FADS1
Domain
The histidine box domains may contain the active site and/or be involved in metal ion binding.
Function
Isoform 1
Acts as a front-end fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 5 located between a preexisting double bond and the carboxyl end of the fatty acyl chain. Involved in biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors. Specifically, desaturates dihomo-gamma-linoleoate (DGLA) (20:3n-6) and eicosatetraenoate (ETA) (20:4n-3) to generate arachidonate (AA) (20:4n-6) and eicosapentaenoate (EPA) (20:5n-3), respectively (PubMed:10601301, PubMed:10769175). As a rate limiting enzyme for DGLA (20:3n-6) and AA (20:4n-6)-derived eicosanoid biosynthesis, controls the metabolism of inflammatory lipids like prostaglandin E2, critical for efficient acute inflammatory response and maintenance of epithelium homeostasis. Contributes to membrane phospholipid biosynthesis by providing AA (20:4n-6) as a major acyl chain esterified into phospholipids. In particular, regulates phosphatidylinositol-4,5-bisphosphate levels, modulating inflammatory cytokine production in T-cells (By similarity). Also desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathway of LA (18:2n-6) (By similarity).
Isoform 2
Does not exhibit any catalytic activity toward 20:3n-6, but it may enhance FADS2 activity.
Pathway
Lipid metabolism; polyunsaturated fatty acid biosynthesis.
Sequence Similarities
Belongs to the fatty acid desaturase type 1 family.
Tissue Specificity
Widely expressed, with highest levels in liver, brain, adrenal gland and heart. Highly expressed in fetal liver and brain.
Cellular localization
- Isoform 1
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Mitochondrion
- Isoform 2
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
FADSD5, FADS1, Acyl-CoA (8-3)-desaturase, Delta(5) fatty acid desaturase, Fatty acid desaturase 1, D5D, Delta(5) desaturase, Delta-5 desaturase