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UniProtKB/Swiss-Prot entry O14756


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name H17B6_HUMAN
Primary accession number O14756
Secondary accession number O43275
Integrated into Swiss-Prot on September 11, 2007
Sequence was last modified on January 1, 1998 (Sequence version 1)
Annotations were last modified on    December 16, 2008 (Entry version 66)
Name and origin of the protein
Protein name Hydroxysteroid 17-beta dehydrogenase 6 [Precursor]
Synonyms EC 1.1.1.62
EC 1.1.1.63
EC 1.1.1.105
17-beta-HSD6
Oxidative 3-alpha hydroxysteroid dehydrogenase
3-alpha->beta-hydroxysteroid epimerase
3-alpha->beta-HSE
Gene name
Name: HSD17B6
Synonyms: RODH
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=Prostate;
DOI=10.1074/jbc.272.25.15959; PubMed=9188497 [NCBI, ExPASy, EBI, Israel, Japan]
Biswas M.G., Russell D.W.;
"Expression cloning and characterization of oxidative 17beta- and 3alpha-hydroxysteroid dehydrogenases from rat and human prostate.";
J. Biol. Chem. 272:15959-15966(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
TISSUE=Liver;
DOI=10.1074/jbc.M000562200; PubMed=10896656 [NCBI, ExPASy, EBI, Israel, Japan]
Huang X.-F., Luu-The V.;
"Molecular characterization of a first human 3(alpha-->beta)-hydroxysteroid epimerase.";
J. Biol. Chem. 275:29452-29457(2000).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
DOI=10.1006/abbi.2000.2203; PubMed=11360992 [NCBI, ExPASy, EBI, Israel, Japan]
Chetyrkin S.V., Hu J., Gough W.H., Dumaual N., Kedishvili N.Y.;
"Further characterization of human microsomal 3alpha-hydroxysteroid dehydrogenase.";
Arch. Biochem. Biophys. 386:1-10(2001).
[5]
FUNCTION.
DOI=10.1016/S0167-4781(01)00247-0; PubMed=11513953 [NCBI, ExPASy, EBI, Israel, Japan]
Huang X.-F., Luu-The V.;
"Gene structure, chromosomal localization and analysis of 3-ketosteroid reductase activity of the human 3(alpha-->beta)-hydroxysteroid epimerase.";
Biochim. Biophys. Acta 1520:124-130(2001).
Comments
  • FUNCTION: 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.
  • CATALYTIC ACTIVITY: Estradiol-17-beta + NAD(P)+ = estrone + NAD(P)H.
  • CATALYTIC ACTIVITY: Testosterone + NAD+ = androst-4-ene-3,17-dione + NADH.
  • CATALYTIC ACTIVITY: Retinol + NAD+ = retinal + NADH.
  • BIOPHYSICOCHEMICAL PROPERTIES:
    Kinetic parameters:   KM=0.19 µM for NAD;
    KM=0.18 µM for NADH;
    KM=54 µM for NADPH;
    KM=940 µM for NADP;
    KM=3.2 µM for all-trans-retinol;
    KM=0.24 µM for allopregnanolone;
    KM=0.13 µM for 3-alpha-androstanediol;
    KM=0.23 µM for androsterone;
    KM=0.13 µM for dehydroepiandrosterone;
    Vmax=1.2 nmol/min/mg enzyme with all-trans-retinol;
    Vmax=14.7 nmol/min/mg enzyme with allopregnanolone;
    Vmax=16.5 nmol/min/mg enzyme with 3-alpha-androstanediol;
    Vmax=35 nmol/min/mg enzyme with androsterone;
    Vmax=0.90 nmol/min/mg enzyme with dehydroepiandrosterone;
    Note=the kinetic parameters were determined using microsomes from transfected cells;
  • SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane protein; Lumenal side. Early endosome membrane; Peripheral membrane protein; Lumenal side (Potential).
  • TISSUE SPECIFICITY: 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.
  • SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
  • SEQUENCE CAUTION:
    • Sequence=AAB88252.1; Type=Frameshift; Positions=158, 174;
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U89281; AAB88252.1; ALT_FRAME; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF016509; AAB67236.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF223225; AAF81017.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC020710; AAH20710.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_003716.2; -.
UniGene Hs.524513
3D structure databases
HSSP P14061; 1FDS. [HSSP ENTRY / PDB]
ModBase O14756.
Organism-specific databases
GeneCards GC12P055444; -.
HGNC HGNC:23316; HSD17B6.
GenAtlas HSD17B6.
MIM 606623; gene. [NCBI / EBI]
PharmGKB PA142671671; -.
GeneCards O14756.
Gene expression databases
ArrayExpress O14756; -.
CleanEx HS_HSD17B6; -.
Ontologies
GO
GO:0031901; Cellular component: early endosome membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005783; Cellular component: endoplasmic reticulum (inferred from electronic annotation from UniProtKB-KW).
GO:0005792; Cellular component: microsome (inferred from electronic annotation from UniProtKB-KW).
GO:0005488; Molecular function: binding (inferred from electronic annotation from InterPro).
GO:0009055; Molecular function: electron carrier activity (traceable author statement from UniProtKB).
GO:0004303; Molecular function: estradiol 17-beta-dehydrogenase activity (inferred from electronic annotation from EC).
GO:0004745; Molecular function: retinol dehydrogenase activity (inferred from electronic annotation from EC).
GO:0050327; Molecular function: testosterone 17-beta-dehydrogenase activity (inferred from electronic annotation from EC).
GO:0006702; Biological process: androgen biosynthetic process (non-traceable author statement from UniProtKB).
GO:0006710; Biological process: androgen catabolic process (traceable author statement from UniProtKB).
GO:0055114; Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR002198; DHase_sc/Rdtase_SDR.
IPR002347; Glc/ribitol_DHase.
IPR016040; NAD(P)-bd.
Graphical view of domain structure.
Gene3D G3DSA:3.40.50.720; NAD(P)-bd; 1.
PANTHER PTHR19410; ADH_short_C2; 1.
Pfam PF00106; adh_short; 1.
Pfam graphical view of domain structure.
PRINTS PR00081; GDHRDH.
PR00080; SDRFAMILY.
PROSITE PS00061; ADH_SHORT; 1.
Proteomics databases
PRIDE O14756; -.
Genome annotation databases
Ensembl ENSG00000025423; Homo sapiens. [Contig view]
GeneID 8630; -.
KEGG hsa:8630; -.
Phylogenomic databases
HOGENOM O14756; -.
HOVERGEN O14756; -.
Other
DrugBank DB00139; Succinic acid.
NextBio 32349; -.
SOURCE HSD17B6; Homo sapiens.
ProtoNet O14756.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Endoplasmic reticulum; Endosome; Glycoprotein; Lipid metabolism; Membrane; Microsome; NAD; Oxidoreductase; Signal; Steroid metabolism.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
SIGNAL   1    17  17     Potential. 
CHAIN   18   317  300     Hydroxysteroid 17-beta dehydrogenase 6. PRO_0000303211
NP_BIND   33    57  25     NAD (By similarity). 
ACT_SITE   176   176        Proton acceptor (By similarity). 
BINDING   164   164        Substrate (Potential). 
CARBOHYD   161   161        N-linked (GlcNAc...) (Potential). 
CARBOHYD   215   215        N-linked (GlcNAc...) (Potential). 
CARBOHYD   256   256        N-linked (GlcNAc...) (Potential). 
CONFLICT   63    63        E -> D (in Ref. 1; AAB88252). 
CONFLICT   105   105        G -> R (in Ref. 1; AAB88252). 
Sequence information
Length: 317 AA [This is the length of the unprocessed precursor] Molecular weight: 35966 Da [This is the MW of the unprocessed precursor] CRC64: 46F1E940605CBEE9 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MWLYLAAFVG LYYLLHWYRE RQVVSHLQDK YVFITGCDSG FGNLLARQLD ARGLRVLAAC 

        70         80         90        100        110        120 
LTEKGAEQLR GQTSDRLETV TLDVTKMESI AAATQWVKEH VGDRGLWGLV NNAGILTPIT 

       130        140        150        160        170        180 
LCEWLNTEDS MNMLKVNLIG VIQVTLSMLP LVRRARGRIV NVSSILGRVA FFVGGYCVSK 

       190        200        210        220        230        240 
YGVEAFSDIL RREIQHFGVK ISIVEPGYFR TGMTNMTQSL ERMKQSWKEA PKHIKETYGQ 

       250        260        270        280        290        300 
QYFDALYNIM KEGLLNCSTN LNLVTDCMEH ALTSVHPRTR YSAGWDAKFF FIPLSYLPTS 

       310 
LADYILTRSW PKPAQAV 

O14756 in FASTA format

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