Vps1302 (Vps13b, SPBC16C6.02c) is a 3131-residue member of the VPS13 family of bridge-like lipid transfer proteins, with an N-terminal chorein domain and an SHR-BD (VAB) domain. It belongs to the same PANTHER subfamily (PTHR16166:SF93) as budding yeast Vps13 and is the fission yeast counterpart of that protein, whereas the other S. pombe family member, Vps1301, falls in a separate subfamily. By homology with budding yeast Vps13, whose N-terminal region binds tens of glycerophospholipids and transfers them between membranes in vitro, Vps1302 is expected to form an extended hydrophobic groove that conducts phospholipids between apposed organelle membranes at contact sites involving endosomes, vacuoles and the mitochondrial outer membrane. None of these activities or localizations has yet been demonstrated for the fission yeast protein itself. The deletion mutant is viable; it secretes about half the wild-type level of acid phosphatase, is moderately sensitive to micafungin and FK506, and has normal vacuole fusion. The last 133 residues of Vps1302 (2999-3131) are identical to the sporulation protein Spo2, which is made from the 3' end of the same locus during meiosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005543 phospholipid binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred by sequence similarity from S. cerevisiae Vps13 (Q07878), which is in the same PANTHER subfamily (SF93). Purified budding yeast Vps13 binds glycerophospholipids and phosphoinositides directly. Not tested for the S. pombe protein. Reason: The transfer is phylogenetically grounded: Vps1302 and S. cerevisiae Vps13 are in the same subfamily, and the donor annotation rests on direct binding assays (PMID:30093493, PMID:28122955). Lipid binding is a mechanistic prerequisite of the core phospholipid transfer activity, not a separate function, so it is kept as non-core. It is not a GO ancestor of phospholipid transfer activity, so TOO_GENERAL does not apply. Supporting Evidence: PMID:30093493 Vps13Ξ± bound to glycerophospholipids but not other lipid species, with enrichment of PC relative to the glycerolipid content of cellular membranes PMID:28122955 Purified Vps13p binds to yeast membranes in an ATP-stimulated fashion and exhibits strong, specific interactions with phosphatidic acid (PA), PI(4,5)P2, and PI(4)P file:SCHPO/vps1302/vps1302-bioinformatics/RESULTS.md O42926 (vps1302) is in PTHR16166:SF93 "INTERMEMBRANE LIPID TRANSFER PROTEIN VPS13", |
| GO:0005741 mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT placement at PTN000414879, seeded by budding yeast Vps13 and human VPS13C/VPS13A. Budding yeast Vps13 is recruited to the mitochondrial outer membrane by Mcp1 and acts at vacuole-mitochondria and endosome-mitochondria contacts. No S. pombe localization data exist (the ORFeome GFP fusion gave no signal). Reason: Vps1302 lies within the clade that inherited the node, and nothing specific to Vps1302 suggests loss. The mitochondrial contact-site location is part of how Vps13 proteins deliver lipids to mitochondria. The adaptor that recruits fission yeast Vps1302 has not been identified. Supporting Evidence: PMID:28864540 Here we show that the mitochondrial outer membrane protein Mcp1 functions in the same pathway as Vps13 by recruiting it to mitochondria and promoting its association to vacuole-mitochondria contacts. PMID:27280386 In different growth conditions, Vps13 localizes to endosome-mitochondrion contacts and to the nuclear-vacuole junctions, indicating that Vps13 may function at membrane contact sites. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic mapping from the UniProt subcellular-location line, which states trans-Golgi network by similarity (ECO:0000250). The basis is budding yeast Vps13, which binds Golgi membranes through Arf1 and its C-terminal PH-like domain and is directly required for TGN-to-prevacuolar compartment transport in vitro. No S. pombe localization data exist. Reason: Golgi association is supported for the budding yeast protein in the same subfamily (PMID:34830155, PMID:28122955), and decreased acid phosphatase secretion in S. pombe vps1302 deletion cells is consistent with a secretory-pathway role (PMID:21850271). PAINT did not propagate any Golgi term to the SF93 clade. The transferred evidence therefore supports Golgi membranes in general and no more precise term. This is a peripheral location relative to the contact-site lipid transfer function, so the row is kept as non-core rather than refined. Supporting Evidence: PMID:34830155 Furthermore, we characterized the PH-like domain of Vps13 as being responsible for the localization of Vps13 to Golgi membranes through an interaction with Arf1. PMID:28122955 we show that Vps13p is directly required both for transport from the trans-Golgi network (TGN) to the late endosome/prevacuolar compartment (PVC) and for TGN homotypic fusion PMID:21850271 The results showed that in Ξapm1, Ξvps1302 and Ξgos1 cells the acid phosphatase secretion index was dramatically decreased to approximately 50% of that in wild-type cells (Figure 4). |
| GO:0007005 mitochondrion organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT placement at PTN000414879, seeded by several metazoan and yeast VPS13 members. In budding yeast, Vps13 maintains mitochondrial integrity and acts in parallel with ERMES. Gain-of-function Vps13 alleles bypass loss of ERMES, which is attributed to lipid supply to mitochondria at vacuole-mitochondria contacts. Reason: The IBA rests on several independent donors and Vps1302 sits inside the inheriting clade, so the annotation is kept. It describes a consequence of the protein's lipid-supply activity at mitochondrial contacts rather than its core activity, and there are no S. pombe mitochondrial phenotypes for vps1302. It is therefore non-core. Supporting Evidence: PMID:27280386 This study demonstrates that VPS13 is also important for mitochondrial integrity. PMID:26370498 Combined loss of VPS13 and ERMES is lethal, indicating that Vps13 and ERMES function in redundant pathways. |
| GO:0010008 endosome membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT placement at PTN000414879. Budding yeast Vps13 is recruited to endosomal and vacuolar membranes by the sorting nexin Ypt35 and is concentrated at late endosomes. Drosophila and human members also localize to endosomes. Reason: The localization is conserved across the clade that contains Vps1302, and there is no evidence of divergence. Endosomes are one of the main membranes on which VPS13 proteins act. Supporting Evidence: PMID:30018089 Yeast Vps13 dynamically localizes to membrane contacts that connect the ER, mitochondria, endosomes, and vacuoles and is recruited to the prospore membrane in meiosis PMID:27280386 In different growth conditions, Vps13 localizes to endosome-mitochondrion contacts and to the nuclear-vacuole junctions |
| GO:0016236 macroautophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT placement at PTN000414879, seeded by Drosophila, budding yeast and Dictyostelium VPS13 proteins. Budding yeast Vps13 is needed to package the ER into autophagosomes during ER-phagy, and is proposed to supply or remove phospholipid from ER and endosomal membranes during this process. Not tested in S. pombe. Reason: Several independent donors support the node. In autophagy the VPS13 contribution is proposed to be lipid transfer between membranes, which is the protein's own activity, so the process term is plausible participation and not just necessity. The mechanism is still a proposal even in budding yeast, autophagy is peripheral to the core contact-site lipid transfer role, and the more specific budding yeast term (reticulophagy) was not propagated. The row is therefore kept as non-core. Supporting Evidence: PMID:32690699 Based on the prominent localization of Vps13 to the late endosome and the accumulation of the ER at the late endosome in vps13 mutant cells, we propose that within the context of ER-phagy, Vps13 acts to exchange phospholipid between the ER and late endosome. |
| GO:0120009 intermembrane lipid transfer | IBA GO_REF:0000033 | MODIFY | Summary: PAINT placement at the deep eukaryotic node PTN000414878, seeded by budding yeast Vps13, whose N-terminal fragment transfers glycerolipids between liposomes in vitro. This is the defining process of the family. Reason: The term is correct, and Vps1302 is inside the inheriting clade. The donor evidence, however, shows that the transported lipids are glycerophospholipids, and the same PAINT node gives the gene phospholipid transfer activity. The more specific child term intermembrane phospholipid transfer (GO:0120010), which the gene already carries, is therefore warranted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000414878 SUPPORTS TRANSFER Node placement is sound for Vps1302 (SF93). The propagated process term is broader than the donor evidence, which shows glycerophospholipid transfer. Proposed replacements: intermembrane phospholipid transfer Supporting Evidence: PMID:30093493 Thus, in vitro transfer assays showed that Vps13Ξ± can transfer glycerolipids between membranes in vitro. PMID:30093493 We were successful in purifying Vps13Ξ± from Saccharomyces cerevisiae (residues 1β1,350) |
| GO:0120009 intermembrane lipid transfer | ISS GO_REF:0000024 | MODIFY | Summary: Similarity-based transfer from budding yeast Vps13 (Q07878, same PANTHER subfamily). This is the same claim as the IBA row for this term. Reason: Consistent with the IBA row: the claim is sound, but the evidence supports the more specific phospholipid term, GO:0120010. Proposed replacements: intermembrane phospholipid transfer Supporting Evidence: PMID:30093493 Thus, in vitro transfer assays showed that Vps13Ξ± can transfer glycerolipids between membranes in vitro. |
| GO:0120010 intermembrane phospholipid transfer | TAS PMID:32213462 Inter-organelle lipid transfer: a channel model for Vps13 an... | ACCEPT | Summary: PomBase traceable author statement citing the Lees & Reinisch review, which describes Vps13 and chorein-N proteins as bulk lipid transporters with an extended hydrophobic channel. The review discusses the family, not the S. pombe protein specifically. Reason: This is the core process of VPS13-family proteins. Vps1302 belongs to the subfamily of budding yeast Vps13, whose glycerophospholipid transfer has been shown in vitro (PMID:30093493), and to the family whose structure shows a long hydrophobic groove (PMID:32182622). The function is inferred for S. pombe, not demonstrated there. Supporting Evidence: PMID:32213462 Here, we highlight the recently identified chorein_N family of lipid transporters, including the Vps13 proteins and the autophagy protein Atg2. PMID:32182622 The structure suggests that VPS13 and related proteins, like the autophagy protein ATG2, can act as bridges between organelle membranes to allow bulk lipid flow between organelles. |
| GO:0120014 phospholipid transfer activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT placement at the eukaryotic node PTN000414878, seeded by budding yeast Vps13 (IDA, PMID:30093493). This is the defining molecular activity of the VPS13 family. Reason: A single well-characterized donor is sufficient for a sound node, and the activity is consistent with the conserved chorein-N/groove architecture that Vps1302 shares. The activity is inferred, not measured, for the S. pombe protein. Supporting Evidence: PMID:30093493 Thus, in vitro transfer assays showed that Vps13Ξ± can transfer glycerolipids between membranes in vitro. PMID:32182622 A single particle cryo-EM reconstruction of an βΌ160-kD N-terminal fragment of the lipid transport protein VPS13 reveals an βΌ160-Γ
long channel lined with hydrophobic residues suitable for solubilizing multiple lipid fatty acid moieties. |
| GO:0120014 phospholipid transfer activity | ISS GO_REF:0000024 | ACCEPT | Summary: Similarity-based transfer from budding yeast Vps13, consistent with the IBA row for the same term. Reason: Same subfamily as the experimentally characterized donor. This is the core activity. Supporting Evidence: PMID:30093493 Thus, in vitro transfer assays showed that Vps13Ξ± can transfer glycerolipids between membranes in vitro. |
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Download this section (compressed HTML)Q: Which adaptors recruit S. pombe Vps1302 to endosomes, vacuoles or mitochondria, given that the budding yeast adaptors (Ypt35, Mcp1, Spo71) may not all have fission yeast counterparts?
Q: Are the meiotic phenotypes of vps1302 deletion strains caused by loss of the full-length protein or by loss of the nested Spo2 product made from the 3' end of the locus?
Q: How are functions divided between Vps1302 (SF93, Vps13 subfamily) and Vps1301 (separate subfamily SF145) in S. pombe?
Experiment: Endogenously tag Vps1302 at an internal site that preserves function (avoiding the C-terminus, which overlaps Spo2) and image it with organelle markers to test localization to endosome, vacuole and mitochondrial contacts.
Type: fluorescence microscopy
Experiment: Express the N-terminal chorein/groove region of Vps1302 and test glycerophospholipid binding and liposome-to-liposome transfer in vitro.
Type: in vitro lipid transfer assay
Experiment: Build a vps1302 allele that inactivates the long protein but leaves the spo2 ORF and its meiotic transcript intact (for example, an early in-frame stop), and compare its meiotic phenotypes with those of the full deletion.
Type: genetic separation-of-function analysis
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