HSD17B10
entrez
3028
canonical
uniprot
Q99714
canonical
ensembl
ENSG00000072506
resolver
ensp
ENSP00000168216
resolver
ensp
ENSP00000364453
resolver
genesymbol
HSD17B10
resolver
genesymbol_syn
ERAB
resolver
genesymbol_syn
HADH2
resolver
genesymbol_syn
MRPP2
resolver
genesymbol_syn
SCHAD
resolver
genesymbol_syn
SDR5C1
resolver
genesymbol_syn
XH98G2
resolver
hgnc
HGNC:4800
resolver
uniprot
A0A0S2Z410
resolver
uniprot
Q5H927
resolver
uniprot
Q6IBS9
resolver
uniprot
Q8TCV9
resolver
uniprot
Q96HD5
resolver
uniprot_entry
A0A0S2Z410_HUMAN
resolver
uniprot_entry
HCD2_HUMAN
resolver
uniprot_sec
Q5H927
resolver
uniprot_sec
Q6IBS9
resolver
uniprot_sec
Q8TCV9
resolver
uniprot_sec
Q96HD5
resolver
activity_regulation
ACTIVITY REGULATION: The phospholipase C-like activity toward cardiolipin is inhibited by amyloid-beta peptide. {ECO:0000269|PubMed:26338420}.
uniprot
proteins
amino_acid_sequence
MAAACRSVKGLVAVITGGASGLGLATAERLVGQGASAVLLDLPNSGGEAQAKKLGNNCVFAPADVTSEKDVQTALALAKGKFGRVDVAVNCAGIAVASKTYNLKKGQTHTLEDFQRVLDVNLMGTFNVIRLVAGEMGQNEPDQGGQRGVIINTASVAAFEGQVGQAAYSASKGGIVGMTLPIARDLAPIGIRVMTIAPGLFGTPLLTSLPEKVCNFLASQVPFPSRLGDPAEYAHLVQAIIENPFLNGEVIRLDGAIRMQP
uniprot
proteins
disease_involvement
DISEASE: HSD10 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.
uniprot
proteins
ec_number
1.1.1.159
uniprot
proteins
ec_number
1.1.1.178
uniprot
proteins
ec_number
1.1.1.239
uniprot
proteins
ec_number
1.1.1.35
uniprot
proteins
ec_number
1.1.1.53
uniprot
proteins
ec_number
1.1.1.62
uniprot
proteins
function
FUNCTION: Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism (PubMed:10600649, PubMed:12917011, PubMed:18996107, PubMed:19706438, PubMed:20077426, PubMed:25925575, PubMed:26950678, PubMed:28888424, PubMed:9553139). 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:10600649, PubMed:12917011, PubMed:25925575, PubMed:26950678, PubMed:9553139). 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:18996107, PubMed:19706438, PubMed:20077426). 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}.
uniprot
proteins
mass_dalton
26923
uniprot
proteins
mutagenesis
MUTAGEN 20; /note="S->F: Decreased dehydrogenase activity. Does not affect mitochondrial tRNA 5'-end processing. Does not affect tRNA methylation."; /evidence="ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25925575"; MUTAGEN 172; /note="K->A: Abolishes dehydrogenase activity. Does not affect mitochondrial tRNA 5'-end processing. Does not affect tRNA methylation. Does not affect homotetramerization."; /evidence="ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25925575
uniprot
proteins
pathway_participation
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}.
uniprot
proteins
protein_family
Short-chain dehydrogenases/reductases (SDR) family
uniprot
proteins
pubmed
10600649
uniprot
proteins
pubmed
12696021
uniprot
proteins
pubmed
12917011
uniprot
proteins
pubmed
15087549
uniprot
proteins
pubmed
15342248
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
16148061
uniprot
proteins
pubmed
17236142
uniprot
proteins
pubmed
18984158
uniprot
proteins
pubmed
18996107
uniprot
proteins
pubmed
19706438
uniprot
proteins
pubmed
20077426
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22132097
uniprot
proteins
pubmed
23042678
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24549042
uniprot
proteins
pubmed
24703694
uniprot
proteins
pubmed
25575635
uniprot
proteins
pubmed
25925575
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26338420
uniprot
proteins
pubmed
26950678
uniprot
proteins
pubmed
28888424
uniprot
proteins
pubmed
29040705
uniprot
proteins
pubmed
9338779
uniprot
proteins
pubmed
9553139
uniprot
proteins
pubmed
9671743
uniprot
proteins
sequence_length
261
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:18984158}. Mitochondrion matrix, mitochondrion nucleoid {ECO:0000269|PubMed:24703694}.
uniprot
proteins