Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis.
-
All four human HACD proteins (HACD1-4) are 3-hydroxyacyl-CoA dehydratases catalyzing the third step of the very-long-chain fatty acid elongation cycle, shown by PHS1-shutoff yeast complementation and in-vitro 3-hydroxypalmitoyl-CoA dehydratase assays; HACD proteins interact with the ELOVL1-7 condensation enzymes.
"all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases"
Congenital myopathy is caused by mutation of HACD1.
-
A homozygous nonsense HACD1 variant (p.Tyr248Stop) causes autosomal recessive congenital myopathy and completely abrogates the dehydratase activity, confirming HACD1's role in the third step of VLCFA elongation.
"the enzymatic activity of dehydration of 3-hydroxyacyl-CoA, the third step in the elongation of very long-chain fatty acids (VLCFAs)"
A reference map of the human binary protein interactome.
The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with trans-2-enoyl-CoA reductase involved in substrates transfer in very long chain fatty acid elongation.
-
HACD1/2 form a complex with the trans-2-enoyl-CoA reductase TECR, coupling the dehydration (step 3) and reduction (step 4) reactions of the VLCFA elongation cycle.
"we confirmed the critical interactions between TECR and HACD1/2"
PTPLs dehydrate VLC3HA-CoA to VLCTDA-CoA
Synthesis of very long-chain fatty acyl-CoAs