UniProt functional annotation for Q99714



	UniProt functional annotation for Q99714

UniProt code: Q99714.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). {ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:19706438, ECO:0000269|PubMed:20077426, ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26338420, ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:28888424, ECO:0000269|PubMed:9553139}.

Function: 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 N(1)-methylguanine and N(1)-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. {ECO:0000269|PubMed:18984158, ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:24549042, ECO:0000269|PubMed:24703694, ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:28888424, ECO:0000269|PubMed:29040705}.

Catalytic activity: Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35; Evidence={ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433; Evidence={ECO:0000305|PubMed:12917011}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22434; Evidence={ECO:0000305|PubMed:10600649, ECO:0000305|PubMed:12917011, ECO:0000305|PubMed:25925575, ECO:0000305|PubMed:26950678, ECO:0000305|PubMed:9553139};

Catalytic activity: Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methyl-3- oxobutanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:13281, ChEBI:CHEBI:15378, ChEBI:CHEBI:57312, ChEBI:CHEBI:57335, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.178; Evidence={ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:19706438, ECO:0000269|PubMed:20077426}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13282; Evidence={ECO:0000305|PubMed:18996107, ECO:0000305|PubMed:19706438, ECO:0000305|PubMed:20077426};

Catalytic activity: Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422, ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.239; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta- hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004, ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH; Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62; Evidence={ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613; Evidence={ECO:0000305|PubMed:10600649, ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=cholate + NAD(+) = 3alpha,12alpha-dihydroxy-7-oxo-5beta- cholanate + H(+) + NADH; Xref=Rhea:RHEA:19409, ChEBI:CHEBI:11893, ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.159; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19410; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=(3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:30799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286, ChEBI:CHEBI:57316, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30800; Evidence={ECO:0000305|PubMed:12917011}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30801; Evidence={ECO:0000305|PubMed:10600649, ECO:0000305|PubMed:25925575, ECO:0000305|PubMed:9553139};

Catalytic activity: Reaction=(3S)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31195, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62617, ChEBI:CHEBI:62619; Evidence={ECO:0000269|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31196; Evidence={ECO:0000305}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31197; Evidence={ECO:0000305|PubMed:9553139};

Catalytic activity: Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378, ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62613; Evidence={ECO:0000269|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160; Evidence={ECO:0000305}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31161; Evidence={ECO:0000305|PubMed:9553139};

Catalytic activity: Reaction=17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha- androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:41992, ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41993; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=5alpha-pregnan-20beta-ol-3-one + NAD(+) = 5alpha-pregnane- 3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:42008, ChEBI:CHEBI:15378, ChEBI:CHEBI:28952, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78594; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42009; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=3alpha-hydroxy-5alpha-pregnan-20-one + NAD(+) = 5alpha- pregnane-3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:41980, ChEBI:CHEBI:15378, ChEBI:CHEBI:28952, ChEBI:CHEBI:50169, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:19706438, ECO:0000269|PubMed:28888424}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41981; Evidence={ECO:0000305|PubMed:19706438, ECO:0000305|PubMed:28888424};

Catalytic activity: Reaction=cortisone + NAD(+) = 17alpha-hydroxypregn-4-en-3,11,20-trione- 21-al + H(+) + NADH; Xref=Rhea:RHEA:42016, ChEBI:CHEBI:15378, ChEBI:CHEBI:16962, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78596; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42017; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=11-dehydrocorticosterone + NAD(+) = H(+) + NADH + pregn-4-ene- 3,11,20,21-tetraone; Xref=Rhea:RHEA:42020, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78600, ChEBI:CHEBI:78601; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42021; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=cortisol + NAD(+) = 11beta,17alpha-dihydroxypregn-4-ene- 3,20,21-trione + H(+) + NADH; Xref=Rhea:RHEA:42012, ChEBI:CHEBI:15378, ChEBI:CHEBI:17650, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78595; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42013; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=chenodeoxycholate + NAD(+) = 7-oxolithocholate + H(+) + NADH; Xref=Rhea:RHEA:42036, ChEBI:CHEBI:15378, ChEBI:CHEBI:36234, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78605; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42037; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=NAD(+) + ursodeoxycholate = 7-oxolithocholate + H(+) + NADH; Xref=Rhea:RHEA:42028, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78604, ChEBI:CHEBI:78605; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42029; Evidence={ECO:0000305|PubMed:12917011};

Catalytic activity: Reaction=3beta,7beta-dihydroxy-5beta-cholan-24-oate + NAD(+) = 3beta- hydroxy-7-oxo-5beta-cholan-24-oate + H(+) + NADH; Xref=Rhea:RHEA:42024, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78602, ChEBI:CHEBI:78603; Evidence={ECO:0000269|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42025; Evidence={ECO:0000305|PubMed:12917011};

Activity regulation: The phospholipase C-like activity toward cardiolipin is inhibited by amyloid-beta peptide. {ECO:0000269|PubMed:26338420}.

Biophysicochemical properties: Kinetic parameters: KM=25.7 uM for acetoacetyl-CoA (in the presence of 0.2 mM NADH, at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=85.2 uM for beta-hydroxybutyryl-CoA (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=41 uM for androsterone (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=5 uM for 5-alpha-pregnan-20-beta-ol-3-one (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=219 uM for isoursodeoxycholic acid (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=36.4 uM for chenodeoxycholic acid (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=1.7 uM for dehydrocorticosterone (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=30.6 uM for NADH (in the presence of acetoacetyl-CoA, at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=42.3 uM for NAD (in the presence of beta-hydroxybutyryl-CoA, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; KM=69 uM for DL-3-hydroxybutyryl-CoA {ECO:0000269|PubMed:28888424}; KM=7.7 uM for 3alpha-hydroxy-5alpha-pregnan-20-one/allopregnanolone {ECO:0000269|PubMed:28888424}; KM=30 uM for 3alpha-hydroxy-5alpha-pregnan-20-one/allopregnanolone {ECO:0000269|PubMed:19706438}; KM=140 uM for tetramyristoyl cardiolipin {ECO:0000269|PubMed:26338420}; KM=148 uM for tetralinoleoyl cardiolipin {ECO:0000269|PubMed:26338420}; KM=40 uM for oxidized tetralinoleoyl cardiolipin {ECO:0000269|PubMed:26338420}; KM=7.1 uM for (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA {ECO:0000269|PubMed:19706438}; Vmax=14.8 umol/min/mg enzyme toward (2S,3S)-3-hydroxy-2- methylbutanoyl-CoA {ECO:0000269|PubMed:19706438}; Vmax=150 umol/min/mg enzyme 3alpha-hydroxy-5alpha-pregnan-20- one/allopregnanolone {ECO:0000269|PubMed:19706438}; Note=Kcat is 458 min(-1) for DL-3-hydroxybutyryl-CoA (PubMed:28888424). Kcat is 706 min(-1) for allopregnanolone (PubMed:28888424). {ECO:0000269|PubMed:28888424}; pH dependence: Optimum pH is 9.3 for the dehydrogenase reaction at 25 degrees Celsius, and 7.0 for the reductase reaction at 25 degrees Celsius. {ECO:0000269|PubMed:12917011};

Pathway: Amino-acid degradation; L-isoleucine degradation. {ECO:0000269|PubMed:19706438}.

Pathway: Lipid metabolism; fatty acid beta-oxidation. {ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:9553139}.

Pathway: Steroid metabolism. {ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011}.

Pathway: Lipid metabolism; bile acid biosynthesis. {ECO:0000269|PubMed:12917011}.

Subunit: Homotetramer (PubMed:15342248, PubMed:20077426, PubMed:25925575). Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3 (PubMed:18984158, PubMed:25925575, PubMed:26950678, PubMed:28888424). Interacts with TRMT10C/MRPP1; forming the MRPP1-MRPP2 subcomplex of the mitochondrial ribonuclease P complex (PubMed:23042678, PubMed:29040705). {ECO:0000269|PubMed:15342248, ECO:0000269|PubMed:18984158, ECO:0000269|PubMed:20077426, ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:28888424, ECO:0000269|PubMed:29040705}.

Subcellular location: Mitochondrion {ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:18984158}. Mitochondrion matrix, mitochondrion nucleoid {ECO:0000269|PubMed:24703694}.

Tissue specificity: Ubiquitously expressed in normal tissues but is overexpressed in neurons affected in AD. {ECO:0000269|PubMed:9338779}.

Disease: HDS10 mitochondrial disease (HSD10MD) [MIM:300438]: 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. {ECO:0000269|PubMed:12696021, ECO:0000269|PubMed:16148061, ECO:0000269|PubMed:17236142, ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:19706438, ECO:0000269|PubMed:20077426, ECO:0000269|PubMed:22132097, ECO:0000269|PubMed:24549042, ECO:0000269|PubMed:25575635, ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26338420, ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:28888424}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the short-chain dehydrogenases/reductases (SDR) family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). {ECO:0000269\|PubMed:10600649, ECO:0000269\|PubMed:12917011, ECO:0000269\|PubMed:18996107, ECO:0000269\|PubMed:19706438, ECO:0000269\|PubMed:20077426, ECO:0000269\|PubMed:25925575, ECO:0000269\|PubMed:26338420, ECO:0000269\|PubMed:26950678, ECO:0000269\|PubMed:28888424, ECO:0000269\|PubMed:9553139}.



Function:		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 N(1)-methylguanine and N(1)-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. {ECO:0000269\|PubMed:18984158, ECO:0000269\|PubMed:23042678, ECO:0000269\|PubMed:24549042, ECO:0000269\|PubMed:24703694, ECO:0000269\|PubMed:25925575, ECO:0000269\|PubMed:26950678, ECO:0000269\|PubMed:28888424, ECO:0000269\|PubMed:29040705}.


Catalytic activity:		Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35; Evidence={ECO:0000269\|PubMed:10600649, ECO:0000269\|PubMed:12917011, ECO:0000269\|PubMed:25925575, ECO:0000269\|PubMed:26950678, ECO:0000269\|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433; Evidence={ECO:0000305\|PubMed:12917011}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22434; Evidence={ECO:0000305\|PubMed:10600649, ECO:0000305\|PubMed:12917011, ECO:0000305\|PubMed:25925575, ECO:0000305\|PubMed:26950678, ECO:0000305\|PubMed:9553139};
Catalytic activity:		Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methyl-3- oxobutanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:13281, ChEBI:CHEBI:15378, ChEBI:CHEBI:57312, ChEBI:CHEBI:57335, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.178; Evidence={ECO:0000269\|PubMed:18996107, ECO:0000269\|PubMed:19706438, ECO:0000269\|PubMed:20077426}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13282; Evidence={ECO:0000305\|PubMed:18996107, ECO:0000305\|PubMed:19706438, ECO:0000305\|PubMed:20077426};
Catalytic activity:		Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422, ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.239; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta- hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004, ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH; Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62; Evidence={ECO:0000269\|PubMed:10600649, ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613; Evidence={ECO:0000305\|PubMed:10600649, ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=cholate + NAD(+) = 3alpha,12alpha-dihydroxy-7-oxo-5beta- cholanate + H(+) + NADH; Xref=Rhea:RHEA:19409, ChEBI:CHEBI:11893, ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.159; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19410; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=(3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:30799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286, ChEBI:CHEBI:57316, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269\|PubMed:10600649, ECO:0000269\|PubMed:12917011, ECO:0000269\|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30800; Evidence={ECO:0000305\|PubMed:12917011}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30801; Evidence={ECO:0000305\|PubMed:10600649, ECO:0000305\|PubMed:25925575, ECO:0000305\|PubMed:9553139};
Catalytic activity:		Reaction=(3S)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31195, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62617, ChEBI:CHEBI:62619; Evidence={ECO:0000269\|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31196; Evidence={ECO:0000305}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31197; Evidence={ECO:0000305\|PubMed:9553139};
Catalytic activity:		Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378, ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62613; Evidence={ECO:0000269\|PubMed:9553139}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160; Evidence={ECO:0000305}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31161; Evidence={ECO:0000305\|PubMed:9553139};
Catalytic activity:		Reaction=17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha- androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:41992, ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41993; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=5alpha-pregnan-20beta-ol-3-one + NAD(+) = 5alpha-pregnane- 3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:42008, ChEBI:CHEBI:15378, ChEBI:CHEBI:28952, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78594; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42009; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=3alpha-hydroxy-5alpha-pregnan-20-one + NAD(+) = 5alpha- pregnane-3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:41980, ChEBI:CHEBI:15378, ChEBI:CHEBI:28952, ChEBI:CHEBI:50169, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269\|PubMed:19706438, ECO:0000269\|PubMed:28888424}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41981; Evidence={ECO:0000305\|PubMed:19706438, ECO:0000305\|PubMed:28888424};
Catalytic activity:		Reaction=cortisone + NAD(+) = 17alpha-hydroxypregn-4-en-3,11,20-trione- 21-al + H(+) + NADH; Xref=Rhea:RHEA:42016, ChEBI:CHEBI:15378, ChEBI:CHEBI:16962, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78596; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42017; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=11-dehydrocorticosterone + NAD(+) = H(+) + NADH + pregn-4-ene- 3,11,20,21-tetraone; Xref=Rhea:RHEA:42020, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78600, ChEBI:CHEBI:78601; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42021; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=cortisol + NAD(+) = 11beta,17alpha-dihydroxypregn-4-ene- 3,20,21-trione + H(+) + NADH; Xref=Rhea:RHEA:42012, ChEBI:CHEBI:15378, ChEBI:CHEBI:17650, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78595; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42013; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=chenodeoxycholate + NAD(+) = 7-oxolithocholate + H(+) + NADH; Xref=Rhea:RHEA:42036, ChEBI:CHEBI:15378, ChEBI:CHEBI:36234, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78605; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42037; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=NAD(+) + ursodeoxycholate = 7-oxolithocholate + H(+) + NADH; Xref=Rhea:RHEA:42028, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78604, ChEBI:CHEBI:78605; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42029; Evidence={ECO:0000305\|PubMed:12917011};
Catalytic activity:		Reaction=3beta,7beta-dihydroxy-5beta-cholan-24-oate + NAD(+) = 3beta- hydroxy-7-oxo-5beta-cholan-24-oate + H(+) + NADH; Xref=Rhea:RHEA:42024, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78602, ChEBI:CHEBI:78603; Evidence={ECO:0000269\|PubMed:12917011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42025; Evidence={ECO:0000305\|PubMed:12917011};
Activity regulation:		The phospholipase C-like activity toward cardiolipin is inhibited by amyloid-beta peptide. {ECO:0000269\|PubMed:26338420}.
Biophysicochemical properties:		Kinetic parameters: KM=25.7 uM for acetoacetyl-CoA (in the presence of 0.2 mM NADH, at pH 7.0 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=85.2 uM for beta-hydroxybutyryl-CoA (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=41 uM for androsterone (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=5 uM for 5-alpha-pregnan-20-beta-ol-3-one (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=219 uM for isoursodeoxycholic acid (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=36.4 uM for chenodeoxycholic acid (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=1.7 uM for dehydrocorticosterone (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=30.6 uM for NADH (in the presence of acetoacetyl-CoA, at pH 7.0 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=42.3 uM for NAD (in the presence of beta-hydroxybutyryl-CoA, at pH 9.3 and 25 degrees Celsius) {ECO:0000269\|PubMed:12917011}; KM=69 uM for DL-3-hydroxybutyryl-CoA {ECO:0000269\|PubMed:28888424}; KM=7.7 uM for 3alpha-hydroxy-5alpha-pregnan-20-one/allopregnanolone {ECO:0000269\|PubMed:28888424}; KM=30 uM for 3alpha-hydroxy-5alpha-pregnan-20-one/allopregnanolone {ECO:0000269\|PubMed:19706438}; KM=140 uM for tetramyristoyl cardiolipin {ECO:0000269\|PubMed:26338420}; KM=148 uM for tetralinoleoyl cardiolipin {ECO:0000269\|PubMed:26338420}; KM=40 uM for oxidized tetralinoleoyl cardiolipin {ECO:0000269\|PubMed:26338420}; KM=7.1 uM for (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA {ECO:0000269\|PubMed:19706438}; Vmax=14.8 umol/min/mg enzyme toward (2S,3S)-3-hydroxy-2- methylbutanoyl-CoA {ECO:0000269\|PubMed:19706438}; Vmax=150 umol/min/mg enzyme 3alpha-hydroxy-5alpha-pregnan-20- one/allopregnanolone {ECO:0000269\|PubMed:19706438}; Note=Kcat is 458 min(-1) for DL-3-hydroxybutyryl-CoA (PubMed:28888424). Kcat is 706 min(-1) for allopregnanolone (PubMed:28888424). {ECO:0000269\|PubMed:28888424}; pH dependence: Optimum pH is 9.3 for the dehydrogenase reaction at 25 degrees Celsius, and 7.0 for the reductase reaction at 25 degrees Celsius. {ECO:0000269\|PubMed:12917011};
Pathway:		Amino-acid degradation; L-isoleucine degradation. {ECO:0000269\|PubMed:19706438}.
Pathway:		Lipid metabolism; fatty acid beta-oxidation. {ECO:0000269\|PubMed:10600649, ECO:0000269\|PubMed:12917011, ECO:0000269\|PubMed:9553139}.
Pathway:		Steroid metabolism. {ECO:0000269\|PubMed:10600649, ECO:0000269\|PubMed:12917011}.
Pathway:		Lipid metabolism; bile acid biosynthesis. {ECO:0000269\|PubMed:12917011}.
Subunit:		Homotetramer (PubMed:15342248, PubMed:20077426, PubMed:25925575). Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3 (PubMed:18984158, PubMed:25925575, PubMed:26950678, PubMed:28888424). Interacts with TRMT10C/MRPP1; forming the MRPP1-MRPP2 subcomplex of the mitochondrial ribonuclease P complex (PubMed:23042678, PubMed:29040705). {ECO:0000269\|PubMed:15342248, ECO:0000269\|PubMed:18984158, ECO:0000269\|PubMed:20077426, ECO:0000269\|PubMed:23042678, ECO:0000269\|PubMed:25925575, ECO:0000269\|PubMed:26950678, ECO:0000269\|PubMed:28888424, ECO:0000269\|PubMed:29040705}.
Subcellular location:		Mitochondrion {ECO:0000269\|PubMed:12917011, ECO:0000269\|PubMed:18984158}. Mitochondrion matrix, mitochondrion nucleoid {ECO:0000269\|PubMed:24703694}.
Tissue specificity:		Ubiquitously expressed in normal tissues but is overexpressed in neurons affected in AD. {ECO:0000269\|PubMed:9338779}.
Disease:		HDS10 mitochondrial disease (HSD10MD) [MIM:300438]: 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. {ECO:0000269\|PubMed:12696021, ECO:0000269\|PubMed:16148061, ECO:0000269\|PubMed:17236142, ECO:0000269\|PubMed:18996107, ECO:0000269\|PubMed:19706438, ECO:0000269\|PubMed:20077426, ECO:0000269\|PubMed:22132097, ECO:0000269\|PubMed:24549042, ECO:0000269\|PubMed:25575635, ECO:0000269\|PubMed:25925575, ECO:0000269\|PubMed:26338420, ECO:0000269\|PubMed:26950678, ECO:0000269\|PubMed:28888424}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the short-chain dehydrogenases/reductases (SDR) family. {ECO:0000305}.