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Protein

Estradiol 17-beta-dehydrogenase 8

Gene

Hsd17b8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol. Has very low activity towards testosterone (PubMed:9712896). The heterotetramer with CBR4 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity, and thereby plays a role in mitochondrial fatty acid biosynthesis. Within the heterotetramer, HSD17B8 binds NADH; CBR4 binds NADPD.By similarity1 Publication

Catalytic activityi

17-beta-estradiol + NAD(P)+ = estrone + NAD(P)H.1 Publication
Testosterone + NAD+ = androstenedione + NADH.1 Publication

Kineticsi

  1. KM=0.110 µM for estradiol1 Publication
  2. KM=0.422 µM for testosterone1 Publication
  3. KM=0.368 µM for estrone1 Publication
  4. KM=0.360 µM for dihydrotestosterone1 Publication
  1. Vmax=0.405 nmol/min/mg enzyme for estradiol as substrate1 Publication
  2. Vmax=0.123 nmol/min/mg enzyme for testosterone as substrate1 Publication
  3. Vmax=0.186 nmol/min/mg enzyme for estrone as substrate1 Publication
  4. Vmax=0.081 nmol/min/mg enzyme for dihydrotestosterone as substrate1 Publication

Pathwayi: fatty acid biosynthesis

This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.By similarity
View 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 Publication
View all proteins of this organism that are known to be involved in the pathway estrogen biosynthesis and in Steroid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei154SubstrateBy similarity1
Active sitei167Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi13 – 21NADBy similarity9
Nucleotide bindingi40 – 41NADBy similarity2
Nucleotide bindingi72 – 74NADBy similarity3
Nucleotide bindingi167 – 171NADBy similarity5
Nucleotide bindingi200 – 202NADBy similarity3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis
LigandNAD

Enzyme and pathway databases

ReactomeiR-MMU-75105 Fatty acyl-CoA biosynthesis
SABIO-RKP50171
UniPathwayiUPA00094
UPA00769

Names & Taxonomyi

Protein namesi
Recommended name:
Estradiol 17-beta-dehydrogenase 8 (EC:1.1.1.621 Publication)
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 (EC:1.1.1.-By similarity)
Protein Ke6
Short name:
Ke-6
Testosterone 17-beta-dehydrogenase 8 (EC:1.1.1.2391 Publication)
Gene namesi
Name:Hsd17b8
Synonyms:H2-Ke6, Hke6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:95911 H2-Ke6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000545991 – 259Estradiol 17-beta-dehydrogenase 8Add BLAST259

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei58PhosphoserineCombined sources1
Modified residuei66N6-acetyllysineCombined sources1
Modified residuei158N6-succinyllysineCombined sources1
Modified residuei171N6-succinyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP50171
MaxQBiP50171
PaxDbiP50171
PeptideAtlasiP50171
PRIDEiP50171

2D gel databases

REPRODUCTION-2DPAGEP50171

PTM databases

iPTMnetiP50171
PhosphoSitePlusiP50171

Expressioni

Tissue specificityi

Kidney, liver, testis, ovary, oviduct, uterus, mammary gland, vagina, prostate, clitoral gland and moderately in spleen, heart, dorsal skin, brain and lung.

Gene expression databases

BgeeiENSMUSG00000073422
CleanExiMM_H2-KE6
ExpressionAtlasiP50171 baseline and differential
GenevisibleiP50171 MM

Interactioni

Subunit structurei

Heterotetramer with CBR4; contains two molecules of HSD17B8 and CBR4.By similarity

Protein-protein interaction databases

IntActiP50171, 1 interactor
MINTiP50171
STRINGi10090.ENSMUSP00000038069

Structurei

3D structure databases

ProteinModelPortaliP50171
SMRiP50171
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1200 Eukaryota
COG1028 LUCA
GeneTreeiENSGT00910000144076
HOVERGENiHBG002145
InParanoidiP50171
KOiK13370
OMAiGSRNIRC
OrthoDBiEOG091G0N2V
PhylomeDBiP50171
TreeFamiTF313099

Family and domain databases

InterProiView protein in InterPro
IPR036291 NAD(P)-bd_dom_sf
IPR020904 Sc_DH/Rdtase_CS
IPR002347 SDR_fam
PRINTSiPR00081 GDHRDH
PR00080 SDRFAMILY
SUPFAMiSSF51735 SSF51735, 1 hit
PROSITEiView protein in PROSITE
PS00061 ADH_SHORT, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Short (identifier: P50171-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:259
Mass (Da):26,588
Last modified:April 20, 2010 - v2
Checksum:iC4704F02B63C275F
GO
Isoform Long (identifier: P50171-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     256-259: GLFM → MRPSWGGGQENRTQVVMRK

Show »
Length:274
Mass (Da):28,339
Checksum:i22B1785EA3F82B37
GO

Sequence cautioni

The sequence AAC69902 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti229E → EG in AAC53573 (PubMed:8441417).Curated1
Sequence conflicti229E → EG in AAC53574 (PubMed:8441417).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006030256 – 259GLFM → MRPSWGGGQENRTQVVMRK in isoform Long. Curated4

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
CCDSiCCDS50071.1 [P50171-1]
PIRiA48154
RefSeqiNP_038571.2, NM_013543.2 [P50171-1]
UniGeneiMm.275452

Genome annotation databases

EnsembliENSMUST00000045467; ENSMUSP00000038069; ENSMUSG00000073422 [P50171-1]
GeneIDi14979
KEGGimmu:14979
UCSCiuc008cat.2 mouse [P50171-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDHB8_MOUSE
AccessioniPrimary (citable) accession number: P50171
Secondary accession number(s): Q5M9K0
, Q60958, Q60959, Q9Z1W2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 20, 2010
Last modified: May 23, 2018
This is version 154 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health