ELOVL3 (very long chain fatty acid elongase 3; also known as ELOVL fatty acid elongase 3, 3-keto/oxoacyl-CoA synthase ELOVL3, or cold-inducible glycoprotein CIG30) is a multipass endoplasmic reticulum membrane enzyme of the ELO family. It catalyzes the first and rate-limiting condensation step of the microsomal (very-)long-chain fatty acid elongation cycle, condensing an acyl-CoA with malonyl-CoA to yield a 3-oxoacyl-CoA plus CO2 and CoA (EC 2.3.1.199); the 3-oxoacyl-CoA is subsequently reduced, dehydrated and reduced by the other elongation-cycle enzymes (KAR/HSD17B12, HACD1/2, TECR) to extend the chain by two carbons per cycle. ELOVL3 is a condensing enzyme with activity toward saturated and unsaturated acyl-CoA substrates in roughly the C16-C22 range, showing higher activity toward C18 (especially C18:0) acyl-CoAs, thereby producing mid-chain saturated and monounsaturated very-long-chain fatty acids that serve as precursors of membrane lipids and lipid mediators. It is highly expressed in brown adipose tissue, skin (sebaceous glands) and hair follicles, where it contributes to cold-induced thermogenesis and to skin/hair lipid-barrier formation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ELOVL3 is a multipass endoplasmic reticulum membrane protein and the elongation condensation step occurs at the ER membrane. Correct and specific location; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0009922 fatty acid elongase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. GO:0009922 is defined as the condensation reaction (very-long-chain acyl-CoA + malonyl-CoA = very-long-chain 3-oxoacyl-CoA + CO2 + CoA), exactly matching ELOVL3's EC 2.3.1.199 activity. Well supported by phylogeny and experiment; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt Catalyzes the first and rate-limiting reaction of the four |
| GO:0042761 very long-chain fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: ELOVL3 elongates acyl-CoAs into (very-)long-chain fatty acids; this is its core biological process. Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt of 2 carbons to the chain of long- and very long-chain fatty acids |
| GO:0030148 sphingolipid biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: VLC acyl-CoAs produced by elongases can feed sphingolipid synthesis, but for ELOVL3 specifically this is a downstream pathway contribution rather than its core direct function (the sphingolipid link is best established for ELOVL1/C24-CoA production). Keep as non-core. |
| GO:0034626 fatty acid elongation, polyunsaturated fatty acid | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ELOVL3 can elongate some polyunsaturated acyl-CoAs (e.g. C18:2, C18:3), but its higher activity is toward saturated/monounsaturated C18 substrates. Correct but a secondary activity; keep as non-core. |
| GO:0019367 fatty acid elongation, saturated fatty acid | IBA GO_REF:0000033 | ACCEPT | Summary: ELOVL3 preferentially elongates saturated acyl-CoAs (highest activity toward C18:0). Well supported process; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. |
| GO:0034625 fatty acid elongation, monounsaturated fatty acid | IBA GO_REF:0000033 | ACCEPT | Summary: ELOVL3 also elongates monounsaturated acyl-CoAs (e.g. C18:1). Supported by IDA in PMID:20937905; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt production of saturated and monounsaturated VLCFAs |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Correct organelle, but the ER membrane (GO:0005789) is the more informative location supported by direct evidence. The whole-ER term is a less-specific parent; keep as non-core. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Correct location, redundant with the experimentally supported ER membrane annotation. Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006636 unsaturated fatty acid biosynthetic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: ELOVL3 elongates some unsaturated acyl-CoAs, so this general process is not wrong, but it over-emphasizes the unsaturated role when ELOVL3's higher activity is on saturated C18:0. General/secondary; keep as non-core. |
| GO:0009922 fatty acid elongase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Redundant electronic support for the core MF (GO:0009922), consistent with EC 2.3.1.199 and the Rhea reaction. Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt EC=2.3.1.199 |
| GO:0016020 membrane | IEA GO_REF:0000120 | REMOVE | Summary: Uninformative high-level location. ELOVL3 is specifically an ER membrane protein (GO:0005789); the bare "membrane" term is an over-annotation. As an IEA it can be removed in favor of the specific term. |
| GO:0019367 fatty acid elongation, saturated fatty acid | IEA GO_REF:0000120 | ACCEPT | Summary: Redundant electronic support for the saturated-FA elongation process, also supported by IDA. Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. |
| GO:0030497 fatty acid elongation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Correct but general parent of the specific saturated/monounsaturated elongation terms. Keep as non-core. |
| GO:0034625 fatty acid elongation, monounsaturated fatty acid | IEA GO_REF:0000120 | ACCEPT | Summary: Redundant electronic support for monounsaturated-FA elongation, also supported by IDA (PMID:20937905). Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt production of saturated and monounsaturated VLCFAs |
| GO:0034626 fatty acid elongation, polyunsaturated fatty acid | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Secondary activity (ELOVL3 elongates some PUFA-CoAs). Correct but non-core; keep as non-core. |
| GO:0035338 long-chain fatty-acyl-CoA biosynthetic process | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Products of the elongation cycle are long-chain acyl-CoAs; correct but a general pathway-level term. Keep as non-core. |
| GO:0042761 very long-chain fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Redundant electronic support for the core VLCFA biosynthesis process, also supported by IDA. Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt of 2 carbons to the chain of long- and very long-chain fatty acids |
| GO:0120162 positive regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Elovl3 (O35949), where cold-induced upregulation and knockout phenotypes implicate it in brown-adipose-tissue thermogenesis. This is a downstream physiological/regulatory role, not the enzyme's molecular function; keep as non-core. |
| GO:0035338 long-chain fatty-acyl-CoA biosynthetic process | TAS Reactome:R-HSA-75876 | KEEP AS NON CORE | Summary: Reactome pathway "Synthesis of very long-chain fatty acyl-CoAs". Correct but general pathway-level term; keep as non-core. |
| GO:0036109 alpha-linolenic acid metabolic process | TAS Reactome:R-HSA-2046106 | KEEP AS NON CORE | Summary: Reactome places ELOVL3 in ALA (n-3 PUFA) metabolism, reflecting its ability to elongate C18:3 n-3 acyl-CoA. A pathway-context annotation for a secondary substrate; keep as non-core. |
| GO:0043651 linoleic acid metabolic process | TAS Reactome:R-HSA-2046105 | KEEP AS NON CORE | Summary: Reactome places ELOVL3 in LA (n-6 PUFA) metabolism, reflecting elongation of C18:2 n-6 acyl-CoA. Pathway-context annotation for a secondary substrate; keep as non-core. |
| GO:0009922 fatty acid elongase activity | EXP PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in ... | ACCEPT | Summary: Core MF (fatty acid elongase / condensing activity). The cited paper's abstract actually describes cloning of HELO1 (ELOVL5), a paralog on chromosome 6 that elongates long-chain PUFAs (C18:3->C20:3, the ELOVL5 signature), so the reference is likely mis-attributed to ELOVL3; however the GO term itself is correct for ELOVL3 and independently supported by experimental assays (PMID:19575253, PMID:20937905). Accept the term; the citation problem is noted in reference_review. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt EC=2.3.1.199 |
| GO:0009922 fatty acid elongase activity | TAS Reactome:R-HSA-548814 | ACCEPT | Summary: Reactome reaction "ELOVL3,6,7 elongate PALM-CoA and Mal-CoA to 3OOD-CoA" supports the core elongase MF (palmitoyl-CoA + malonyl-CoA condensation). Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt hexadecanoyl-CoA + malonyl-CoA + H(+) = 3-oxooctadecanoyl-CoA |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | ACCEPT | Summary: Experimentally supported ER membrane localization (UniProt cites this paper for subcellular location). Core location; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0009922 fatty acid elongase activity | EXP PMID:19575253 Development of a high-density assay for long-chain fatty acy... | ACCEPT | Summary: Direct enzymatic assay of recombinant human ELOVL3 (with ELOVL1,-2,-5,-6); ELOVL1/3/6 preferentially elongate saturated acyl-CoAs. Strong experimental support for the core elongase MF. Accept. Supporting Evidence: PMID:19575253 ELOVL1, -3 and -6 preferably elongated the saturated fatty acyl-CoAs |
| GO:0009922 fatty acid elongase activity | EXP PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | ACCEPT | Summary: In vitro determination of the substrate specificities of all ELOVLs including ELOVL3; UniProt derives ELOVL3's EC 2.3.1.199 catalytic activity (multiple Rhea reactions) from this paper. Core MF; accept. Supporting Evidence: PMID:20937905 we determined the precise substrate specificities of all the ELOVLs by in vitro analyses |
| GO:0005515 protein binding | IPI PMID:38422897 The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with tran... | MARK AS OVER ANNOTATED | Summary: Records the ELOVL3-TECR interaction (with UniProtKB:Q9NZ01 = TECR), a functionally meaningful pairing since TECR catalyzes the fourth step of the same elongation cycle. However GO:0005515 "protein binding" is uninformative as a molecular function; the biology belongs in a complex/pathway statement. Kept but flagged as over-annotated (experimental IPI, not removed per policy). Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt Interacts with TECR. |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:16326704 ELOVL3 is an important component for early onset of lipid re... | KEEP AS NON CORE | Summary: Based on mouse Elovl3: its mRNA is induced >200-fold in cold-stressed mice and Elovl3-null mice fail to hyperrecruit brown adipose tissue, implicating it in cold-induced thermogenesis. This is a physiological role of the gene, distinct from its core enzymatic function; keep as non-core. Supporting Evidence: PMID:16326704 the mRNA level of the fatty acyl chain elongase Elovl3 is elevated more than 200-fold in cold-stressed mice |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-2046088 | ACCEPT | Summary: Correct ER membrane location (Reactome). Redundant with the experimentally supported annotation; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-2046094 | ACCEPT | Summary: Correct ER membrane location (Reactome). Redundant duplicate; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-548800 | ACCEPT | Summary: Correct ER membrane location (Reactome). Redundant duplicate; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-548814 | ACCEPT | Summary: Correct ER membrane location (Reactome). Redundant duplicate; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0034626 fatty acid elongation, polyunsaturated fatty acid | IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | KEEP AS NON CORE | Summary: Direct assay showing ELOVL3 elongates some polyunsaturated acyl-CoAs (UniProt records C18:2 and C18:3 substrate reactions from this paper). A secondary activity relative to its saturated-FA preference; keep as non-core. Supporting Evidence: PMID:20937905 we determined the precise substrate specificities of all the ELOVLs by in vitro analyses |
| GO:0042761 very long-chain fatty acid biosynthetic process | IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | ACCEPT | Summary: Direct in vitro evidence that ELOVL3 produces very-long-chain acyl-CoAs (e.g. C20->C22, C22->C24 reactions). Core biological process; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt production of saturated and monounsaturated VLCFAs of different |
| GO:0005515 protein binding | IPI PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" IPI with UniProtKB:Q96G23 (CERS2, ceramide synthase 2). In this paper the CERS2 regulatory partnership was established for ELOVL1, not ELOVL3, and GO:0005515 is uninformative as a molecular function regardless. Kept but flagged as over-annotated (experimental IPI, not removed per policy). |
| GO:0005783 endoplasmic reticulum | IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | KEEP AS NON CORE | Summary: Direct evidence of ER localization. The more specific ER membrane term (GO:0005789) is the informative location; this whole-ER term is a less-specific parent, kept as non-core. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0019367 fatty acid elongation, saturated fatty acid | IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | ACCEPT | Summary: Direct in vitro evidence that ELOVL3 elongates saturated acyl-CoAs (its preferred substrate class, highest activity toward C18:0). Core process; accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. |
| GO:0034625 fatty acid elongation, monounsaturated fatty acid | IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | ACCEPT | Summary: Direct in vitro evidence that ELOVL3 elongates monounsaturated acyl-CoAs (e.g. C18:1). Accept. Supporting Evidence: file:human/ELOVL3/ELOVL3-uniprot.txt production of saturated and monounsaturated VLCFAs |
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