UniProtKB - P50171 (DHB8_MOUSE)
(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, 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).
By similarity1 PublicationCatalytic activityi
- EC:1.1.1.n12By similarityThis reaction proceeds in the forwardBy similarity direction.
- EC:1.1.1.621 Publication
- EC:1.1.1.2391 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=0.110 µM for estradiol1 Publication
- KM=0.422 µM for testosterone1 Publication
- KM=0.368 µM for estrone1 Publication
- KM=0.360 µM for dihydrotestosterone1 Publication
- Vmax=0.405 nmol/min/mg enzyme for estradiol as substrate1 Publication
- Vmax=0.123 nmol/min/mg enzyme for testosterone as substrate1 Publication
- Vmax=0.186 nmol/min/mg enzyme for estrone as substrate1 Publication
- Vmax=0.081 nmol/min/mg enzyme for dihydrotestosterone as substrate1 Publication
: fatty acid biosynthesis Pathwayi
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: estrogen biosynthesis
This protein is involved in the pathway estrogen biosynthesis, which is part of Steroid biosynthesis.1 PublicationView all proteins of this organism that are known to be involved in the pathway estrogen biosynthesis and in Steroid biosynthesis.
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
- 3-hydroxyacyl-CoA dehydrogenase activity Source: MGI
- 3-oxoacyl-[acyl-carrier-protein] reductase (NADH) activity Source: MGI
- estradiol 17-beta-dehydrogenase activity Source: MGI
- 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: MGI
GO - Biological processi
- androgen metabolic process Source: MGI
- estrogen biosynthetic process Source: UniProtKB
- estrogen metabolic process Source: MGI
- 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
Reactomei | R-MMU-75105, Fatty acyl-CoA biosynthesis |
SABIO-RKi | P50171 |
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:1.1.1.621 Publication) Protein Ke61 Publication Short name: Ke-61 Publication Testosterone 17-beta-dehydrogenase 8 (EC:1.1.1.2391 Publication) |
Gene namesi | Name:Hsd17b8 Synonyms:H2-Ke6, Hke6 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:95911, H2-Ke6 |
VEuPathDBi | HostDB:ENSMUSG00000073422 |
Subcellular locationi
Mitochondrion
- Mitochondrion matrix By similarity
Mitochondrion
- mitochondrial envelope Source: MGI
- mitochondrial matrix Source: MGI
- mitochondrion Source: MGI
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- membrane Source: MGI
- oxidoreductase complex Source: MGI
Keywords - Cellular componenti
MitochondrionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000054599 | 1 – 259 | (3R)-3-hydroxyacyl-CoA dehydrogenaseAdd BLAST | 259 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 58 | PhosphoserineCombined sources | 1 | |
Modified residuei | 66 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 158 | N6-succinyllysineCombined sources | 1 | |
Modified residuei | 171 | N6-succinyllysineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P50171 |
jPOSTi | P50171 |
MaxQBi | P50171 |
PaxDbi | P50171 |
PeptideAtlasi | P50171 |
PRIDEi | P50171 |
ProteomicsDBi | 277329 [P50171-1] 277330 [P50171-2] |
2D gel databases
REPRODUCTION-2DPAGEi | P50171 |
PTM databases
iPTMneti | P50171 |
PhosphoSitePlusi | P50171 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000073422, Expressed in muscle tissue and 77 other tissues |
ExpressionAtlasi | P50171, baseline and differential |
Genevisiblei | P50171, MM |
Interactioni
Subunit structurei
Heterotetramer with CBR4; contains two molecules of HSD17B8 and CBR4.
By similarityProtein-protein interaction databases
BioGRIDi | 200159, 4 interactors |
STRINGi | 10090.ENSMUSP00000038069 |
Miscellaneous databases
RNActi | P50171, protein |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1200, Eukaryota |
GeneTreei | ENSGT00940000160668 |
HOGENOMi | CLU_010194_1_3_1 |
InParanoidi | P50171 |
OMAi | QLLMRMS |
OrthoDBi | 1226147at2759 |
PhylomeDBi | P50171 |
TreeFami | TF313099 |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MASQLRLRSA LALVTGAGSG IGRAISVRLA AEGAAVAACD LDGAAAQDTV
60 70 80 90 100
RLLGSPGSED GAPRGKHAAF QADVSQGPAA RRLLEEVQAC FSRPPSVVVS
110 120 130 140 150
CAGITRDEFL LHMSEEDWDR VIAVNLKGTF LVTQAAAQAL VSSGGRGSII
160 170 180 190 200
NISSIIGKVG NIGQTNYASS KAGVIGLTQT AARELGRHGI RCNSVLPGFI
210 220 230 240 250
ATPMTQKMPE KVKDKVTAMI PLGHMGDPED VADVVAFLAS EDSGYITGAS
VEVSGGLFM
The sequence of this isoform differs from the canonical sequence as follows:
256-259: GLFM → MRPSWGGGQENRTQVVMRK
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3UX44 | G3UX44_MOUSE | H2-K region-expressed gene 6 | H2-Ke6 | 234 | Annotation score: | ||
A0A494BA51 | A0A494BA51_MOUSE | H2-K region-expressed gene 6 | H2-Ke6 | 138 | Annotation score: | ||
A0A494BAF4 | A0A494BAF4_MOUSE | H2-K region-expressed gene 6 | H2-Ke6 | 147 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 229 | E → EG in AAC53573 (PubMed:8441417).Curated | 1 | |
Sequence conflicti | 229 | E → EG in AAC53574 (PubMed:8441417).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_006030 | 256 – 259 | GLFM → MRPSWGGGQENRTQVVMRK in isoform Long. Curated | 4 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U34072 Genomic DNA Translation: AAC53573.1 U34072 Genomic DNA Translation: AAC53574.1 AF100956 Genomic DNA Translation: AAC69902.1 Sequence problems. BC086927 mRNA Translation: AAH86927.1 |
CCDSi | CCDS50071.1 [P50171-1] |
PIRi | A48154 |
RefSeqi | NP_038571.2, NM_013543.2 [P50171-1] |
Genome annotation databases
Ensembli | ENSMUST00000045467; ENSMUSP00000038069; ENSMUSG00000073422 [P50171-1] ENSMUST00000237759; ENSMUSP00000157769; ENSMUSG00000073422 [P50171-2] |
GeneIDi | 14979 |
KEGGi | mmu:14979 |
UCSCi | uc008cat.2, mouse [P50171-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U34072 Genomic DNA Translation: AAC53573.1 U34072 Genomic DNA Translation: AAC53574.1 AF100956 Genomic DNA Translation: AAC69902.1 Sequence problems. BC086927 mRNA Translation: AAH86927.1 |
CCDSi | CCDS50071.1 [P50171-1] |
PIRi | A48154 |
RefSeqi | NP_038571.2, NM_013543.2 [P50171-1] |
3D structure databases
SMRi | P50171 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200159, 4 interactors |
STRINGi | 10090.ENSMUSP00000038069 |
PTM databases
iPTMneti | P50171 |
PhosphoSitePlusi | P50171 |
2D gel databases
REPRODUCTION-2DPAGEi | P50171 |
Proteomic databases
EPDi | P50171 |
jPOSTi | P50171 |
MaxQBi | P50171 |
PaxDbi | P50171 |
PeptideAtlasi | P50171 |
PRIDEi | P50171 |
ProteomicsDBi | 277329 [P50171-1] 277330 [P50171-2] |
Protocols and materials databases
Antibodypediai | 28972, 223 antibodies from 28 providers |
DNASUi | 14979 |
Genome annotation databases
Ensembli | ENSMUST00000045467; ENSMUSP00000038069; ENSMUSG00000073422 [P50171-1] ENSMUST00000237759; ENSMUSP00000157769; ENSMUSG00000073422 [P50171-2] |
GeneIDi | 14979 |
KEGGi | mmu:14979 |
UCSCi | uc008cat.2, mouse [P50171-1] |
Organism-specific databases
CTDi | 14979 |
MGIi | MGI:95911, H2-Ke6 |
VEuPathDBi | HostDB:ENSMUSG00000073422 |
Phylogenomic databases
eggNOGi | KOG1200, Eukaryota |
GeneTreei | ENSGT00940000160668 |
HOGENOMi | CLU_010194_1_3_1 |
InParanoidi | P50171 |
OMAi | QLLMRMS |
OrthoDBi | 1226147at2759 |
PhylomeDBi | P50171 |
TreeFami | TF313099 |
Enzyme and pathway databases
UniPathwayi | UPA00094 UPA00660 UPA00769 |
Reactomei | R-MMU-75105, Fatty acyl-CoA biosynthesis |
SABIO-RKi | P50171 |
Miscellaneous databases
BioGRID-ORCSi | 14979, 3 hits in 67 CRISPR screens |
ChiTaRSi | H2-Ke6, mouse |
PROi | PR:P50171 |
RNActi | P50171, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000073422, Expressed in muscle tissue and 77 other tissues |
ExpressionAtlasi | P50171, baseline and differential |
Genevisiblei | P50171, MM |
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_MOUSE | |
Accessioni | P50171Primary (citable) accession number: P50171 Secondary accession number(s): Q5M9K0 Q9Z1W2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | April 20, 2010 | |
Last modified: | February 23, 2022 | |
This is version 174 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families