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Protein

Estradiol 17-beta-dehydrogenase 8

Gene

Hsd17b8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol. Has very low activity towards testosterone (By similarity). The heterotetramer with CBR4 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity. May play a role in biosynthesis of fatty acids in mitochondria (By similarity).By similarity

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: estrogen biosynthesis

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei154 – 1541SubstrateBy similarity
Active sitei167 – 1671Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi13 – 219NADBy similarity
Nucleotide bindingi40 – 412NADBy similarity
Nucleotide bindingi72 – 743NADBy similarity
Nucleotide bindingi167 – 1715NADBy similarity
Nucleotide bindingi200 – 2023NADBy similarity

GO - Molecular functioni

GO - Biological processi

  • androgen metabolic process Source: MGI
  • estrogen biosynthetic process Source: UniProtKB
  • estrogen metabolic process Source: MGI
  • fatty acid biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis

Keywords - Ligandi

NAD

Enzyme and pathway databases

SABIO-RKP50171.
UniPathwayiUPA00094.
UPA00769.

Names & Taxonomyi

Protein namesi
Recommended name:
Estradiol 17-beta-dehydrogenase 8 (EC:1.1.1.62)
Alternative name(s):
17-beta-hydroxysteroid dehydrogenase 8
Short name:
17-beta-HSD 8
3-oxoacyl-[acyl-carrier-protein] reductase (EC:1.1.1.-)
Protein Ke6
Short name:
Ke-6
Testosterone 17-beta-dehydrogenase 8 (EC:1.1.1.239)
Gene namesi
Name:Hsd17b8
Synonyms:H2-Ke6, Hke6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:95911. H2-Ke6.

Subcellular locationi

GO - Cellular componenti

  • membrane Source: MGI
  • mitochondrial envelope Source: MGI
  • mitochondrial matrix Source: MGI
  • mitochondrion Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 259259Estradiol 17-beta-dehydrogenase 8PRO_0000054599Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei58 – 581PhosphoserineCombined sources
Modified residuei66 – 661N6-acetyllysineCombined sources
Modified residuei158 – 1581N6-succinyllysineCombined sources
Modified residuei171 – 1711N6-succinyllysineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP50171.
MaxQBiP50171.
PaxDbiP50171.
PeptideAtlasiP50171.
PRIDEiP50171.

2D gel databases

REPRODUCTION-2DPAGEP50171.

PTM databases

iPTMnetiP50171.
PhosphoSiteiP50171.

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

BgeeiP50171.
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 interaction.
MINTiMINT-1861146.
STRINGi10090.ENSMUSP00000038069.

Structurei

3D structure databases

ProteinModelPortaliP50171.
SMRiP50171. Positions 4-259.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1200. Eukaryota.
COG1028. LUCA.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG002145.
InParanoidiP50171.
KOiK13370.
OMAiLPAMIEQ.
OrthoDBiEOG73Z2VD.
PhylomeDBiP50171.
TreeFamiTF313099.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 2 hits.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]

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 AAC69902.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti229 – 2291E → EG in AAC53573 (PubMed:8441417).Curated
Sequence conflicti229 – 2291E → EG in AAC53574 (PubMed:8441417).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei256 – 2594GLFM → MRPSWGGGQENRTQVVMRK in isoform Long. CuratedVSP_006030

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

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

3D structure databases

ProteinModelPortaliP50171.
SMRiP50171. Positions 4-259.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP50171. 1 interaction.
MINTiMINT-1861146.
STRINGi10090.ENSMUSP00000038069.

PTM databases

iPTMnetiP50171.
PhosphoSiteiP50171.

2D gel databases

REPRODUCTION-2DPAGEP50171.

Proteomic databases

EPDiP50171.
MaxQBiP50171.
PaxDbiP50171.
PeptideAtlasiP50171.
PRIDEiP50171.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi14979.
MGIiMGI:95911. H2-Ke6.

Phylogenomic databases

eggNOGiKOG1200. Eukaryota.
COG1028. LUCA.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG002145.
InParanoidiP50171.
KOiK13370.
OMAiLPAMIEQ.
OrthoDBiEOG73Z2VD.
PhylomeDBiP50171.
TreeFamiTF313099.

Enzyme and pathway databases

UniPathwayiUPA00094.
UPA00769.
SABIO-RKP50171.

Miscellaneous databases

PROiP50171.
SOURCEiSearch...

Gene expression databases

BgeeiP50171.
CleanExiMM_H2-KE6.
ExpressionAtlasiP50171. baseline and differential.
GenevisibleiP50171. MM.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 2 hits.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Downregulation of Ke 6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease."
    Aziz N., Maxwell M.M., St Jacques B., Brenner B.M.
    Mol. Cell. Biol. 13:1847-1853(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: DBA/2J.
    Tissue: Kidney.
  2. Erratum
    Aziz N., Maxwell M.M., St Jacques B., Brenner B.M.
    Mol. Cell. Biol. 13:6614-6614(1993)
  3. "Ke 6 gene. Sequence and organization and aberrant regulation in murine polycystic kidney disease."
    Maxwell M.M., Nearing J., Aziz N.
    J. Biol. Chem. 270:25213-25219(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: C57BL/6J.
  4. "Sequence of the mouse major histocomaptibility locus class II region."
    Rowen L., Qin S., Madan A., Loretz C., James R., Dors M., Mix L., Hall J., Lasky S., Hood L.
    Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: 129/SvJ.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
    Tissue: Kidney.
  6. "Characterization of Ke 6, a new 17beta-hydroxysteroid dehydrogenase, and its expression in gonadal tissues."
    Fomitcheva J., Baker M.E., Anderson E., Lee G.Y., Aziz N.
    J. Biol. Chem. 273:22664-22671(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
  7. "Localization of type 8 17beta-hydroxysteroid dehydrogenase mRNA in mouse tissues as studied by in situ hybridization."
    Pelletier G., Luu-The V., Li S., Labrie F.
    J. Histochem. Cytochem. 53:1257-1271(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  8. "Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
    Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
    Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  10. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-158 AND LYS-171, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. "Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
    Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
    Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-66, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiDHB8_MOUSE
AccessioniPrimary (citable) accession number: P50171
Secondary accession number(s): Q5M9K0
, Q60958, Q60959, Q9Z1W2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 20, 2010
Last modified: July 6, 2016
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.