ACSL1 (long-chain-fatty-acid--CoA ligase 1) is a Mg2+-dependent member of the ANL superfamily of adenylate-forming enzymes and one of five mammalian long-chain acyl-CoA synthetases. It catalyzes the ATP-dependent thioesterification of long-chain fatty acids (preferentially C16-C18 unsaturated fatty acids such as palmitoleate, oleate and linoleate, as well as palmitate and arachidonate) with coenzyme A, forming acyl-CoAs that are the obligatory activated intermediates for both catabolism and lipid synthesis. ACSL1 is an integral membrane protein anchored by an N-terminal segment with its active site facing the cytosol; it resides on the outer mitochondrial membrane, where it channels fatty acids into carnitine-dependent mitochondrial beta-oxidation, and on the endoplasmic reticulum membrane, where its acyl-CoAs feed glycerolipid (triacylglycerol and phospholipid) synthesis; a peroxisomal pool is reported in rodents. Highly expressed in liver, heart, skeletal muscle, kidney and adipose tissue, it contributes most of the long-chain acyl-CoA synthetase activity of heart and adipose tissue and about half of that of liver, and tissue-specific loss in mice impairs fatty acid oxidation, causing cold intolerance (adipose) and cardiac hypertrophy (heart). By trapping incoming fatty acids as acyl-CoA it indirectly increases cellular fatty acid uptake. ACSL1 expression is induced in inflammatory macrophages and in microglia, where it drives triacylglycerol synthesis and associated lipid droplet accumulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000038 very long-chain fatty acid metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ACSL1 activates long-chain fatty acids (C16-C20, including arachidonate); the rat ortholog has some reported activity toward very long-chain substrates, and Reactome places ACSL-mediated activation upstream of VLCFA elongation. Reason: ACSL1 substrate preference is long-chain (palmitoleate, oleate, linoleate); very long-chain fatty acid metabolism is a minor/peripheral role, better captured by ACSL family members such as SLC27A/ACSVL. Retained as non-core rather than removed given the PAINT node placement. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt PubMed:24269233). Preferentially uses palmitoleate, oleate and Reactome:R-HSA-75876 In humans, activation is catalyzed by one of five acyl-CoA synthetase long-chain (ACSL) enzymes |
| GO:0000038 very long-chain fatty acid metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ACSL1 activates long-chain fatty acids (C16-C20, including arachidonate); the rat ortholog has some reported activity toward very long-chain substrates, and Reactome places ACSL-mediated activation upstream of VLCFA elongation. Reason: ACSL1 substrate preference is long-chain (palmitoleate, oleate, linoleate); very long-chain fatty acid metabolism is a minor/peripheral role, better captured by ACSL family members such as SLC27A/ACSVL. Retained as non-core rather than removed given the PAINT node placement. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt PubMed:24269233). Preferentially uses palmitoleate, oleate and Reactome:R-HSA-75876 In humans, activation is catalyzed by one of five acyl-CoA synthetase long-chain (ACSL) enzymes |
| GO:0001676 long-chain fatty acid metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that ACSL1 participates in long-chain fatty acid metabolism, consistent with its catalytic activation of C12-C20 fatty acids. Reason: ACSL1 performs the activation step of long-chain fatty acid metabolism; appropriate process term. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Catalyzes the conversion of long-chain fatty acids to their |
| GO:0001676 long-chain fatty acid metabolic process | IDA PMID:22022213 Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4... | ACCEPT | Summary: ACSL1 overexpression in HuH7/HepG2 increased ACS activity and long-chain fatty acid (oleate, Bodipy-C12) uptake and esterification. Reason: Direct human cell evidence that ACSL1 activates long-chain fatty acids. Supporting Evidence: PMID:22022213 Overexpression of FATP2, FATP4 and ACSL1 highly increased ACS activity as well as the uptake of [3H]-oleic acid and fluorescent Bodipy-C12 (B12) fatty acid. |
| GO:0001676 long-chain fatty acid metabolic process | IDA PMID:24269233 Identification of acyl-CoA synthetases involved in the mamma... | ACCEPT | Summary: Human ACSL1 restored long-chain fatty acid (trans-2-hexadecenoic acid/palmitate) metabolism in an acyl-CoA synthetase-deficient yeast strain. Reason: Direct functional evidence; ACSL1 activates long-chain fatty acids feeding glycerophospholipid synthesis. Supporting Evidence: PMID:24269233 in addition to the previously identified ACSL family members (ACSL1, 3, 4, 5, and 6), we found that ACSVL1, ACSVL4, and ACSBG1 also restored metabolism. |
| GO:0001676 long-chain fatty acid metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara ortholog transfer; consistent with experimental human data. Reason: Correct and consistent with the core activity. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Catalyzes the conversion of long-chain fatty acids to their |
| GO:0004467 long-chain fatty acid-CoA ligase activity | EXP PMID:22633490 The SjΓΆgren-Larsson syndrome gene encodes a hexadecenal dehy... | ACCEPT | Summary: ACSL1 is a long-chain fatty acid-CoA ligase (EC 6.2.1.3), its defining catalytic activity. Kihara lab showed mammalian ACSLs activate trans-2-hexadecenoic acid/palmitate in the S1P-to-glycerolipid pathway; UniProt cites this paper as experimental evidence for the human ACSL1 reaction. Abstract-only in cache; deferring to the curator who read the full text. Reason: Core molecular function of ACSL1; supported by direct human assays and conserved across ACSL family. Supporting Evidence: PMID:22633490 mammalian ACSL family members are acyl-CoA synthetases involved in the sphingolipid-to-glycerolipid metabolic pathway file:human/ACSL1/ACSL1-uniprot.txt Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl- |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IDA PMID:21242590 Long-chain acyl-CoA synthetase 4 modulates prostaglandin Eβ ... | ACCEPT | Summary: ACSL1 is a long-chain fatty acid-CoA ligase (EC 6.2.1.3), its defining catalytic activity. Paper is focused on ACSL4 in arterial smooth muscle cells, but UniProt cites it as experimental evidence for human ACSL1 activity on palmitate and oleate (ACSL1 presumably assayed alongside in the full text, which is not cached). Activity is unambiguously correct for ACSL1; defer to curator. Reason: Core molecular function of ACSL1; supported by direct human assays and conserved across ACSL family. Supporting Evidence: PMID:21242590 Long-chain acyl-CoA synthetases (ACSLs) catalyze the thioesterification of long-chain FAs into their acyl-CoA derivatives. file:human/ACSL1/ACSL1-uniprot.txt Reaction=(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IDA PMID:22022213 Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4... | ACCEPT | Summary: ACSL1 is a long-chain fatty acid-CoA ligase (EC 6.2.1.3), its defining catalytic activity. Overexpression of ACSL1 in human hepatoma cells increased cellular acyl-CoA synthetase activity. Reason: Core molecular function of ACSL1; supported by direct human assays and conserved across ACSL family. Supporting Evidence: PMID:22022213 Overexpression of FATP2, FATP4 and ACSL1 highly increased ACS activity as well as the uptake of [3H]-oleic acid and fluorescent Bodipy-C12 (B12) fatty acid. |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IDA PMID:24269233 Identification of acyl-CoA synthetases involved in the mamma... | ACCEPT | Summary: ACSL1 is a long-chain fatty acid-CoA ligase (EC 6.2.1.3), its defining catalytic activity. Human ACSL1 complemented a yeast faa1 faa4 acyl-CoA synthetase mutant; UniProt records substrate preference for palmitoleate, oleate and linoleate from this work. Reason: Core molecular function of ACSL1; supported by direct human assays and conserved across ACSL family. Supporting Evidence: PMID:24269233 in addition to the previously identified ACSL family members (ACSL1, 3, 4, 5, and 6), we found that ACSVL1, ACSVL4, and ACSBG1 also restored metabolism. file:human/ACSL1/ACSL1-uniprot.txt PubMed:24269233). Preferentially uses palmitoleate, oleate and |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ACSL1 is a long-chain fatty acid-CoA ligase (EC 6.2.1.3), its defining catalytic activity. Electronic annotation from EC 6.2.1.3/Rhea mapping, consistent with experimental data. Reason: Core molecular function of ACSL1; supported by direct human assays and conserved across ACSL family. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl- |
| GO:0004467 long-chain fatty acid-CoA ligase activity | TAS Reactome:R-HSA-201035 | ACCEPT | Summary: ACSL1 is a long-chain fatty acid-CoA ligase (EC 6.2.1.3), its defining catalytic activity. Reactome reaction for ACSL-mediated palmitoyl-CoA formation. Reason: Core molecular function of ACSL1; supported by direct human assays and conserved across ACSL family. Supporting Evidence: Reactome:R-HSA-201035 Membrane-associated acyl-CoA synthetase long-chain family members 1,3,5 and 6 (ACSL1,3,5,6) catalyse the conjugation of palmitate (PALM) with CoA to form palmitoyl-CoA |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: ACSL1 is localized to mitochondria, specifically the outer mitochondrial membrane where it channels fatty acids to beta-oxidation. Detected in a high-throughput human mitochondrial proteome (MitoCoP). Reason: Well supported in human cells and orthologs; the more precise location is GO:0005741 mitochondrial outer membrane. Supporting Evidence: PMID:30190326 In highly oxidative tissues, ACSL1 is located on the outer mitochondrial membrane (OMM) and directs fatty acids into mitochondria for Ξ²-oxidation. |
| GO:0005739 mitochondrion | IDA PMID:22022213 Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4... | ACCEPT | Summary: ACSL1 is localized to mitochondria, specifically the outer mitochondrial membrane where it channels fatty acids to beta-oxidation. Immunofluorescence localized ACSL1 to mitochondria in HuH7 and HepG2 cells. Reason: Well supported in human cells and orthologs; the more precise location is GO:0005741 mitochondrial outer membrane. Supporting Evidence: PMID:22022213 ACSL1 was located at mitochondria in both cell lines. |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | ACCEPT | Summary: ACSL1 is localized to mitochondria, specifically the outer mitochondrial membrane where it channels fatty acids to beta-oxidation. Ortholog transfer. Reason: Well supported in human cells and orthologs; the more precise location is GO:0005741 mitochondrial outer membrane. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250}; |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: ACSL1 is localized to mitochondria, specifically the outer mitochondrial membrane where it channels fatty acids to beta-oxidation. Sequence-similarity transfer from rat Acsl1. Reason: Well supported in human cells and orthologs; the more precise location is GO:0005741 mitochondrial outer membrane. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250}; |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: ACSL1 is a single-pass type III membrane protein of the outer mitochondrial membrane (rat IDA; human mitochondrial immunofluorescence). Reason: Core location; supports channeling of acyl-CoA toward CPT1 and beta-oxidation. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250}; PMID:30190326 In highly oxidative tissues, ACSL1 is located on the outer mitochondrial membrane (OMM) and directs fatty acids into mitochondria for Ξ²-oxidation. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-1989778 | ACCEPT | Summary: Reactome places the ACSL1 gene product in the mitochondrial outer membrane. Reason: Consistent with experimental data from human and rodent cells. Supporting Evidence: PMID:30190326 In highly oxidative tissues, ACSL1 is located on the outer mitochondrial membrane (OMM) and directs fatty acids into mitochondria for Ξ²-oxidation. PMID:24503477 intracellular localization of FATP4 to the endoplasmic reticulum, and of ACSL1 to mitochondria. |
| GO:0005778 peroxisomal membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Peroxisomal membrane localization is based on rat studies (rat IDA in GOA) and UniProt by-similarity. Reason: Plausible minor pool; not demonstrated for human ACSL1, and mitochondrial/ER pools dominate. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt membrane protein {ECO:0000250}. Peroxisome |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: ACSL1 is active at the endoplasmic reticulum. Reason: Supported by human localization data (PMID:24269233) and hepatic ER pool (PMID:30190326). Supporting Evidence: PMID:24269233 All 8 ACSs were localized either exclusively or partly to the endoplasmic reticulum (ER), where S1P metabolism takes place. PMID:30190326 In the liver, however, about 50% of ACSL1 is located on the endoplasmic reticulum (ER) where its metabolic function is unclear. |
| GO:0005783 endoplasmic reticulum | IDA PMID:24269233 Identification of acyl-CoA synthetases involved in the mamma... | ACCEPT | Summary: Exogenously expressed human ACSL1 localized (partly) to the ER. Reason: Direct human evidence. Supporting Evidence: PMID:24269233 All 8 ACSs were localized either exclusively or partly to the endoplasmic reticulum (ER), where S1P metabolism takes place. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:24269233 Identification of acyl-CoA synthetases involved in the mamma... | ACCEPT | Summary: Human ACSL1 localized at least partly to the ER, consistent with an integral ER-membrane pool. Reason: Direct human evidence; ER membrane is a core location. Supporting Evidence: PMID:24269233 All 8 ACSs were localized either exclusively or partly to the endoplasmic reticulum (ER), where S1P metabolism takes place. file:human/ACSL1/ACSL1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (Endoplasmic reticulum membrane). Reason: Correct. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-201035 | ACCEPT | Summary: Reactome places ACSL1-catalyzed fatty acid activation at the ER membrane. Reason: Consistent with experimental ER localization (PMID:24269233). Supporting Evidence: Reactome:R-HSA-201035 available data suggest that it is associated specifically with the membrane of the endoplasmic reticulum PMID:24269233 All 8 ACSs were localized either exclusively or partly to the endoplasmic reticulum (ER), where S1P metabolism takes place. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-2046085 | ACCEPT | Summary: Reactome places ACSL1-catalyzed fatty acid activation at the ER membrane. Reason: Consistent with experimental ER localization (PMID:24269233). Supporting Evidence: Reactome:R-HSA-2046085 activated to a high energy form known as alpha-linolenoyl-CoA PMID:24269233 All 8 ACSs were localized either exclusively or partly to the endoplasmic reticulum (ER), where S1P metabolism takes place. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-2046098 | ACCEPT | Summary: Reactome places ACSL1-catalyzed fatty acid activation at the ER membrane. Reason: Consistent with experimental ER localization (PMID:24269233). Supporting Evidence: Reactome:R-HSA-2046098 The dietary essential fatty acid (EFA) linoleic acid (LA) is activated to a high energy form known as linoleoyl-CoA by the action of long-chain acyl-CoA synthetases (ACSLs). PMID:24269233 All 8 ACSs were localized either exclusively or partly to the endoplasmic reticulum (ER), where S1P metabolism takes place. |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: General fatty acid metabolism term from automated pipelines. Reason: Correct but general; the more specific GO:0001676 and GO:0035338 annotations capture the role better. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Catalyzes the conversion of long-chain fatty acids to their |
| GO:0007584 response to nutrient | IEA GO_REF:0000107 | REMOVE | Summary: Transferred from a rat IEP (expression changes with nutritional state). Reason: Expression responsiveness does not show ACSL1 executes a response-to-nutrient process; over-propagated IEA. |
| GO:0008610 lipid biosynthetic process | IDA PMID:21242590 Long-chain acyl-CoA synthetase 4 modulates prostaglandin Eβ ... | ACCEPT | Summary: ACSL activity supplies acyl-CoA for glycerolipid synthesis; UniProt cites this paper for human ACSL1 activity. Abstract-only cache focuses on ACSL4; deferring to the curator. Reason: ACSL1-derived acyl-CoAs are incorporated into triacylglycerol and phospholipids, a genuine participation in lipid biosynthesis (the acyl chain becomes part of the product). Supporting Evidence: PMID:21242590 Long-chain acyl-CoA synthetases (ACSLs) catalyze the thioesterification of long-chain FAs into their acyl-CoA derivatives. |
| GO:0008610 lipid biosynthetic process | IMP PMID:25592151 Long noncoding RNA HULC modulates abnormal lipid metabolism ... | ACCEPT | Summary: In hepatoma cells, HULC-PPARA-driven ACSL1 expression promoted triglyceride and cholesterol accumulation. Reason: Supports a role in lipid synthesis (TAG and cholesterol accumulation), albeit in a cancer-signalling context; consistent with ACSL1 supplying acyl-CoA to lipid biosynthesis. Supporting Evidence: PMID:25592151 ACSL1 overexpression that generates cholesterol was sufficient to enhance the proliferation of hepatoma cells. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | TOO GENERAL | Summary: Transferred from a rat IEP (expression induced by xenobiotics such as PPAR agonists). Reason: Response to xenobiotic stimulus is entailed by the more specific xenobiotic catabolic process annotation kept in this review, so the broad term is true of ACSL1 but adds nothing to it. The rat source of this particular row is an expression-induction (IEP) observation, which on its own would not show that ACSL1 takes part in the response. |
| GO:0010747 positive regulation of long-chain fatty acid import across plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer; ACSL1 increases cellular fatty acid uptake indirectly through metabolic trapping (vectorial acylation). Reason: Indirect effect on uptake; framing as regulation of import is appropriate but non-core. Supporting Evidence: PMID:24503477 the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping. |
| GO:0010747 positive regulation of long-chain fatty acid import across plasma membrane | ISS PMID:24503477 Protein mediated fatty acid uptake: synergy between CD36/FAT... | KEEP AS NON CORE | Summary: ACSL1 expression in MDCK cells enhanced fatty acid uptake, synergizing with CD36, by metabolic trapping. Reason: Indirect effect on uptake; ACSL1 is intracellular (mitochondrial) and not a transporter. Supporting Evidence: PMID:24503477 the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping. PMID:24503477 intracellular localization of FATP4 to the endoplasmic reticulum, and of ACSL1 to mitochondria. |
| GO:0015908 fatty acid transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer of fatty acid transport. Reason: ACSL1 is not a transporter; it promotes net uptake by esterifying incoming fatty acids. Non-core. Supporting Evidence: PMID:24503477 the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping. |
| GO:0015908 fatty acid transport | IMP PMID:32521232 Local Mitochondrial ATP Production Regulates Endothelial Fat... | KEEP AS NON CORE | Summary: In endothelial cells ACSL1 knockdown decreased fatty acid uptake. Reason: Supports an indirect role in uptake (metabolic trapping), not transport per se; non-core. Supporting Evidence: PMID:32521232 Knockdown of ACSL1, another protein exhibiting ACS activity, also decreased FA uptake, while knockdown of ACSL3, ACSL4 and CD36 had no effect PMID:24503477 the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Detected in an NK-cell membrane proteome. Reason: True but uninformative; specific membranes (MOM, ER) are annotated. |
| GO:0016020 membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Generic membrane localization from phylogeny. Reason: True but uninformative relative to MOM/ER membrane annotations. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250}; |
| GO:0019432 triglyceride biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: ACSL1 supplies long-chain acyl-CoA for glycerolipid/triacylglycerol synthesis; hepatocytes lacking ACSL1 incorporate less oleate into TAG, and ACSL1 drives TAG synthesis in human iPSC-derived microglia. Reason: The acyl-CoA product of ACSL1 is the acyl donor incorporated into TAG; ACSL1 does part of the work of TAG biosynthesis. Supporting Evidence: PMID:19648649 in isolated primary hepatocytes the absence of ACSL1 diminished the incorporation of [(14)C]oleate into triacylglycerol. PMID:38480892 ACSL1 is a key enzyme in LD biogenesis and overexpression of ACSL1 is sufficient to induce triglyceride-specific LD formation in several cell types |
| GO:0034201 response to oleic acid | IEA GO_REF:0000107 | REMOVE | Summary: Transferred from a rat IEP for oleic acid exposure. Reason: Expression change is not evidence of function in a response process; ACSL1 role with oleate is captured by its ligase activity terms. |
| GO:0035338 long-chain fatty-acyl-CoA biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: ACSL1 synthesizes long-chain fatty acyl-CoAs from free long-chain fatty acids. Reason: This is precisely the process carried out by ACSL1 catalysis; core process term. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Catalyzes the conversion of long-chain fatty acids to their file:human/ACSL1/ACSL1-uniprot.txt Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl- |
| GO:0035338 long-chain fatty-acyl-CoA biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog transfer of long-chain fatty-acyl-CoA biosynthesis; correct. Reason: Core process, consistent with direct human evidence. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl- |
| GO:0035338 long-chain fatty-acyl-CoA biosynthetic process | TAS Reactome:R-HSA-75876 | ACCEPT | Summary: Reactome places ACSL-mediated activation as the first step of VLCFA elongation, i.e. formation of long-chain acyl-CoA. Reason: Supports long-chain acyl-CoA biosynthesis by ACSL1. Supporting Evidence: Reactome:R-HSA-75876 In humans, activation is catalyzed by one of five acyl-CoA synthetase long-chain (ACSL) enzymes |
| GO:0042178 xenobiotic catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from a rat IDA reporting activation (CoA conjugation) of xenobiotic carboxylic acids by acyl-CoA synthetase. Reason: Acyl-CoA synthetases can conjugate xenobiotic carboxylic acids, a known minor role; not shown for human ACSL1, so kept as non-core. |
| GO:0044539 long-chain fatty acid import into cell | IDA PMID:22022213 Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4... | KEEP AS NON CORE | Summary: ACSL1 overexpression increased oleate and Bodipy-C12 uptake into hepatoma cells. Reason: Authors propose ACS enzymes drive uptake indirectly by esterification; retained as non-core. Supporting Evidence: PMID:22022213 Overexpression of FATP2, FATP4 and ACSL1 highly increased ACS activity as well as the uptake of [3H]-oleic acid and fluorescent Bodipy-C12 (B12) fatty acid. PMID:22022213 We propose that ACS enzymes drive FA uptake indirectly by esterification. |
| GO:0044539 long-chain fatty acid import into cell | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer of long-chain fatty acid import into cell. Reason: Indirect (metabolic trapping); non-core. Supporting Evidence: PMID:24503477 the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping. |
| GO:0044539 long-chain fatty acid import into cell | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of long-chain fatty acid import into cell. Reason: Indirect (metabolic trapping); non-core. Supporting Evidence: PMID:24503477 the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping. |
| GO:0047676 arachidonate-CoA ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Arachidonate-CoA ligase activity, inferred from rat Acsl1 (rat IDA); arachidonate (C20:4) is a long-chain substrate within the ACSL1 range. Reason: Specific substrate activity consistent with ACSL1 biochemistry; accepted as a specific instance of the core ligase activity. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = |
| GO:0047676 arachidonate-CoA ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Arachidonate-CoA ligase activity, inferred from rat Acsl1 (rat IDA); arachidonate (C20:4) is a long-chain substrate within the ACSL1 range. Reason: Specific substrate activity consistent with ACSL1 biochemistry; accepted as a specific instance of the core ligase activity. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = |
| GO:0047676 arachidonate-CoA ligase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Arachidonate-CoA ligase activity, inferred from rat Acsl1 (rat IDA); arachidonate (C20:4) is a long-chain substrate within the ACSL1 range. Reason: Specific substrate activity consistent with ACSL1 biochemistry; accepted as a specific instance of the core ligase activity. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = |
| GO:0050197 phytanate-CoA ligase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Phytanate-CoA ligase activity inferred from rat Acsl1 (rat IDA on branched-chain substrate). Reason: Branched-chain substrate activity is plausible but minor and not shown for human ACSL1. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=3,7,11,15-tetramethylhexadecanoate + ATP + CoA = phytanoyl-CoA |
| GO:0050197 phytanate-CoA ligase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Phytanate-CoA ligase activity inferred from rat Acsl1 (rat IDA on branched-chain substrate). Reason: Branched-chain substrate activity is plausible but minor and not shown for human ACSL1. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=3,7,11,15-tetramethylhexadecanoate + ATP + CoA = phytanoyl-CoA |
| GO:0070251 pristanate-CoA ligase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Pristanate-CoA ligase activity inferred from rat Acsl1 (rat EXP) / Rhea mapping. Reason: Branched-chain substrate activity is plausible but minor and not shown for human ACSL1. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=2,6,10,14-tetramethylpentadecanoate + ATP + CoA = pristanoyl- |
| GO:0070251 pristanate-CoA ligase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Pristanate-CoA ligase activity inferred from rat Acsl1 (rat EXP) / Rhea mapping. Reason: Branched-chain substrate activity is plausible but minor and not shown for human ACSL1. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=2,6,10,14-tetramethylpentadecanoate + ATP + CoA = pristanoyl- |
| GO:0090434 oleoyl-CoA ligase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Oleoyl-CoA ligase activity; oleate is a preferred human ACSL1 substrate. Reason: Specific instance of the core activity, supported by UniProt human data. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + file:human/ACSL1/ACSL1-uniprot.txt PubMed:24269233). Preferentially uses palmitoleate, oleate and |
| GO:0090434 oleoyl-CoA ligase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Oleoyl-CoA ligase activity; oleate is a preferred human ACSL1 substrate. Reason: Specific instance of the core activity, supported by UniProt human data. Supporting Evidence: file:human/ACSL1/ACSL1-uniprot.txt Reaction=(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + file:human/ACSL1/ACSL1-uniprot.txt PubMed:24269233). Preferentially uses palmitoleate, oleate and |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:20620995 Adipose acyl-CoA synthetase-1 directs fatty acids toward bet... | KEEP AS NON CORE | Summary: Adipose-specific Acsl1 knockout mice are cold intolerant because brown/white adipocytes cannot activate fatty acids for beta-oxidation. Reason: ACSL1 supplies acyl-CoA fuel for thermogenic oxidation; a physiological, tissue-specific consequence of the core activity rather than a regulatory role. Non-core. Supporting Evidence: PMID:20620995 Acsl1(A-/-) mice were markedly cold intolerant, and beta(3)-adrenergic agonists did not increase oxygen consumption, despite normal adrenergic signaling in brown adipose tissue. PMID:20620995 ACSL1 has a specific function in directing the metabolic partitioning of FAs toward beta-oxidation in adipocytes. |
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Download this section (compressed HTML)Q: Does ACSL1 protein associate with the lipid droplet surface (as ACSL3 does) in microglia or hepatocytes, or does it drive lipid droplet accumulation solely by supplying acyl-CoA for ER triacylglycerol synthesis?
Q: What determines partitioning of ACSL1 between the outer mitochondrial membrane and ER (about 50% ER in liver), and does this switch its acyl-CoA product between oxidation and esterification?
Q: Are the branched-chain (phytanate, pristanate) and eicosanoid (EET/HETE) activities inferred from rat Acsl1 conserved in human ACSL1?
Experiment: Immunogold EM or super-resolution imaging of endogenous ACSL1 with lipid droplet (PLIN2) and ER/mitochondrial markers in fibrillar amyloid-beta-treated human iPSC-derived microglia, plus lipid droplet fractionation proteomics, to test whether ACSL1 is LD-resident.
Experiment: Purified human ACSL1 kinetic profiling across saturated, unsaturated, branched-chain and oxidized fatty acid substrates to confirm substrate specificity inferred from rat.
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