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Protein

Estradiol 17-beta-dehydrogenase 8

Gene

HSD17B8

Organism
Homo sapiens (Human)
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 (PubMed:17978863). The heterotetramer with CBR4 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity, and thereby plays a role in mitochondrial fatty acid biosynthesis (PubMed:19571038, PubMed:25203508). Within the heterotetramer, HSD17B8 binds NADH; CBR4 binds NADPD (PubMed:25203508).3 Publications

Catalytic activityi

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

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.

Pathwayi: fatty acid biosynthesis

This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.1 Publication
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)DescriptionActionsGraphical viewLength
Binding sitei156SubstrateBy similarity1
Active sitei169Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 23NADCombined sources2 Publications9
Nucleotide bindingi42 – 43NADCombined sources2 Publications2
Nucleotide bindingi74 – 76NADCombined sources2 Publications3
Nucleotide bindingi169 – 173NADCombined sources2 Publications5
Nucleotide bindingi202 – 204NADCombined sources1 Publication3

GO - Molecular functioni

  • 3-hydroxyacyl-CoA dehydrogenase activity Source: UniProtKB
  • 3-oxoacyl-[acyl-carrier-protein] reductase (NADH) activity Source: UniProtKB
  • estradiol 17-beta-dehydrogenase activity Source: UniProtKB
  • NADH binding Source: UniProtKB
  • 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
  • oxidation-reduction process Source: UniProtKB
  • protein heterotetramerization Source: UniProtKB
  • steroid biosynthetic process Source: UniProtKB-KW
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

BioCyciZFISH:HS03575-MONOMER.
ReactomeiR-HSA-535734. Fatty acid, triacylglycerol, and ketone body metabolism.
SABIO-RKQ92506.
UniPathwayiUPA00094.
UPA00769.

Chemistry databases

SwissLipidsiSLP:000001271.

Names & Taxonomyi

Protein namesi
Recommended name:
Estradiol 17-beta-dehydrogenase 8 (EC:1.1.1.621 Publication)
Alternative name(s):
17-beta-hydroxysteroid dehydrogenase 81 Publication
Short name:
17-beta-HSD 8
3-ketoacyl-[acyl-carrier-protein] reductase alpha subunit1 Publication
Short name:
KAR alpha subunit1 Publication
3-oxoacyl-[acyl-carrier-protein] reductase (EC:1.1.1.-2 Publications)
Protein Ke6
Short name:
Ke-6
Really interesting new gene 2 protein
Short chain dehydrogenase/reductase family 30C member 1
Testosterone 17-beta-dehydrogenase 8 (EC:1.1.1.239)
Gene namesi
Name:HSD17B8
Synonyms:FABGL, HKE6, RING2, SDR30C1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3554. HSD17B8.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial envelope Source: Ensembl
  • mitochondrial matrix Source: UniProtKB
  • plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42D → A: Reduced NADH-dependent reductase activity with acetoacetyl-CoA. Reduced NADH-dependent reductase activity with 9,10-phenanthrene quinone. Increases NADPH-dependent reductase activitites. No effect on the ability to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
Mutagenesisi148R → E: No effect on the ability to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
Mutagenesisi169Y → A: Strongly reduced NADH-dependent reductase activity with acetoacetyl-CoA. Strongly reduced NADH-dependent reductase activity with 9,10-phenanthrene quinone. Decreases NADPH-dependent reductase activitity with acetoacetyl-CoA, but increases NADPH-dependent reductase activitity with 9,10-phenanthrene quinone. No effect on the ability to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
Mutagenesisi173K → A: Abolishes NADH-dependent reductase activity with acetoacetyl-CoA. Strongly reduced NADH-dependent reductase activity with 9,10-phenanthrene quinone. Slightly decreases NADPH-dependent reductase activitity with acetoacetyl-CoA, but increases NADPH-dependent reductase activitity with 9,10-phenanthrene quinone. No effect on the ability to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
Mutagenesisi189R → E: No effect on the ability to restore growth of an OAR1-deficient yeast mutant. 1 Publication1

Organism-specific databases

DisGeNETi7923.
OpenTargetsiENSG00000112474.
ENSG00000204228.
ENSG00000225312.
ENSG00000228357.
ENSG00000228712.
ENSG00000232357.
PharmGKBiPA29484.

Polymorphism and mutation databases

BioMutaiHSD17B8.
DMDMi12643402.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000545981 – 261Estradiol 17-beta-dehydrogenase 8Add BLAST261

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei60PhosphoserineBy similarity1
Modified residuei160N6-succinyllysineBy similarity1
Modified residuei173N6-succinyllysineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92506.
MaxQBiQ92506.
PaxDbiQ92506.
PeptideAtlasiQ92506.
PRIDEiQ92506.
TopDownProteomicsiQ92506.

PTM databases

iPTMnetiQ92506.
PhosphoSitePlusiQ92506.

Expressioni

Tissue specificityi

Highly expressed in placenta, liver and pancreas, lower in the skeletal muscle and kidney. Widely expressed.1 Publication

Inductioni

Up-regulated by estradiol.1 Publication

Gene expression databases

BgeeiENSG00000112474.
CleanExiHS_HSD17B8.
GenevisibleiQ92506. HS.

Organism-specific databases

HPAiHPA042132.

Interactioni

Subunit structurei

Heterotetramer with CBR4; contains two molecules of HSD17B8 and CBR4.2 Publications

Protein-protein interaction databases

BioGridi113653. 16 interactors.
IntActiQ92506. 2 interactors.
STRINGi9606.ENSP00000363794.

Structurei

Secondary structure

1261
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni8 – 11Combined sources4
Beta strandi13 – 17Combined sources5
Turni18 – 20Combined sources3
Helixi22 – 33Combined sources12
Beta strandi37 – 44Combined sources8
Helixi45 – 53Combined sources9
Beta strandi70 – 73Combined sources4
Helixi79 – 93Combined sources15
Beta strandi98 – 102Combined sources5
Helixi112 – 114Combined sources3
Helixi117 – 127Combined sources11
Helixi129 – 145Combined sources17
Beta strandi149 – 154Combined sources6
Helixi158 – 161Combined sources4
Helixi167 – 187Combined sources21
Helixi188 – 190Combined sources3
Beta strandi192 – 199Combined sources8
Beta strandi201 – 204Combined sources4
Turni207 – 209Combined sources3
Helixi212 – 216Combined sources5
Helixi219 – 221Combined sources3
Helixi230 – 241Combined sources12
Helixi243 – 245Combined sources3
Beta strandi252 – 256Combined sources5
Turni257 – 260Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PD6X-ray2.00A/B/C/D6-261[»]
4CQLX-ray2.85A/D/E/H/I/L/M/P1-261[»]
4CQMX-ray2.34A/D/E/H/I/L/M/P1-261[»]
ProteinModelPortaliQ92506.
SMRiQ92506.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92506.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1200. Eukaryota.
COG1028. LUCA.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG002145.
InParanoidiQ92506.
KOiK13370.
OMAiHMSEEDW.
OrthoDBiEOG091G0N2V.
PhylomeDBiQ92506.
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]

Sequencei

Sequence statusi: Complete.

Q92506-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASQLQNRLR SALALVTGAG SGIGRAVSVR LAGEGATVAA CDLDRAAAQE
60 70 80 90 100
TVRLLGGPGS KEGPPRGNHA AFQADVSEAR AARCLLEQVQ ACFSRPPSVV
110 120 130 140 150
VSCAGITQDE FLLHMSEDDW DKVIAVNLKG TFLVTQAAAQ ALVSNGCRGS
160 170 180 190 200
IINISSIVGK VGNVGQTNYA ASKAGVIGLT QTAARELGRH GIRCNSVLPG
210 220 230 240 250
FIATPMTQKV PQKVVDKITE MIPMGHLGDP EDVADVVAFL ASEDSGYITG
260
TSVEVTGGLF M
Length:261
Mass (Da):26,974
Last modified:January 24, 2001 - v2
Checksum:i8B8B2D7131714D71
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti117E → R in BAA11529 (PubMed:8812499).Curated1
Sequence conflicti193R → P in BAA11529 (PubMed:8812499).Curated1
Sequence conflicti208Q → K in BAA11529 (PubMed:8812499).Curated1
Sequence conflicti212Q → K in BAA11529 (PubMed:8812499).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035844158V → L in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_052316190H → R.Corresponds to variant rs34491699dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT007239 mRNA. Translation: AAP35903.1.
AL031228 Genomic DNA. Translation: CAC38444.1.
AL662824, AL713971 Genomic DNA. Translation: CAI17616.1.
AL713971, AL662824 Genomic DNA. Translation: CAI17657.1.
AL645940 Genomic DNA. Translation: CAI18068.1.
AL844527 Genomic DNA. Translation: CAI41840.1.
CR759786 Genomic DNA. Translation: CAQ08245.1.
CR759733 Genomic DNA. Translation: CAQ10302.1.
CR847841 Genomic DNA. Translation: CAQ10313.1.
CH471081 Genomic DNA. Translation: EAX03682.1.
BC008185 mRNA. Translation: AAH08185.1.
D82061 mRNA. Translation: BAA11529.1.
CCDSiCCDS4769.1.
RefSeqiNP_055049.1. NM_014234.4.
UniGeneiHs.415058.

Genome annotation databases

EnsembliENST00000230236; ENSP00000230236; ENSG00000112474.
ENST00000374662; ENSP00000363794; ENSG00000204228.
ENST00000414463; ENSP00000387753; ENSG00000228357.
ENST00000422433; ENSP00000406488; ENSG00000232357.
ENST00000427295; ENSP00000403538; ENSG00000228712.
ENST00000454191; ENSP00000413950; ENSG00000225312.
GeneIDi7923.
KEGGihsa:7923.
UCSCiuc003odi.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT007239 mRNA. Translation: AAP35903.1.
AL031228 Genomic DNA. Translation: CAC38444.1.
AL662824, AL713971 Genomic DNA. Translation: CAI17616.1.
AL713971, AL662824 Genomic DNA. Translation: CAI17657.1.
AL645940 Genomic DNA. Translation: CAI18068.1.
AL844527 Genomic DNA. Translation: CAI41840.1.
CR759786 Genomic DNA. Translation: CAQ08245.1.
CR759733 Genomic DNA. Translation: CAQ10302.1.
CR847841 Genomic DNA. Translation: CAQ10313.1.
CH471081 Genomic DNA. Translation: EAX03682.1.
BC008185 mRNA. Translation: AAH08185.1.
D82061 mRNA. Translation: BAA11529.1.
CCDSiCCDS4769.1.
RefSeqiNP_055049.1. NM_014234.4.
UniGeneiHs.415058.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PD6X-ray2.00A/B/C/D6-261[»]
4CQLX-ray2.85A/D/E/H/I/L/M/P1-261[»]
4CQMX-ray2.34A/D/E/H/I/L/M/P1-261[»]
ProteinModelPortaliQ92506.
SMRiQ92506.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113653. 16 interactors.
IntActiQ92506. 2 interactors.
STRINGi9606.ENSP00000363794.

Chemistry databases

SwissLipidsiSLP:000001271.

PTM databases

iPTMnetiQ92506.
PhosphoSitePlusiQ92506.

Polymorphism and mutation databases

BioMutaiHSD17B8.
DMDMi12643402.

Proteomic databases

EPDiQ92506.
MaxQBiQ92506.
PaxDbiQ92506.
PeptideAtlasiQ92506.
PRIDEiQ92506.
TopDownProteomicsiQ92506.

Protocols and materials databases

DNASUi7923.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230236; ENSP00000230236; ENSG00000112474.
ENST00000374662; ENSP00000363794; ENSG00000204228.
ENST00000414463; ENSP00000387753; ENSG00000228357.
ENST00000422433; ENSP00000406488; ENSG00000232357.
ENST00000427295; ENSP00000403538; ENSG00000228712.
ENST00000454191; ENSP00000413950; ENSG00000225312.
GeneIDi7923.
KEGGihsa:7923.
UCSCiuc003odi.3. human.

Organism-specific databases

CTDi7923.
DisGeNETi7923.
GeneCardsiHSD17B8.
HGNCiHGNC:3554. HSD17B8.
HPAiHPA042132.
MIMi601417. gene.
neXtProtiNX_Q92506.
OpenTargetsiENSG00000112474.
ENSG00000204228.
ENSG00000225312.
ENSG00000228357.
ENSG00000228712.
ENSG00000232357.
PharmGKBiPA29484.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1200. Eukaryota.
COG1028. LUCA.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG002145.
InParanoidiQ92506.
KOiK13370.
OMAiHMSEEDW.
OrthoDBiEOG091G0N2V.
PhylomeDBiQ92506.
TreeFamiTF313099.

Enzyme and pathway databases

UniPathwayiUPA00094.
UPA00769.
BioCyciZFISH:HS03575-MONOMER.
ReactomeiR-HSA-535734. Fatty acid, triacylglycerol, and ketone body metabolism.
SABIO-RKQ92506.

Miscellaneous databases

ChiTaRSiHSD17B8. human.
EvolutionaryTraceiQ92506.
GeneWikiiHSD17B8.
GenomeRNAii7923.
PROiQ92506.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112474.
CleanExiHS_HSD17B8.
GenevisibleiQ92506. HS.

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...

Entry informationi

Entry nameiDHB8_HUMAN
AccessioniPrimary (citable) accession number: Q92506
Secondary accession number(s): A6NLX7, Q5STP7, Q9UIQ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 24, 2001
Last modified: November 2, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.