11-beta-hydroxysteroid dehydrogenase type 2

UniProt P80365 Organism Homo sapiens Gene HSD11B2, HSD11K, SDR9C3 EC 1.1.1.-

Also known as: HSD11B2, HSD11K, SDR9C3

Function

Catalyzes the conversion of biologically active 11beta-hydroxyglucocorticoids (11beta-hydroxysteroid) such as cortisol, to inactive 11-ketoglucocorticoids (11-oxosteroid) such as cortisone, in the presence of NAD(+). Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. Plays an important role in maintaining glucocorticoids balance during preimplantation and protects the fetus from excessive maternal corticosterone exposure (By similarity). Catalyzes the oxidation of 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one) to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), a major bioactive androgen. Catalyzes the conversion of 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione) to 11-ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be further metabolized to 11-ketotestosterone. Converts 7-beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro. 7-beta-25-dihydroxycholesterol (not 7-oxo-25-hydroxycholesterol) 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. May protect ovulating oocytes and fertilizing spermatozoa from the adverse effects of cortisol (By similarity). Catalyzes the conversion of 7-beta-hydroxycholesterol into 7-ketocholesterol (7-oxocholesterol), a precursor of 7-keto,27-hydroxycholesterol, which activates smoothened (SMO) and the smoothened signaling pathway (By similarity).

Classification

Family (Pfam): PF00106 adh_short
InterPro: NAD(P)-bd_dom_sf, Sc_DH/Rdtase_CS, SDR_fam
Functional cluster: Secreted Growth Factors & Cytokines

Gene Ontology · 13

Disease associations

apparent mineralocorticoid excess MONDO:0009025

Drugs targeting this protein · 1

CARBENOXOLONE inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

11-beta-hydroxysteroid dehydrogenase type 2 3 shared papers
11-beta-hydroxysteroid dehydrogenase 1 4 shared papers
11-beta-hydroxysteroid dehydrogenase type 2 2 shared papers
Mineralocorticoid receptor 1 shared papers
11-beta-hydroxysteroid dehydrogenase 1 1 shared papers
3-oxo-5-alpha-steroid 4-dehydrogenase 2 1 shared papers
17-beta-hydroxysteroid dehydrogenase type 3 1 shared papers
17-beta-hydroxysteroid dehydrogenase type 3 1 shared papers
3-oxo-5-alpha-steroid 4-dehydrogenase 1 1 shared papers
Cytochrome P450 11B2, mitochondrial 1 shared papers
Cytochrome P450 11B1, mitochondrial 1 shared papers

Literature · 27 cited papers

Species-specific differences in the inhibition of 11beta-hydroxysteroid dehydrogenase 2 by itraconazole and posaconazole. Toxicol. Appl. Pharmacol. · 2021
Enzymatic interconversion of the oxysterols 7beta,25-dihydroxycholesterol and 7-keto,25-hydroxycholesterol by 11beta-hydroxysteroid dehydrogenase type 1 and 2. J. Steroid Biochem. Mol. Biol. · 2019
Absence of 11-keto reduction of cortisone and 11-ketotestosterone in the model organism zebrafish. J. Endocrinol. · 2017
11beta-hydroxyandrostenedione, the product of androstenedione metabolism in the adrenal, is metabolized in LNCaP cells by 5alpha-reductase yielding 11beta-hydroxy-5alpha-androstanedione. J. Steroid Biochem. Mol. Biol. · 2013
Species-specific differences in the inhibition of human and zebrafish 11beta-hydroxysteroid dehydrogenase 2 by thiram and organotins. Toxicology · 2012
Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess. J. Am. Soc. Nephrol. · 2007
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. J. Clin. Endocrinol. Metab. · 2003
The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2. J. Biol. Chem. · 2001
A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension. J. Clin. Endocrinol. Metab. · 2001
Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess. Hypertension · 1999
The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane. J. Biol. Chem. · 1999
… and 15 more in the literature graph

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