SELENOI (ethanolaminephosphotransferase 1, EPT1/hEPT1; also known as Selenoprotein I) is a multi-pass endoplasmic reticulum membrane enzyme of the CDP-alcohol phosphatidyltransferase class-I family. It catalyzes the final (third) step of the CDP-ethanolamine branch of the Kennedy pathway, transferring a phosphoethanolamine group from CDP-ethanolamine to a diacylglycerol acceptor to produce phosphatidylethanolamine (PE) plus CMP (EC 2.7.8.1); catalysis requires a divalent cation (Mg2+ or Mn2+). It is specific for CDP-ethanolamine (rather than CDP-choline) as the phosphobase donor. In addition to diacyl-PE, it uses 1-O-alkyl-2-acylglycerol acceptors to make ether-linked PE (plasmanyl-/plasmenyl-PE, a plasmalogen precursor), contributing to the pool of ether-linked phospholipids important for myelin. As a selenoprotein, it incorporates a selenocysteine near its C-terminus (residue 387). PE is the second most abundant membrane glycerophospholipid in mammalian cells, and SELENOI-mediated PE and plasmalogen synthesis supports membrane biogenesis, myelination and neurodevelopment. Loss-of-function variants cause an autosomal recessive complicated hereditary spastic paraplegia (SPG81) with hypomyelinating white-matter disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004307 ethanolaminephosphotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred core molecular function. This is the correct, specific MF for SELENOI/EPT1 and is directly corroborated by experimental IDA/IMP evidence. |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred ER-membrane localization, consistent with the experimentally supported (IDA, TAS) and UniProt-curated ER-membrane location. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetic (IBA) over-propagation from the broader CEPT/EPT family; some paralogous family members (e.g. CEPT1) localize partly to Golgi/nuclear envelope, but SELENOI/EPT1 itself is established as an endoplasmic reticulum membrane enzyme by UniProt subcellular location, Reactome (TAS), and the IDA annotation. Not a demonstrated location for this gene product. Retained rather than removed because it is an evolutionary-model inference, not experimental. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred core biological process; matches the specific role of SELENOI as the final enzyme of PE biosynthesis via the CDP-ethanolamine pathway and is corroborated by experimental IDA/IMP evidence. |
| GO:0004307 ethanolaminephosphotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (ARBA/RHEA/EC 2.7.8.1) assertion of the correct core MF. Redundant with the experimental IDA/IMP annotations but consistent; accepted as the core catalytic function. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping from the UniProt subcellular-location vocabulary (SL-0097). Correct; matches the curated ER-membrane location. |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Correct but a high-level generalization. The specific, experimentally supported process is phosphatidylethanolamine biosynthesis (GO:0006646); this generic term adds little and is over-annotated relative to the specific child. |
| GO:0008654 phospholipid biosynthetic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO mapping. Correct in direction but too general; the specific process is PE biosynthesis (GO:0006646). Over-annotated relative to the more informative child term. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO mapping reflecting the multi-pass membrane topology. Correct but generic; the specific, experimentally supported localization is the endoplasmic reticulum membrane (GO:0005789). |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping to the parent of the specific activity. This is the direct is-a parent of ethanolaminephosphotransferase activity (GO:0004307); the specific term is available and experimentally supported, so this should be replaced by the more informative child. Proposed replacements: ethanolaminephosphotransferase activity |
| GO:0008611 ether lipid biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Automated ortholog transfer (from mouse Q80TA1). Supported: EPT1 uses 1-O-alkyl-2-acylglycerol acceptors to make ether-linked PE (plasmanyl-/plasmenyl-PE), and its loss reduces plasmenyl-PE (PMID:29500230). A genuine but secondary function relative to the core diacyl-PE synthesis. Supporting Evidence: PMID:29500230 most plasmenyl-PE species were significantly decreased in the patient's cells, |
| GO:0042552 myelination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Automated ortholog transfer. Myelination is a downstream/physiological consequence of SELENOI-dependent PE and plasmalogen synthesis (plasmalogens are major myelin components), not a molecular activity or process the enzyme directly executes. Biologically relevant but pleiotropic/consequential, so kept as non-core. Supporting Evidence: PMID:29500230 the indispensable role of EPT1 in the |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway (UPA00558) mapping to the correct, specific biosynthetic process. Consistent with the curated PATHWAY (PE from ethanolamine, step 3/3) and the experimental IDA/IMP annotations. |
| GO:0004307 ethanolaminephosphotransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of the core MF (from mouse). Correct and redundant with the human experimental evidence. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:28052917 A mutation of EPT1 (SELENOI) underlies a new disorder of Ken... | ACCEPT | Summary: Experimental localization. In this study human EPT1 expressed in yeast partitioned to the membrane fraction as expected for an integral membrane protein; combined with UniProt subcellular location and Reactome, the ER-membrane assignment is well established. Accepted as the core cellular location. (The direct assay was membrane-fraction partitioning in a heterologous system rather than ER imaging, but the ER location is corroborated by multiple independent sources.) Supporting Evidence: PMID:28052917 membrane fraction as would be expected for an integral membrane protein |
| GO:0008611 ether lipid biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of the ether-lipid role. Genuinely supported (plasmanyl-/ plasmenyl-PE synthesis), but a secondary activity relative to core diacyl-PE synthesis. Supporting Evidence: PMID:29500230 most plasmenyl-PE species were significantly decreased in the patient's cells, |
| GO:0042552 myelination | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer. As with the Ensembl IEA myelination call, this reflects a downstream physiological consequence of PE/plasmalogen synthesis rather than a direct enzyme function; kept as non-core. Supporting Evidence: PMID:29500230 the indispensable role of EPT1 in the |
| GO:0004307 ethanolaminephosphotransferase activity | IMP PMID:29500230 EPT1 (selenoprotein I) is critical for the neural developmen... | ACCEPT | Summary: Experimental (mutant/knockout) evidence for the core ethanolaminephosphotransferase activity: an EPT1 exon-skipping mutation and EPT1-KO HeLa cells reduce EPT activity and ethanolamine glycerophospholipid synthesis. Core molecular function. Supporting Evidence: PMID:29500230 is an enzyme that transfers phosphoethanolamine from cytidine |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IMP PMID:29500230 EPT1 (selenoprotein I) is critical for the neural developmen... | ACCEPT | Summary: Experimental evidence that loss of EPT1 reduces synthesis of PE species (and plasmenyl-PE), supporting the core PE biosynthetic process. Supporting Evidence: PMID:29500230 most plasmenyl-PE species were significantly decreased in the patient's cells, |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IMP PMID:28052917 A mutation of EPT1 (SELENOI) underlies a new disorder of Ken... | ACCEPT | Summary: Experimental loss-of-function evidence: the SPG81 p.Arg112Pro variant reduced PE synthesis (14C-ethanolamine incorporation only 3% of wild type) in a yeast complementation assay, supporting the core PE biosynthetic process. Supporting Evidence: PMID:28052917 only 3% that of wild-type EPT1 |
| GO:0004307 ethanolaminephosphotransferase activity | IMP PMID:28052917 A mutation of EPT1 (SELENOI) underlies a new disorder of Ken... | ACCEPT | Summary: Experimental evidence for the core catalytic activity via functional complementation in a yeast strain devoid of endogenous ethanolaminephosphotransferase activity; the disease variant markedly reduced activity. Core molecular function. Supporting Evidence: PMID:28052917 devoid of endogenous ethanolaminephosphotransferase activity |
| GO:0004307 ethanolaminephosphotransferase activity | IDA PMID:17132865 Identification and characterization of human ethanolaminepho... | ACCEPT | Summary: Direct assay: recombinant hEPT1 specifically used CDP-ethanolamine as the phosphobase donor to produce PE, activated by Mn2+ and Mg2+. Definitive experimental support for the core molecular function. Supporting Evidence: PMID:17132865 specifically used CDP-ethanolamine as the phosphobase donor to |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IDA PMID:17132865 Identification and characterization of human ethanolaminepho... | ACCEPT | Summary: Direct evidence that hEPT1 produces PE via the Kennedy (CDP-ethanolamine) pathway. Core biological process. Supporting Evidence: PMID:17132865 produce PE with the activation by both Mn(2+) and Mg(2+) |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-1482962 | ACCEPT | Summary: Reactome curated statement placing the CEPT1/EPT1 reaction at the endoplasmic reticulum membrane. Consistent with the core ER-membrane localization. |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)