Overview
| Uniprot ID | P50171 |
|---|
| Protein Name | (3R)-3-hydroxyacyl-CoA dehydrogenase |
|---|
| Gene Name | Hsd17b8 |
|---|
| Organism | Mus musculus |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 66 |
EDGAPRGKHAAFQAD |
Function
Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex, acts as scaffold protein, required for the stability of carbonyl reductase type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-ACP reductase activity, thereby participating in mitochondrial fatty acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain length preference, this enzymatic activity is not needed for the KAR function. Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays enzymatic activity only in the presence of NAD(+)(H). Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they constitute an alternative route to the auxiliary enzyme pathways for the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters (By similarity). NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol. It efficiently catalyzes the oxidation of estradiol (E2), testosterone, and dihydrotestosterone. Primarily an oxidative enzyme, it can switch to a reductive mode determined in the appropriate physiologic milieu and catalyze the reduction of estrone (E1) to form biologically active estradiol (E2) (PubMed:9712896)
Protein Sequence
10
MASQLRLRSA
20
LALVTGAGSG
30
IGRAISVRLA
40
AEGAAVAACD
50
LDGAAAQDTV
60
RLLGSPGSED
70
GAPRGKHAAF
80
QADVSQGPAA
90
RRLLEEVQAC
100
FSRPPSVVVS
110
CAGITRDEFL
120
LHMSEEDWDR
130
VIAVNLKGTF
140
LVTQAAAQAL
150
VSSGGRGSII
160
NISSIIGKVG
170
NIGQTNYASS
180
KAGVIGLTQT
190
AARELGRHGI
200
RCNSVLPGFI
210
ATPMTQKMPE
220
KVKDKVTAMI
230
PLGHMGDPED
240
VADVVAFLAS
250
EDSGYITGAS
VEVSGGLFM
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005783 |
endoplasmic reticulum |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0005740 |
mitochondrial envelope |
| Cellular Component |
GO:0005759 |
mitochondrial matrix |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:1990204 |
oxidoreductase complex |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0106386 |
(3R)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity |
| Molecular Function |
GO:0004303 |
estradiol 17-beta-dehydrogenase [NAD(P)+] activity |
| Molecular Function |
GO:0070404 |
NADH binding |
| Molecular Function |
GO:0048038 |
quinone binding |
| Molecular Function |
GO:0047035 |
testosterone dehydrogenase (NAD+) activity |
| Biological Process |
GO:0008209 |
androgen metabolic process |
| Biological Process |
GO:0006703 |
estrogen biosynthetic process |
| Biological Process |
GO:0008210 |
estrogen metabolic process |
| Biological Process |
GO:0006633 |
fatty acid biosynthetic process |
| Biological Process |
GO:0051290 |
protein heterotetramerization |
Reference
[1] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.