P37058 · DHB3_HUMAN
- Protein17-beta-hydroxysteroid dehydrogenase type 3
- GeneHSD17B3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids310 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids (PubMed:16216911, PubMed:26545797, PubMed:27927697, PubMed:8075637).
Favors the reduction of androstenedione to testosterone (PubMed:16216911, PubMed:26545797, PubMed:27927697).
Testosterone is the key androgen driving male development and function (PubMed:8075637).
Uses NADPH while the two other EDH17B enzymes use NADH (PubMed:16216911, PubMed:26545797, PubMed:8075637).
Androgens such as epiandrosterone, dehydroepiandrosterone, androsterone and androstanedione are accepted as substrates and reduced at C-17 (PubMed:16216911).
Can reduce 11-ketoandrostenedione as well as 11beta-hydroxyandrostenedione at C-17 to the respective testosterone forms (PubMed:16216911, PubMed:27927697).
Favors the reduction of androstenedione to testosterone (PubMed:16216911, PubMed:26545797, PubMed:27927697).
Testosterone is the key androgen driving male development and function (PubMed:8075637).
Uses NADPH while the two other EDH17B enzymes use NADH (PubMed:16216911, PubMed:26545797, PubMed:8075637).
Androgens such as epiandrosterone, dehydroepiandrosterone, androsterone and androstanedione are accepted as substrates and reduced at C-17 (PubMed:16216911).
Can reduce 11-ketoandrostenedione as well as 11beta-hydroxyandrostenedione at C-17 to the respective testosterone forms (PubMed:16216911, PubMed:27927697).
Catalytic activity
- a 17beta-hydroxy steroid + NADP+ = a 17-oxo steroid + H+ + NADPHThis reaction proceeds in the backward direction.
- 3beta-hydroxyandrost-5-en-17-one + H+ + NADPH = androst-5-en-3beta,17beta-diol + NADP+This reaction proceeds in the forward direction.
- 17beta-hydroxy-5alpha-androstan-3-one + NADP+ = 5alpha-androstan-3,17-dione + H+ + NADPHThis reaction proceeds in the backward direction.
- androsterone + H+ + NADPH = 5alpha-androstane-3alpha,17beta-diol + NADP+This reaction proceeds in the forward direction.
- 3beta-hydroxy-5alpha-androstan-17-one + H+ + NADPH = 5alpha-androstane-3beta,17beta-diol + NADP+This reaction proceeds in the forward direction.
- androst-4-ene-3,11,17-trione + H+ + NADPH = 17beta-hydroxyandrost-4-ene-3,11-dione + NADP+This reaction proceeds in the forward direction.
- 11beta-hydroxyandrost-4-ene-3,17-dione + H+ + NADPH = 11beta,17beta-dihydroxyandrost-4-ene-3-one + NADP+This reaction proceeds in the forward direction.
Pathway
Hormone biosynthesis; testosterone biosynthesis.
Steroid metabolism.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Molecular Function | 17-beta-hydroxysteroid dehydrogenase (NADP+) activity | |
Molecular Function | estradiol 17-beta-dehydrogenase [NAD(P)+] activity | |
Molecular Function | testosterone 17-beta-dehydrogenase (NADP+) activity | |
Molecular Function | testosterone dehydrogenase [NAD(P)+] activity | |
Biological Process | androgen biosynthetic process | |
Biological Process | male genitalia development | |
Biological Process | steroid biosynthetic process | |
Biological Process | testosterone biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended name17-beta-hydroxysteroid dehydrogenase type 3
- Short names17-beta-HSD 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP37058
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Male pseudohermaphrodism with gynecomastia (MPH)
- Note
- DescriptionAn autosomal recessive disorder that manifests, in males, as undermasculinization characterized by hypoplastic-to-normal internal genitalia (epididymis, vas deferens, seminal vesicles, and ejaculatory ducts) but female external genitalia and the absence of a prostate. This phenotype is caused by inadequate testicular synthesis of testosterone, which, in turn, results in insufficient formation of dihydrotestosterone in the anlage of the external genitalia and prostate during fetal development. At the expected time of puberty, there is a marked increase in plasma leuteinizing hormone and, consequently, in testicular secretion of androstenedione. Hence, a diagnostic hallmark of this disorder is a decreased plasma testosterone-to-androstenedione ratio. Significant amounts of the circulating androstenedione are, however, converted to testosterone, in peripheral tissues, thereby causing virilization.
- See alsoMIM:264300
Natural variants in MPH
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_016067 | 56 | A>T | in MPH; Cambridge-2; affects NADPH cofactor binding; dbSNP:rs119481078 | |
VAR_016068 | 65 | S>L | in MPH; dbSNP:rs747329682 | |
VAR_006953 | 80 | R>Q | in MPH; Gaza; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs119481075 | |
VAR_006954 | 80 | R>W | in MPH; dbSNP:rs119481077 | |
VAR_016069 | 130 | N>S | in MPH; Cambridge-1; complete loss of activity; dbSNP:rs119481079 | |
VAR_075369 | 133 | G>R | in MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; no effect on protein abundance; no effect on endoplasmic reticulum location; dbSNP:rs747724352 | |
VAR_016070 | 176 | Q>P | in MPH; dbSNP:rs767259718 | |
VAR_006955 | 203 | A>V | in MPH; loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs119481076 | |
VAR_016071 | 205 | V>E | in MPH; dbSNP:rs372027264 | |
VAR_016072 | 208 | F>I | in MPH | |
VAR_016203 | 215 | E>D | in MPH; dbSNP:rs115063639 | |
VAR_006956 | 232 | S>L | in MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs28939085 | |
VAR_006957 | 235 | M>V | in MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs119481074 | |
VAR_016073 | 268 | C>Y | in MPH; complete loss of activity; dbSNP:rs119481080 | |
VAR_016074 | 282 | P>L | in MPH; dbSNP:rs144809928 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_014870 | 31 | in dbSNP:rs2066480 | |||
Sequence: V → I | ||||||
Natural variant | VAR_016067 | 56 | in MPH; Cambridge-2; affects NADPH cofactor binding; dbSNP:rs119481078 | |||
Sequence: A → T | ||||||
Natural variant | VAR_016068 | 65 | in MPH; dbSNP:rs747329682 | |||
Sequence: S → L | ||||||
Natural variant | VAR_006953 | 80 | in MPH; Gaza; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs119481075 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_006954 | 80 | in MPH; dbSNP:rs119481077 | |||
Sequence: R → W | ||||||
Natural variant | VAR_016069 | 130 | in MPH; Cambridge-1; complete loss of activity; dbSNP:rs119481079 | |||
Sequence: N → S | ||||||
Natural variant | VAR_075369 | 133 | in MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; no effect on protein abundance; no effect on endoplasmic reticulum location; dbSNP:rs747724352 | |||
Sequence: G → R | ||||||
Mutagenesis | 133 | Has 70% of wild-type testosterone 17-beta-dehydrogenase (NADP+) activity. | ||||
Sequence: G → A | ||||||
Mutagenesis | 133 | Almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity. | ||||
Sequence: G → F | ||||||
Mutagenesis | 133 | Almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity. | ||||
Sequence: G → Q | ||||||
Natural variant | VAR_016070 | 176 | in MPH; dbSNP:rs767259718 | |||
Sequence: Q → P | ||||||
Natural variant | VAR_006955 | 203 | in MPH; loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs119481076 | |||
Sequence: A → V | ||||||
Natural variant | VAR_016071 | 205 | in MPH; dbSNP:rs372027264 | |||
Sequence: V → E | ||||||
Natural variant | VAR_016072 | 208 | in MPH | |||
Sequence: F → I | ||||||
Natural variant | VAR_016203 | 215 | in MPH; dbSNP:rs115063639 | |||
Sequence: E → D | ||||||
Natural variant | VAR_006956 | 232 | in MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs28939085 | |||
Sequence: S → L | ||||||
Natural variant | VAR_006957 | 235 | in MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP+) activity; dbSNP:rs119481074 | |||
Sequence: M → V | ||||||
Natural variant | VAR_016073 | 268 | in MPH; complete loss of activity; dbSNP:rs119481080 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_016074 | 282 | in MPH; dbSNP:rs144809928 | |||
Sequence: P → L | ||||||
Natural variant | VAR_061844 | 289 | in dbSNP:rs2066479 | |||
Sequence: G → C | ||||||
Natural variant | VAR_061845 | 289 | in dbSNP:rs2066479 | |||
Sequence: G → R | ||||||
Natural variant | VAR_014871 | 289 | in dbSNP:rs2066479 | |||
Sequence: G → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 339 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000054573 | 1-310 | 17-beta-hydroxysteroid dehydrogenase type 3 | |||
Sequence: MGDVLEQFFILTGLLVCLACLAKCVRFSRCVLLNYWKVLPKSFLRSMGQWAVITGAGDGIGKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRSVKIIQADFTKDDIYEHIKEKLAGLEIGILVNNVGMLPNLLPSHFLNAPDEIQSLIHCNITSVVKMTQLILKHMESRQKGLILNISSGIALFPWPLYSMYSASKAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTKYLNTNVITKTADEFVKESLNYVTIGGETCGCLAHEILAGFLSLIPAWAFYSGAFQRLLLTHYVAYLKLNTKVR |
Proteomic databases
PTM databases
Expression
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P37058 | NCS1 P62166 | 3 | EBI-2932988, EBI-746987 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P37058-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length310
- Mass (Da)34,516
- Last updated1995-11-01 v2
- Checksum0643FF35ED979185
P37058-2
- Name2
- Differences from canonical
- 225-274: Missing
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0S2Z413 | A0A0S2Z413_HUMAN | HSD17B3 | 192 | ||
A0A0S2Z3U6 | A0A0S2Z3U6_HUMAN | HSD17B3 | 284 | ||
A0A0S2Z406 | A0A0S2Z406_HUMAN | HSD17B3 | 108 | ||
A0A0S2Z3V7 | A0A0S2Z3V7_HUMAN | HSD17B3 | 157 | ||
A0A3B3ITT4 | A0A3B3ITT4_HUMAN | HSD17B3 | 245 | ||
A0A3B3ITW2 | A0A3B3ITW2_HUMAN | HSD17B3 | 74 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056640 | 225-274 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U05659 EMBL· GenBank· DDBJ | AAC50066.1 EMBL· GenBank· DDBJ | mRNA | ||
AY341031 EMBL· GenBank· DDBJ | AAP88937.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT019371 EMBL· GenBank· DDBJ | AAV38178.1 EMBL· GenBank· DDBJ | mRNA | ||
AL160269 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC034281 EMBL· GenBank· DDBJ | AAH34281.1 EMBL· GenBank· DDBJ | mRNA |