elo2 (SPAC1B2.03c) encodes the very-long-chain fatty acid elongase (ELO/ELOVL family 3-ketoacyl-CoA synthase) of fission yeast, a multi-pass membrane protein of the endoplasmic reticulum and the continuous nuclear envelope. It catalyses the condensation of long/very-long-chain acyl-CoA with malonyl-CoA to a 3-oxoacyl-CoA two carbons longer, the first and rate-limiting, chain-length-selective step of the ER elongation cycle whose remaining steps are carried out by the 3-ketoreductase ifa38, the dehydratase phs1 and the enoyl reductase tsc13. Elo2 produces the C24:0 fatty acid that is the acyl chain of the major S. pombe phytoceramide (t20:0/24:0) and hence of complex sphingolipids; S. pombe has only one other ELO-family elongase (elo1). Loss of elo2 is rescued by human ELOVLs, and increased Elo2 restores ceramide levels and suppresses lethal nuclear envelope ruptures in lem2 and bqt4 mutants, linking VLCFA supply to nuclear membrane integrity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Genome-wide ORFeome YFP-tagging (Matsuyama et al. 2006) localised Elo2 to the ER; consistent with the experimental ER/nuclear-membrane localisation of Kinugasa et al. 2019. GO:0005789 is the more precise term. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins file:SCHPO/elo2/elo2-uniprot.txt Endoplasmic reticulum |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning rule ARBA00028672 assigns ER; correct for this ELO-family elongase, though less precise than ER membrane. Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:30975915 The very-long-chain fatty acid elongase Elo2 rescues lethal ... | ACCEPT | Summary: Kinugasa et al. 2019 localised Elo2 to the ER and nuclear membranes in S. pombe; UniProt cites this paper for ER membrane localisation. The ER membrane is where the elongation cycle operates. Supporting Evidence: PMID:30975915 We found that the very-long-chain fatty acid elongase Elo2 is located in the nuclear membrane file:SCHPO/elo2/elo2-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the ELO/ELOVL node PTN000125390 (donors include S. cerevisiae ELO1/2/3, human ELOVL1-7 and S. pombe elo2 itself). ER membrane residence is conserved across ELO/ELOVL elongases and is experimentally confirmed for S. pombe Elo2. Supporting Evidence: PMID:30975915 We found that the very-long-chain fatty acid elongase Elo2 is located in the nuclear membrane file:SCHPO/elo2/elo2-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0097) from the curated 'Endoplasmic reticulum membrane' entry, itself backed by PMID:16823372 and PMID:30975915. Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: PomBase ISS from human ELOVL4 (Q9GZR5). Correct and redundant with the direct experimental ER-membrane annotation. Supporting Evidence: PMID:30975915 We found that the very-long-chain fatty acid elongase Elo2 is located in the nuclear membrane |
| GO:0009922 fatty acid elongase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the ELO/ELOVL node PTN000125390 (donors include S. cerevisiae ELO1/2/3, human ELOVL1-7 and S. pombe elo2 itself). The condensing (3-ketoacyl-CoA synthase) activity is the defining activity of the clade; S. pombe elo2 retains the HxxHH catalytic motif and has its own experimental support. Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt Reaction=docosanoyl-CoA + malonyl-CoA + H(+) = 3-oxotetracosanoyl-CoA + file:SCHPO/elo2/elo2-uniprot.txt SIMILARITY: Belongs to the ELO family. |
| GO:0009922 fatty acid elongase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from InterPro IPR002076 (ELO family), RHEA:32727 and EC 2.3.1.199. Correct for this protein. Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt Reaction=docosanoyl-CoA + malonyl-CoA + H(+) = 3-oxotetracosanoyl-CoA + |
| GO:0009922 fatty acid elongase activity | IMP PMID:30975915 The very-long-chain fatty acid elongase Elo2 rescues lethal ... | ACCEPT | Summary: Kinugasa et al. 2019: Elo2 is required for C24:0-containing phytoceramide and its loss is rescued by human ELOVL orthologs; UniProt records the docosanoyl-CoA condensation (C22 to 3-oxo-C24) with experimental evidence from this paper. Core activity. Supporting Evidence: PMID:30975915 Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe PMID:30975915 loss of S. pombe Elo2 can be rescued by its human orthologs file:SCHPO/elo2/elo2-uniprot.txt Reaction=docosanoyl-CoA + malonyl-CoA + H(+) = 3-oxotetracosanoyl-CoA + |
| GO:0009922 fatty acid elongase activity | ISS GO_REF:0000024 | ACCEPT | Summary: PomBase ISS from S. cerevisiae ELO3 (P40319), the C24-to-C26 elongase. Correct activity; note that S. pombe elo2 is the only VLCFA elongase and covers the ELO2+ELO3 chain-length range up to C24 rather than mapping 1:1 to ELO3. Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt Reaction=docosanoyl-CoA + malonyl-CoA + H(+) = 3-oxotetracosanoyl-CoA + |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR002076) assigns generic 'membrane'. True but uninformative; the specific membrane is the ER membrane (and nuclear envelope). Reason: More precise location is experimentally established. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt Endoplasmic reticulum |
| GO:0019367 fatty acid elongation, saturated fatty acid | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the ELO/ELOVL node PTN000125390 (donors include S. cerevisiae ELO1/2/3, human ELOVL1-7 and S. pombe elo2 itself). Saturated-chain elongation is supported for S. pombe Elo2, whose main product is the saturated C24:0 acyl chain of phytoceramide. Supporting Evidence: PMID:30975915 Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe |
| GO:0030148 sphingolipid biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA from the ELO/ELOVL node PTN000125390 (donors include S. cerevisiae ELO1/2/3, human ELOVL1-7 and S. pombe elo2 itself). Elo2 supplies the C24:0 fatty acid of S. pombe ceramide, so it contributes to sphingolipid biosynthesis upstream; the enzyme itself acts in fatty-acid elongation, not in ceramide/sphingolipid assembly. Reason: Downstream consequence of VLCFA supply; kept as non-core, consistent with the S. cerevisiae ELO2 review. Supporting Evidence: PMID:30975915 Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe |
| GO:0031965 nuclear membrane | EXP PMID:30975915 The very-long-chain fatty acid elongase Elo2 rescues lethal ... | ACCEPT | Summary: Kinugasa et al. 2019 showed Elo2 in the nuclear membrane (continuous with the ER); UniProt records 'Nucleus membrane' from this paper. Relevant to its role in nuclear-envelope integrity. Supporting Evidence: PMID:30975915 We found that the very-long-chain fatty acid elongase Elo2 is located in the nuclear membrane file:SCHPO/elo2/elo2-uniprot.txt SUBCELLULAR LOCATION: Nucleus membrane |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0182 Nucleus membrane), derived from the experimental UniProt entry. Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt SUBCELLULAR LOCATION: Nucleus membrane |
| GO:0034625 fatty acid elongation, monounsaturated fatty acid | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA from the ELO/ELOVL node PTN000125390 (donors include S. cerevisiae ELO1/2/3, human ELOVL1-7 and S. pombe elo2 itself). The monounsaturated-substrate branch was seeded by animal ELOVLs (ELOVL1/3/7, Elovl6 etc.); no S. pombe data show Elo2 elongating monounsaturated acyl-CoAs, and its documented product is saturated C24:0. Reason: Substrate-saturation specialisations differ among ELO paralogs; not supported for S. pombe Elo2. Same call as for S. cerevisiae ELO2. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000125390 · PTN000125390 SUPPORTS SOURCE BUT NOT TARGET Monounsaturated-substrate elongation is shown for animal ELOVL paralogs, not for S. pombe Elo2. Supporting Evidence: PMID:30975915 Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe |
| GO:0034626 fatty acid elongation, polyunsaturated fatty acid | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA from the ELO/ELOVL node PTN000125390 (donors include S. cerevisiae ELO1/2/3, human ELOVL1-7 and S. pombe elo2 itself). The PUFA-elongation branch derives from animal ELOVL2/4/5/7 donors. S. pombe makes no polyunsaturated fatty acids for Elo2 to elongate, and its characterised product is saturated C24:0. Reason: Pathway context absent in the organism (no PUFA substrates); paralog-specific function over-propagated from animal ELOVL2/5. Consistent with the REMOVE in the S. cerevisiae ELO2 review. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000125390 · PTN000125390 SUPPORTS SOURCE BUT NOT TARGET PUFA elongation is a property of animal ELOVL2/4/5 donors; fission yeast has no PUFA substrates. Supporting Evidence: PMID:30975915 Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe |
| GO:0042761 very long-chain fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the ELO/ELOVL node PTN000125390 (donors include S. cerevisiae ELO1/2/3, human ELOVL1-7 and S. pombe elo2 itself). VLCFA synthesis is the core process; S. pombe Elo2 produces C24 VLCFA. Supporting Evidence: file:SCHPO/elo2/elo2-uniprot.txt elongation system, which produces the 24-carbon very long-chain fatty PMID:30975915 Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe |
| GO:0071763 nuclear membrane organization | IMP PMID:30975915 The very-long-chain fatty acid elongase Elo2 rescues lethal ... | KEEP AS NON CORE | Summary: Kinugasa et al. 2019: elo2 is needed to prevent lethal nuclear-membrane rupture in lem2/bqt4 mutants and its overexpression suppresses those defects. The effect is mediated through VLCFA/ceramide supply rather than a structural role in organising the nuclear membrane. Reason: Genuine experimental phenotype but an indirect, downstream role; the gene product's own activity is VLCFA elongation. Supporting Evidence: PMID:30975915 elongase producing the ceramide component is essential for nuclear membrane integrity and cell viability in eukaryotes PMID:30975915 We found that the very-long-chain fatty acid elongase Elo2 is located in the nuclear membrane |
Loading supporting content…
Download this section (compressed HTML)Q: What is the substrate chain-length window of S. pombe Elo2 versus Elo1 in vitro, and does Elo2 alone account for all C20-C24 elongation?
Loading supporting content…
Download this section (compressed HTML)