Q6QLL4 · DHI1_CAVPO
- Protein11-beta-hydroxysteroid dehydrogenase 1
- GeneHSD11B1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids300 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Controls the reversible conversion of biologically active glucocorticoids such as cortisone to cortisol, and 11-dehydrocorticosterone to corticosterone in the presence of NADP(H) (PubMed:10699594, PubMed:19507261).
Participates in the corticosteroid receptor-mediated anti-inflammatory response, as well as metabolic and homeostatic processes (By similarity).
Bidirectional in vitro, predominantly functions as a reductase in vivo, thereby increasing the concentration of active glucocorticoids. It has broad substrate specificity, besides glucocorticoids, it accepts other steroid and sterol substrates. Interconverts 7-oxo- and 7-hydroxy-neurosteroids such as 7-oxopregnenolone and 7beta-hydroxypregnenolone, 7-oxodehydroepiandrosterone (3beta-hydroxy-5-androstene-7,17-dione) and 7beta-hydroxydehydroepiandrosterone (3beta,7beta-dihydroxyandrost-5-en-17-one), among others (By similarity).
Catalyzes the stereo-specific conversion of the major dietary oxysterol, 7-ketocholesterol (7-oxocholesterol), into the more polar 7-beta-hydroxycholesterol metabolite (By similarity).
7-oxocholesterol is one of the most important oxysterols, it participates in several events such as induction of apoptosis, accumulation in atherosclerotic lesions, lipid peroxidation, and induction of foam cell formation (By similarity).
Mediates the 7-oxo reduction of 7-oxolithocholate mainly to chenodeoxycholate, and to a lesser extent to ursodeoxycholate, both in its free form and when conjugated to glycine or taurine, providing a link between glucocorticoid activation and bile acid metabolism (By similarity).
Catalyzes the synthesis of 7-beta-25-dihydroxycholesterol from 7-oxo-25-hydroxycholesterol in vitro, which acts as a ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration (By similarity).
Participates in the corticosteroid receptor-mediated anti-inflammatory response, as well as metabolic and homeostatic processes (By similarity).
Bidirectional in vitro, predominantly functions as a reductase in vivo, thereby increasing the concentration of active glucocorticoids. It has broad substrate specificity, besides glucocorticoids, it accepts other steroid and sterol substrates. Interconverts 7-oxo- and 7-hydroxy-neurosteroids such as 7-oxopregnenolone and 7beta-hydroxypregnenolone, 7-oxodehydroepiandrosterone (3beta-hydroxy-5-androstene-7,17-dione) and 7beta-hydroxydehydroepiandrosterone (3beta,7beta-dihydroxyandrost-5-en-17-one), among others (By similarity).
Catalyzes the stereo-specific conversion of the major dietary oxysterol, 7-ketocholesterol (7-oxocholesterol), into the more polar 7-beta-hydroxycholesterol metabolite (By similarity).
7-oxocholesterol is one of the most important oxysterols, it participates in several events such as induction of apoptosis, accumulation in atherosclerotic lesions, lipid peroxidation, and induction of foam cell formation (By similarity).
Mediates the 7-oxo reduction of 7-oxolithocholate mainly to chenodeoxycholate, and to a lesser extent to ursodeoxycholate, both in its free form and when conjugated to glycine or taurine, providing a link between glucocorticoid activation and bile acid metabolism (By similarity).
Catalyzes the synthesis of 7-beta-25-dihydroxycholesterol from 7-oxo-25-hydroxycholesterol in vitro, which acts as a ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration (By similarity).
Catalytic activity
- an 11beta-hydroxysteroid + NADP+ = an 11-oxosteroid + H+ + NADPHThis reaction proceeds in the forward and the backward directions.
- cortisone + H+ + NADPH = cortisol + NADP+This reaction proceeds in the forward and the backward directions.
- corticosterone + NADP+ = 11-dehydrocorticosterone + H+ + NADPHThis reaction proceeds in the forward and the backward directions.
- 7-oxocholesterol + H+ + NADPH = 7beta-hydroxycholesterol + NADP+This reaction proceeds in the forward direction.
- chenodeoxycholate + NADP+ = 7-oxolithocholate + H+ + NADPHThis reaction proceeds in the backward direction.
- 7-oxolithocholate + H+ + NADPH = NADP+ + ursodeoxycholateThis reaction proceeds in the forward direction.
- glycochenodeoxycholate + NADP+ = 7-oxoglycolithocholate + H+ + NADPHThis reaction proceeds in the backward direction.
- NADP+ + taurochenodeoxycholate = 7-oxotaurolithocholate + H+ + NADPHThis reaction proceeds in the backward direction.
- NADP+ + tauroursodeoxycholate = 7-oxotaurolithocholate + H+ + NADPHThis reaction proceeds in the backward direction.
- glycoursodeoxycholate + NADP+ = 7-oxoglycolithocholate + H+ + NADPHThis reaction proceeds in the backward direction.
- 7-oxopregnenolone + H+ + NADPH = 7beta-hydroxypregnenolone + NADP+This reaction proceeds in the forward direction.
- 3beta,7alpha-dihydroxyandrost-5-en-17-one + NADP+ = 3beta-hydroxy-5-androstene-7,17-dione + H+ + NADPHThis reaction proceeds in the forward direction.
- 3beta-hydroxy-5-androstene-7,17-dione + H+ + NADPH = 3beta,7beta-dihydroxyandrost-5-en-17-one + NADP+This reaction proceeds in the forward direction.
- 3beta-hydroxy-5alpha-androstane-7,17-dione + H+ + NADPH = 3beta,7beta-dihydroxy-5alpha-androstan-17-one + NADP+This reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.85 μM | cortisol | |||||
2.77 μM | cortisone | |||||
4.09 μM | cortisone |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 41-67 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GASKGIGREIAYHLAKMGAHVVVTARS | ||||||
Binding site | 92-93 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SM | ||||||
Binding site | 119-123 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: NHVLY | ||||||
Binding site | 170 | substrate | ||||
Sequence: S | ||||||
Active site | 183 | Proton acceptor | ||||
Sequence: Y | ||||||
Binding site | 183-187 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: YSASK | ||||||
Binding site | 218-222 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: IDTET |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | 7-beta-hydroxysteroid dehydrogenase (NADP+) activity | |
Molecular Function | cortisol dehydrogenase activity | |
Molecular Function | NADP binding | |
Molecular Function | protein homodimerization activity | |
Molecular Function | steroid binding | |
Biological Process | lung development | |
Biological Process | steroid catabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name11-beta-hydroxysteroid dehydrogenase 1
- EC number
- Short names11-DH; 11-beta-HSD1
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Hystricomorpha > Caviidae > Cavia
Accessions
- Primary accessionQ6QLL4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass type II membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-7 | Cytoplasmic | ||||
Sequence: MAFLKKY | ||||||
Transmembrane | 8-24 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: LLTILMVFLAYYYYSAN | ||||||
Topological domain | 25-300 | Lumenal | ||||
Sequence: EKFRPEMLQGKKVIVTGASKGIGREIAYHLAKMGAHVVVTARSKEALQKVVARCLELGAASAHYIAGSMEDMTFAEEFVAEAGNLMGGLDMLILNHVLYNRLTFFHGEIDNVRKSMEVNFHSFVVLSVAAMPMLMQSQGSIAVVSSVAGKITYPLIAPYSASKFALDGFFSTLRSEFLVNKVNVSITLCILGLIDTETAIKATSGIYLGPASPKEECALEIIKGTALRQDEMYYVGSRWVPYLLGNPGRKIMEFLSAAEYNWDNVLSNEKLYGRWA |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000054618 | 1-300 | 11-beta-hydroxysteroid dehydrogenase 1 | |||
Sequence: MAFLKKYLLTILMVFLAYYYYSANEKFRPEMLQGKKVIVTGASKGIGREIAYHLAKMGAHVVVTARSKEALQKVVARCLELGAASAHYIAGSMEDMTFAEEFVAEAGNLMGGLDMLILNHVLYNRLTFFHGEIDNVRKSMEVNFHSFVVLSVAAMPMLMQSQGSIAVVSSVAGKITYPLIAPYSASKFALDGFFSTLRSEFLVNKVNVSITLCILGLIDTETAIKATSGIYLGPASPKEECALEIIKGTALRQDEMYYVGSRWVPYLLGNPGRKIMEFLSAAEYNWDNVLSNEKLYGRWA | ||||||
Glycosylation | 207 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
PTM databases
Expression
Tissue specificity
Widely expressed in all peripheral tissues, with highest expression in liver, followed by kidney and lung, and very low expression in heart, lung, spleen, stomach, small intestine, colon, skin, skeletal muscle, and ovary.
Gene expression databases
Interaction
Structure
Sequence
- Sequence statusComplete
- Length300
- Mass (Da)33,226
- Last updated2007-01-23 v3
- Checksum8D8A9725F7A6D912
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 22 | in Ref. 1; AAF01249 | ||||
Sequence: S → P | ||||||
Sequence conflict | 103 | in Ref. 1; AAF01249 | ||||
Sequence: V → A |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF188005 EMBL· GenBank· DDBJ | AAF01249.1 EMBL· GenBank· DDBJ | mRNA | ||
AY535424 EMBL· GenBank· DDBJ | AAS47491.1 EMBL· GenBank· DDBJ | mRNA |