Mammals have different sphingoid bases that differ in their length and/or pattern of desaturation and hydroxyl groups. The predominant sphingoid base in mammalian ceramides is sphing-4-enine (sphingosine or SPH) which has a trans desaturation at carbon 4. FADS3 is a ceramide desaturase that introduces a cis double bond between carbon 14 and carbon 15 of the SPH-containing ceramides, producing sphinga-4,14-dienine-containing ceramides (SPD ceramides). SPD ceramides occur widely in mammalian tissues and cells. 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 (By similarity). 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. 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). an N-acylsphing-4-enine + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = an N-acyl-sphinga-4E,14Z-dienine + 2 Fe(III)-[cytochrome b5] + 2 H2O 2 Fe(II)-[cytochrome b5] + 2 H(+) + N-(hexanoyl)sphing-4-enine + O2 = 2 Fe(III)-[cytochrome b5] + 2 H2O + N-hexanoyl-sphinga-4E,14Z-dienine (11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (11E,13Z)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O Lipid metabolism; polyunsaturated fatty acid biosynthesis. Lipid metabolism; sphingolipid metabolism. Highly expressed in liver and kidney (at protein level). 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. Two potential isoforms are detected in various tissues. A 75 kDa isoform is expressed in lung. A 37 kDa isoform is expressed in lung, liver and kidney. Belongs to the fatty acid desaturase type 1 family.