Vas2 (also called Aps1; locus SPAP27G11.06c) is the 162-residue sigma (small) subunit of the heterotetrameric AP-1 clathrin adaptor complex of fission yeast, which also contains the gamma subunit Apl4, the beta subunit Apl2 and the mu subunit Apm1. Vas2 has the longin-like fold typical of sigma adaptins and has no catalytic activity. It binds Apl4 independently of the other two subunits, forming the gamma/sigma half of the core. All four subunits are needed to assemble the complex and recruit it to Golgi and endosomal membranes. There AP-1 selects transmembrane cargo for clathrin-coated carriers and drives cargo exit from endosomes. Cells lacking vas2 accumulate the v-SNARE Syb1 in endosomes and are hypersensitive to valproic acid, the phenotype that gave the gene its name. In AP-1 complexes from other species, the gamma/sigma1 hemicomplex forms the binding site for dileucine-based sorting signals.
HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...
MARK AS OVER ANNOTATED
Summary: A nuclear signal from a proteome-wide YFP-fusion localization screen. The targeted study of this protein does not support it, and no nuclear role is known for AP-1.
Reason: The only source is the high-throughput ORFeome YFP-tagging screen. Its tagged ORFs were expressed from a construct rather than at the endogenous locus. Vas2 is an 18.6 kDa protein, so a YFP fusion of it is small enough to enter the nucleus passively. Nuclear plus cytoplasmic signal is a common default in this kind of screen for small soluble proteins. The targeted study of the fission yeast AP-1 subunits found the complex on endosomes. No sigma adaptin in any species has a characterised nuclear function. The row is kept but marked as an over-annotation instead of being removed, because the screen did record the signal and the full image data are not available here.
Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
Consistently, the deletion of any subunit generally caused the disassociation of the heterotetrameric complex from endosomes, although some subunits weakly localized to endosomes.
Summary: UniProt SubCell mapping of the same nuclear signal from the ORFeome screen.
Reason: The UniProt "Nucleus" subcellular location cites only the ORFeome screen (PMID:16823372). This electronic row therefore restates the HDA row and gets the same action. No AP-1 function in the nucleus is known.
Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
EXP PMID:16823372 ORFeome cloning and global analysis of protein localization ...
MODIFY
Summary: Correct but general. AP-1 is a peripheral membrane coat recruited from a soluble cytosolic pool, and the gene already carries the more specific cytosol, Golgi and endosome terms.
Reason: The cytoplasm term is true, but the gene already carries more specific locations that are part of the cytoplasm. Cytosol (GO:0005829, is_a cytoplasm) comes from the same screen, and Golgi apparatus and endosome come from the targeted AP-1 study. The cytosol term describes the unassembled soluble pool, so this row is refined to cytosol. The membrane-bound pool is already covered by the Golgi and endosome rows.
Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
Consistently, the deletion of any subunit generally caused the disassociation of the heterotetrameric complex from endosomes, although some subunits weakly localized to endosomes.
Summary: SubCell mapping of the same cytoplasmic observation. Correct but general.
Reason: This row has the same basis as the EXP cytoplasm row (UniProt cites PMID:16823372), so it is refined in the same way, to cytosol. The membrane-associated pool is covered by the Golgi and endosome rows.
IDA PMID:19624755 Deletion mutants of AP-1 adaptin subunits display distinct p...
ACCEPT
Summary: The fission yeast AP-1 heterotetramer localizes to endosomes and needs every subunit, including Aps1/Vas2, to stay there. Endosomes are where AP-1 drives cargo exit.
Reason: In the targeted study, deletion of any one subunit released the complex from endosomes, which shows that Aps1 is needed for the complex to act there. Syb1 accumulates in endosomes in aps1 deletion cells, which places the defect at this compartment. This is a core location.
Consistently, the deletion of any subunit generally caused the disassociation of the heterotetrameric complex from endosomes, although some subunits weakly localized to endosomes.
IDA PMID:19624755 Deletion mutants of AP-1 adaptin subunits display distinct p...
ACCEPT
Summary: AP-1 acts at the Golgi/TGN-endosome interface. PomBase curated Golgi localization from the targeted AP-1 subunit study.
Reason: The cached abstract mentions only endosomes. The curators read the full text and recorded Golgi apparatus as well. Fission yeast AP-1 puncta are Golgi/endosomal, and AP-1 complexes in all species act at the trans-Golgi network. I defer to the curator on the detail and accept this as a core location.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...
KEEP AS NON CORE
Summary: The soluble, unassembled pool of AP-1 subunits is cytosolic. This location is correct but not where the complex does its work.
Reason: Cytosol is as precise as the screen allows, and it fits a peripheral coat protein that cycles between the cytosol and membranes. AP-1 does its sorting on Golgi and endosome membranes, so cytosol is kept as a non-core location.
Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
Summary: Wrong process. Intercellular transport means movement between cells, through structures such as plasmodesmata. AP-1 sorts cargo between compartments inside a single cell.
Reason: GO:0010496 is defined as movement of substances between cells. S. pombe is unicellular and has no intercellular channels. The established Vas2/AP-1 function is intracellular sorting at the Golgi and endosomes. The term comes from an ARBA machine-learning rule with no independent support. Its likely origin is plant AP-1 annotations to plasmodesmata-related transport, which do not apply to a fungus.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
Summary: True but general. The specific AP-1-dependent protein transport route is already annotated from the targeted study.
Reason: Vas2 does take part in transporting membrane-protein cargo, but GO:0099638 endosome to plasma membrane protein transport, which the gene already carries by IDA, is_a GO:0015031 protein transport. Following the refinement rule, this broad InterPro-mapped term is replaced with that specific descendant.
Summary: A sound PAINT inference placed at the root of the sigma-adaptin family (PTN000204281). It is correct for vas2, but the target's own experiments support more specific routes.
Reason: PTN000204281 covers the whole PTHR11753 family, so the curator put this process at the root, where only the broad term holds for AP-1 through AP-4. Vas2 is inside that clade (subfamily SF5 AP COMPLEX SUBUNIT SIGMA, together with S. cerevisiae APS1), and its own PomBase IDA annotation is one of the descendant evidences. That self-inclusion is expected and is not circular. The inference holds, but for vas2 itself the target-specific IDA rows support two descendants of GO:0016192, namely retrograde transport, endosome to Golgi (GO:0042147) and endosome to plasma membrane protein transport (GO:0099638). Both are listed as replacements.
Propagation Review
Root cause:TERM SCOPING PROBLEM
Failure modes:GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN000204281 · PTN000204281 SUPPORTS TRANSFER
Family-root node of PTHR11753 (AP-1 to AP-4 sigma chains). The broad process is correct for vas2 (subfamily SF5), and the target's own PomBase IDA annotation is among the descendant evidences, as expected. The refinement reflects target-specific IDA evidence, not a placement error.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
Summary: The same general process as the IBA row, from combined automated methods.
Reason: This row makes the same claim as the IBA row and gets the same refinement to the two transport routes supported by IDA. The IPR044733 AP-1 sigma signature puts vas2 in AP-1, which fits.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
IDA PMID:19624755 Deletion mutants of AP-1 adaptin subunits display distinct p...
ACCEPT
Summary: Direct experimental evidence that Aps1/Vas2 is a subunit of fission yeast AP-1. It binds Apl4 (gamma) independently of the other subunits and is needed for the heterotetramer to form.
Reason: Pull-down assays showed that Apl4 binds Aps1 even without Apm1 and Apl2, which defines the gamma/sigma hemicomplex. Every subunit is needed to form the complex. Membership is the core identity of this protein, and it agrees with the AP-1 sigma signature (IPR044733) and the SF5 subfamily placement.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
Here, we show that in Schizosaccharomyces pombe the deletion strains of each individual subunit of the AP-1 complex [Apl2 (beta), Apl4 (gamma), Apm1 (mu) and Aps1 (sigma)] caused distinct phenotypes on growth sensitivity to temperature or drugs.
Summary: Clathrin binding is a property of the assembled AP-1 complex, mainly through the beta subunit's clathrin box and the gamma subunit. The sigma subunit is not known to bind clathrin.
Reason: The orthology donor, S. cerevisiae APS1 (SGD:S000004160), is in the same PANTHER subfamily (SF5), so the orthology itself is sound. The October 2026 QuickGO annotation set for P35181 no longer contains a clathrin binding annotation, however. APS1 has only AP-1 complex membership, generic protein-binding IPIs to other AP-1 subunits, and a process annotation, so the experimental basis for this transfer is no longer visible in the donor. UniProt records clathrin interaction only for the complex, by similarity. The PAINT node for this family (PTN000204281) also does not propagate clathrin binding. A function of the complex has been assigned to its smallest subunit, so the row is marked as an over-annotation. The complex-level clathrin adaptor role is captured by contributes_to clathrin-cargo adaptor activity.
Propagation Review
Root cause:SOURCE STALE OR MISSING
Failure modes:ROLE CONFLATION
Sources checked:
SGD:S000004160 · S. cerevisiae APS1 (P35181) SOURCE STALE OR MISSING
Same PANTHER subfamily (SF5) as vas2, so the orthology is sound. QuickGO (October 2026) shows no clathrin binding annotation on P35181. Clathrin binding by AP-1 is a property of the complex and is not attributed to the sigma subunit.
Summary: AP-1 is the membrane-attached adaptor layer of clathrin-coated vesicles that form at the TGN and endosomes.
Reason: UniProt bases this location on the AP-1 study and on curator inference (ECO:0000305). Assembled AP-1 sits on the membrane of the clathrin-coated carriers it helps make, so the location follows directly from the complex's role.
Summary: Vas2 contributes to the cargo-adaptor activity of the AP-1 heterotetramer. The contributes_to qualifier is the correct way to express a subunit's part in a complex activity.
Reason: The activity belongs to the assembled AP-1 complex. Vas2 is needed for the complex to form and to reach membranes. In AP-1 complexes of other species the gamma/sigma1 hemicomplex forms the dileucine-signal binding site, so the sigma subunit contributes directly to cargo recognition. That mechanistic point comes from mammalian AP-1 sigma1, which is in a different PANTHER subfamily (SF14) from vas2 (SF5). It is used here only as a property shared by AP-1 sigma chains, not as a subfamily-specific transfer. This is the core molecular function.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
We report that the gamma/sigma1 or alpha/sigma2 hemicomplexes bound the dileucine-based motifs of several proteins quite strongly, whereas binding by the beta1/mu1 and beta2/mu2 hemicomplexes, and the individual beta or mu subunits, was extremely weak or undetectable.
Summary: An InterPro2GO mapping from the AP-1 sigma signature that names the right activity. In fact the sigma subunit contributes to the activity as part of the complex.
Reason: The term is the correct activity and agrees with the IC row, so it gets the same action. Its "enables" qualifier is looser than the complex-level reality. The IC row's contributes_to is the precise form, and the core function below uses contributes_to.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
GO:0042147 retrograde transport, endosome to Golgi
IDA PMID:19624755 Deletion mutants of AP-1 adaptin subunits display distinct p...
ACCEPT
Summary: The AP-1 subunits are needed for cargo exit from endosomes, including the return of the v-SNARE Syb1, which accumulates in endosomes when any subunit is deleted.
Reason: The abstract reports that every subunit deletion, including aps1, causes the same endosomal accumulation of Syb1 and concludes that the subunits are needed for AP-1 exit transport from endosomes. The curators read the full text and assigned the endosome-to-Golgi route. Recycling of exocytic SNAREs through the Golgi is a conserved AP-1-dependent step, so this is accepted as a core process.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
GO:0099638 endosome to plasma membrane protein transport
IDA PMID:19624755 Deletion mutants of AP-1 adaptin subunits display distinct p...
ACCEPT
Summary: AP-1 is needed for the endosomal exit of Syb1, a v-SNARE that must reach the plasma membrane and polarized secretion sites.
Reason: Syb1 normally works at the plasma membrane. When the AP-1 subunits are lost it is trapped in endosomes, which supports a role for the complex in moving it from endosomes toward the cell surface. The curators assigned this route from the full text, and I accept it as a core process.
In addition, the deletion of individual subunits caused similar endosomal accumulation of v-SNARE synaptobrevin Syb1.
Core Functions
Sigma subunit of the AP-1 clathrin adaptor complex. It forms the gamma/sigma hemicomplex with Apl4, is needed for AP-1 assembly and recruitment to Golgi and endosomal membranes, and contributes to the complex's selection of membrane cargo for clathrin-coated carriers. Through this activity it drives cargo exit from endosomes, including the return of the v-SNARE Syb1 toward the Golgi and plasma membrane.
Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes.
We report that the gamma/sigma1 or alpha/sigma2 hemicomplexes bound the dileucine-based motifs of several proteins quite strongly, whereas binding by the beta1/mu1 and beta2/mu2 hemicomplexes, and the individual beta or mu subunits, was extremely weak or undetectable.
Q: Which dileucine-type sorting signals in fission yeast cargoes (for example Syb1 or the GPI-anchored proteins that depend on AP-1) are recognised by the Apl4-Vas2 hemicomplex, and do they follow the mammalian gamma/sigma1 preference against an aspartate at position -4?
Q: Why do vas2 and apl4 deletions give milder phenotypes than apm1 and apl2 deletions, given that every subunit is needed for heterotetramer assembly? Does an Apm1-Apl2 hemicomplex keep partial activity without the gamma/sigma half?
Suggested Experiments
Experiment: Express the Apl4-Vas2 hemicomplex and run GST pull-downs against cytoplasmic tails of candidate S. pombe cargoes, comparing wild-type tails with dileucine-to-alanine mutants. This would test directly whether Vas2 contributes to dileucine-signal recognition in fission yeast.
Type: biochemical binding assay
Experiment: Tag Vas2 at its endogenous locus with GFP and image it against Golgi (Anp1) and endosome (FM4-64) markers, in wild-type and apl4 deletion backgrounds. This would show where the native protein localizes and test whether the nuclear signal from the overexpression screen is real.
Type: live-cell fluorescence microscopy
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Vas2/Aps1 supports AP-1-mediated membrane-protein sorting and exit transport from endosomes. Intracellular protein transport is supported but less precise than the established cargo-transport routes.
Review rationale: Fission yeast Aps1/Vas2 deletion and pull-down experiments establish AP-1 assembly and exit transport from endosomes, including trafficking of the membrane protein Syb1. GOA already records endosome-to-Golgi and endosome-to-plasma-membrane protein transport. The predicted intracellular protein transport is correct but less precise than those established routes. The unrelated ARBA intercellular-transport assertion means movement between cells and is not evidence supporting this assessment. GO:0099638 endosome to plasma membrane protein transport is_a descendant of GO:0006886 (OLS4 ancestry), and the gene review accepts that specific IDA term as the refinement of the broad InterPro-mapped protein transport row.
Supporting Evidence:
PMID:19624755: "In pull-down assay, Apm1 binds Apl2 even in the absence of Aps1 and Apl4, and Apl4 binds Aps1 even in the absence of Apm1 and Apl2. Consistently, the deletion of any subunit generally caused the disassociation of the heterotetrameric complex from endosomes, although some subunits weakly localized to endosomes. In addition, the deletion of individual subunits caused similar endosomal accumulation of v-SNARE synaptobrevin Syb1. Altogether, results suggest that the four subunits are all essential for the heterotetrameric complex formation and for the AP-1 function in exit transport from endosomes."