HSD17B10

This gene encodes 3-hydroxyacyl-CoA dehydrogenase type II, a member of the short-chain dehydrogenase/reductase superfamily. The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids, and is a subunit of mitochondrial ribonuclease P, which is involved in tRNA maturation. The protein has been implicated in the development of Alzheimer disease, and mutations in the gene are the cause of 17beta-hydroxysteroid dehydrogenase type 10 (HSD10) deficiency. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Aug 2014]

Hydroxysteroid 17-Beta Dehydrogenase 10

Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism (PubMed:9553139, PubMed:10600649, PubMed:12917011, PubMed:20077426, PubMed:18996107, PubMed:19706438, PubMed:25925575, PubMed:26950678, PubMed:28888424).

Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid beta-oxidation, a major degradation pathway of fatty acids. Catalyzes the third step in the beta-oxidation cycle, namely the reversible conversion of (S)-3-hydroxyacyl-CoA to 3-ketoacyl-CoA. Preferentially accepts straight medium- and short-chain acyl-CoA substrates with highest efficiency for (3S)-hydroxybutanoyl-CoA (PubMed:9553139, PubMed:10600649, PubMed:12917011, PubMed:25925575, PubMed:26950678).

Acts as 3-hydroxy-2-methylbutyryl-CoA dehydrogenase in branched-chain amino acid catabolic pathway. Catalyzes the oxidation of 3-hydroxy-2-methylbutanoyl-CoA into 2-methyl-3-oxobutanoyl-CoA, a step in isoleucine degradation pathway (PubMed:20077426, PubMed:18996107, PubMed:19706438).

Has hydroxysteroid dehydrogenase activity toward steroid hormones and bile acids. Catalyzes the oxidation of 3alpha-, 17beta-, 20beta- and 21-hydroxysteroids and 7alpha- and 7beta-hydroxy bile acids (PubMed:10600649, PubMed:12917011).

Oxidizes allopregnanolone/brexanolone at the 3alpha-hydroxyl group, which is known to be critical for the activation of gamma-aminobutyric acid receptors (GABAARs) chloride channel (PubMed:19706438, PubMed:28888424).

Has phospholipase C-like activity toward cardiolipin and its oxidized species. Likely oxidizes the 2'-hydroxyl in the head group of cardiolipin to form a ketone intermediate that undergoes nucleophilic attack by water and fragments into diacylglycerol, dihydroxyacetone and orthophosphate. Has higher affinity for cardiolipin with oxidized fatty acids and may degrade these species during the oxidative stress response to protect cells from apoptosis (PubMed:26338420).

By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD) (PubMed:9338779).

Essential for structural and functional integrity of mitochondria (PubMed:20077426).

In addition to mitochondrial dehydrogenase activity, moonlights as a component of mitochondrial ribonuclease P, a complex that cleaves tRNA molecules in their 5'-ends (PubMed:18984158, PubMed:24549042, PubMed:25925575, PubMed:26950678, PubMed:28888424).

Together with TRMT10C/MRPP1, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity (PubMed:23042678, PubMed:29040705).

The MRPP1-MRPP2 subcomplex catalyzes the formation of N1-methylguanine and N1-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; HSD17B10/MRPP2 acting as a non-catalytic subunit (PubMed:23042678, PubMed:25925575, PubMed:28888424).

The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after ELAC2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme (PubMed:29040705).

Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly.

Androgen metabolic process Source: UniProtKB
Bile acid biosynthetic process Source: UniProtKB
Brexanolone metabolic process Source: UniProtKB
C21-steroid hormone metabolic process Source: UniProtKB
Estrogen metabolic process Source: UniProtKB
Fatty acid beta-oxidation Source: UniProtKB
Fatty acid metabolic process Source: GO_Central
Isoleucine catabolic process Source: UniProtKB
Lipid metabolic process Source: ProtInc
Mitochondrial tRNA 3'-end processing Source: UniProtKB
Mitochondrial tRNA 5'-end processing Source: UniProtKB
Mitochondrial tRNA methylation Source: UniProtKB
Mitochondrion organization Source: UniProtKB
Protein homotetramerization Source: UniProtKB

Mitochondrion; Mitochondrion nucleoid

HDS10 mitochondrial disease (HSD10MD):
An X-linked multisystemic disorder with highly variable severity. Age at onset ranges from the neonatal period to early childhood. Features include progressive neurodegeneration, psychomotor retardation, loss of mental and motor skills, seizures, cardiomyopathy, and visual and hearing impairment. Some patients manifest lactic acidosis and metabolic acidosis.