Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
Combined Automated Annotation using Multiple IEA Methods
Cloning, expression, and fatty acid regulation of the human delta-5 desaturase.
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FADS1 encodes the delta-5 desaturase, one of two rate-limiting enzymes in PUFA biosynthesis. Expression in CHO cells demonstrated conversion of 20:3(n-6) to 20:4(n-6).
"One of the two rate-limiting steps in the production of these polyenoic fatty acids is the desaturation of 20:3(n-6) and 20:4(n-3) by Delta-5 desaturase"
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FADS1 contains two membrane-spanning domains, three histidine-rich regions, and a cytochrome b5 domain.
"The Delta-5 desaturase contains two membrane-spanning domains, three histidine-rich regions, and a cytochrome b(5) domain that all align perfectly with the same domains located in the Delta-6 desaturase."
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Delta-5 and Delta-6 desaturase genes reside head-to-head on chromosome 11 separated by less than 11,000 base pairs.
"the Delta-5 and Delta-6 desaturase genes reside in reverse orientation on chromosome 11 and that they are separated by <11,000 base pairs."
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Expression is highest in liver, brain, and heart, and is nutritionally regulated (suppressed by dietary PUFA).
"When rats were fed a diet containing 10% safflower oil or menhaden fish oil, the level of hepatic mRNA for Delta-5 and Delta-6 desaturase was only 25% of that found in the liver of rats fed a fat-free diet or a diet containing triolein"
cDNA cloning and characterization of human Delta5-desaturase involved in the biosynthesis of arachidonic acid.
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Expression of FADS1 ORF in mouse fibroblast cells demonstrated delta-5 desaturase activity by conversion of DGLA (20:3n-6) to AA (20:4n-6).
"Expression of this ORF in mouse fibroblast cells demonstrated that the encoded protein was a Delta(5)-desaturase, as determined by the conversion of dihomo-gamma-linolenic acid (C(20:3,n-6)) into arachidonic acid (C(20:4,n-6))."
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FADS1 contains an N-terminal cytochrome b5-like domain and three histidine-rich domains.
"The human Delta(5)-desaturase contained a predicted N-terminal cytochrome b(5)-like domain, as well as three histidine-rich domains."
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Highly expressed in fetal liver, fetal brain, adult brain, and adrenal gland.
"A tissue expression profile revealed that this gene is highly expressed in fetal liver, fetal brain, adult brain and adrenal gland."
Defining the membrane proteome of NK cells.
A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid precursor fatty acids.
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Identified alternative FADS1 isoform (FADS1AT1) that lacks catalytic activity but may enhance FADS2 function.
"FADS1 alternative transcript 1 (FADS1AT1) enhances desaturation of FADS2, leading to increased production of eicosanoid precursors, the first case of an isoform modulating the enzymatic activity encoded by another gene."
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FADS1 isoform 1 localizes to both ER and mitochondria.
"FADS1, but not FADS1AT1, localizes to endoplasmic reticulum and mitochondria."
Desaturation of eicosatetraenoyl-CoA to eicosapentaenoyl-CoA
Desaturation of dihomo-gamma-lenolenoyl-CoA to arachidonoyl-CoA
Linoleic acid (LA) metabolism
alpha-linolenic acid (ALA) metabolism
Deep research summary for FADS1
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FADS1 performs the delta-5 desaturation step in LC-PUFA biosynthesis, converting DGLA to AA and ETA to EPA.
"FADS1 encodes the microsomal delta-5 desaturase that introduces a double bond at the delta-5 position of C20 polyunsaturated acyl-CoAs. Canonical reactions in humans include dihomo-gamma-linolenic acid (DGLA; 20:3n-6) to arachidonic acid (AA; 20:4n-6) and eicosatetraenoic acid (ETA; 20:4n-3) to eicosapentaenoic acid (EPA; 20:5n-3)."
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FADS variants are strong determinants of LC-PUFA biosynthesis with marked frequency differences across ancestries.
"FADS1/FADS2 genotypes show marked frequency differences across ancestries and contribute to gene-diet interactions and evolutionary signatures."
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FADS1 upregulation in colorectal cancer increases AA in tumor interstitium and elevates PGE2.
"Xu et al. 2023 demonstrated that FADS1 upregulation is an early event in CRC, increases AA in the tumor interstitium, enriches gram-negative microbes, activates TLR4/MYD88 signaling, and elevates PGE2."
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D5D inhibitor (D5D-IN-326) reduced CRC cell/organoid growth, suggesting therapeutic potential of targeting FADS1.
"A D5D inhibitor (D5D-IN-326) reduced CRC cell/organoid growth (e.g., P=0.003 in SW480; 0.008 HCT-116; 0.006 organoid)."