Squalene-hopene cyclase enzyme catalyzing oxygen-independent cyclization of squalene to hopanoids, enabling anaerobic growth in S. japonicus. Horizontally acquired from Acetobacter bacteria, this enzyme provides sterol surrogates when oxygen-dependent ergosterol biosynthesis is impaired.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0051007 squalene-hopene cyclase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This molecular function annotation is strongly supported by experimental evidence. Shc1 catalyzes the oxygen-independent cyclization of squalene to hopanoids (PMID:34353908, PMID:40195311), with enzyme activity directly validated through heterologous expression in S. cerevisiae and knockout studies. Reason: The squalene-hopene cyclase activity is the core molecular function of Shc1, validated by multiple lines of evidence including functional expression studies, knockout phenotypes, and detection of hopanoid products. This is the primary and defining molecular function of the enzyme. Supporting Evidence: PMID:34353908 Mass spectrometry of lipid fractions of anaerobically grown Sch. japonicus showed the presence of hopanoids, a class of cyclic triterpenoids not previously detected in yeasts, including hop-22(29)-ene, hop-17(21)-ene, hop-21(22)-ene, and hopan-22-ol PMID:40195311 The S. japonicus shc1Ξ mutant did not produce hopanoids, demonstrating that Shc1 is indeed responsible for hopanoid synthesis in this organism file:SCHJY/shc1/shc1-deep-research.md Shc1 is an ER-associated enzyme that traffics or anchors at multiple membrane sites |
| GO:0005811 lipid droplet | IEA GO_REF:0000002 | REMOVE | Summary: No experimental evidence supports lipid droplet localization. Shc1-sfGFP localization studies show membrane association (ER, nuclear envelope, plasma membrane, vacuolar membrane) but not lipid droplets (PMID:40195311). Reason: The IEA annotation likely derives from InterPro domain predictions, but experimental localization data clearly shows Shc1 at membrane sites involved in lipid biosynthesis, not lipid storage organelles. The enzyme functions in membrane lipid production, not storage. Supporting Evidence: PMID:40195311 Shc1 tagged at its endogenous locus with superfolder GFP (Shc1-sfGFP) localized to cellular membranes, including the nuclear envelope (NE), cortical endoplasmic reticulum (ER) and/or the plasma membrane, and the vacuolar membranes (Fig |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000117 | MODIFY | Summary: Accurate but overly general. Shc1 specifically catalyzes hopanoid biosynthesis, a specialized form of triterpenoid lipid biosynthesis (PMID:34353908, PMID:40195311). Reason: While technically correct, this term is too broad. The more specific term GO:0019746 (hopanoid biosynthetic process) precisely captures the enzyme function. Hopanoids are a specific class of pentacyclic triterpenoid lipids. Proposed replacements: hopanoid biosynthetic process Supporting Evidence: PMID:34353908 In anaerobic cultures, the content of diplopterol, the major hopanoid detected in Sch. japonicus, was similar to the ergosterol content of sterol-supplemented anaerobic cultures |
| GO:0016104 triterpenoid biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: Correct general classification but could be more specific. Hopanoids are pentacyclic triterpenoids, and the specific process (hopanoid biosynthesis) is well-characterized (PMID:34353908, PMID:40195311). Reason: While accurate, GO:0019746 (hopanoid biosynthetic process) is more specific and informative. Hopanoids are a distinct class of triterpenoids with specific biological functions as sterol surrogates. Proposed replacements: hopanoid biosynthetic process Supporting Evidence: PMID:40195311 hopanoids are cyclized from squalene in a single, oxygen-independent step catalyzed by a squalene-hopene cyclase (SHC) |
| GO:0016829 lyase activity | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Keyword-mapped lyase activity. Squalene-hopene cyclases also catalyze water capture to form hopan-22-ol (diplopterol; squalene + H2O = hopan-22-ol, EC 4.2.1.129, a hydro-lyase reaction), the most abundant hopanoid in S. japonicus, so the lyase classification is not wrong, but it is a very general grouping term. Reason: Earlier REMOVE judgment was based on the incorrect premise that the enzyme performs no lyase chemistry; UniProt assigns both EC 5.4.99.17 and EC 4.2.1.129. GO has no specific squalene-hopanol cyclase activity term, so the general parent is retained as non-core. Supporting Evidence: PMID:40195311 S. japonicus wild-type cells produced high levels of hopanoids even in the presence of oxygen, with diplopterol being the most abundant |
| GO:0016853 isomerase activity | IEA GO_REF:0000043 | MODIFY | Summary: Partially correct but imprecise. While squalene-hopene cyclases do perform intramolecular rearrangements, they are specifically classified as intramolecular transferases that catalyze cyclization reactions (PMID:40195311). Reason: Isomerase activity is too broad. The enzyme specifically performs intramolecular transferase activity (GO:0016866) during cyclization. The specific activity is already captured by GO:0051007 (squalene-hopene cyclase activity). Proposed replacements: intramolecular transferase activity Supporting Evidence: PMID:40195311 SHCs synthesize hopanoids in an oxygen-independent manner |
| GO:0016866 intramolecular transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Correct molecular function classification. Squalene-hopene cyclases are intramolecular transferases that catalyze the cyclization of squalene through intramolecular rearrangement (PMID:40195311). Reason: This is the correct broad molecular function category for squalene-hopene cyclases. These enzymes catalyze intramolecular rearrangements to form cyclic structures. GO:0051007 (squalene-hopene cyclase activity) is a child term of this category. Supporting Evidence: PMID:40195311 hopanoids are cyclized from squalene in a single, oxygen-independent step catalyzed by a squalene-hopene cyclase (SHC) |
| GO:0005774 vacuolar membrane | EXP PMID:40195311 Horizontal acquisition of prokaryotic hopanoid biosynthesis ... | ACCEPT | Summary: Experimentally validated localization. Shc1-sfGFP fluorescence microscopy directly demonstrated vacuolar membrane localization (PMID:40195311). Reason: Direct experimental evidence from endogenous Shc1-sfGFP tagging shows clear vacuolar membrane localization. This is consistent with the enzyme role in membrane lipid metabolism. Supporting Evidence: PMID:40195311 Shc1 tagged at its endogenous locus with superfolder GFP (Shc1-sfGFP) localized to cellular membranes, including the nuclear envelope (NE), cortical endoplasmic reticulum (ER) and/or the plasma membrane, and the vacuolar membranes |
| GO:0005783 endoplasmic reticulum | EXP PMID:40195311 Horizontal acquisition of prokaryotic hopanoid biosynthesis ... | ACCEPT | Summary: Experimentally validated localization. Shc1-sfGFP shows clear ER localization including cortical ER and nuclear envelope (PMID:40195311). Reason: Direct experimental evidence from fluorescence microscopy of endogenously tagged Shc1-sfGFP demonstrates ER localization. This is the expected location for lipid biosynthetic enzymes working with squalene substrate. Supporting Evidence: PMID:40195311 Shc1 tagged at its endogenous locus with superfolder GFP (Shc1-sfGFP) localized to cellular membranes, including the nuclear envelope (NE), cortical endoplasmic reticulum (ER) |
| GO:0005886 plasma membrane | EXP PMID:40195311 Horizontal acquisition of prokaryotic hopanoid biosynthesis ... | ACCEPT | Summary: Experimentally observed but interpretation is ambiguous. The study notes cortical ER and/or plasma membrane localization, suggesting difficulty distinguishing these closely apposed membranes (PMID:40195311). Reason: While the authors note uncertainty between cortical ER versus plasma membrane signal, some plasma membrane localization is observed. This could represent ER-PM contact sites or direct PM localization for local hopanoid incorporation. Supporting Evidence: PMID:40195311 Shc1 tagged at its endogenous locus with superfolder GFP (Shc1-sfGFP) localized to cellular membranes, including the nuclear envelope (NE), cortical endoplasmic reticulum (ER) and/or the plasma membrane |
| GO:0006629 lipid metabolic process | EXP PMID:40195311 Horizontal acquisition of prokaryotic hopanoid biosynthesis ... | MODIFY | Summary: Experimentally validated but overly broad. The study specifically demonstrates hopanoid biosynthesis through GC-MS detection of hopanoid products (PMID:40195311). Reason: While correct, this term is too general. The experimental evidence specifically shows hopanoid biosynthesis (GO:0019746), which is a more informative annotation for this specialized lipid biosynthetic function. Proposed replacements: hopanoid biosynthetic process Supporting Evidence: PMID:40195311 S. japonicus wild-type cells produced high levels of hopanoids even in the presence of oxygen, with diplopterol being the most abundant. We also detected the hopenes hop-22(29)-ene and hop-17(21)-ene |
| GO:0019746 hopanoid biosynthetic process | IEA | NEW | Summary: Core biological process catalyzed by Shc1 Reason: Shc1 specifically catalyzes the biosynthesis of hopanoids from squalene. This is the precise biological process for this enzyme but was missing from existing annotations. Supporting Evidence: PMID:40195311 The S. japonicus shc1Ξ mutant did not produce hopanoids, demonstrating that Shc1 is indeed responsible for hopanoid synthesis in this organism PMID:40195311 hopanoids are cyclized from squalene in a single, oxygen-independent step catalyzed by a squalene-hopene cyclase (SHC) |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA-predicted lipid metabolic process. Correct but very general; Shc1 catalyzes the single cyclization step that produces hopanoids from squalene. Reason: Same judgment as the EXP lipid metabolic process row; the informative process is hopanoid biosynthetic process (GO:0019746). Proposed replacements: hopanoid biosynthetic process Supporting Evidence: PMID:40195311 hopanoids are cyclized from squalene in a single, oxygen-independent step catalyzed by a squalene-hopene cyclase (SHC) |
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