ELOVL5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: ELOVL5 is an integral membrane protein of the endoplasmic reticulum. Multiple studies confirm ER localization including PMID:20937905 showing ER localization in mammalian cells and PMID:25065913 showing wild-type ELOVL5 localizes to the ER in transfection experiments. UniProt describes it as a multi-pass ER membrane protein with seven transmembrane helices. Reason: Well-supported by phylogenetic inference (IBA), consistent with direct experimental evidence from multiple publications and the known biology of the ELOVL enzyme family which functions exclusively in the ER elongation cycle. Supporting Evidence: PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. PMID:25065913 2014 Jul 24. ELOVL5 mutations cause spinocerebellar ataxia 38. file:human/ELOVL5/ELOVL5-deep-research-falcon.md model: Edison Scientific Literature
GO:0009922 fatty acid elongase activity	IBA GO_REF:0000033	ACCEPT	Summary: ELOVL5 is a bona fide fatty acid elongase that catalyzes the condensation of acyl-CoA with malonyl-CoA (EC 2.3.1.199). This is the first and rate-limiting step of the four-reaction VLCFA elongation cycle. PMID:10970790 originally cloned and characterized this activity; PMID:20937905 performed systematic in vitro substrate specificity analysis. Reason: Core enzymatic function of ELOVL5 supported by extensive experimental evidence and phylogenetic conservation across the ELOVL family. Supporting Evidence: PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.
GO:0030148 sphingolipid biosynthetic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: While ELOVL1 is specifically linked to C24 sphingolipid synthesis (PMID:20937905), ELOVL5 preferentially elongates PUFAs rather than the saturated/monounsaturated fatty acids that are primary sphingolipid precursors. The IBA annotation may reflect broader family-level inference from yeast ELO genes. ELOVL5 contribution to sphingolipid metabolism is indirect at best. Reason: ELOVL5 substrate specificity is primarily toward PUFAs (C18-C20 polyunsaturated), not the saturated/monounsaturated VLCFAs that are incorporated into sphingolipids. PMID:20937905 specifically attributes C24 sphingolipid synthesis to ELOVL1, not ELOVL5. While phylogenetically related, functional differentiation of ELOVL family members means this annotation overstates ELOVL5's role. Supporting Evidence: PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.
GO:0034626 fatty acid elongation, polyunsaturated fatty acid	IBA GO_REF:0000033	ACCEPT	Summary: PUFA elongation is the primary function of ELOVL5. The enzyme preferentially elongates C18-C20 PUFAs of both n-3 and n-6 series. PMID:10970790 demonstrated elongation of gamma-linolenic acid, alpha-linolenic acid, stearidonic acid, arachidonic acid, and eicosapentaenoic acid. Reason: Core function strongly supported by original cloning paper and subsequent biochemical studies. ELOVL5 is specifically adapted for PUFA substrates. Supporting Evidence: PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids.
GO:0042761 very long-chain fatty acid biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: ELOVL5 catalyzes elongation to produce VLCFAs (>20 carbons). Products include dihomo-gamma-linolenic acid (20:3n-6), adrenic acid (22:4n-6), and docosapentaenoic acid (22:5n-3). Reason: Appropriately captures the biosynthetic outcome of ELOVL5 activity, producing VLCFAs from long-chain PUFA substrates. Supporting Evidence: PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids.
GO:0019367 fatty acid elongation, saturated fatty acid	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: While ELOVL5 can elongate some saturated fatty acids, its substrate preference is strongly toward PUFAs. The deep research and UniProt both emphasize PUFA specificity. Saturated FA elongation is primarily performed by ELOVL1, ELOVL3, and ELOVL6. Reason: ELOVL5 has detectable activity toward some saturated substrates, so the annotation is not incorrect, but this is not the primary function. The IBA inference from family members is technically valid but oversimplifies isoform-specific substrate preferences. Supporting Evidence: PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.
GO:0034625 fatty acid elongation, monounsaturated fatty acid	IBA GO_REF:0000033	ACCEPT	Summary: ELOVL5 can elongate monounsaturated fatty acids including palmitoleic acid (16:1n-7) and oleic acid (18:1n-9). UniProt catalytic activity entries include reactions for (9Z)-hexadecenoyl-CoA and (9Z)-octadecenoyl-CoA. This is a secondary activity. Reason: Supported by experimental evidence in UniProt showing ELOVL5 can elongate monounsaturated substrates. While PUFA elongation is the primary activity, MUFA elongation is also a verified function. Supporting Evidence: PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based inference of ER localization based on the ELOVL5 subfamily signature (IPR033677). Consistent with experimental data. Reason: The broader ER term is acceptable as redundant with the more specific ER membrane annotation. Both are well-supported.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation for ER membrane localization. Redundant with IBA annotation but independently supported. Reason: Consistent with experimental evidence and IBA annotation. ER membrane is the correct subcellular location.
GO:0006629 lipid metabolic process	IEA GO_REF:0000043	ACCEPT	Summary: Broad term inferred from UniProt keyword mapping. ELOVL5 is clearly involved in lipid metabolism as a fatty acid elongase. Reason: Correct but very general. The more specific fatty acid elongation terms are more informative but this parental term is not incorrect.
GO:0006631 fatty acid metabolic process	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-based inference of fatty acid metabolism involvement. Correct and appropriate. Reason: ELOVL5 is a fatty acid elongase, so involvement in fatty acid metabolic process is accurate.
GO:0006633 fatty acid biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation. ELOVL5 elongates fatty acids, contributing to biosynthesis of longer-chain products. Reason: Elongation is part of fatty acid biosynthesis; this is accurate.
GO:0006636 unsaturated fatty acid biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: ELOVL5 produces unsaturated fatty acid products (PUFAs) from unsaturated precursors. Reason: The enzyme primarily acts on unsaturated (PUFA) substrates to produce unsaturated products. This is accurate.
GO:0009922 fatty acid elongase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation of core enzymatic function. Redundant with IBA and experimental annotations. Reason: Core molecular function, redundant but correct.
GO:0016020 membrane	IEA GO_REF:0000120	ACCEPT	Summary: ELOVL5 is a multi-pass transmembrane protein. This very general term is correct but uninformative compared to the specific ER membrane annotation. Reason: Correct but very general. More specific terms (ER membrane) are preferred but this is not incorrect.
GO:0016740 transferase activity	IEA GO_REF:0000043	ACCEPT	Summary: ELOVL5 catalyzes transfer of the acyl group; EC 2.3.1.199 is a transferase. Reason: Correct parental term for the enzymatic activity, though the more specific fatty acid elongase activity term is preferred.
GO:0019367 fatty acid elongation, saturated fatty acid	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-based inference. Redundant with IBA annotation for same term. Reason: As noted above, ELOVL5 can act on saturated substrates but this is not its primary function. Same assessment as IBA annotation.
GO:0030425 dendrite	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular location mapping. PMID:25065913 shows ELOVL5 localizes to dendrites in Purkinje cells, validated by immunohistochemistry. Reason: Supported by direct experimental evidence in PMID:25065913 showing dendritic localization in cerebellar Purkinje cells. Relevant to SCA38 pathophysiology. Supporting Evidence: PMID:25065913 2014 Jul 24. ELOVL5 mutations cause spinocerebellar ataxia 38.
GO:0030497 fatty acid elongation	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine learning inference of fatty acid elongation involvement. Reason: Correct parental term for the more specific elongation processes.
GO:0034625 fatty acid elongation, monounsaturated fatty acid	IEA GO_REF:0000104	ACCEPT	Summary: UniRule-based inference. Redundant with IBA annotation. Reason: Consistent with IBA annotation; MUFA elongation is a verified secondary activity.
GO:0034626 fatty acid elongation, polyunsaturated fatty acid	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation. Redundant with IBA annotation for core function. Reason: Core function, redundant with IBA but correct.
GO:0035338 long-chain fatty-acyl-CoA biosynthetic process	IEA GO_REF:0000104	ACCEPT	Summary: UniRule inference. ELOVL5 produces fatty-acyl-CoA products as part of elongation. Reason: The product of ELOVL5 catalysis (via subsequent steps of the elongation cycle) is elongated acyl-CoA, so this is accurate.
GO:0042761 very long-chain fatty acid biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation. Redundant with IBA for same term. Reason: Core function of producing VLCFAs.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: High-throughput binary protein interactome study identified multiple interaction partners for ELOVL5. While technically valid IPI evidence, protein binding is uninformative for annotation purposes. Reason: Per curation guidelines, protein binding is too vague to be informative. The interactions detected in high-throughput screens may not reflect physiologically relevant function. More specific interaction terms should be used if the binding has known functional significance. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence-based localization to ER. Reason: Direct experimental evidence for ER localization consistent with known biology.
GO:0035338 long-chain fatty-acyl-CoA biosynthetic process	TAS Reactome:R-HSA-75876	ACCEPT	Summary: Reactome pathway annotation for VLCFA-CoA synthesis. ELOVL5 is annotated to the "Synthesis of very long-chain fatty acyl-CoAs" pathway. Reason: Appropriate pathway annotation. Reactome correctly places ELOVL5 in the VLCFA synthesis pathway. Supporting Evidence: Reactome:R-HSA-75876
GO:0036109 alpha-linolenic acid metabolic process	TAS Reactome:R-HSA-2046106	ACCEPT	Summary: Reactome pathway for ALA (18:3n-3) metabolism. ELOVL5 elongates ALA-derived intermediates in the n-3 PUFA synthesis pathway. Reason: PMID:10970790 demonstrated ELOVL5 converts alpha-linolenic acid to omega3- eicosatrienoic acid. This pathway annotation is correct. Supporting Evidence: PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids.
GO:0043651 linoleic acid metabolic process	TAS Reactome:R-HSA-2046105	ACCEPT	Summary: Reactome pathway for LA (18:2n-6) metabolism. ELOVL5 elongates LA-derived intermediates including GLA to DGLA in the n-6 PUFA synthesis pathway. Reason: ELOVL5 is part of the linoleic acid metabolic pathway, elongating intermediates derived from LA via delta-6 desaturase. Demonstrated by PMID:10970790. Supporting Evidence: PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. Reactome:R-HSA-2046105
GO:0009922 fatty acid elongase activity	EXP PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in ...	ACCEPT	Summary: Original cloning paper that demonstrated ELOVL5 (then called HELO1) fatty acid elongase activity by expression in S. cerevisiae and measurement of PUFA elongation. Reason: Primary experimental characterization of enzymatic activity. Strong EXP evidence. Supporting Evidence: PMID:10970790 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids.
GO:0009922 fatty acid elongase activity	TAS Reactome:R-HSA-2046083	ACCEPT	Summary: Reactome reaction annotation for elongation of arachidonyl-CoA to docosatetraenoyl-CoA. Reason: Specific reaction annotation supported by biochemical evidence.
GO:0009922 fatty acid elongase activity	TAS Reactome:R-HSA-2046100	ACCEPT	Summary: Reactome reaction annotation for elongation of eicosapentaenoyl-CoA to docosapentaenoyl-CoA. Reason: Specific reaction annotation supported by biochemical evidence.
GO:0005515 protein binding	IPI PMID:38422897 The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with tran...	KEEP AS NON CORE	Summary: Study showed ELOVL5 interacts with TECR (trans-2-enoyl-CoA reductase) as part of the fatty acid elongation complex. This interaction is functionally relevant for substrate channeling in the elongation cycle. Reason: Unlike generic protein binding from high-throughput screens, this interaction with TECR has clear functional relevance - both enzymes function in the same elongation cycle. However, a more specific interaction term would be preferable if available. Supporting Evidence: PMID:38422897 The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with trans-2-enoyl-CoA reductase involved in substrates transfer in very long chain fatty acid elongation.
GO:0045723 positive regulation of fatty acid biosynthetic process	IMP PMID:23749231 MicroRNA-30c reduces hyperlipidemia and atherosclerosis in m...	ACCEPT	Summary: This paper studied miR-30c effects on lipid metabolism. siRNA knockdown of ELOVL5 reduced de novo lipogenesis. The IMP annotation suggests ELOVL5 positively regulates fatty acid biosynthesis based on mutant phenotype. Reason: The study shows siELOVL5 reduces lipogenesis (Fig 4g), supporting a positive role in fatty acid biosynthesis. This is consistent with its enzymatic function. Supporting Evidence: PMID:23749231 MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion.
GO:0043025 neuronal cell body	IDA PMID:25065913 ELOVL5 mutations cause spinocerebellar ataxia 38.	ACCEPT	Summary: Immunohistochemistry on human and mouse brain showed ELOVL5 localization in Purkinje cell soma. Relevant to SCA38 pathophysiology. Reason: Direct experimental evidence showing neuronal cell body localization in cerebellar Purkinje cells, providing context for the SCA38 disease mechanism. Supporting Evidence: PMID:25065913 2014 Jul 24. ELOVL5 mutations cause spinocerebellar ataxia 38.
GO:0097447 dendritic tree	IDA PMID:25065913 ELOVL5 mutations cause spinocerebellar ataxia 38.	ACCEPT	Summary: Immunohistochemistry showed ELOVL5 in the proximal dendritic tree of Purkinje cells. Reason: Direct experimental evidence from the SCA38 paper. This neuronal localization is consistent with the cerebellar ataxia phenotype of ELOVL5 mutations. Supporting Evidence: PMID:25065913 2014 Jul 24. ELOVL5 mutations cause spinocerebellar ataxia 38.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: Proteomics study of NK cell membrane proteins detected ELOVL5. Reason: High-throughput experimental data consistent with known membrane localization. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2046083	ACCEPT	Summary: Reactome reaction annotation specifying ER membrane as reaction location. Reason: Consistent with known localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2046088	ACCEPT	Summary: Reactome reaction annotation for stearidonoyl-CoA elongation. Reason: Consistent with known localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2046094	ACCEPT	Summary: Reactome reaction annotation for gamma-linolenoyl-CoA elongation. Reason: Consistent with known localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2046100	ACCEPT	Summary: Reactome reaction annotation for eicosapentaenoyl-CoA elongation. Reason: Consistent with known localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-548800	ACCEPT	Summary: Reactome reaction annotation for arachidonate elongation. Reason: Consistent with known localization.
GO:0034626 fatty acid elongation, polyunsaturated fatty acid	IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol...	ACCEPT	Summary: Ohno et al. systematically characterized ELOVL substrate specificities in vitro, demonstrating ELOVL5 activity toward PUFAs. Reason: Strong experimental evidence from systematic biochemical characterization. Supporting Evidence: PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.
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: Same study demonstrating ELOVL5 produces VLCFAs from C18-C20 substrates. Reason: Direct experimental characterization of VLCFA production. Supporting Evidence: PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.
GO:0009922 fatty acid elongase activity	IDA PMID:20427700 Validation of the health ABC heart failure model for inciden...	UNDECIDED	Summary: Note that PMID:20427700 title in the reference list appears to be incorrect (it shows a cardiovascular study title). This may be a database error. The annotation claims IDA evidence for fatty acid elongase activity. Reason: Cannot verify - the PMID appears misattributed in the reference list (title is about heart failure, not fatty acid elongation). Requires verification that this PMID actually contains evidence for ELOVL5 elongase activity. Supporting Evidence: PMID:20427700 Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.
GO:0034625 fatty acid elongation, monounsaturated fatty acid	IDA PMID:20427700 Validation of the health ABC heart failure model for inciden...	UNDECIDED	Summary: Same PMID attribution issue as above. Reason: Cannot verify due to apparent PMID misattribution. Supporting Evidence: PMID:20427700 Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.
GO:0034626 fatty acid elongation, polyunsaturated fatty acid	IDA PMID:20427700 Validation of the health ABC heart failure model for inciden...	UNDECIDED	Summary: Same PMID attribution issue as above. Reason: Cannot verify due to apparent PMID misattribution. Supporting Evidence: PMID:20427700 Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.
GO:0042761 very long-chain fatty acid biosynthetic process	IDA PMID:20427700 Validation of the health ABC heart failure model for inciden...	UNDECIDED	Summary: Same PMID attribution issue as above. Reason: Cannot verify due to apparent PMID misattribution. Supporting Evidence: PMID:20427700 Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.
GO:0005515 protein binding	IPI PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol...	REMOVE	Summary: Interaction with unspecified partner detected in the context of the systematic ELOVL characterization study. Reason: Per guidelines, generic protein binding annotations are uninformative. The main contribution of this paper is the enzymatic characterization, not protein interactions. Supporting Evidence: PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.
GO:0005783 endoplasmic reticulum	IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol...	ACCEPT	Summary: ER localization demonstrated in the systematic ELOVL characterization study. Reason: Direct experimental evidence consistent with known biology. Supporting Evidence: PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.

Gene Description

Existing Annotations Review

Core Functions

ELOVL5 catalyzes the rate-limiting condensation step of the VLCFA elongation cycle, condensing acyl-CoA substrates with malonyl-CoA to produce 3-ketoacyl-CoA intermediates (EC 2.3.1.199). This is the first of four enzymatic steps in the ER-localized elongation cycle that adds two carbons per cycle.

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