|
Symbol: fat-3 Name: FATty acid desaturase Entrez gene ID: 177820 Ensembl gene ID: W08D2.4 Species: Worm (Taxid: 6239) Functional description: Protein FAT-3; FATty acid desaturase family member (fat-3) [Source:RefSeq peptide;Acc:NP_501752] [Ensembl]; The fat-3 gene encodes a delta-6 fatty acid desaturase ('linoleoyl-CoA desaturase') containing an N-terminal cytochrome b5 domain; FAT-3 expressed in yeast uses linoleic and alpha-linolenic acid as substrates; FAT-3 is absolutely required in vivo for synthesis of delta-6 fatty acids, and also required for fully normal synthesis of C20 fatty acids; FAT-3 is required for a normally fast growth rate and movement speed, and for normal defecation rhythms and fertility. Homozygous fat-3 mutants have low levels of 20:2n6 and 20:3n3 fatty acids, with no other detectable C20 fatty acids, indicating that delta-6 desaturation of C18 fatty acids is required for elongation to 20 carbons. One fat-3 allele contains a mutation in a conserved histidine residue of the first histidine-rich motif (H-box), and is probably a null; while homozygotes carrying any fat-3 mutant alleles are viable and fertile, they grow slowly, move sluggishly, display abnormally long and long and irregular defecation rhythms, and have a reduced brood size. The chimeric structure (N-terminal cytochrome b5, C-terminal desaturase) is conserved in a plant delta-6 fatty acid desaturase and in C. elegans FAT-4 as well. It is possible that this structure is made necessary by the FAT-3 enzyme being a 'front-end' enzyme that desaturates positions between the carboxyl moiety and preexisting double bonds, whereas other enzymes desaturate sequentially towards the methyl group. When heterologously expressed in S. cerevisiae, FAT-3 specifically acts on two 18-carbon substrates (linoleic and alpha-linolenic acid) and always desaturates in an methylene interrupted pattern (one double bond in every three carbons). fat-3 and fat-4 are closely related paralogs, transcribed in tandem and spaced 5.3 kb apart; they are thus likely to have arisen from a local duplication. Despite their similarity (46% identity), FAT-3 and FAT-4 have absolutely non-overlapping substrate specificities. FAT-3 belongs to a family of diiron-oxo integral membrane proteins that use cytochrome b5 and NADH-cytochrome b5 reductase as cofactors, and whose protein sequences contain conserved motifs consisting of three histidine-rich sequences (H-boxes) and two long stretches (>40 residues each) of hydrophobic residues; the H-boxes are thought to coordinate the diiron-oxo structure at the active sites, while the hydrophobic stretches are thought to bind the lipid bilayer and put H-boxes into an active site. Each histidine residue in the H-boxes is required for function when assayed by site-directed mutagenesis. [WormBase] Observation: fat-3 RNAi at adulthood extended lifespan by 10-15% [19301819]. See also Ref 10,12 in Shmookler Reis et al., 2011. Interventions: Assays: Median: 10-15 Classification: Aging Relevance Analysis/Source:  GenAge GenDRHomologs Edit \ Update (Admin) | Delete |
Comment on This Data Unit