ELOVL4

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation placing ELOVL4 activity in the ER membrane. This is the correct, experimentally corroborated site of action for this multipass ER elongase. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt Endoplasmic reticulum membrane
GO:0009922 fatty acid elongase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to the core molecular function. This is the correct specific MF for ELOVL4, the condensing enzyme of the elongation cycle. Supporting Evidence: file:human/ELOVL4/ELOVL4-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: Phylogenetic (IBA) annotation to the core biological process. ELOVL4 uniquely elongates fatty acids into the very-long/ultra-long-chain range; well supported. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
GO:0030148 sphingolipid biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic annotation. ELOVL4-derived ultra-long-chain fatty acids are incorporated into (acyl)ceramides/sphingolipids (notably epidermal omega-O-acylceramides), so ELOVL4 contributes upstream to sphingolipid biosynthesis. This is a downstream/indirect process rather than the core elongase function; retained as non-core.
GO:0034626 fatty acid elongation, polyunsaturated fatty acid	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation to the polyunsaturated sub-process of fatty-acid elongation. ELOVL4 elongates VLC-PUFA (retina/brain); consistent with function. This is one product-class-specific facet of the single core elongation activity. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
GO:0019367 fatty acid elongation, saturated fatty acid	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation to the saturated sub-process of fatty-acid elongation. ELOVL4 produces VLC-SFA (skin barrier); consistent with function. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt very long chain saturated (VLC-SFA)
GO:0034625 fatty acid elongation, monounsaturated fatty acid	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic annotation to the monounsaturated sub-process. ELOVL4 elongates monounsaturated ULCFA species; plausible and consistent with the family. A product-class facet of the core elongase activity; kept as non-core.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation to endoplasmic reticulum. Correct compartment but less specific than the experimentally supported ER membrane term; there is also a direct IDA annotation to this term. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (UniRule/SubCell) to the ER membrane, the correct and experimentally supported localization. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt Endoplasmic reticulum membrane
GO:0006636 unsaturated fatty acid biosynthetic process	IEA GO_REF:0000104	KEEP AS NON CORE	Summary: Electronic annotation. ELOVL4 elongates unsaturated (mono- and polyunsaturated) VLC fatty acids, so it contributes to unsaturated fatty-acid biosynthesis. This is a broad parent process relative to the more specific elongation terms; retained as non-core.
GO:0009584 detection of visible light	IEA GO_REF:0000108	REMOVE	Summary: Inter-ontology electronic annotation derived (GO_REF:0000108) from the incorrect GO:0008020 'G protein-coupled photoreceptor activity' MF annotation. ELOVL4 is an ER-membrane fatty-acid elongase and has no role in phototransduction; the parent MF annotation is itself erroneous. Removed.
GO:0009922 fatty acid elongase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to the core molecular function; corroborated by experimental (EXP) evidence. Correct. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt Catalyzes the first and rate-limiting reaction of the four
GO:0016020 membrane	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Generic 'membrane' electronic annotation. Not incorrect but uninformative given the more specific ER-membrane annotation; over-general.
GO:0019367 fatty acid elongation, saturated fatty acid	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to the saturated FA elongation sub-process; consistent with the experimental IDA annotation to the same term. Correct. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt very long chain saturated (VLC-SFA)
GO:0030497 fatty acid elongation	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation to the general fatty-acid elongation process. This is the accurate high-level process for ELOVL4 and captures its role in the elongation cycle. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt long-chain fatty acids elongation cycle
GO:0034626 fatty acid elongation, polyunsaturated fatty acid	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to the polyunsaturated FA elongation sub-process; consistent with ISS evidence to the same term and with ELOVL4 VLC-PUFA synthesis. Correct. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
GO:0035338 long-chain fatty-acyl-CoA biosynthetic process	IEA GO_REF:0000104	KEEP AS NON CORE	Summary: Electronic annotation. The elongation reaction produces 3-oxoacyl-CoA thioesters, so ELOVL4 participates in acyl-CoA biosynthesis. Accurate but a broad/parent framing of the same activity; retained as non-core.
GO:0042761 very long-chain fatty acid biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to the core biological process; corroborated by IDA and ISS evidence. Correct. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare 'protein binding' from the HuRI large-scale binary interactome (systematic Y2H). Uninformative for molecular function and, for a polytopic ER membrane protein, largely non-specific. Not removed (per policy on GO:0005515 IPI) but marked as over-annotation.
GO:0005515 protein binding	IPI PMID:38422897 The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with tran...	MARK AS OVER ANNOTATED	Summary: Bare 'protein binding' IPI (ELOVL4-TECR interaction). Although the underlying interaction with TECR is biologically meaningful (both are members of the same ER elongation machinery), the term itself is uninformative. Not removed; marked as over-annotation. A specific complex/adaptor term would be preferable.
GO:0007623 circadian rhythm	IEA GO_REF:0000107	REMOVE	Summary: Electronic annotation transferred from a rat ortholog (Ensembl Compara). There is no evidence that human ELOVL4's molecular function is involvement in circadian rhythm; this is an over-propagated ortholog phenotype term unrelated to the core elongase activity. Removed (IEA).
GO:0061886 negative regulation of mini excitatory postsynaptic potential	IEA GO_REF:0000107	REMOVE	Summary: Electronic annotation transferred from a rat ortholog. This highly specific synaptic-physiology term is not a demonstrated function of human ELOVL4 and is an over-propagated ortholog annotation for a metabolic enzyme. Removed (IEA).
GO:0097151 positive regulation of inhibitory postsynaptic potential	IEA GO_REF:0000107	REMOVE	Summary: Electronic annotation transferred from a rat ortholog; a specific synaptic-physiology term without support for human ELOVL4 and unrelated to the core elongase function. Removed (IEA).
GO:1990926 short-term synaptic potentiation	IEA GO_REF:0000107	REMOVE	Summary: Electronic annotation transferred from a rat ortholog; a specific synaptic-plasticity term without support for human ELOVL4 and unrelated to the core elongase function. Removed (IEA).
GO:0006633 fatty acid biosynthetic process	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: UniPathway-derived electronic annotation to the broad 'fatty acid biosynthetic process'. Accurate but general; the more specific VLCFA biosynthesis / fatty acid elongation terms better capture the function.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol...	ACCEPT	Summary: Experimental (EXP) localization to the ER membrane. Correct and a primary support for the core localization. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt Endoplasmic reticulum membrane
GO:0009922 fatty acid elongase activity	EXP PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol...	ACCEPT	Summary: Experimental (EXP) annotation to the core molecular function, from in vitro determination of ELOVL substrate specificities. This is the primary evidence for the core function and the correct, most specific MF term available. Supporting Evidence: PMID:20937905 In the present study, we determined the precise substrate specificities of all the ELOVLs by in vitro analyses.
GO:0009922 fatty acid elongase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation to the core MF (from mouse ortholog Q9EQC4). Consistent with and corroborated by the human EXP annotation. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt Catalyzes the first and rate-limiting reaction of the four
GO:0034626 fatty acid elongation, polyunsaturated fatty acid	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation to the polyunsaturated FA elongation sub-process (from mouse ortholog). Consistent with ELOVL4 VLC-PUFA synthesis. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
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 (partner Q96G23). Uninformative MF term; not removed (per policy on GO:0005515 IPI) but marked as over-annotation.
GO:0005783 endoplasmic reticulum	IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol...	ACCEPT	Summary: Direct experimental localization to the endoplasmic reticulum. Correct; slightly less specific than the ER-membrane term but accurate. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	IDA PMID:16036915 Dominant negative mechanism underlies autosomal dominant Sta...	ACCEPT	Summary: Direct experimental localization to the ER membrane (WT ELOVL4 with its ER-retention sequence localizes to the ER). Correct core localization. Supporting Evidence: PMID:16036915 Wild type ELOVL4 containing an endoplasmic reticulum retention sequence was localized to the endoplasmic reticulum as expected.
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 experimental annotation to saturated FA elongation, from in vitro substrate-specificity analysis of ELOVL4. Consistent with VLC-SFA production (skin barrier). Correct. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt very long chain saturated (VLC-SFA)
GO:0042761 very long-chain fatty acid biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation to the core BP (from paralog/ortholog). Corroborated by the human IDA annotation to the same term. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
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 experimental annotation to the core biological process, from in vitro demonstration of very-long-chain fatty acid elongation by ELOVL4. Primary support for the core BP. Supporting Evidence: file:human/ELOVL4/ELOVL4-uniprot.txt the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
GO:0006633 fatty acid biosynthetic process	NAS PMID:11138005 A 5-bp deletion in ELOVL4 is associated with two related for...	KEEP AS NON CORE	Summary: Author statement (NAS) to the broad fatty-acid biosynthetic process, from the 2001 identification paper noting homology to yeast VLCFA-biosynthesis proteins. Accurate in direction but general; the more specific VLCFA/elongation terms are preferable, so retained as non-core. Supporting Evidence: PMID:11138005 it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids.
GO:0008020 G protein-coupled photoreceptor activity	NAS PMID:11138005 A 5-bp deletion in ELOVL4 is associated with two related for...	REMOVE	Summary: Author-statement (NAS) annotation to a GPCR/photoreceptor molecular function. This is incorrect: ELOVL4 is a multipass ER-membrane fatty-acid elongase (acyltransferase), not a G-protein-coupled receptor, and the cited 2001 paper identified it as a retina-specific gene homologous to yeast VLCFA-biosynthesis proteins - it did not demonstrate photoreceptor/GPCR activity. This is a legacy mis-annotation (likely from the gene being retinal photoreceptor-specific) and is not experimental. Removed.

Gene Description

Existing Annotations Review

Core Functions

Fatty acid elongase (condensing enzyme) catalyzing the first, rate-limiting condensation step of the ER microsomal fatty-acid elongation cycle, uniquely extending fatty acids into the ultra-long-chain range.

Elongation of ultra-long-chain fatty acids contributing to the general fatty-acid elongation process, producing saturated/monounsaturated ULCFA (epidermal barrier omega-O-acylceramides, meibum) and ultra-long-chain PUFA (retina photoreceptors, brain).

References

📚 Additional Documentation

Notes

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