HSD17B8
Function
Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex that acts as a scaffold protein required for the stability of carbonyl reductase type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-ACP reductase activity, thereby participating in mitochondrial fatty acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain length preference; this enzymatic activity is not needed for the KAR function (PubMed:19571038, PubMed:25203508, PubMed:30508570). Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays enzymatic activity only in the presence of NAD(+) (PubMed:19571038). Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they constitute an alternative route to the auxiliary enzyme pathways for the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters (Probable) (PubMed:30508570). NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol (17beta-estradiol or E2). Has very low activity towards testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one). Primarily an oxidative enzyme, it can switch to a reductive mode determined in the appropriate physiologic milieu and catalyze the reduction of estrone (E1) to form biologically active 17beta-estradiol (PubMed:17978863).
Pathway
Steroid biosynthesis; estrogen biosynthesis.
Lipid metabolism; fatty acid biosynthesis.
Lipid metabolism; mitochondrial fatty acid beta-oxidation.
Sequence Similarities
Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Tissue Specificity
Widely expressed, particularly abundant in prostate, placenta and kidney (PubMed:17978863). Expressed at protein level in various tissues like brain, cerebellum, heart, lung, kidney, ovary, testis, adrenals and prostate (PubMed:30508570).
Cellular localization
- Mitochondrion matrix
Alternative names
FABGL, HKE6, RING2, SDR30C1, HSD17B8, (3R)-3-hydroxyacyl-CoA dehydrogenase, 17-beta-hydroxysteroid dehydrogenase 8, 3-ketoacyl-[acyl-carrier-protein] reductase alpha subunit, 3-oxoacyl-[acyl-carrier-protein] reductase, Estradiol 17-beta-dehydrogenase 8, Protein Ke6, Short chain dehydrogenase/reductase family 30C member 1, Testosterone 17-beta-dehydrogenase 8, 17-beta-HSD 8, KAR alpha subunit, Ke6