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Overview

Uniprot IDO70351
Protein Name3-hydroxyacyl-CoA dehydrogenase type-2
Gene NameHsd17b10
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
105 IKTYHEKKNQVHTLE
53 EGETEAKKLGGNCIF

Function

Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism. 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. 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. 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. 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. 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. By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD). Essential for structural and functional integrity of mitochondria

Protein Sequence

10 MAAAVRSVKG 20 LVAVITGGAS 30 GLGLSTAKRL 40 VGQGATAVLL 50 DVPNSEGETE 60 AKKLGGNCIF 70 APANVTSEKE 80 VQAALTLAKE 90 KFGRIDVAVN 100 CAGIAVAIKT 110 YHEKKNQVHT 120 LEDFQRVINV 130 NLIGTFNVIR 140 LVAGVMGQNE 150 PDQGGQRGVI 160 INTASVAAFE 170 GQVGQAAYSA 180 SKGGIVGMTL 190 PIARDLAPIG 200 IRVVTIAPGL 210 FATPLLTTLP 220 DKVRNFLASQ 230 VPFPSRLGDP 240 AEYAHLVQMV 250 IENPFLNGEV 260 IRLDGAIRMQ P

Gene Ontology

Classification GO ID Description
Cellular Component GO:1902494 catalytic complex
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:1902555 endoribonuclease complex
Cellular Component GO:0042645 mitochondrial nucleoid
Cellular Component GO:0030678 mitochondrial ribonuclease P complex
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0043527 tRNA methyltransferase complex
Molecular Function GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
Molecular Function GO:0044594 17-beta-hydroxysteroid dehydrogenase (NAD+) activity
Molecular Function GO:0047015 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity
Molecular Function GO:0018454 acetoacetyl-CoA reductase activity
Molecular Function GO:0001540 amyloid-beta binding
Molecular Function GO:0047044 androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity
Molecular Function GO:0160241 cardiolipin dehydrogenase (NAD+) activity
Molecular Function GO:0106281 chenodeoxycholate 7-alpha-dehydrogenase (NAD+) activity
Molecular Function GO:0008709 cholate 7-alpha-dehydrogenase (NAD+) activity
Molecular Function GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0106282 isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity
Molecular Function GO:0051287 NAD binding
Molecular Function GO:0030331 nuclear estrogen receptor binding
Molecular Function GO:0005496 steroid binding
Molecular Function GO:0047035 testosterone dehydrogenase (NAD+) activity
Molecular Function GO:0000049 tRNA binding
Molecular Function GO:0106283 ursodeoxycholate 7-beta-dehydrogenase (NAD+) activity
Biological Process GO:0008209 androgen metabolic process
Biological Process GO:0006699 bile acid biosynthetic process
Biological Process GO:0062173 brexanolone metabolic process
Biological Process GO:0008207 C21-steroid hormone metabolic process
Biological Process GO:0008210 estrogen metabolic process
Biological Process GO:0006635 fatty acid beta-oxidation
Biological Process GO:0006631 fatty acid metabolic process
Biological Process GO:0006550 L-isoleucine catabolic process
Biological Process GO:0033327 Leydig cell differentiation
Biological Process GO:0008584 male gonad development
Biological Process GO:1990180 mitochondrial tRNA 3'-end processing
Biological Process GO:0097745 mitochondrial tRNA 5'-end processing
Biological Process GO:0070901 mitochondrial tRNA methylation
Biological Process GO:0007005 mitochondrion organization
Biological Process GO:0051289 protein homotetramerization
Biological Process GO:0042780 tRNA 3'-end processing
Biological Process GO:0001680 tRNA 3'-terminal CCA addition

Reference

[1] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.