GPI inositol-deacylase that catalyzes removal of inositol-linked acyl chains from GPI-anchored proteins in the ER, essential for GPI-AP biosynthesis, ER-Golgi transport, and cytokinesis
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly identifies ER localization, consistent with comprehensive evidence from recent studies and UniProt annotation Reason: The ER localization is well-supported across multiple lines of evidence. The deep research document states "Bst1 localizes primarily to two distinct cellular compartments within the secretory pathway the endoplasmic reticulum and early Golgi apparatus" and "Within the ER, the protein exhibits a characteristic distribution pattern extending from the nuclear envelope ER to peripheral ER tubules and sheets" [bst1-deep-research-perplexity.md]. UniProt annotation confirms "Endoplasmic reticulum membrane" localization [bst1-uniprot.txt]. The IBA phylogenetic inference is supported by conservation of this localization across orthologs including mammalian PGAP1 and budding yeast Bst1 [bst1-deep-research-perplexity.md]. Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md Bst1 localizes primarily to two distinct cellular compartments within the secretory pathway: the endoplasmic reticulum and early Golgi apparatus. Within the ER, the protein exhibits a characteristic distribution pattern extending from the nuclear envelope ER to peripheral ER tubules and sheets. file:SCHPO/bst1/bst1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. file:SCHPO/bst1/bst1-deep-research-falcon.md These data support Bst1 acting in the **early secretory pathway**, consistent with its conserved ER-resident deacylase role. |
| GO:0160215 deacylase activity | IBA GO_REF:0000033 | MODIFY | Summary: While technically correct, this general deacylase activity term is too broad and should be replaced with the more specific GO:0050185 (phosphatidylinositol deacylase activity) that accurately reflects the enzyme's substrate specificity Reason: The IBA annotation uses a very general molecular function term that lacks informative value about the actual biochemical function. Bst1 specifically catalyzes "removal of inositol-linked acyl chains from GPI-anchored proteins" [bst1-deep-research-perplexity.md], not general deacylation. UniProt records the function as "GPI inositol-deacylase" with EC 3.1.-.- [bst1-uniprot.txt]. The deep research extensively documents that "The primary enzymatic function of Bst1 is the catalysis of inositol deacylation, a critical step in the post-translational modification of glycosylphosphatidylinositol-anchored proteins" and "Bst1 catalyzes the hydrolytic removal of this inositol-acyl chain" [bst1-deep-research-perplexity.md]. Note that there is already an IBA annotation in the full GOA for GO:0050185 (phosphatidylinositol deacylase activity), which is the appropriate specific term. Proposed replacements: phosphatidylinositol deacylase activity Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md The primary enzymatic function of Bst1 is the catalysis of inositol deacylation, a critical step in the post-translational modification of glycosylphosphatidylinositol-anchored proteins. Bst1 catalyzes the hydrolytic removal of this inositol-acyl chain, converting the triacylated GPI structure into a diacylated form. file:SCHPO/bst1/bst1-uniprot.txt RecName: Full=GPI inositol-deacylase; EC=3.1.-.- file:SCHPO/bst1/bst1-deep-research-falcon.md Hydrolytic cleavage of the **ester-linked acyl chain** attached to the **2-hydroxyl of inositol** within the GPI anchor on a newly GPI-anchored protein (GPI-AP). file:SCHPO/bst1/bst1-deep-research-falcon.md 2024 structural/biochemical work indicates PGAP1 achieves specificity by **binding the lipid and glycan features of GPI-AP substrates** within a specialized cavity, helping avoid indiscriminate hydrolysis of bulk membrane lipids. |
| GO:0006506 GPI anchor biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly captures core biological function as Bst1 catalyzes the essential first post-attachment remodeling step in GPI-AP biosynthesis Reason: This IBA annotation accurately reflects Bst1's essential role in GPI anchor biosynthesis. The deep research extensively documents that "Within this post-attachment phase, Bst1-catalyzed inositol deacylation represents the first and rate-limiting step" and "The biosynthesis of GPI-anchored proteins represents one of the most complex post-translational modification pathways in eukaryotic cells" [bst1-deep-research-perplexity.md]. UniProt function states "Involved in inositol deacylation of GPI-anchored proteins which plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins" [bst1-uniprot.txt]. This is clearly a core function. Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md Within this post-attachment phase, Bst1-catalyzed inositol deacylation represents the first and rate-limiting step. The biosynthesis of GPI-anchored proteins represents one of the most complex post-translational modification pathways in eukaryotic cells, involving more than twenty catalytic steps divided into synthesis and post-attachment phases. file:SCHPO/bst1/bst1-uniprot.txt FUNCTION: Involved in inositol deacylation of GPI-anchored proteins which plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins. file:SCHPO/bst1/bst1-deep-research-falcon.md Bst1 acts **after GPI attachment to protein and before efficient ER export**, as the first remodeling step in the post-attachment GPI lipid-remodeling pathway |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000117 | ACCEPT | Summary: Computational IEA annotation is consistent with experimental evidence and IBA annotation, redundant but accurate Reason: This ARBA machine learning annotation is correct and consistent with all other evidence for ER localization, though redundant with the IBA annotation. The annotation is broadly supported by the same evidence cited for the IBA annotation above [bst1-deep-research-perplexity.md, bst1-uniprot.txt]. Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md Bst1 localizes primarily to two distinct cellular compartments within the secretory pathway: the endoplasmic reticulum and early Golgi apparatus. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location mapping correctly identifies ER membrane localization, consistent with multi-pass transmembrane architecture Reason: This annotation based on UniProt subcellular location vocabulary is accurate and more specific than general ER localization. UniProt explicitly states "Endoplasmic reticulum membrane; Multi-pass membrane protein" [bst1-uniprot.txt]. The deep research confirms "The transmembrane architecture of Bst1 is essential for its proper localization and function" and "The protein contains multiple transmembrane domains that anchor it within the ER membrane with its catalytic domain positioned toward the ER lumen" [bst1-deep-research-perplexity.md]. The protein has 9 predicted transmembrane helices according to UniProt features [bst1-uniprot.txt]. Supporting Evidence: file:SCHPO/bst1/bst1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. file:SCHPO/bst1/bst1-deep-research-perplexity.md The protein contains multiple transmembrane domains that anchor it within the ER membrane with its catalytic domain positioned toward the ER lumen where nascent GPI-APs emerge. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from UniProt keyword mapping is accurate but general, capturing Bst1's role in regulating ER-to-Golgi transport of GPI-APs and other secretory cargo Reason: This annotation from UniProt "Protein transport" keyword is technically accurate though somewhat general. Bst1 plays a critical role in protein transport, specifically regulating ER-to-Golgi transport. The deep research states "The role of Bst1 in regulating early secretory pathway transport extends beyond its direct catalytic activity on GPI-APs to encompass broader coordination of ER-to-Golgi transport and COPII vesicle dynamics" and "acid phosphatase secretion is significantly reduced in bst1 deletion mutants, indicating that the transport of multiple secretory cargo types is compromised" [bst1-deep-research-perplexity.md]. UniProt keywords include "Protein transport; Transport" [bst1-uniprot.txt]. While not the most specific term, it captures an important function. Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md The role of Bst1 in regulating early secretory pathway transport extends beyond its direct catalytic activity on GPI-APs to encompass broader coordination of ER-to-Golgi transport and COPII vesicle dynamics. Acid phosphatase secretion is significantly reduced in bst1 deletion mutants, indicating that the transport of multiple secretory cargo types is compromised. file:SCHPO/bst1/bst1-uniprot.txt KW Protein transport; Transport. file:SCHPO/bst1/bst1-deep-research-falcon.md Deacylation is required for binding to **p24-family cargo receptors** and recruitment of GPI-APs into **COPII vesicles**, promoting efficient ER export and secretion. file:SCHPO/bst1/bst1-deep-research-falcon.md Reduced secretion in an **acid phosphatase secretion assay** (qualitatively described as significantly decreased). |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: IEA annotation from UniProt keyword is technically correct but too general, superseded by more specific terms for deacylase and phosphatidylinositol deacylase activity Reason: This very general molecular function term from UniProt "Hydrolase" keyword is technically accurate since Bst1 is a serine hydrolase, but provides minimal informative value. The deep research describes "The catalytic mechanism of Bst1 and its human ortholog PGAP1" involving "a serine hydrolase lipase domain" with "serine hydrolase-type catalysis" [bst1-deep-research-perplexity.md]. However, this general term should be superseded by the specific GO:0050185 (phosphatidylinositol deacylase activity). This represents over-annotation up the hierarchy. Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md The catalytic mechanism of Bst1 and its human ortholog PGAP1 has been clarified through recent structural studies that revealed the enzyme adopts a distinctive 10-transmembrane architecture containing both a serine hydrolase lipase domain and a jelly-roll domain. The lipase domain exhibits a characteristic Ξ±/Ξ² hydrolase fold containing a catalytic serine residue that acts as the nucleophile in the deacylation reaction. |
| GO:0016788 hydrolase activity, acting on ester bonds | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: IEA annotation from InterPro domain mapping correctly reflects the ester bond cleavage mechanism, but like the parent hydrolase term it is superseded by the specific phosphatidylinositol deacylase activity and represents over-annotation up the hierarchy Reason: This InterPro-based annotation accurately captures the chemical mechanism. The deep research explains "Bst1 catalyzes the hydrolytic removal of this inositol-acyl chain" involving "cleavage of the ester bond linking the acyl chain to the inositol ring" [bst1-deep-research-perplexity.md]. UniProt features include "ACT_SITE 264" and the PROSITE pattern "PS00120 LIPASE_SER" [bst1-uniprot.txt]. InterPro domains IPR012908 (PGAP1-ab_dom-like) and IPR039529 (PGAP1/BST1) map to this GO term [bst1-uniprot.txt]. However, GO:0016788 lies on the ancestry path to the specific GO:0050185 (phosphatidylinositol deacylase activity), which already captures the ester-bond hydrolase mechanism. For consistency with the MARK_AS_OVER_ANNOTATED decision on the parent term GO:0016787 (hydrolase activity), this intermediate term is likewise over-annotated and superseded by GO:0050185. Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md Bst1 catalyzes the hydrolytic removal of this inositol-acyl chain, converting the triacylated GPI structure into a diacylated form. The serine hydrolase-type catalysis involves formation of a tetrahedral intermediate stabilized by a catalytic glutamate residue, leading to cleavage of the ester bond linking the acyl chain to the inositol ring. file:SCHPO/bst1/bst1-uniprot.txt DR InterPro; IPR012908; PGAP1-ab_dom-like. DR InterPro; IPR039529; PGAP1/BST1. DR PROSITE; PS00120; LIPASE_SER; 1. file:SCHPO/bst1/bst1-deep-research-falcon.md Hydrolytic cleavage of the **ester-linked acyl chain** attached to the **2-hydroxyl of inositol** within the GPI anchor on a newly GPI-anchored protein (GPI-AP). |
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: High-throughput localization study using YFP tagging provides experimental support for ER localization, though specific details are not available in the publication abstract Reason: PMID:16823372 is a large-scale ORFeome cloning and protein localization study that "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" [PMID:16823372]. While the full text is not available to verify the specific data for bst1, this high-throughput experimental dataset (HDA evidence code) provides direct experimental support for ER localization, consistent with all other evidence. The annotation is valid experimental evidence, though less detailed than focused studies like Ye et al. 2025 described in the deep research. Supporting Evidence: PMID:16823372 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. |
| GO:0005794 Golgi apparatus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: High-throughput localization study provides experimental evidence for Golgi localization, consistent with recent detailed studies showing early Golgi/cis-Golgi localization Reason: The HDA annotation from PMID:16823372 ORFeome localization study supports Golgi localization [PMID:16823372]. This is strongly corroborated by recent detailed studies showing "Complementary to this ER localization, Bst1 is also detected in punctate cytoplasmic structures that frequently overlap with Anp1, a component of the Golgi mannan polymerase I complex that serves as a cis-Golgi marker" and "Bst1 shows minimal overlap with Sec72, an Arf GEF protein that localizes to the trans-Golgi apparatus, indicating that Bst1 functions specifically at early stages of the secretory pathway" [bst1-deep-research-perplexity.md]. The Golgi localization is valid, though more precisely it is early/cis-Golgi. Supporting Evidence: PMID:16823372 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. file:SCHPO/bst1/bst1-deep-research-perplexity.md Complementary to this ER localization, Bst1 is also detected in punctate cytoplasmic structures that frequently overlap with Anp1, a component of the Golgi mannan polymerase I complex that serves as a cis-Golgi marker. In contrast, Bst1 shows minimal overlap with Sec72, an Arf GEF protein that localizes to the trans-Golgi apparatus, indicating that Bst1 functions specifically at early stages of the secretory pathway. |
| GO:0005789 endoplasmic reticulum membrane | IC GO_REF:0000036 | ACCEPT | Summary: Curator inference from combined evidence (ER localization + membrane protein) is valid and well-supported by protein architecture Reason: This IC (Inferred by Curator) annotation combines GO:0005783 (endoplasmic reticulum) with GO:0016020 (membrane) to infer ER membrane localization. This is a sound inference given that Bst1 is a multi-pass transmembrane protein with 9 predicted transmembrane helices [bst1-uniprot.txt]. The deep research confirms "The protein contains multiple transmembrane domains that anchor it within the ER membrane" [bst1-deep-research-perplexity.md]. This curator inference is consistent with direct experimental evidence and represents good annotation practice for combining orthogonal data sources. Redundant with IEA annotation but uses different evidence. Supporting Evidence: file:SCHPO/bst1/bst1-deep-research-perplexity.md The protein contains multiple transmembrane domains that anchor it within the ER membrane with its catalytic domain positioned toward the ER lumen where nascent GPI-APs emerge. |
| GO:0005801 cis-Golgi network | IDA PMID:39813093 Fission yeast GPI inositol deacylase Bst1 regulates ER-Golgi... | NEW | Summary: Bst1 localizes to the cis-Golgi as shown by colocalization with Anp1 marker Reason: Ye et al. 2025 show that Bst1-mScarlet puncta colocalize (66%) with the cis-Golgi marker Anp1 but rarely (12%) with the trans-Golgi marker Sec72 in S. pombe. Supporting Evidence: PMID:39813093 Most (66%) punctate Bst1-mScarlet structures colocalized with Anp1-GFP, but colocalization with Sec72-GFP was rarer PMID:39813093 These data suggest that Bst1 localizes to ER and cis-Golgi and is involved in early ER transport file:SCHPO/bst1/bst1-deep-research-falcon.md 66%** overlap with **Anp1-GFP** (cis-Golgi/ERβGolgi transport marker) |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IMP PMID:39813093 Fission yeast GPI inositol deacylase Bst1 regulates ER-Golgi... | NEW | Summary: Bst1 is required for ER-to-Golgi transport; mutants show defective transport Reason: Ye et al. 2025 show bst1Ξ mutants accumulate the cis-Golgi marker Anp1 at the nuclear ER and have altered COPII (Sec13/Sec24) distribution, indicating defective early ER-to-Golgi transport. Supporting Evidence: PMID:39813093 bst1Ξ cells had increased signal of Anp1-GFP at the nuclear ER (neER) besides the cytosolic puncta, unlike Anp1-GFP in WT cells PMID:39813093 suggesting that loss of bst1 leads to defect in early ER transport file:SCHPO/bst1/bst1-deep-research-falcon.md Increased numbers of **COPII subunit puncta** (Sec13, Sec24) file:SCHPO/bst1/bst1-deep-research-falcon.md Deacylation is required for binding to **p24-family cargo receptors** and recruitment of GPI-APs into **COPII vesicles**, promoting efficient ER export and secretion. |
| GO:0000281 mitotic cytokinesis | IMP PMID:39813093 Fission yeast GPI inositol deacylase Bst1 regulates ER-Golgi... | NEW | Summary: bst1 mutants show prolonged contractile ring constriction during cytokinesis Reason: Ye et al. 2025 show contractile-ring constriction is dramatically slowed in bst1Ξ (78.4 min vs 34.2 min in WT), with bst1 mutants displaying morphology, septation, and cytokinesis defects. Supporting Evidence: PMID:39813093 the contractile ring constricted and disassembled (from the start of fast phase of ring constriction to ring disappearance at the division site) significantly slower with big variation in speed in bst1Ξ (78.4 Β± 31.5 min) than in WT cells (34.2 Β± 3.5 min, p < 0.001) file:SCHPO/bst1/bst1-deep-research-falcon.md Contractile-ring constriction time: **34.2 Β± 3.5 min (WT)** vs **78.4 Β± 31.5 min (bst1Ξ)** (p < 0.001) |
| GO:0000920 septum digestion after cytokinesis | IMP PMID:39813093 Fission yeast GPI inositol deacylase Bst1 regulates ER-Golgi... | NEW | Summary: bst1 mutants show defective septum degradation due to reduced glucanase delivery Reason: Ye et al. 2025 show division-site targeting of the glucanases Eng1 and Agn1 (required for primary septum digestion and cell separation) is reduced in bst1Ξ, impairing daughter cell separation. Supporting Evidence: PMID:39813093 In bst1Ξ mutant, the levels of Eng1-NeonGreen and Agn1-NeonGreen at the division site were significantly lower than those in WT cells PMID:39813093 These results indicate that Bst1 regulates the trafficking of glucanases Eng1 and Agn1 to the division site and is important for daughter cell separation file:SCHPO/bst1/bst1-deep-research-falcon.md Reduced division-site localization of secreted glucanases **Eng1** and **Agn1**, enzymes required for septum digestion and daughter separation. |
| GO:0097466 ubiquitin-dependent glycoprotein ERAD pathway | ISO PMID:16319176 Inositol deacylation by Bst1p is required for the quality co... | NEW | Summary: Bst1 is required for ERAD of misfolded GPI-anchored proteins, inferred by orthology from S. cerevisiae Reason: Inferred from sequence orthology (ISO) with the S. cerevisiae ortholog BST1. The supporting evidence is the Fujita et al. 2006 study (PMID:16319176) in budding yeast, where disruption of BST1 delayed ERAD of the misfolded GPI-anchored protein Gas1*p; no S. pombe-specific ERAD experiment was performed (the Ye et al. 2025 S. pombe study did not test misfolded GPI-AP degradation). The IMP evidence code was incorrect because no S. pombe mutant-phenotype ERAD assay exists; this is a cross-species inference based on the conserved GPI inositol deacylase function. S. pombe bst1 (Q9UT41) and S. cerevisiae BST1 are members of the same PGAP1/BST1 family. Supporting Evidence: PMID:16319176 Disruption of BST1, which encodes GPI inositol deacylase, caused a delay in the degradation of Gas1*p PMID:16319176 Our data suggest that GPI inositol deacylation plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins file:SCHPO/bst1/bst1-deep-research-falcon.md Budding-yeast bst1 disruption also affects quality control of misfolded GPI-APs retained in the ER (Gas1*p), consistent with a role in ER quality control/ERAD for GPI-APs. |
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