ELOVL7 (very long chain fatty acid elongase 7) is a multipass endoplasmic reticulum membrane enzyme of the ELO/ELOVL family (EC 2.3.1.199). It is a 3-keto acyl-CoA synthase that catalyzes the first and rate-limiting condensation step of the microsomal fatty-acid elongation cycle, joining a (very-)long-chain acyl-CoA with malonyl-CoA to yield a 3-oxoacyl-CoA plus CO2 and CoA; the three subsequent steps of each two-carbon elongation cycle are performed by a 3-ketoacyl-CoA reductase (KAR/HSD17B12), a 3-hydroxyacyl-CoA dehydratase (HACD1/2), and trans-2-enoyl-CoA reductase (TECR). ELOVL7 elongates C16-C20 acyl-CoAs spanning saturated, monounsaturated, and polyunsaturated species, with strongest activity toward C18 acyl-CoAs (especially C18:3), thereby producing C20-C22 very-long-chain fatty acids that serve as precursors of membrane lipids, sphingolipids, and lipid mediators. It has a seven-transmembrane inverted-barrel fold with a buried active site centred on a conserved HxxHH histidine motif and forms a homodimer. ELOVL7 is expressed in most tissues and its saturated-VLCFA and cholesteryl-ester metabolism has been implicated in prostate cancer growth.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assertion that ELOVL7 acts in the ER membrane. This is correct and is the site of the enzyme's catalysis; supported by experimental data (PMID:20937905, PMID:34117479) and UniProt subcellular location. Core localization. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0009922 fatty acid elongase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the family molecular function. This is the core function of ELOVL7 and is strongly supported experimentally (EXP/IDA from PMID:19826053, PMID:20937905, PMID:21959040, PMID:34117479). Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. |
| GO:0042761 very long-chain fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the biological process. ELOVL7 elongates C16-C20 acyl-CoAs to make C20-C22 VLCFAs; this is the process its activity serves. Core process, independently supported by IDA (PMID:19826053, PMID:20937905). Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt allows the addition 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: Phylogenetic (IBA) assignment. ELOVL-family enzymes supply the VLCFA moieties incorporated into ceramides and sphingolipids, so the family inference is defensible. However, the direct experimental link to sphingolipid synthesis in PMID:20937905 is for ELOVL1 (the C24 sphingolipid story), not ELOVL7, and ELOVL7's own preference is C18->C20 elongation rather than the C22->C24 step that feeds sphingolipids. This is a downstream/contributory process rather than ELOVL7's core function; keep as non-core. |
| GO:0034626 fatty acid elongation, polyunsaturated fatty acid | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) assignment. ELOVL7 elongates polyunsaturated acyl-CoAs (e.g. C18:3, C20:4), so this substrate-class refinement of the elongation process is correct and is also supported by IDA (PMID:20937905). This is a substrate-specific facet of the single fatty acid elongase activity rather than a distinct core process. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs |
| GO:0019367 fatty acid elongation, saturated fatty acid | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) assignment. ELOVL7 elongates saturated acyl-CoAs (C16:0, C18:0), so this substrate-class refinement is correct and is also supported by IDA (PMID:19826053). A substrate-specific facet of the single fatty acid elongase activity. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids |
| GO:0034625 fatty acid elongation, monounsaturated fatty acid | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) assignment. ELOVL7 is active toward monounsaturated acyl-CoAs (C18:1, and the curated catalytic activity for (9Z)-octadecenoyl-CoA/oleoyl-CoA). Correct substrate-class refinement of the single elongase activity; non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO (IEA) location. Correct but less precise than the experimentally supported ER membrane term; the enzyme is a multipass ER membrane protein, not free in the ER lumen. Retain as a valid but generic localization. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA, UniRule/SubCell) ER-membrane localization. Correct and matches the experimentally supported core localization. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006636 unsaturated fatty acid biosynthetic process | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Electronic (IEA) process. ELOVL7 does elongate unsaturated acyl-CoAs (mono- and polyunsaturated), so this is not wrong, but it is a broad ancestor of the more specific monounsaturated/polyunsaturated elongation terms and does not capture ELOVL7's activity on saturated substrates. Redundant with the more specific elongation terms; non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs |
| GO:0009922 fatty acid elongase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA, UniRule/InterPro/EC/RHEA) assignment of the core molecular function. Correct and redundant with the experimental EXP annotations; accept. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Electronic (IEA) generic membrane localization. Correct in that ELOVL7 is an integral membrane protein, but far less informative than the ER membrane annotation. Over-general. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0019367 fatty acid elongation, saturated fatty acid | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic (IEA) duplicate of the IBA/IDA-supported saturated fatty acid elongation term. Correct substrate-class facet of the elongase activity; non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids |
| GO:0030497 fatty acid elongation | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic (IEA, ARBA) generic fatty acid elongation process. Correct and is the parent of the substrate-specific elongation terms; captures the core process at a general level. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids |
| GO:0034625 fatty acid elongation, monounsaturated fatty acid | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Electronic (IEA) duplicate of the IBA-supported monounsaturated elongation term. Correct substrate-class facet; non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs |
| GO:0034626 fatty acid elongation, polyunsaturated fatty acid | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Electronic (IEA) duplicate of the IBA/IDA-supported polyunsaturated elongation term. Correct substrate-class facet; non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs |
| GO:0035338 long-chain fatty-acyl-CoA biosynthetic process | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Electronic (IEA) process. The immediate products of ELOVL7 catalysis are 3-oxoacyl-CoAs (and, after the full cycle, elongated acyl-CoAs), so the acyl-CoA biosynthesis framing is defensible. It is a parallel, more generic way of describing the same elongation activity; keep as non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt a very-long- chain 3-oxoacyl-CoA + CO2 + CoA |
| GO:0042761 very long-chain fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA) duplicate of the IBA/IDA-supported core process. Accept. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a proteome-scale binary interactome (Y2H) screen; the recorded partner here is DTNBP1 (dysbindin, Q96EV8). This is a single-method high-throughput interaction with no functional interpretation for ELOVL7 and the term is uninformative. Per policy, retain an IPI protein-binding annotation but flag as over-annotated. |
| 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 a reference binary-interactome map (HuRI, Y2H); partners recorded for ELOVL7 include LRCH4, SERF1B, VAMP1, EMP3, SYNJ2BP, RTP2, SLC41A1, UBE2J2, TMEM14C and ADGRE2. High-throughput single-method interactions with no functional interpretation; uninformative term. MARK_AS_OVER_ANNOTATED (policy forbids REMOVE of IPI protein binding). |
| GO:0035338 long-chain fatty-acyl-CoA biosynthetic process | TAS Reactome:R-HSA-75876 | KEEP AS NON CORE | Summary: TAS from Reactome pathway "Synthesis of very long-chain fatty acyl-CoAs". ELOVL7 performs the condensation step of this pathway; the products are acyl-CoAs. Correct but a generic/parallel framing of the elongase activity; keep as non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt a very-long- chain 3-oxoacyl-CoA + CO2 + CoA |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000041 | MARK AS OVER ANNOTATED | Summary: Electronic (IEA, UniPathway UPA00094) process, matching the UniProt PATHWAY "Lipid metabolism; fatty acid biosynthesis." Correct but a broad ancestor of the specific VLCFA-elongation terms; over-general. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt PATHWAY: Lipid metabolism; fatty acid biosynthesis. |
| GO:0009922 fatty acid elongase activity | EXP PMID:19826053 Novel lipogenic enzyme ELOVL7 is involved in prostate cancer... | ACCEPT | Summary: Experimental (EXP) core molecular function. Tamura et al. showed by in vitro fatty acid elongation assay that ELOVL7 elongates saturated very-long-chain fatty acids. Directly supports the fatty acid elongase activity. Core function. Supporting Evidence: PMID:19826053 In vitro fatty acid elongation assay and fatty acid composition analysis indicated that ELOVL7 was preferentially involved in fatty acid elongation of |
| GO:0009922 fatty acid elongase activity | TAS Reactome:R-HSA-548814 | ACCEPT | Summary: TAS from Reactome reaction "ELOVL3,6,7 elongate PALM-CoA and Mal-CoA to 3OOD-CoA". Correctly asserts the core condensing (elongase) activity of ELOVL7 on palmitoyl-CoA + malonyl-CoA. Accept. Supporting Evidence: file:human/ELOVL7/ELOVL7-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: Experimental (EXP) ER-membrane localization from the ELOVL substrate- specificity study (Ohno et al.). Consistent with UniProt and the crystal structure of the multipass ER-membrane enzyme. Core localization. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt SUBCELLULAR LOCATION: 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) core molecular function. Ohno et al. determined the substrate specificities of all seven ELOVLs by in vitro elongase assays; the source of several curated ELOVL7 catalytic activities. Core function. Supporting Evidence: PMID:20937905 we determined the precise substrate specificities of all the ELOVLs by in vitro analyses |
| GO:0009922 fatty acid elongase activity | EXP PMID:21959040 Biochemical characterization of the very long-chain fatty ac... | ACCEPT | Summary: Experimental (EXP) core molecular function. Naganuma et al. purified ELOVL7 and reconstituted it into proteoliposomes, showing high elongase activity toward C18 acyl-CoAs with measured Km values, and that His-150/His-151 are required. Strong direct support for the core elongase activity. Supporting Evidence: PMID:21959040 Purified ELOVL7 exhibited high activity toward acyl-CoAs with C18 carbon chain length. |
| GO:0009922 fatty acid elongase activity | EXP PMID:34117479 The structural basis of fatty acid elongation by the ELOVL e... | ACCEPT | Summary: Experimental (EXP) core molecular function, from the crystal structure study. Nie et al. solved the human ELOVL7 structure with a covalently bound 3-keto acyl-CoA product analogue and demonstrated the condensation (elongase) chemistry via an acyl-imidazole intermediate on His-150. Direct structural and mechanistic support for the core function. Supporting Evidence: PMID:34117479 The first, rate-limiting step of the FA elongation cycle is catalysed by 3-keto acyl-CoA synthases and consists of a condensation reaction between an acyl-CoA and malonyl-CoA to yield a 3-keto acyl-CoA |
| GO:0005515 protein binding | IPI PMID:38422897 The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with tran... | MARK AS OVER ANNOTATED | Summary: IPI protein binding, partner TECR (Q9NZ01). This interaction is functionally meaningful, because TECR carries out the final reductase step of the same VLCFA elongation cycle in which ELOVL7 performs the first step, consistent with an elongation multi-enzyme complex; UniProt records "Interacts with TECR". However, the GO term itself ("protein binding") is uninformative and does not capture the specific function. Retain but flag as over-annotated; the biology is captured under core elongase activity. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Interacts with TECR |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-548814 | ACCEPT | Summary: TAS from Reactome; ER-membrane localization consistent with experimental evidence and UniProt. Accept. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-548815 | ACCEPT | Summary: TAS from Reactome reaction "ELOVL7 elongates ICS-CoA and Mal-CoA to 3ODC-CoA"; ER-membrane localization consistent with experimental evidence. Accept. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0019367 fatty acid elongation, saturated fatty acid | IDA PMID:19826053 Novel lipogenic enzyme ELOVL7 is involved in prostate cancer... | KEEP AS NON CORE | Summary: Direct assay (IDA). Tamura et al. showed ELOVL7 is preferentially involved in elongation of saturated very-long-chain fatty acids in prostate cancer cells. Correct substrate-class facet of the core elongase activity; a well-supported biological process for ELOVL7 but non-core relative to the general elongation/MF terms. Supporting Evidence: PMID:19826053 preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids |
| GO:0042761 very long-chain fatty acid biosynthetic process | IDA PMID:19826053 Novel lipogenic enzyme ELOVL7 is involved in prostate cancer... | ACCEPT | Summary: Direct assay (IDA) supporting the core VLCFA biosynthetic process. Tamura et al. demonstrated ELOVL7 elongation activity producing saturated VLCFAs. Core process. Supporting Evidence: PMID:19826053 preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids |
| 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 Q53GQ0). Uninformative GO term with no specific functional content for ELOVL7. Retain per policy but flag as over-annotated. |
| GO:0005783 endoplasmic reticulum | IDA PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | KEEP AS NON CORE | Summary: Direct assay (IDA) ER localization. Correct, though less precise than the ER membrane term also supported by the same study; the enzyme is a multipass ER-membrane protein. Keep as a valid, more general localization. Supporting Evidence: file:human/ELOVL7/ELOVL7-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 (IDA). Ohno et al. characterized ELOVL7 elongation of polyunsaturated acyl-CoAs (e.g. C20:4, C18:3). Correct substrate-class facet of the core elongase activity; non-core. Supporting Evidence: file:human/ELOVL7/ELOVL7-uniprot.txt Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs |
| 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 assay (IDA) supporting the core VLCFA biosynthetic process. Ohno et al. determined ELOVL7's substrate specificity, showing it elongates C16-C20 acyl-CoAs into longer VLCFAs. Core process. Supporting Evidence: PMID:20937905 we determined the precise substrate specificities of all the ELOVLs by in vitro analyses |
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