DEGS1, also called DES1, is a membrane sphingolipid delta-4 desaturase (EC 1.14.19.17) that converts dihydroceramide to ceramide by introducing a trans double bond into the N-acyl sphingoid backbone. Its oxygen- and cytochrome-b5-dependent reaction supplies ceramide for complex sphingolipid synthesis. The protein contains conserved histidine-rich membrane-desaturase motifs and is predicted to span the membrane multiple times. It acts principally at the cytoplasmic face of the endoplasmic reticulum and is enriched at ER–mitochondrial contact domains; mitochondrial localization has also been reported in specific cellular contexts. Disruption of this lipid conversion causes hypomyelinating leukodystrophy 18 and disturbs myelin and membrane homeostasis. Retinol isomerization is experimentally supported, while its physiological contribution to retinal chromophore regeneration remains unsettled.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0042284 sphingolipid delta-4 desaturase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited sphingolipid delta-4 desaturase activity matches the directly characterized human enzyme. Reason: The PAINT assertion is placed at PANTHER:PTN001767866, and the current PTHR12879 tree places human O15121 beneath that node. Human DES1 expressed in sur2-deficient yeast produces delta-4-unsaturated sphingolipids, and human cellular loss-of-function studies independently support this chemistry. The target in the descendant evidence is legitimate experimental grounding, not circular transfer. The N-acyl sphingoid backbone is desaturated; the whole-cell hydrolysis assays are not purified free-sphinganine kinetics. |
| GO:0046513 ceramide biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: DEGS1 catalyzes the desaturation step of ceramide biosynthesis. Reason: PAINT node PTN001767866 includes human DEGS1 and carries the ceramide-biosynthesis assertion. This transfer agrees with direct human desaturation and patient/cellular dihydroceramide accumulation. DEGS1 executes a chemical step in the process; the annotation does not rest solely on a downstream disease phenotype. |
| GO:0003824 catalytic activity | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA catalytic-activity assertion is true but adds no specificity. Reason: ARBA00027533 contains an applicable condition set requiring IPR011388, IPR013866 and PTHR12879. Official target records contain these signatures, including the IPR013866 N-terminal match at residues 5–43. The rule is not rejected as a wrong-family transfer. GO:0042284, accepted elsewhere, entails GO:0003824 through the checked is_a chain via GO:0016717, GO:0016705 and GO:0016491. The broad assertion is therefore uninformative, not biologically excessive. Refine this broad assertion to sphingolipid delta-4 desaturase activity under the project instruction to specify supported replacements. The term is already represented, so this adds specificity without additional biological coverage. Proposed replacements: sphingolipid delta-4 desaturase activity Supporting Evidence: |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt ER-membrane mapping agrees with human localization and catalytic evidence. Reason: The SL-0097 mapping represents the principal membrane site of DEGS1. Human EGFP-DEGS1 colocalizes strongly with ER PDI, and human fibroblast/brain-fraction experiments show enrichment in ER domains contacting mitochondria. This does not exclude other source-specific locations. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Lipid metabolism is a correct but very broad domain-derived description. Reason: IPR005804 is a real target domain match at residues 68–291 and maps to lipid metabolic process. The accepted ceramide-biosynthesis term GO:0046513 entails GO:0006629 through GO:0006672 and GO:0006665. This is a specificity judgment, not evidence that the InterPro mapping is false. Refine this broad assertion to ceramide biosynthetic process under the project instruction to specify supported replacements. The term is already represented, so this adds specificity without additional biological coverage. Proposed replacements: ceramide biosynthetic process |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The general membrane annotation is already entailed by the established ER-membrane location. Reason: IPR011388 matches O15121 and maps to membrane. GO:0005789 is_a GO:0031090 is_a GO:0016020 in the checked ontology paths. Retain the more informative ER-membrane assertions elsewhere; this broad row does not establish exclusive ER residence or contradict mitochondrial or granule-associated observations. Refine this broad assertion to endoplasmic reticulum membrane under the project instruction to specify supported replacements. The term is already represented, so this adds specificity without additional biological coverage. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: |
| GO:0030148 sphingolipid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: Sphingolipid biosynthesis is an informative pathway-level description of the desaturation reaction. Reason: The IPR011388 target match and its sphingolipid-biosynthesis mapping agree with the human enzyme activity. DEGS1 chemically converts dihydroceramide to ceramide, rather than merely influencing a remote phenotype. The pathway term remains informative alongside the more specific ceramide step. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the curated mitochondrial-membrane mapping as a secondary localization. Reason: The source is the UniProt mitochondrial-membrane vocabulary mapping, not an assertion that mitochondria are the exclusive or principal site. PMID:19647031 reports myristoylation-dependent recombinant mitochondrial localization and native activity in rat liver ER and mitochondrial fractions. The full original and exact recombinant construct species were not recovered; no human construct or detailed membrane topology is inferred from its abstract. Human localization evidence also supports mitochondrion-associated pools, with ER-contact enrichment requiring distinction from organelle residence. |
| GO:0042284 sphingolipid delta-4 desaturase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic mappings identify the correct desaturase reaction. Reason: The InterPro family assignment, EC 1.14.19.17 and Rhea:46544 converge on N-acylsphinganine delta-4 desaturation. Direct human expression and cellular loss-of-function evidence support the same molecular activity. No fatty-acid-chain desaturase activity is inferred from the broader family name. |
| GO:0050251 retinol isomerase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Retinol isomerization is supported experimentally but is not a settled physiological core function. Reason: The Rhea:19141 mapping is compatible with the equilibrium retinol-isomerase activity reported in PMID:23143414. That study includes human DES1 expression-cell assays and rescue by human DES1 in mice, while the purified GST enzyme and Müller-cell knockdown experiments use chicken DES1. Later mouse conditional deletion and zebrafish knockout experiments limit a universal requirement in cone vision; residual expression, species and assay conditions prevent treating those results as a refutation of the biochemical activity. Supporting Evidence: PMID:30645148 had no effect on cone sensitivity or dark adaptation |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The DEGS1–ARLN interaction is supported by HuRI pairwise evidence. Reason: IntAct records the human O15121–Q8WVX3-2 pair, including validated two-hybrid interaction EBI-24800565 (IM-25472-159295), with associated assay configurations. The HuRI original describes quadruplicate pair retesting and sequence confirmation; this is not pair-specific orthogonal validation or proof of native stoichiometry. ARLN is a SERCA regulator, not itself an ATPase. Binding this partner does not establish that DEGS1 regulates SERCA or has adaptor activity, and no evidence-backed narrower molecular function was established. Preserve the positive interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The DEGS1–SEMA4G interaction is supported by HuRI pairwise evidence. Reason: IntAct records human O15121–Q9NTN9-2, including validated two-hybrid interaction EBI-24564431 (IM-25472-138437). The HuRI methods support retested, sequence-confirmed pair identity; endogenous co-compartmentalization and a physiological complex are not established for this pair. SEMA4G is a membrane semaphorin associated with receptor-binding/guidance functions. The observed interaction does not make DEGS1 a semaphorin receptor, receptor agonist or signaling adaptor. No supported narrower function was established, so retain the interaction as non-core. Supporting Evidence: |
| GO:0030148 sphingolipid biosynthetic process | TAS Reactome:R-HSA-1660661 | ACCEPT | Summary: The Reactome pathway includes the DEGS1-catalyzed desaturation reaction. Reason: R-HSA-1660661 contains R-HSA-428259, whose catalyst activity 428230 is sphingolipid delta-4 desaturase activity of DEGS1 at the ER membrane. This is direct enzymatic participation in sphingolipid biosynthesis, not assignment based only on pathway proximity. |
| GO:0042284 sphingolipid delta-4 desaturase activity | TAS Reactome:R-HSA-428259 | ACCEPT | Summary: Reactome assigns the established dihydroceramide-desaturation reaction to DEGS1. Reason: The event R-HSA-428259 has catalyst activity 428230, GO:0042284, and DEGS1 entity R-HSA-428201. The reaction is consistent with direct human expression and human cellular studies. Reactome explicitly distinguishes the human gene assignment from cofactor/stoichiometry evidence inferred from rat microsome experiments. |
| GO:0046513 ceramide biosynthetic process | IDA PMID:1317856 Subcellular localization and membrane topology of serine pal... | ACCEPT | Summary: Ceramide biosynthesis is established for DEGS1, although this early reference could not be fully audited. Reason: PMID:1317856 is available as an abstract describing mouse-liver upstream sphingolipid enzymes. Its full original was not recovered, so no claim is made about all experiments seen by the curator or about misattribution. The existing process assertion is independently clear from direct human DEGS1 chemistry and loss-of-function evidence, and is retained with that source-access limitation. |
| GO:0098554 cytoplasmic side of endoplasmic reticulum membrane | IDA PMID:1317856 Subcellular localization and membrane topology of serine pal... | ACCEPT | Summary: Cytoplasmic ER-face placement is supported by the target-specific reaction model. Reason: The original PMID1317856 topology experiment remains unverified because its full text was unavailable; its abstract is not treated as a human DEGS1 leaflet assay. Nevertheless, the independently inspected DEGS1 reaction R-HSA-428259 explicitly places the enzyme on the cytosolic face of the ER. This target-specific curated model corroborates the existing placement, with reaction details partly inferred from rat microsomes. Retain the annotation with curator deference and this independent support, without claiming that the older experiment was recovered or that complete human membrane topology was directly measured. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human immunofluorescence supports a mitochondrion-associated DEGS1 signal. Reason: The current Human Protein Atlas record for ENSG00000143753 lists mitochondria as the main subcellular location with supported reliability for antibody HPA076422; the mapped epitope is within canonical O15121. This supports the location assertion without specifying mitochondrial membrane topology or a separate catalytic core. ER/MAM enrichment and antibody-based mitochondrial localization need not be mutually exclusive. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:19647031 N-Myristoylation targets dihydroceramide Delta4-desaturase 1... | ACCEPT | Summary: ER-membrane localization is consistent with the myristoylation study and independently established human evidence. Reason: The PMID:19647031 abstract reports native desaturase activity in rat liver ER and mitochondrial fractions and preferential ER localization of a nonmyristoylatable recombinant protein in COS-7 cells. The full original and recombinant construct identity were not recovered. The broad ER-membrane claim is nevertheless independently supported by human DEGS1 imaging and fractionation; no unverified human construct or organelle-purity control is attributed to the inaccessible paper. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:30620338 DEGS1-associated aberrant sphingolipid metabolism impairs ne... | ACCEPT | Summary: Human DEGS1 localizes strongly to the ER membrane in the cited study. Reason: The recovered original reports sequence-verified human NM_003676.3 WT and A280V EGFP constructs in HeLa cells and strong overlap with ER marker PDI. Only little overlap with Tim23 was observed; that qualifier does not establish absence from mitochondria. The localization supports the principal ER site of desaturation. Supporting Evidence: |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:9188692 The product of the MLD gene is a member of the membrane fatt... | ACCEPT | Summary: The original human MLD study supports ER localization. Reason: The PMID:9188692 abstract explicitly reports human MLD expression, ER localization and detergent-dependent membrane extraction. Those observations support this broad ER-membrane assertion, independently corroborated by later human DEGS1 imaging. The full 1997 paper remains unavailable, so additional assay details are not supplied from inference. |
| GO:0031966 mitochondrial membrane | EXP PMID:19647031 N-Myristoylation targets dihydroceramide Delta4-desaturase 1... | KEEP AS NON CORE | Summary: Retain the reported mitochondrial-membrane localization with the original access limitation. Reason: PMID:19647031 reports mitochondrial targeting associated with recombinant DES1 myristoylation and native activity in rat liver mitochondrial fractions. The abstract provides positive location evidence, but construct species, fraction-purity controls and membrane topology could not be checked in the inaccessible full original. This existing curator-backed location is retained as non-core without recasting it as a demonstrated human endogenous mitochondrial catalytic mechanism. Supporting Evidence: PMID:19647031 native dihydroceramide Delta4-desaturase activity was found in both the endoplasmic reticulum and mitochondria in rat hepatocytes. |
| GO:0031966 mitochondrial membrane | EXP PMID:30620338 DEGS1-associated aberrant sphingolipid metabolism impairs ne... | KEEP AS NON CORE | Summary: The cited human experiment reports a small mitochondrial overlap rather than exclusive ER localization. Reason: Human EGFP-DEGS1 WT and A280V in HeLa cells showed strong PDI overlap and only little overlap with Tim23 in the recovered original. Retain this limited, existing mitochondrial-membrane assertion as non-core; the microscopy does not determine inner versus outer membrane or prove a physiologically separate mitochondrial enzyme pool. Later MAM enrichment further cautions against equating every adjacent signal with organelle residence. |
| GO:0042284 sphingolipid delta-4 desaturase activity | EXP PMID:11937514 Identification and characterization of a sphingolipid delta ... | ACCEPT | Summary: Human DES1 directly produces delta-4-unsaturated sphingolipids in the cited heterologous expression experiment. Reason: The recovered original identifies full-length human DES1 clone IMAGE 2578328/AF466375, expressed from pYES2 in sur2-deficient yeast. Hydrolyzed cellular sphingolipids contained the delta-4-unsaturated sphingoid product, absent with empty vector. This is direct human-product evidence, not merely a mouse DES2 result. Minor hydroxylated products were also reported across human/fly/fungal enzymes; predominant desaturation does not imply absolute absence of side activity. Supporting Evidence: PMID:11937514 identification of the enzyme sphingolipid Delta4-desaturase (dihydroceramide desaturase) from Homo sapiens |
| GO:0042284 sphingolipid delta-4 desaturase activity | IMP PMID:30620338 DEGS1-associated aberrant sphingolipid metabolism impairs ne... | ACCEPT | Summary: Human cellular and patient evidence supports DEGS1 desaturase activity. Reason: The recovered original measures labeled sphingolipid formation in patient fibroblasts and human HAP1 knockouts. A280V cells retain about one-fifth of control desaturation-associated conversion, while DEGS1 knockout shifts the pool strongly toward dihydrosphingolipids; DEGS2 knockout does not reproduce that effect. These cellular assays support the established N-acyl substrate reaction and do not demonstrate purified conversion of free sphinganine. Supporting Evidence: PMID:30620338 The enzymatic activity in patient fibroblasts was reduced by 80% |
| GO:0006686 sphingomyelin biosynthetic process | IDA PMID:24209621 A four-step cycle driven by PI(4)P hydrolysis directs sterol... | UNDECIDED | Summary: The cited source-specific sphingomyelin-biosynthesis evidence could not be adjudicated. Reason: PMID:24209621 was retrieved only as metadata and abstract; the original article and relevant DEGS1 experiments were not recovered. Its focus on OSBP does not establish that the curator misattributed the annotation. DEGS1 supplies ceramide used in sphingomyelin synthesis, but that biochemical relationship alone does not reconstruct this IDA assertion. Leave this row undecided pending access to its target-specific evidence. Supporting Evidence: |
| GO:0006688 glycosphingolipid biosynthetic process | IDA PMID:34080016 Glucosylceramide and galactosylceramide, small glycosphingol... | KEEP AS NON CORE | Summary: Retain glycosphingolipid biosynthesis as broader pathway participation through ceramide production. Reason: The cited full review describes glycosphingolipid synthesis beginning with ER ceramide production and assigns the sugar-transfer steps to UGCG and UGT8. DEGS1 executes the ceramide-desaturation step upstream, supported by human enzyme and lipidomic studies. This existing pathway assertion is retained as non-core; the review is not a new direct DEGS1 assay, and no glycosyltransferase activity is attributed to DEGS1. |
| GO:0046513 ceramide biosynthetic process | IDA PMID:16120614 Serinc, an activity-regulated protein family, incorporates s... | ACCEPT | Summary: The ceramide-biosynthesis assertion agrees with established DEGS1 chemistry. Reason: PMID:16120614 is available only as an abstract about SERINC proteins and serine incorporation; full-text recovery did not succeed. No unobserved DEGS1 experiment is claimed, and the title is not treated as evidence of wrong-gene attribution. The process itself is independently established for human DEGS1 by its direct desaturation reaction and cellular loss-of-function studies. |
| GO:0098554 cytoplasmic side of endoplasmic reticulum membrane | IDA PMID:16120614 Serinc, an activity-regulated protein family, incorporates s... | ACCEPT | Summary: Cytoplasmic ER-face placement is supported by the target-specific reaction model. Reason: The original PMID16120614 topology experiment remains unverified because its full text was unavailable; its abstract is not treated as a human DEGS1 leaflet assay. Nevertheless, the independently inspected DEGS1 reaction R-HSA-428259 explicitly places the enzyme on the cytosolic face of the ER. This target-specific curated model corroborates the existing placement, with reaction details partly inferred from rat microsomes. Retain the annotation with curator deference and this independent support, without claiming that the older experiment was recovered or that complete human membrane topology was directly measured. |
| GO:0050251 retinol isomerase activity | IDA PMID:23143414 Identification of DES1 as a vitamin A isomerase in Müller gl... | KEEP AS NON CORE | Summary: The cited original supports retinol-isomerase activity with important species and assay boundaries. Reason: Human DES1 in transfected 293T homogenates increases retinol-isomerization activity, and human DES1 overexpression rescues retinoid/response measures in Rpe65-deficient mice. The purified GST-DES1 and Müller-cell knockdown experiments are chicken experiments. These positive biochemical observations remain valid evidence; later mouse conditional and zebrafish knockout studies limit a universal physiological visual-cycle role rather than disproving human biochemical activity. Retain as non-core. Supporting Evidence: PMID:23143414 The rate of 11-cis-ROL synthesis was dramatically higher for DES1 versus the other membrane desaturases |
| GO:0042284 sphingolipid delta-4 desaturase activity | IMP PMID:30620337 Loss of the sphingolipid desaturase DEGS1 causes hypomyelina... | ACCEPT | Summary: Patient and model evidence corroborates DEGS1 dihydroceramide desaturation. Reason: The recovered full JCI original shows altered dihydroceramide/ceramide ratios in human patient cells and reduced degs1 function in a zebrafish splice-morpholino model. Lipidomics supports loss of the known desaturation step; it is not a purified human substrate-specificity assay. The positive IMP assertion agrees with direct human DES1 expression evidence. Supporting Evidence: PMID:30620337 detected a marked increase of the substrate DhCer and DhCer/Cer ratios |
| GO:0043217 myelin maintenance | IMP PMID:30620337 Loss of the sphingolipid desaturase DEGS1 causes hypomyelina... | KEEP AS NON CORE | Summary: DEGS1-dependent lipid homeostasis supports myelin integrity. Reason: The original describes human hypomyelinating leukodystrophy and impaired lipid composition, together with reduced MBP-positive oligodendrocytes and locomotor defects in a zebrafish knockdown model. These observations support the existing myelin-maintenance assertion as a physiological consequence of sphingolipid synthesis. They do not establish a distinct structural myelin activity or isolate mature-myelin maintenance from developmental myelination in every experiment. Supporting Evidence: |
| GO:0043217 myelin maintenance | IMP PMID:30620338 DEGS1-associated aberrant sphingolipid metabolism impairs ne... | KEEP AS NON CORE | Summary: The human disease study supports a role in preserving myelin through sphingolipid metabolism. Reason: The recovered original reports progressive neurological disease, thin myelin sheaths and impaired nerve conduction alongside defective DEGS1-dependent sphingolipid conversion. Retain the existing myelin-maintenance annotation as non-core. This does not turn the patient phenotype into a separate molecular activity or establish that DEGS1 is a structural myelin component. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6799350 | KEEP AS NON CORE | Summary: The curated neutrophil event explicitly includes DEGS1 at the plasma membrane after granule exocytosis. Reason: R-HSA-6799350 output set R-HSA-6806323 contains DEGS1 entity R-HSA-6806305, assigned to plasma membrane and reference O15121. This exact target path supports the TAS location; an ER principal site is not contrary evidence. The underlying granule-proteomics paper was not recovered in full, so individual peptide and fraction-purity evidence is not independently claimed. Retain the context-specific modeled localization as non-core. Supporting Evidence: Reactome:R-HSA-6799350 |
| GO:0035579 specific granule membrane | TAS Reactome:R-HSA-6799350 | KEEP AS NON CORE | Summary: The same curated event explicitly places DEGS1 in the specific-granule membrane input. Reason: R-HSA-6799350 input set R-HSA-6799368 contains DEGS1 entity R-HSA-6799512, assigned to GO:0035579 and reference O15121. This is a target-specific source assertion, not merely membership in an unrelated pathway. It does not show granule-specific catalysis, and the underlying proteomics was not independently re-audited. The location is retained as non-core rather than rejected because DEGS1 mainly acts at the ER. Supporting Evidence: Reactome:R-HSA-6799350 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-428259 | ACCEPT | Summary: Reactome places the DEGS1 catalyst in the ER membrane. Reason: The catalyst activity and physical entity of R-HSA-428259 explicitly identify DEGS1 in the ER membrane. Human localization evidence independently supports this principal catalytic site, including enrichment in ER domains contacting mitochondria. |
| GO:0009055 electron transfer activity | TAS PMID:9188692 The product of the MLD gene is a member of the membrane fatt... | KEEP AS NON CORE | Summary: Electron-transfer activity is compatible with the redox chemistry but is not a separate core assignment. Reason: Retain this broad historical TAS as non-core with curator deference. The current GO:0009055 definition includes directed electron transfer in enzymatic redox reactions, not only mobile carriers; DEGS1 performs the terminal lipid desaturation in a cytochrome-b5-dependent redox reaction. Cytochrome b5 is the separate electron-supplying partner, and DEGS1 is not assigned a fused b5 domain, free-carrier role or additional electron-transport core. The PMID9188692 full original remains unavailable, so no independent electron-transfer assay is claimed. The specific desaturase activity captures the principal chemistry; a typed ancestor relation to GO:0009055 was not found and is not asserted. Supporting Evidence: Reactome:R-HSA-428259 PMID:23143414 DES1 is coupled to the cytochrome b5 electron-transport chain |
| GO:0005783 endoplasmic reticulum | TAS PMID:9188692 The product of the MLD gene is a member of the membrane fatt... | ACCEPT | Summary: The human MLD study supports the ER location. Reason: The accessible original abstract explicitly describes ER localization of the human protein. Later human EGFP imaging and fibroblast/brain fractionation independently support this cellular compartment. The broad ER term remains a useful location descriptor and does not imply absence from other membrane compartments. Supporting Evidence: PMID:9188692 MLD is widely expressed in human tissues and is localized to the endoplasmic reticulum. |
| GO:0005886 plasma membrane | TAS PMID:9188692 The product of the MLD gene is a member of the membrane fatt... | KEEP AS NON CORE | Summary: Retain context-specific plasma-membrane localization with explicit source-access limits. Reason: The PMID9188692 abstract establishes human ER association, but its full original and plasma-membrane experiment remain unavailable. Independent positive corroboration comes from the Reactome exocytosis event R-HSA-6799350: output set R-HSA-6806323 contains the O15121 DEGS1 entity R-HSA-6806305 at the plasma membrane. Retain this existing location non-core, consistently with the Reactome-derived row, without treating that model as recovery of the 1997 experiment or making plasma membrane the principal catalytic compartment. The underlying granule-proteomics assignments were not independently re-audited. |
| GO:0006636 unsaturated fatty acid biosynthetic process | TAS PMID:9188692 The product of the MLD gene is a member of the membrane fatt... | MODIFY | Summary: Replace the early fatty-acid pathway description with the established ceramide-biosynthesis step. Reason: The checked GO:0006636 definition concerns formation of unsaturated fatty acids. Later direct human DES1 experiments identify delta-4 desaturation of the sphingoid backbone in sphingolipids, and the curated reaction converts N-acylsphinganine to N-acylsphing-4-enine without desaturating its attached fatty-acid chain. GO:0046513 therefore describes the demonstrated process. The 1997 full text remains unavailable; this correction uses positive later chemistry, not a claim of wrong-gene attribution or an assertion that every unobserved experiment was negative. Proposed replacements: ceramide biosynthetic process |
| GO:0016020 membrane | TAS PMID:9188692 The product of the MLD gene is a member of the membrane fatt... | MODIFY | Summary: The broad membrane location is already entailed by accepted ER-membrane annotations. Reason: The original abstract supports membrane association, so the assertion is not false. The checked is_a path GO:0005789 → GO:0031090 → GO:0016020 supplies the more informative existing location. This specificity judgment does not imply exclusive ER localization. Refine this broad assertion to endoplasmic reticulum membrane under the project instruction to specify supported replacements. The term is already represented, so this adds specificity without additional biological coverage. Proposed replacements: endoplasmic reticulum membrane |
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Download this section (compressed HTML)Q: Under which physiological cellular and species contexts does DEGS1 retinol-isomerase activity materially contribute to visual chromophore regeneration, independently of its effects on sphingolipid composition?
Q: Which endogenous human DEGS1 pools reside within mitochondrial membranes, and which reside in adjacent ER contact domains, under basal and altered myristoylation conditions?
Experiment: Resolve endogenous human DEGS1 membrane topology and ER-contact versus mitochondrial residence using validated compartment markers and orthogonal localization assays.
Experiment: Compare human DEGS1 desaturation and retinol-isomerization activities in matched reconstituted preparations and active-site variants. Quantify both products with authentic standards, and control protein abundance, folding, membrane insertion and electron-donor availability, so loss of activity can be distinguished from misfolding or mistargeting.
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