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Details on Person UniProt:Q99714 HSD17B10

Class:IdReferenceGeneProduct:56390
_chainChangeLoginitiator methionine:1 added on Fri February 6 2015;chain:2-261 added on Fri February 6 2015;initiator methionine:1 for 56390 removed on Fri Nov 03 2023;initiator methionine: for 56390 added on Fri Nov 03 2023;initiator methionine: for 56390 removed on Fri Aug 15 2025;initiator methionine:1 for 56390 added on Fri Aug 15 2025
_displayNameUniProt:Q99714 HSD17B10
_timestamp2025-08-15 21:07:43
chaininitiator methionine:1
chain:2-261
checksum9E74F242E3E6FEF1
commentFUNCTION 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).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.CATALYTIC ACTIVITY a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + NADH + H(+)CATALYTIC ACTIVITY (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methyl-3-oxobutanoyl-CoA + NADH + H(+)CATALYTIC ACTIVITY testosterone + NAD(+) = androst-4-ene-3,17-dione + NADH + H(+)CATALYTIC ACTIVITY 5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADH + H(+)CATALYTIC ACTIVITY 17beta-estradiol + NAD(+) = estrone + NADH + H(+)CATALYTIC ACTIVITY cholate + NAD(+) = 3alpha,12alpha-dihydroxy-7-oxo-5beta-cholanate + NADH + H(+)CATALYTIC ACTIVITY (3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + NADH + H(+)CATALYTIC ACTIVITY (3S)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + NADH + H(+)CATALYTIC ACTIVITY (3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + NADH + H(+)CATALYTIC ACTIVITY 17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha-androstan-3,17-dione + NADH + H(+)CATALYTIC ACTIVITY 5alpha-pregnan-20beta-ol-3-one + NAD(+) = 5alpha-pregnane-3,20-dione + NADH + H(+)CATALYTIC ACTIVITY 3alpha-hydroxy-5alpha-pregnan-20-one + NAD(+) = 5alpha-pregnane-3,20-dione + NADH + H(+)CATALYTIC ACTIVITY cortisone + NAD(+) = 17alpha-hydroxypregn-4-en-3,11,20-trione-21-al + NADH + H(+)CATALYTIC ACTIVITY 11-dehydrocorticosterone + NAD(+) = pregn-4-ene-3,11,20,21-tetraone + NADH + H(+)CATALYTIC ACTIVITY cortisol + NAD(+) = 11beta,17alpha-dihydroxypregn-4-ene-3,20,21-trione + NADH + H(+)CATALYTIC ACTIVITY chenodeoxycholate + NAD(+) = 7-oxolithocholate + NADH + H(+)CATALYTIC ACTIVITY ursodeoxycholate + NAD(+) = 7-oxolithocholate + NADH + H(+)CATALYTIC ACTIVITY 3beta,7beta-dihydroxy-5beta-cholan-24-oate + NAD(+) = 3beta-hydroxy-7-oxo-5beta-cholan-24-oate + NADH + H(+)ACTIVITY REGULATION The phospholipase C-like activity toward cardiolipin is inhibited by amyloid-beta peptide.BIOPHYSICOCHEMICAL PROPERTIES kcat is 458 min(-1) for DL-3-hydroxybutyryl-CoA (PubMed:28888424). kcat is 706 min(-1) for allopregnanolone (PubMed:28888424).PATHWAY Amino-acid degradation; L-isoleucine degradation.PATHWAY Lipid metabolism; fatty acid beta-oxidation.PATHWAY Steroid metabolism.PATHWAY Lipid metabolism; bile acid biosynthesis.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).INTERACTION Ubiquitously expressed in normal tissues but is overexpressed in neurons affected in AD.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the short-chain dehydrogenases/reductases (SDR) family.
descriptionrecommendedName: 3-hydroxyacyl-CoA dehydrogenase type-2 ecNumber evidence="2 4 18 20 24"1.1.1.35 alternativeName: 17-beta-estradiol 17-dehydrogenase ecNumber evidence="2 4"1.1.1.62 alternativeName: fullName evidence="26"2-methyl-3-hydroxybutyryl-CoA dehydrogenase shortName evidence="26"MHBD alternativeName: 3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+)) ecNumber evidence="4"1.1.1.239 alternativeName: 3-hydroxy-2-methylbutyryl-CoA dehydrogenase ecNumber evidence="10 11 12"1.1.1.178 alternativeName: 3-hydroxyacyl-CoA dehydrogenase type II alternativeName: 3alpha(or 20beta)-hydroxysteroid dehydrogenase ecNumber evidence="4"1.1.1.53 alternativeName: 7-alpha-hydroxysteroid dehydrogenase ecNumber evidence="4"1.1.1.159 alternativeName: Endoplasmic reticulum-associated amyloid beta-peptide-binding protein alternativeName: Mitochondrial ribonuclease P protein 2 shortName: Mitochondrial RNase P protein 2 alternativeName: Short chain dehydrogenase/reductase family 5C member 1 alternativeName: Short-chain type dehydrogenase/reductase XH98G2 alternativeName: Type II HADH
geneNameHSD17B10
ERAB
HADH2
MRPP2
SCHAD
SDR5C1
XH98G2
identifierQ99714
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Alternative splicing
Disease variant
Fatty acid metabolism
Intellectual disability
Lipid metabolism
Mitochondrion
Mitochondrion nucleoid
NAD
Neurodegeneration
Oxidoreductase
Proteomics identification
Reference proteome
Steroid metabolism
tRNA processing
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameHSD17B10
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8990740] ENSEMBL:ENSG00000072506 HSD17B10 [Homo sapiens]
secondaryIdentifierHCD2_HUMAN
Q5H927
Q6IBS9
Q8TCV9
Q96HD5
sequenceLength261
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:148317] UniProt:Q99714-2 HSD17B10 [Homo sapiens]
[ReferenceIsoform:413168] UniProt:Q99714-1 HSD17B10 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:70831] HSD17B10 [mitochondrial matrix] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q99714 HSD17B10 (56390)
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