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Protein

17-beta-hydroxysteroid dehydrogenase type 6

Gene

HSD17B6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

NAD-dependent oxidoreductase with broad substrate specificity that shows both oxidative and reductive activity (in vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro). Converts 5-alpha-androstan-3-alpha,17-beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro). Has retinol dehydrogenase activity towards all-trans-retinol (in vitro). Can convert androsterone to epi-androsterone. Androsterone is first oxidized to 5-alpha-androstane-3,17-dione and then reduced to epi-andosterone. Can act on both C-19 and C-21 3-alpha-hydroxysteroids.3 Publications

Catalytic activityi

17-beta-estradiol + NAD(P)+ = estrone + NAD(P)H.
Testosterone + NAD+ = androstenedione + NADH.
All-trans-retinol-[cellular-retinol-binding-protein] + NAD+ = all-trans-retinal-[cellular-retinol-binding-protein] + NADH.

Kineticsi

The kinetic parameters were determined using microsomes from transfected cells.
  1. KM=0.19 µM for NAD2 Publications
  2. KM=0.18 µM for NADH2 Publications
  3. KM=54 µM for NADPH2 Publications
  4. KM=940 µM for NADP2 Publications
  5. KM=3.2 µM for all-trans-retinol2 Publications
  6. KM=0.24 µM for allopregnanolone2 Publications
  7. KM=0.13 µM for 3-alpha-androstanediol2 Publications
  8. KM=0.23 µM for androsterone2 Publications
  9. KM=0.13 µM for dehydroepiandrosterone2 Publications
  1. Vmax=1.2 nmol/min/mg enzyme with all-trans-retinol2 Publications
  2. Vmax=14.7 nmol/min/mg enzyme with allopregnanolone2 Publications
  3. Vmax=16.5 nmol/min/mg enzyme with 3-alpha-androstanediol2 Publications
  4. Vmax=35 nmol/min/mg enzyme with androsterone2 Publications
  5. Vmax=0.90 nmol/min/mg enzyme with dehydroepiandrosterone2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei164SubstrateSequence analysis1
Active sitei176Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi33 – 57NADBy similarityAdd BLAST25

GO - Molecular functioni

  • catalytic activity Source: ProtInc
  • electron transfer activity Source: UniProtKB
  • estradiol 17-beta-dehydrogenase activity Source: UniProtKB-EC
  • oxidoreductase activity Source: UniProtKB
  • retinol dehydrogenase activity Source: UniProtKB-EC
  • testosterone dehydrogenase (NAD+) activity Source: UniProtKB-EC

GO - Biological processi

  • androgen biosynthetic process Source: UniProtKB
  • androgen catabolic process Source: UniProtKB

Keywordsi

Molecular functionOxidoreductase
Biological processLipid metabolism, Steroid metabolism
LigandNAD

Enzyme and pathway databases

BRENDAi1.1.1.62 2681
ReactomeiR-HSA-2453902 The canonical retinoid cycle in rods (twilight vision)
SABIO-RKiO14756

Chemistry databases

SwissLipidsiSLP:000000807

Names & Taxonomyi

Protein namesi
Recommended name:
17-beta-hydroxysteroid dehydrogenase type 6 (EC:1.1.1.105, EC:1.1.1.239, EC:1.1.1.62)
Short name:
17-beta-HSD 6
Short name:
17-beta-HSD6
Alternative name(s):
3-alpha->beta-hydroxysteroid epimerase
Short name:
3-alpha->beta-HSE
Oxidative 3-alpha hydroxysteroid dehydrogenase
Short chain dehydrogenase/reductase family 9C member 6
Gene namesi
Name:HSD17B6
Synonyms:RODH, SDR9C6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000025423.11
HGNCiHGNC:23316 HSD17B6
MIMi606623 gene
neXtProtiNX_O14756

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

Endoplasmic reticulum, Endosome, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi8630
OpenTargetsiENSG00000025423
PharmGKBiPA142671671

Chemistry databases

DrugBankiDB00139 Succinic acid

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000030321118 – 31717-beta-hydroxysteroid dehydrogenase type 6Add BLAST300

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi161N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi215N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi256N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO14756
PeptideAtlasiO14756
PRIDEiO14756

PTM databases

iPTMnetiO14756
PhosphoSitePlusiO14756

Expressioni

Tissue specificityi

Detected in liver and prostate (at protein level). Detected in adult liver, lung, brain, placenta, prostate, adrenal gland, testis, mammary gland, spleen, spinal cord and uterus. Detected in caudate nucleus, and at lower levels in amygdala, corpus callosum, hippocampus, substantia nigra and thalamus. Detected in fetal lung, liver and brain.2 Publications

Gene expression databases

BgeeiENSG00000025423
CleanExiHS_HSD17B6
ExpressionAtlasiO14756 baseline and differential
GenevisibleiO14756 HS

Organism-specific databases

HPAiHPA059141

Interactioni

Protein-protein interaction databases

BioGridi11418313 interactors.
STRINGi9606.ENSP00000318631

Structurei

3D structure databases

ProteinModelPortaliO14756
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1610 Eukaryota
ENOG410Y7FK LUCA
GeneTreeiENSGT00910000144025
HOVERGENiHBG005482
InParanoidiO14756
KOiK13369
OMAiGYFRTGM
OrthoDBiEOG091G0LMI
PhylomeDBiO14756
TreeFamiTF325617

Family and domain databases

InterProiView protein in InterPro
IPR036291 NAD(P)-bd_dom_sf
IPR020904 Sc_DH/Rdtase_CS
IPR002347 SDR_fam
PfamiView protein in Pfam
PF00106 adh_short, 1 hit
PRINTSiPR00081 GDHRDH
PR00080 SDRFAMILY
SUPFAMiSSF51735 SSF51735, 1 hit
PROSITEiView protein in PROSITE
PS00061 ADH_SHORT, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O14756-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWLYLAAFVG LYYLLHWYRE RQVVSHLQDK YVFITGCDSG FGNLLARQLD
60 70 80 90 100
ARGLRVLAAC LTEKGAEQLR GQTSDRLETV TLDVTKMESI AAATQWVKEH
110 120 130 140 150
VGDRGLWGLV NNAGILTPIT LCEWLNTEDS MNMLKVNLIG VIQVTLSMLP
160 170 180 190 200
LVRRARGRIV NVSSILGRVA FFVGGYCVSK YGVEAFSDIL RREIQHFGVK
210 220 230 240 250
ISIVEPGYFR TGMTNMTQSL ERMKQSWKEA PKHIKETYGQ QYFDALYNIM
260 270 280 290 300
KEGLLNCSTN LNLVTDCMEH ALTSVHPRTR YSAGWDAKFF FIPLSYLPTS
310
LADYILTRSW PKPAQAV
Length:317
Mass (Da):35,966
Last modified:January 1, 1998 - v1
Checksum:i46F1E940605CBEE9
GO

Sequence cautioni

The sequence AAB88252 differs from that shown. Reason: Frameshift at positions 158 and 174.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti63E → D in AAB88252 (PubMed:9188497).Curated1
Sequence conflicti105G → R in AAB88252 (PubMed:9188497).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89281 mRNA Translation: AAB88252.1 Frameshift.
AF016509 mRNA Translation: AAB67236.1
AF223225 mRNA Translation: AAF81017.1
BC020710 mRNA Translation: AAH20710.1
CCDSiCCDS8925.1
RefSeqiNP_003716.2, NM_003725.3
XP_005269264.1, XM_005269207.1
XP_005269265.1, XM_005269208.1
XP_005269266.1, XM_005269209.1
XP_006719735.1, XM_006719672.1
XP_011537227.1, XM_011538925.1
XP_011537228.1, XM_011538926.1
XP_011537229.1, XM_011538927.1
UniGeneiHs.524513

Genome annotation databases

EnsembliENST00000322165; ENSP00000318631; ENSG00000025423
ENST00000554150; ENSP00000452273; ENSG00000025423
ENST00000554643; ENSP00000451406; ENSG00000025423
ENST00000555159; ENSP00000450698; ENSG00000025423
ENST00000555805; ENSP00000451753; ENSG00000025423
GeneIDi8630
KEGGihsa:8630
UCSCiuc001smg.3 human

Similar proteinsi

Entry informationi

Entry nameiH17B6_HUMAN
AccessioniPrimary (citable) accession number: O14756
Secondary accession number(s): O43275
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: January 1, 1998
Last modified: March 28, 2018
This is version 157 of the entry and version 1 of the sequence. See 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

Complete proteome, Reference proteome