Human Gene HSD17B6 (ENST00000554643.5) from GENCODE V41
  Description: 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. (from UniProt O14756)
RefSeq Summary (NM_003725): The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor. This gene is a member of the retinol dehydrogenase family. [provided by RefSeq, Aug 2013].
Gencode Transcript: ENST00000554643.5
Gencode Gene: ENSG00000025423.11
Transcript (Including UTRs)
   Position: hg38 chr12:56,752,449-56,787,790 Size: 35,342 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg38 chr12:56,773,853-56,787,342 Size: 13,490 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2022-05-14 09:57:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:56,752,449-56,787,790)mRNA (may differ from genome)Protein (317 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblExonPrimerGencodeGeneCardsHGNC
HPRDLynxMGIneXtProtPubMedReactome
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: H17B6_HUMAN
DESCRIPTION: RecName: Full=17-beta-hydroxysteroid dehydrogenase type 6; Short=17-beta-HSD 6; Short=17-beta-HSD6; EC=1.1.1.105; EC=1.1.1.62; EC=1.1.1.63; AltName: Full=3-alpha->beta-hydroxysteroid epimerase; Short=3-alpha->beta-HSE; AltName: Full=Oxidative 3-alpha hydroxysteroid dehydrogenase; Flags: Precursor;
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: All-trans-retinol-[cellular-retinol-binding- protein] + NAD(+) = all-trans-retinal-[cellular-retinol-binding- protein] + NADH.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.19 uM for NAD; KM=0.18 uM for NADH; KM=54 uM for NADPH; KM=940 uM for NADP; KM=3.2 uM for all-trans-retinol; KM=0.24 uM for allopregnanolone; KM=0.13 uM for 3-alpha-androstanediol; KM=0.23 uM for androsterone; KM=0.13 uM 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;

-  MalaCards Disease Associations
  MalaCards Gene Search: HSD17B6
Diseases sorted by gene-association score: syndromic x-linked intellectual disability type 10 (3), chromosome 3q29 microduplication syndrome (2), apparent mineralocorticoid excess (2), factitious disorder (2), testicular leydig cell tumor (2), d-bifunctional protein deficiency (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 205.97 RPKM in Liver
Total median expression: 452.75 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -138.50349-0.397 Picture PostScript Text
3' UTR -84.80448-0.189 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002198 - DH_sc/Rdtase_SDR
IPR002347 - Glc/ribitol_DH
IPR016040 - NAD(P)-bd_dom
IPR020904 - Sc_DH/Rdtase_CS

Pfam Domains:
PF00106 - short chain dehydrogenase

ModBase Predicted Comparative 3D Structure on O14756
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGI     
Protein Sequence     
Alignment     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003824 catalytic activity
GO:0004303 estradiol 17-beta-dehydrogenase activity
GO:0004745 retinol dehydrogenase activity
GO:0009055 electron carrier activity
GO:0016491 oxidoreductase activity
GO:0047035 testosterone dehydrogenase (NAD+) activity

Biological Process:
GO:0006629 lipid metabolic process
GO:0006702 androgen biosynthetic process
GO:0006710 androgen catabolic process
GO:0008202 steroid metabolic process
GO:0022900 electron transport chain
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005622 intracellular
GO:0005768 endosome
GO:0005783 endoplasmic reticulum
GO:0016020 membrane
GO:0031090 organelle membrane
GO:0031901 early endosome membrane
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  DQ590166 - Homo sapiens piRNA piR-57278, complete sequence.
AK313423 - Homo sapiens cDNA, FLJ93962, highly similar to Homo sapiens hydroxysteroid (17-beta) dehydrogenase 6 (HSD17B6), mRNA.
BC020710 - Homo sapiens hydroxysteroid (17-beta) dehydrogenase 6 homolog (mouse), mRNA (cDNA clone MGC:22483 IMAGE:4700726), complete cds.
U89281 - Human oxidative 3 alpha hydroxysteroid dehydrogenase mRNA, complete cds.
JD073800 - Sequence 54824 from Patent EP1572962.
AF223225 - Homo sapiens 3-hydroxysteroid epimerase mRNA, complete cds.
JX308227 - Homo sapiens 17-beta-hydroxysteroid dehydrogenase type 6 variant 1 (HSD17B6) mRNA, complete cds.
JX308228 - Homo sapiens 17-beta-hydroxysteroid dehydrogenase type 6 variant 2 (HSD17B6) mRNA, complete cds.
JX308229 - Homo sapiens 17-beta-hydroxysteroid dehydrogenase type 6 variant 3 (HSD17B6) mRNA, complete cds.
CU676654 - Synthetic construct Homo sapiens gateway clone IMAGE:100022227 5' read HSD17B6 mRNA.
HQ447624 - Synthetic construct Homo sapiens clone IMAGE:100070970; CCSB012986_01 hydroxysteroid (17-beta) dehydrogenase 6 homolog (mouse) (HSD17B6) gene, encodes complete protein.
KJ892578 - Synthetic construct Homo sapiens clone ccsbBroadEn_01972 HSD17B6 gene, encodes complete protein.
AF016509 - Homo sapiens oxidoreductase mRNA, complete cds.
JD166490 - Sequence 147514 from Patent EP1572962.
JD313290 - Sequence 294314 from Patent EP1572962.
JD244279 - Sequence 225303 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00140 - Steroid hormone biosynthesis
hsa01100 - Metabolic pathways

Reactome (by CSHL, EBI, and GO)

Protein O14756 (Reactome details) participates in the following event(s):

R-HSA-2454081 RDH5 oxidises 11cROL to 11cRAL
R-HSA-2453902 The canonical retinoid cycle in rods (twilight vision)
R-HSA-2187338 Visual phototransduction
R-HSA-418594 G alpha (i) signalling events
R-HSA-388396 GPCR downstream signalling
R-HSA-372790 Signaling by GPCR
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000554643.1, ENST00000554643.2, ENST00000554643.3, ENST00000554643.4, H17B6_HUMAN, O14756, O43275, RODH, U89281, uc001smg.1, uc001smg.2, uc001smg.3
UCSC ID: ENST00000554643.5
RefSeq Accession: NM_003725
Protein: O14756 (aka H17B6_HUMAN)
CCDS: CCDS8925.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.