FADS3
Domain
The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases.
Function
Mammals have different sphingoid bases that differ in their length and/or pattern of desaturation and hydroxyl groups. The predominant sphingoid base that comprises mammalian ceramides is sphing-4-enine (sphingosine or SPH) which has a trans (E) desaturation at carbon 4 (PubMed:31862735, PubMed:31916624). FADS3 is a desaturase that introduces a cis (Z) double bond between carbon 14 and carbon 15 of the sphingoid base (also known as long chain base, LCB), producing LCBs such as sphinga-4,14-dienine (SPD, d18:2(4E,14Z)) from SPH (PubMed:31862735, PubMed:31916624, PubMed:37209771). Prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates (PubMed:31862735, PubMed:31916624, PubMed:37209771). Capable of metabolizing also the SPH in its free form (PubMed:31862735). SPD ceramides occur widely in mammalian tissues and cells (PubMed:31916624). Due to their unusual structure containing a cis double bond, SPD ceramides may have an opposite, negative role in lipid microdomain formation relative to conventional ceramides (PubMed:31916624). Could be involved in the detoxification of 1-deoxy sphingolipids, by desaturating the cytotoxic 1-deoxysphinganine (1-deoxySA, m18:0), produced under pathological conditions, to 1-deoxysphingenine (1-deoxysphingosine, 1-deoxySO, m18:1) (Probable). Although prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates, it also exhibits activity toward dihydrosphingosine-containing CERs (N-acylsphinganines) and produces 14Z-SPH-containing sphingolipids,which can be found in patients with DEGS1 mutations (PubMed:37209771). Its desaturase mechanism involves an electron transfer facilitated by cytochrome b5 (PubMed:37209771). FADS3 also acts as a methyl-end fatty acyl coenzyme A (CoA) desaturase that introduces a cis double bond between the preexisting double bond and the terminal methyl group of the fatty acyl chain (By similarity). Desaturates (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 13 to generate (11E,13Z)-octadecadienoate (also known as conjugated linoleic acid 11E,13Z-CLA) (By similarity).
Pathway
Lipid metabolism; sphingolipid metabolism.
Lipid metabolism; polyunsaturated fatty acid biosynthesis.
Sequence Similarities
Belongs to the fatty acid desaturase type 1 family.
Tissue Specificity
Highly expressed in various organs and tissues including liver, kidney, brain, lung, pancreas, testis, ovary and skeletal muscle (at protein level).
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
CYB5RP, FADS3, Fatty acid desaturase 3, Delta(13) fatty acid desaturase, Delta(13) desaturase