UniProtKB - Q5TJF5 (DHB8_CANLF)
(3R)-3-hydroxyacyl-CoA dehydrogenase
HSD17B8
Functioni
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 that 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+. 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. NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol (17beta-estradiol or E2). Has very low activity towards testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one). 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 17beta-estradiol.
By similarityCatalytic activityi
- EC:1.1.1.n12By similarityThis reaction proceeds in the forwardBy similarity direction.
- EC:1.1.1.62By similarity
- EC:1.1.1.239By similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
: estrogen biosynthesis Pathwayi
This protein is involved in the pathway estrogen biosynthesis, which is part of Steroid biosynthesis.By similarityView all proteins of this organism that are known to be involved in the pathway estrogen biosynthesis and in Steroid biosynthesis.
Pathwayi: fatty acid biosynthesis
This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway fatty acid biosynthesis and in Lipid metabolism.
Pathwayi: mitochondrial fatty acid beta-oxidation
This protein is involved in the pathway mitochondrial fatty acid beta-oxidation, which is part of Lipid metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway mitochondrial fatty acid beta-oxidation and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 154 | SubstrateBy similarity | 1 | |
Active sitei | 167 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 13 – 21 | NADBy similarity | 9 | |
Nucleotide bindingi | 40 – 41 | NADBy similarity | 2 | |
Nucleotide bindingi | 72 – 74 | NADBy similarity | 3 | |
Nucleotide bindingi | 167 – 171 | NADBy similarity | 5 | |
Nucleotide bindingi | 200 – 202 | NADBy similarity | 3 |
GO - Molecular functioni
- (3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity Source: UniProtKB
- 17-beta-hydroxysteroid dehydrogenase (NAD+) activity Source: RHEA
- estradiol 17-beta-dehydrogenase activity Source: UniProtKB
- NADH binding Source: UniProtKB
- oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Source: GO_Central
- quinone binding Source: GO_Central
- testosterone dehydrogenase (NAD+) activity Source: UniProtKB-EC
GO - Biological processi
- androgen metabolic process Source: Ensembl
- estrogen biosynthetic process Source: UniProtKB
- fatty acid biosynthetic process Source: UniProtKB
- protein heterotetramerization Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis |
Ligand | NAD |
Enzyme and pathway databases
UniPathwayi | UPA00094 UPA00660 UPA00769 |
Names & Taxonomyi
Protein namesi | Recommended name: (3R)-3-hydroxyacyl-CoA dehydrogenase (EC:1.1.1.n12By similarity)Alternative name(s): 17-beta-hydroxysteroid dehydrogenase 8 Short name: 17-beta-HSD 8 3-ketoacyl-[acyl-carrier-protein] reductase alpha subunitBy similarity Short name: KAR alpha subunitBy similarity 3-oxoacyl-[acyl-carrier-protein] reductase Estradiol 17-beta-dehydrogenase 8 (EC:1.1.1.62By similarity) Testosterone 17-beta-dehydrogenase 8 (EC:1.1.1.239By similarity) |
Gene namesi | Name:HSD17B8 |
Organismi | Canis lupus familiaris (Dog) (Canis familiaris) |
Taxonomic identifieri | 9615 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › |
Proteomesi |
|
Subcellular locationi
Mitochondrion
- Mitochondrion matrix By similarity
Mitochondrion
- mitochondrial envelope Source: Ensembl
- mitochondrial matrix Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: Ensembl
Other locations
- oxidoreductase complex Source: Ensembl
Keywords - Cellular componenti
MitochondrionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000054597 | 1 – 259 | (3R)-3-hydroxyacyl-CoA dehydrogenaseAdd BLAST | 259 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 58 | PhosphoserineBy similarity | 1 | |
Modified residuei | 158 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 171 | N6-succinyllysineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q5TJF5 |
Interactioni
Subunit structurei
Heterotetramer with CBR4; contains two molecules of HSD17B8 and CBR4.
By similarityProtein-protein interaction databases
STRINGi | 9612.ENSCAFP00000001317 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1200, Eukaryota |
InParanoidi | Q5TJF5 |
Family and domain databases
InterProi | View protein in InterPro IPR036291, NAD(P)-bd_dom_sf IPR020904, Sc_DH/Rdtase_CS IPR002347, SDR_fam |
PRINTSi | PR00081, GDHRDH PR00080, SDRFAMILY |
SUPFAMi | SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00061, ADH_SHORT, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MASPLRLRSA LALVTGAGSG IGRAVSVRLA KEGATVAACD LDRAAACETV
60 70 80 90 100
WLLGGQGSEK VAPGGAHTAF QADVSEAGAV RRLLEQVQAC FSRPPSVVVS
110 120 130 140 150
CAGLTRDEFL LRMSEDDWDR VIAVNLKGIF LVTQAAAQAL VSSGCRGSII
160 170 180 190 200
NISSIVGKVG NVGQTNYAAS KAGVIGLTQT AARELGRHGI RCNSVLPGFI
210 220 230 240 250
TTPMTQKVPQ KVLDKVIGMI PMGHLGDPED VADAVTFLAS EDSGYITGAS
VEVTGGLYM
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ630366 Genomic DNA Translation: CAI11433.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ630366 Genomic DNA Translation: CAI11433.1 |
3D structure databases
SMRi | Q5TJF5 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9612.ENSCAFP00000001317 |
Proteomic databases
PaxDbi | Q5TJF5 |
Phylogenomic databases
eggNOGi | KOG1200, Eukaryota |
InParanoidi | Q5TJF5 |
Enzyme and pathway databases
UniPathwayi | UPA00094 UPA00660 UPA00769 |
Family and domain databases
InterProi | View protein in InterPro IPR036291, NAD(P)-bd_dom_sf IPR020904, Sc_DH/Rdtase_CS IPR002347, SDR_fam |
PRINTSi | PR00081, GDHRDH PR00080, SDRFAMILY |
SUPFAMi | SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00061, ADH_SHORT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DHB8_CANLF | |
Accessioni | Q5TJF5Primary (citable) accession number: Q5TJF5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 6, 2005 |
Last sequence update: | December 21, 2004 | |
Last modified: | February 23, 2022 | |
This is version 91 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families