organelle function in a specialized immune-cell context, not the general core function of ARL8B. Supporting Evidence: PMID:24088571 Arl8b drives the polarization of lytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse |
| GO:0101004 cytolytic granule membrane | IDA PMID:24088571 Arf-like GTPase Arl8b regulates lytic granule polarization a... | KEEP AS NON CORE | Summary: cytolytic granule membrane is supported for NK cells, where ARL8B localizes to lytic granules and promotes polarization toward the immune synapse. Reason: This is a well-supported lysosome-related organelle function in a specialized immune-cell context, not the general core function of ARL8B. Supporting Evidence: PMID:24088571 Arl8b colocalizes with perforin, granzyme B, and LAMP-1, markers of lytic granules. |
| GO:0005515 protein binding | IPI PMID:22172677 Arl8 and SKIP act together to link lysosomes to kinesin-1. | MARK AS OVER ANNOTATED | Summary: PLEKHM2/SKIP binding is central to ARL8B-dependent kinesin recruitment, but protein binding is too generic relative to the lysosome localization process annotation. Reason: ARL8B functions as a regulated small GTPase that recruits specific effectors to endolysosomal membranes; a generic protein binding annotation obscures that biology and is therefore over-annotated. Supporting Evidence: PMID:22172677 Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. |
| GO:0005765 lysosomal membrane | IDA PMID:22172677 Arl8 and SKIP act together to link lysosomes to kinesin-1. | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0032418 lysosome localization | IMP PMID:22172677 Arl8 and SKIP act together to link lysosomes to kinesin-1. | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0005764 lysosome | IDA PMID:28325809 The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traff... | ACCEPT | Summary: lysosome is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0032418 lysosome localization | IDA PMID:28325809 The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traff... | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0061909 autophagosome-lysosome fusion | IMP PMID:28325809 The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traff... | ACCEPT | Summary: ARL8B contributes to autophagosome-lysosome fusion through PLEKHM1/HOPS-linked lysosomal contact sites. Reason: The evidence is stronger for lysosomal tethering/fusion with autophagic cargo than for a separate autophagosome-positioning role. Supporting Evidence: PMID:28325809 Arl8b mediates recruitment of HOPS complex to PLEKHM1-positive vesicle contact sites. PMID:28325809 Arl8b binding is crucial for PLEKHM1 to promote lysosomal degradation of endocytic and autophagic cargo. |
| GO:1902774 late endosome to lysosome transport | IMP PMID:28325809 The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traff... | ACCEPT | Summary: late endosome to lysosome transport is supported by ARL8B loss-of-function cargo-delivery assays and HOPS recruitment evidence. Reason: This captures ARL8B-dependent delivery of endocytic cargo to lysosomes, a core part of its endolysosomal trafficking role. Supporting Evidence: PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. PMID:21802320 Arl8b was found to bind and recruit the VPS41 subunit of the HOPS (homotypic fusion and protein sorting) complex to lysosomes. PMID:28325809 Arl8b, along with its effectors, orchestrates lysosomal transport and fusion. |
| GO:0001778 plasma membrane repair | IMP PMID:29592961 Lysosome-Mediated Plasma Membrane Repair Is Dependent on the... | KEEP AS NON CORE | Summary: plasma membrane repair is supported in membrane injury and Mycobacterium infection models. Reason: ARL8B-dependent lysosome exocytosis is real but context-dependent, so it should be retained as non-core rather than used to define the main gene function. Supporting Evidence: PMID:29592961 Arl8b is required for the process of plasma membrane repair in controlling the Ca2+-dependent exocytosis of lysosomes PMID:29592961 Arl8b-depleted MDMs become necrotic after infection with H37Ra instead of apoptotic. |
| GO:0005764 lysosome | IDA PMID:29592961 Lysosome-Mediated Plasma Membrane Repair Is Dependent on the... | ACCEPT | Summary: lysosome is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0032418 lysosome localization | IMP PMID:29592961 Lysosome-Mediated Plasma Membrane Repair Is Dependent on the... | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:1990927 calcium ion regulated lysosome exocytosis | IMP PMID:29592961 Lysosome-Mediated Plasma Membrane Repair Is Dependent on the... | KEEP AS NON CORE | Summary: calcium ion regulated lysosome exocytosis is supported in membrane injury and Mycobacterium infection models. Reason: ARL8B-dependent lysosome exocytosis is real but context-dependent, so it should be retained as non-core rather than used to define the main gene function. Supporting Evidence: PMID:29592961 Arl8b is required for the process of plasma membrane repair in controlling the Ca2+-dependent exocytosis of lysosomes |
| GO:0002747 antigen processing and presentation following phagocytosis | IMP PMID:21802320 Lysosomal trafficking, antigen presentation, and microbial k... | KEEP AS NON CORE | Summary: antigen processing and presentation following phagocytosis is supported by immune-cell lysosomal trafficking studies but is context-specific. Reason: ARL8B controls delivery of antigen-containing cargo to lysosomal compartments; antigen presentation is a downstream immune-cell outcome rather than the core molecular role. Supporting Evidence: PMID:21802320 phagosome to lysosome delivery and fusion were delayed by Arl8b silencing resulting in a defect in microbial killing. |
| GO:0005515 protein binding | IPI PMID:21802320 Lysosomal trafficking, antigen presentation, and microbial k... | MARK AS OVER ANNOTATED | Summary: VPS41/HOPS binding supports ARL8B-mediated lysosomal cargo delivery, but protein binding is too broad and should not be treated as a useful molecular function term. Reason: ARL8B functions as a regulated small GTPase that recruits specific effectors to endolysosomal membranes; a generic protein binding annotation obscures that biology and is therefore over-annotated. Supporting Evidence: PMID:21802320 Arl8b was found to bind and recruit the VPS41 subunit of the HOPS (homotypic fusion and protein sorting) complex to lysosomes. PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. |
| GO:0005525 GTP binding | IMP PMID:16650381 The Arf-family protein, Arl8b, is involved in the spatial di... | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GTP binding annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0005764 lysosome | IMP PMID:16650381 The Arf-family protein, Arl8b, is involved in the spatial di... | ACCEPT | Summary: lysosome is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0005764 lysosome | IDA PMID:21802320 Lysosomal trafficking, antigen presentation, and microbial k... | ACCEPT | Summary: lysosome is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0019003 GDP binding | IMP PMID:16650381 The Arf-family protein, Arl8b, is involved in the spatial di... | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GDP binding annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. |
| GO:0032418 lysosome localization | IMP PMID:16650381 The Arf-family protein, Arl8b, is involved in the spatial di... | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0032418 lysosome localization | IMP PMID:21802320 Lysosomal trafficking, antigen presentation, and microbial k... | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0090117 endosome to lysosome transport of low-density lipoprotein particle | IMP PMID:21802320 Lysosomal trafficking, antigen presentation, and microbial k... | ACCEPT | Summary: endosome to lysosome transport of low-density lipoprotein particle is supported by ARL8B loss-of-function cargo-delivery assays and HOPS recruitment evidence. Reason: This captures ARL8B-dependent delivery of endocytic cargo to lysosomes, a core part of its endolysosomal trafficking role. Supporting Evidence: PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. |
| GO:0090385 phagosome-lysosome fusion | IMP PMID:21802320 Lysosomal trafficking, antigen presentation, and microbial k... | KEEP AS NON CORE | Summary: Phagosome-lysosome fusion is directly supported in host-defense assays, but it is a context-specific branch of ARL8B lysosomal trafficking. Reason: The annotation is biologically sound, but phagocytic killing is not the broad core role of ARL8B across cell types. Supporting Evidence: PMID:21802320 phagosome to lysosome delivery and fusion were delayed by Arl8b silencing resulting in a defect in microbial killing. |
| GO:0002505 antigen processing and presentation of polysaccharide antigen via MHC class II | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: antigen processing and presentation of polysaccharide antigen via MHC class II is supported by immune-cell lysosomal trafficking studies but is context-specific. Reason: ARL8B controls delivery of antigen-containing cargo to lysosomal compartments; antigen presentation is a downstream immune-cell outcome rather than the core molecular role. Supporting Evidence: PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. |
| GO:1902774 late endosome to lysosome transport | ISS GO_REF:0000024 | ACCEPT | Summary: late endosome to lysosome transport is supported by ARL8B loss-of-function cargo-delivery assays and HOPS recruitment evidence. Reason: This captures ARL8B-dependent delivery of endocytic cargo to lysosomes, a core part of its endolysosomal trafficking role. Supporting Evidence: PMID:21802320 Arl8b silencing resulted in a delay in delivery of fluid phase dextran, receptor-internalized low-density lipoprotein (LDL), and CD1 cargo to lysosomes. PMID:21802320 Arl8b was found to bind and recruit the VPS41 subunit of the HOPS (homotypic fusion and protein sorting) complex to lysosomes. PMID:28325809 Arl8b, along with its effectors, orchestrates lysosomal transport and fusion. |
| GO:0005515 protein binding | IPI PMID:25898167 BORC, a multisubunit complex that regulates lysosome positio... | MARK AS OVER ANNOTATED | Summary: BORCS5/BORC interaction supports ARL8B lysosomal recruitment and positioning, but generic protein binding is not curator-informative. Reason: ARL8B functions as a regulated small GTPase that recruits specific effectors to endolysosomal membranes; a generic protein binding annotation obscures that biology and is therefore over-annotated. Supporting Evidence: PMID:25898167 BORC functions to recruit Arl8 to lysosomes, thereby initiating a chain of interactions that promotes microtubule-guided transport of lysosomes toward the cell periphery. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0005765 lysosomal membrane | IDA PMID:25898167 BORC, a multisubunit complex that regulates lysosome positio... | ACCEPT | Summary: lysosomal membrane is a core localization for ARL8B based on direct localization studies and UniProt synthesis. Reason: ARL8B acts from lysosomal/endolysosomal membranes to recruit effectors controlling motility, tethering, fusion, and cargo sorting. Supporting Evidence: PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0032418 lysosome localization | IMP PMID:25898167 BORC, a multisubunit complex that regulates lysosome positio... | ACCEPT | Summary: Lysosome localization is the best-supported core biological process for ARL8B. Reason: Multiple independent studies show ARL8B-dependent peripheral/anterograde lysosome positioning through BORC, SKIP/kinesin, and regulation by RNF167. Supporting Evidence: PMID:16537643 Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. PMID:22172677 Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. PMID:25898167 BORC acts at an early stage, recruiting Arl8b to the lysosomal membrane and therefore enabling coupling to the SKIP-Kinesin-1 complex |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Generic membrane localization from high-throughput NK-cell membrane proteomics is much less informative than lysosomal membrane localization. Reason: The more specific lysosomal/cytolytic-granule membrane annotations should carry this biology; generic membrane is over-annotated. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: Extracellular exosome comes from broad high-throughput proteomics and is not a defining ARL8B localization or function. Reason: This does not fit the strong mechanistic consensus that ARL8B functions on endolysosomal/lysosomal membranes. Supporting Evidence: PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes. file:human/ARL8B/ARL8B-uniprot.txt Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility |
| GO:0003924 GTPase activity | NAS PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GTPase activity annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0005525 GTP binding | IDA PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GTP binding annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16537643 Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in |
| GO:0005737 cytoplasm | IDA PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | KEEP AS NON CORE | Summary: cytoplasm comes from the early GIE/ARL8B microtubule and mitosis study. Reason: This appears experimentally supported but peripheral to the dominant lysosomal small-GTPase role established by later work. Supporting Evidence: PMID:15331635 Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. |
| GO:0007059 chromosome segregation | IMP PMID:14871887 Drosophila Topors is a RING finger-containing protein that f... | KEEP AS NON CORE | Summary: The term is supported by the ARL8/GIE chromosome-segregation study, but the seeded GOA original PMID points to an unrelated Drosophila Topors paper. Reason: Keep as non-core because PMID:15331635 supports a mitotic phenotype for GIE/ARL8 proteins. The original_reference_id is retained as fetched GOA provenance, while the corrected supporting ARL8B reference is recorded in additional_reference_ids and the upstream source should be checked. Supporting Evidence: PMID:14871887 Drosophila Topors is a RING finger-containing protein that functions as a ubiquitin-protein isopeptide ligase for the hairy basic helix-loop-helix repressor protein. PMID:15331635 Expression of dominant-negative Gie mutants in mammalian cells or knockdown of Gie transcripts using RNA interference in Drosophila S2 cells induced abnormal morphology in the chromosome segregation. |
| GO:0019003 GDP binding | IDA PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | ACCEPT | Summary: ARL8B is a small Arf-like GTPase; the GDP binding annotation is consistent with direct biochemical and sequence evidence. Reason: GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes. Supporting Evidence: PMID:15331635 Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases PMID:16650381 GTP-restricted mutant Arl8b localizes to lysosomes and causes their redistribution to the periphery of the cell and into membrane projections. |
| GO:0030496 midbody | IDA PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | KEEP AS NON CORE | Summary: midbody comes from the early GIE/ARL8B microtubule and mitosis study. Reason: This appears experimentally supported but peripheral to the dominant lysosomal small-GTPase role established by later work. Supporting Evidence: PMID:15331635 Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. |
| GO:0043014 alpha-tubulin binding | IDA PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | KEEP AS NON CORE | Summary: alpha-tubulin binding comes from the early GIE/ARL8B microtubule and mitosis study. Reason: This appears experimentally supported but peripheral to the dominant lysosomal small-GTPase role established by later work. Supporting Evidence: PMID:15331635 Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. |
| GO:0048487 beta-tubulin binding | IDA PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | KEEP AS NON CORE | Summary: beta-tubulin binding comes from the early GIE/ARL8B microtubule and mitosis study. Reason: This appears experimentally supported but peripheral to the dominant lysosomal small-GTPase role established by later work. Supporting Evidence: PMID:15331635 Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. |
| GO:0051233 spindle midzone | IDA PMID:15331635 Novel small GTPase subfamily capable of associating with tub... | KEEP AS NON CORE | Summary: spindle midzone comes from the early GIE/ARL8B microtubule and mitosis study. Reason: This appears experimentally supported but peripheral to the dominant lysosomal small-GTPase role established by later work. Supporting Evidence: PMID:15331635 Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. |
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Download this section (compressed HTML)Q: Should ARL8B be annotated directly to GO:0061906 autophagosome localization from the PN HOPS-BORC bridging projection, or is the current direct evidence better captured by lysosome localization and autophagosome-lysosome fusion?
Q: Can the upstream reference for the GO:0007059 chromosome segregation annotation be corrected from PMID:14871887 to the ARL8B/GIE study PMID:15331635?
Q: Which ARL8B effector branch should be considered core for general gene-product curation versus cell-type-specific extensions such as NK-cell granule polarization, Mtb membrane repair, or beta-coronavirus egress?
Q: Should ARL8B be annotated to retrograde lysosome transport given that it now has two distinct retrograde effector branches (DENND6A/Rab34/RILP/dynein and RUFY3/RUFY4/dynein-dynactin), and how should these be distinguished from the better-established anterograde SKIP/kinesin role?
Experiment: Separate ARL8B lysosome-positioning effects from autophagosome-positioning effects by live imaging of autophagosomes and lysosomes after ARL8B depletion or effector-selective rescue.
Hypothesis: The PN autophagosome-localization signal is mainly an indirect consequence of ARL8B-dependent lysosome positioning and HOPS-mediated fusion rather than direct autophagosome positioning.
Experiment: Use effector-binding mutants of ARL8B to compare PLEKHM2/SKIP, PLEKHM1/HOPS, VPS41, RUFY1, RUFY3/4, and DENND6A outputs in the same cellular background.
Hypothesis: Distinct ARL8B effector interfaces partition lysosome positioning, cargo delivery, and lysosome exocytosis functions.
Experiment: Test whether ARL8B-dependent retrograde lysosome transport requires the DENND6A/Rab34/RILP/dynein cascade by measuring nutrient-dependent juxtanuclear lysosome repositioning and autophagic flux after depletion of DENND6A, Rab34, or RILP versus RUFY3/4.
Hypothesis: ARL8B initiates retrograde lysosome transport through at least two parallel dynein-recruiting branches (DENND6A/Rab34/RILP and RUFY3/4), and these jointly regulate nutrient-responsive lysosome positioning and autophagy.
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