Search Results

Overview

Uniprot IDQ99714
Protein Name3-hydroxyacyl-CoA dehydrogenase type-2
Gene NameHSD17B10
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
105 SKTYNLKKGQTHTLE
52 SGGEAQAKKLGNNCV
53 GGEAQAKKLGNNCVF
79 QTALALAKGKFGRVD
9 AAACRSVKGLVAVIT
99 AGIAVASKTYNLKKG

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)

Protein Sequence

10 MAAACRSVKG 20 LVAVITGGAS 30 GLGLATAERL 40 VGQGASAVLL 50 DLPNSGGEAQ 60 AKKLGNNCVF 70 APADVTSEKD 80 VQTALALAKG 90 KFGRVDVAVN 100 CAGIAVASKT 110 YNLKKGQTHT 120 LEDFQRVLDV 130 NLMGTFNVIR 140 LVAGEMGQNE 150 PDQGGQRGVI 160 INTASVAAFE 170 GQVGQAAYSA 180 SKGGIVGMTL 190 PIARDLAPIG 200 IRVMTIAPGL 210 FGTPLLTSLP 220 EKVCNFLASQ 230 VPFPSRLGDP 240 AEYAHLVQAI 250 IENPFLNGEV 260 IRLDGAIRMQ P

Gene Ontology

Classification GO ID Description
Cellular Component GO:0042645 mitochondrial nucleoid
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0030678 mitochondrial ribonuclease P complex
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005886 plasma membrane
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: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:0106282 isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity
Molecular Function GO:0003723 RNA 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:0006629 lipid metabolic process
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] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[4] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.