Tchem HSD17B1 Estradiol 17-beta-dehydrogenase 1

Protein Summary

Description

Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH. This gene encodes a member of the 17beta-hydroxysteroid dehydrogenase family of short-chain dehydrogenases/reductases. It has a dual function in estrogen activation and androgen inactivation and plays a major role in establishing the estrogen E2 concentration gradient between serum and peripheral tissues. The encoded protein catalyzes the last step in estrogen activation, using NADPH to convert estrogens E1 and E2 and androgens like 4-androstenedione, to testosterone. It has an N-terminal short-chain dehydrogenase domain with a cofactor binding site, and a narrow, hydrophobic C-terminal domain with a steroid substrate binding site. This gene is expressed primarily in the placenta and ovarian granulosa cells, and to a lesser extent, in the endometrium, adipose tissue, and prostate. Polymorphisms in this gene have been linked to breast and prostate cancer. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Uniprot Accession IDs

• P14061
• B3KXS1
• Q2M2L8

Gene Name

• HSD17B1

Ensembl ID

• ENST00000585807
• ENSP00000466799
• ENSG00000108786

Symbol

• E17KSR
• EDH17B1
• EDH17B2
• EDHB17
• SDR28C1
• E2DH
• HSD17
• EDHB17
• EDH17B2
• SDR28C1
• 17-beta-HSD
• 20-alpha-HSD

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
phenotype	0.85
protein domain	0.73
biological term	0.69
gene perturbation	0.69
PubMedID	0.68

Protein Classes

PANTHER Classes

Protein / Oxidoreductase / Reductase / Estradiol 17-beta-dehydrogenase 1

Protein / Oxidoreductase / Dehydrogenase / Estradiol 17-beta-dehydrogenase 1

DTO Classes

Protein / Enzyme / Oxidoreductase / Dehydrogenase / Estradiol 17-beta-dehydrogenase 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 312.74   (req: < 5)

Gene RIFs: 74   (req: <= 3)

Antibodies: 265   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 312.74   (req: >= 5)

Gene RIFs: 74   (req: > 3)

Antibodies: 265   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 8

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 399

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (1)

Explore Approved Drugs

1 – 1 of 1

estrone

HSD17B1Tchem Enzyme

AGONIST pEC50 : 9.15

Active Ligands (399)

Explore Active Ligands

1 – 10 of 399

Apigenin

HSD17B1Tchem Enzyme

pKi : 7.19

CHEMBL1650645

HSD17B1Tchem Enzyme

pIC50 : 8

US8546392, 59

HSD17B1Tchem Enzyme

pIC50 : 7.85

1,6-Bis(3-hydroxyphenyl)-2-naphthol

HSD17B1Tchem Enzyme

pIC50 : 7.44

CHEMBL1650646

HSD17B1Tchem Enzyme

pIC50 : 7.48

CHEMBL570596

HSD17B1Tchem Enzyme

pIC50 : 7.34

CHEMBL577338

HSD17B1Tchem Enzyme

pIC50 : 8.1

Lupinalbin A

HSD17B1Tchem Enzyme

pIC50 : 8.77

CHEMBL4071245

HSD17B1Tchem Enzyme

pIC50 : 8.96

CHEMBL4072794

HSD17B1Tchem Enzyme

pIC50 : 8.85

Protein-Protein Interactions (95)

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1 – 10 of 95

• See Interactions on String-DB

EMB

Tbio

Novelty:  0.00135577

p_int:  0.997334253

p_ni:  0.002489045

p_wrong:  0.000176702

Data Source:  BioPlex

NOCT

Tbio

Novelty:  0.01696096

p_int:  0.966310403

p_ni:  0.033672443

p_wrong:  0.000017154

Data Source:  BioPlex

HMOX1

Tchem

Family:  Enzyme

Novelty:  0.00013981

p_int:  0.954601052

p_ni:  0.045398721

p_wrong:  2.26e-7

Data Source:  BioPlex

RNASEL

Tchem

Family:  Kinase

Novelty:  0.00165549

p_int:  0.952880216

p_ni:  0.046870586

p_wrong:  0.000249198

Data Source:  BioPlex

MPZL1

Tbio

Novelty:  0.03292508

p_int:  0.938204852

p_ni:  0.061653883

p_wrong:  0.000141265

Data Source:  BioPlex

PDLIM5

Tbio

Novelty:  0.0040646

p_int:  0.923610693

p_ni:  0.076389303

p_wrong:  3e-9

Data Source:  BioPlex

RBM10

Tbio

Novelty:  0.02610192

p_int:  0.900758183

p_ni:  0.099241817

Data Source:  BioPlex

RAD21

Tbio

Novelty:  0.00270936

p_int:  0.882986653

p_ni:  0.117012489

p_wrong:  8.58e-7

Data Source:  BioPlex

MCU

Tbio

Family:  IC

Novelty:  0.00114914

p_int:  0.874080362

p_ni:  0.125919638

Data Source:  BioPlex

ATP2B2

Tbio

Family:  Transporter

Novelty:  0.007782

p_int:  0.866793856

p_ni:  0.133206144

Data Source:  BioPlex

Nearest Tclin Targets (5)

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Upstream (2)

Downstream (3)

1 – 2 of 2

CYP3A4

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  2

1: Steroid hormone biosynthesis

2: Metabolic pathways

CYP3A5

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  2

1: Steroid hormone biosynthesis

2: Metabolic pathways

Pathways (57)

Reactome (11)

KEGG (3)

PathwayCommons (1)

UniProt (1)

WikiPathways (41)

Estrogen biosynthesis (R-HSA-193144)

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5

1 – 5 of 11

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Estrogen biosynthesis	6 targets	R-HSA-193144
Reactome	G alpha (i) signalling events	408 targets	R-HSA-418594
Reactome	GPCR downstream signalling	1152 targets	R-HSA-388396
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of lipids	740 targets	R-HSA-556833

Name	Explore in Pharos	Explore in Source
Estrogen biosynthesis	6 targets	R-HSA-193144
G alpha (i) signalling events	408 targets	R-HSA-418594
GPCR downstream signalling	1152 targets	R-HSA-388396
Metabolism	2112 targets	R-HSA-1430728
Metabolism of lipids	740 targets	R-HSA-556833

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (10)

Functions (5)

Components (2)

Processes (3)

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Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
estradiol 17-beta-dehydrogenase activity	Inferred from Direct Assay (IDA)	CAFA
estradiol binding	Inferred from Direct Assay (IDA)	CAFA
steroid binding	Inferred from Direct Assay (IDA)	CAFA
NADP+ binding	Inferred from Mutant Phenotype (IMP)	CAFA
catalytic activity	Traceable Author Statement (TAS)	ProtInc

Disease Associations ()

No disease associations found

GWAS Traits (17)

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5

1 – 5 of 17

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
type II diabetes mellitus	EFO_0001360	4	4	2	1	91.4
waist-hip ratio	EFO_0004343	3	6	6		82
BMI-adjusted waist-hip ratio	EFO_0007788	1	4	4		76.4
sex hormone-binding globulin measurement	EFO_0004696	4	2	4		75.4
triglyceride measurement	EFO_0004530	3	2	3		68.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 17

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
type II diabetes mellitus	EFO_0001360	2	1	91.4
waist-hip ratio	EFO_0004343	6		82
BMI-adjusted waist-hip ratio	EFO_0007788	4		76.4
sex hormone-binding globulin measurement	EFO_0004696	4		75.4
triglyceride measurement	EFO_0004530	3		68.3

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Complete proteome
Cytoplasm
Direct protein sequencing
Lipid biosynthesis
Lipid metabolism
NADP
Oxidoreductase
Polymorphism
Reference proteome

GWAS Trait Find Similar Targets

No Header	No Header
apolipoprotein A 1 measurement
BMI-adjusted waist-hip ratio
C-reactive protein measurement
Drugs used in diabetes use measurement
Eczema
heel bone mineral density
high density lipoprotein cholesterol measurement
leukocyte count
metabolic syndrome
sex hormone-binding globulin measurement

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
endocrine/exocrine gland phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
reproductive system phenotype
vision/eye phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	hydroxysteroid 17-beta dehydrogenase 1		454689
Macaque	hydroxysteroid 17-beta dehydrogenase 1		710392
Mouse	hydroxysteroid (17-beta) dehydrogenase 1	MGI:105077	15485
Rat	hydroxysteroid (17-beta) dehydrogenase 1	RGD:2836	25322
Dog	hydroxysteroid 17-beta dehydrogenase 1	VGNC:41800	607570

Species	Name	OMA	EggNOG	Inparanoid
Chimp	hydroxysteroid 17-beta dehydrogenase 1
Macaque	hydroxysteroid 17-beta dehydrogenase 1
Mouse	hydroxysteroid (17-beta) dehydrogenase 1
Rat	hydroxysteroid (17-beta) dehydrogenase 1
Dog	hydroxysteroid 17-beta dehydrogenase 1

Publication Statistics

PubMed Score 312.74

PubMed score by year

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PubTator Score 297.17

PubTator score by year

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Related Publications

Text Mined References (141)

GeneRif Annotations (74)

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PMID	Year	Title