11-beta-hydroxysteroid dehydrogenase type 2

Details

Name
11-beta-hydroxysteroid dehydrogenase type 2
Synonyms
  • 1.1.1.-
  • 11-beta-HSD type II
  • 11-beta-HSD2
  • 11-beta-hydroxysteroid dehydrogenase type II
  • 11-DH2
  • 11-HSD type II
  • Corticosteroid 11-beta-dehydrogenase isozyme 2
  • HSD11K
  • NAD-dependent 11-beta-hydroxysteroid dehydrogenase
  • SDR9C3
  • Short chain dehydrogenase/reductase family 9C member 3
Gene Name
HSD11B2
UniProtKB Entry
P80365Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0009955|11-beta-hydroxysteroid dehydrogenase type 2
MERWPWPSGGAWLLVAARALLQLLRSDLRLGRPLLAALALLAALDWLCQRLLPPPAALAV
LAAAGWIALSRLARPQRLPVATRAVLITGCDSGFGKETAKKLDSMGFTVLATVLELNSPG
AIELRTCCSPRLRLLQMDLTKPGDISRVLEFTKAHTTSTGLWGLVNNAGHNEVVADAELS
PVATFRSCMEVNFFGALELTKGLLPLLRSSRGRIVTVGSPAGDMPYPCLGAYGTSKAAVA
LLMDTFSCELLPWGVKVSIIQPGCFKTESVRNVGQWEKRKQLLLANLPQELLQAYGKDYI
EHLHGQFLHSLRLAMSDLTPVVDAITDALLAARPRRRYYPGQGLGLMYFIHYYLPEGLRR
RFLQAFFISHCLPRALQPGQPGTTPPQDAAQDPNLSPGPSPAVAR
Number of residues
405
Molecular Weight
44126.06
Theoretical pI
9.58
GO Classification
Functions
11-beta-hydroxysteroid dehydrogenase (NAD+) activity
Processes
cortisol metabolic process / glucocorticoid metabolic process / response to xenobiotic stimulus
Components
intracellular membrane-bounded organelle
General 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(+) (PubMed:10497248, PubMed:12788846, PubMed:17314322, PubMed:22796344, PubMed:27927697, PubMed:30902677, PubMed:33387577, PubMed:7859916, PubMed:8538347). Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids (PubMed:10497248, PubMed:12788846, PubMed:17314322, PubMed:33387577, PubMed:7859916). 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 (PubMed:22796344, PubMed:27927697). 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 (PubMed:27927697). Converts 7-beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro (PubMed:30902677). 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 (PubMed:30902677). May protect ovulating oocytes and fertilizing spermatozoa from the adverse effects of cortisol (By similarity)
Specific Function
11-beta-hydroxysteroid dehydrogenase (nad+) activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Microsome
Gene sequence
>lcl|BSEQ0009956|Corticosteroid 11-beta-dehydrogenase isozyme 2 (HSD11B2)
ATGGAGCGCTGGCCTTGGCCGTCGGGCGGCGCCTGGCTGCTCGTGGCTGCCCGCGCGCTG
CTGCAGCTGCTGCGCTCAGACCTGCGTCTGGGCCGCCCGCTGCTGGCGGCGCTGGCGCTG
CTGGCCGCGCTCGACTGGCTGTGCCAGCGCCTGCTGCCCCCGCCGGCCGCACTCGCCGTG
CTGGCCGCCGCCGGCTGGATCGCGTTGTCCCGCCTGGCGCGCCCGCAGCGCCTGCCGGTG
GCCACTCGCGCGGTGCTCATCACCGGCTGTGACTCTGGTTTTGGCAAGGAGACGGCCAAG
AAACTGGACTCCATGGGCTTCACGGTGCTGGCCACCGTATTGGAGTTGAACAGCCCCGGT
GCCATCGAGCTGCGTACCTGCTGCTCCCCTCGCCTAAGGCTGCTGCAGATGGACCTGACC
AAACCAGGAGACATTAGCCGCGTGCTAGAGTTCACCAAGGCCCACACCACCAGCACCGGC
CTGTGGGGCCTCGTCAACAACGCAGGCCACAATGAAGTAGTTGCTGATGCGGAGCTGTCT
CCAGTGGCCACTTTCCGTAGCTGCATGGAGGTGAATTTCTTTGGCGCGCTCGAGCTGACC
AAGGGCCTCCTGCCCCTGCTGCGCAGCTCAAGGGGCCGCATCGTGACTGTGGGGAGCCCA
GCGGGGGACATGCCATATCCGTGCTTGGGGGCCTATGGAACCTCCAAAGCGGCCGTGGCG
CTACTCATGGACACATTCAGCTGTGAACTCCTTCCCTGGGGGGTCAAGGTCAGCATCATC
CAGCCTGGCTGCTTCAAGACAGAGTCAGTGAGAAACGTGGGTCAGTGGGAAAAGCGCAAG
CAATTGCTGCTGGCCAACCTGCCTCAAGAGCTGCTGCAGGCCTACGGCAAGGACTACATC
GAGCACTTGCATGGGCAGTTCCTGCACTCGCTACGCCTGGCCATGTCCGACCTCACCCCA
GTTGTAGATGCCATCACAGATGCGCTGCTGGCAGCTCGGCCCCGCCGCCGCTATTACCCC
GGCCAGGGCCTGGGGCTCATGTACTTCATCCACTACTACCTGCCTGAAGGCCTGCGGCGC
CGCTTCCTGCAGGCCTTCTTCATCAGTCACTGTCTGCCTCGAGCACTGCAGCCTGGCCAG
CCTGGCACTACCCCACCACAGGACGCAGCCCAGGACCCAAACCTGAGCCCCGGCCCTTCC
CCAGCAGTGGCTCGGTGA
Chromosome Location
16
Locus
16q22.1
External Identifiers
ResourceLink
UniProtKB IDP80365
UniProtKB Entry NameDHI2_HUMAN
GenBank Protein ID565082
GenBank Gene IDU14631
GeneCard IDHSD11B2
GenAtlas IDHSD11B2
HGNC IDHGNC:5209
KEGG IDhsa:3291
IUPHAR/Guide To Pharmacology ID3143
NCBI Gene ID3291
General References
  1. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS: Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol. 1994 Nov;105(2):R11-7. [Article]
  2. Agarwal AK, Rogerson FM, Mune T, White PC: Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase. Genomics. 1995 Sep 1;29(1):195-9. [Article]
  3. Brown RW, Chapman KE, Kotelevtsev Y, Yau JL, Lindsay RS, Brett L, Leckie C, Murad P, Lyons V, Mullins JJ, Edwards CR, Seckl JR: Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2. Biochem J. 1996 Feb 1;313 ( Pt 3):1007-17. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Brown RW, Chapman KE, Murad P, Edwards CR, Seckl JR: Purification of 11 beta-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique. Biochem J. 1996 Feb 1;313 ( Pt 3):997-1005. [Article]
  6. Wilson RC, Harbison MD, Krozowski ZS, Funder JW, Shackleton CH, Hanauske-Abel HM, Wei JQ, Hertecant J, Moran A, Neiberger RE, et al.: Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1995 Nov;80(11):3145-50. [Article]
  7. Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CH, Edwards CR: Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet. 1987 Oct 10;2(8563):821-4. [Article]
  8. Odermatt A, Arnold P, Frey FJ: The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2. J Biol Chem. 2001 Jul 27;276(30):28484-92. Epub 2001 May 11. [Article]
  9. Wilson RC, Krozowski ZS, Li K, Obeyesekere VR, Razzaghy-Azar M, Harbison MD, Wei JQ, Shackleton CH, Funder JW, New MI: A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1995 Jul;80(7):2263-6. [Article]
  10. Mune T, Rogerson FM, Nikkila H, Agarwal AK, White PC: Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase. Nat Genet. 1995 Aug;10(4):394-9. [Article]
  11. Kitanaka S, Katsumata N, Tanae A, Hibi I, Takeyama K, Fuse H, Kato S, Tanaka T: A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1997 Dec;82(12):4054-8. [Article]
  12. Li A, Tedde R, Krozowski ZS, Pala A, Li KX, Shackleton CH, Mantero F, Palermo M, Stewart PM: Molecular basis for hypertension in the "type II variant" of apparent mineralocorticoid excess. Am J Hum Genet. 1998 Aug;63(2):370-9. [Article]
  13. Dave-Sharma S, Wilson RC, Harbison MD, Newfield R, Azar MR, Krozowski ZS, Funder JW, Shackleton CH, Bradlow HL, Wei JQ, Hertecant J, Moran A, Neiberger RE, Balfe JW, Fattah A, Daneman D, Akkurt HI, De Santis C, New MI: Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1998 Jul;83(7):2244-54. [Article]
  14. Rogoff D, Smolenicka Z, Bergada I, Vallejo G, Barontini M, Heinrich JJ, Ferrari P: The codon 213 of the 11beta-hydroxysteroid dehydrogenase type 2 gene is a hot spot for mutations in apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1998 Dec;83(12):4391-3. [Article]
  15. Wilson RC, Dave-Sharma S, Wei JQ, Obeyesekere VR, Li K, Ferrari P, Krozowski ZS, Shackleton CH, Bradlow L, Wiens T, New MI: A genetic defect resulting in mild low-renin hypertension. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10200-5. [Article]
  16. Morineau G, Marc JM, Boudi A, Galons H, Gourmelen M, Corvol P, Pascoe L, Fiet J: Genetic, biochemical, and clinical studies of patients with A328V or R213C mutations in 11betaHSD2 causing apparent mineralocorticoid excess. Hypertension. 1999 Sep;34(3):435-41. [Article]
  17. Nunez BS, Rogerson FM, Mune T, Igarashi Y, Nakagawa Y, Phillipov G, Moudgil A, Travis LB, Palermo M, Shackleton C, White PC: Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess. Hypertension. 1999 Oct;34(4 Pt 1):638-42. [Article]
  18. Odermatt A, Dick B, Arnold P, Zaehner T, Plueschke V, Deregibus MN, Repetto H, Frey BM, Frey FJ, Ferrari P: A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension. J Clin Endocrinol Metab. 2001 Mar;86(3):1247-52. [Article]
  19. Carvajal CA, Gonzalez AA, Romero DG, Gonzalez A, Mosso LM, Lagos ET, Hevia Mdel P, Rosati MP, Perez-Acle TO, Gomez-Sanchez CE, Montero JA, Fardella CE: Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. J Clin Endocrinol Metab. 2003 Jun;88(6):2501-7. [Article]
  20. Atanasov AG, Ignatova ID, Nashev LG, Dick B, Ferrari P, Frey FJ, Odermatt A: Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess. J Am Soc Nephrol. 2007 Apr;18(4):1262-70. Epub 2007 Feb 21. [Article]

Associated Data

Bio-Entities
Bio-EntityType
11-beta-hydroxysteroid dehydrogenase type 2 (Humans)protein
primary
11beta-hydroxysteroid dehydrogenase (Humans and other mammals)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
NADHapproved, nutraceuticalunknowntargetDetails
Formeboloneexperimental, illicitunknowntargetinhibitorDetails
Fluoxymesteroneapproved, illicitunknowntargetinhibitorDetails
Hydrocortisone aceponateexperimental, vet_approvedunknowntargetDetails
Hydrocortisone acetateapproved, vet_approvedunknowntargetDetails
Hydrocortisone butyrateapproved, vet_approvedunknowntargetDetails
Hydrocortisone cypionateapproved, investigational, vet_approvedunknowntargetDetails
Hydrocortisone phosphateapproved, vet_approvedunknowntargetDetails
Hydrocortisone probutateapproved, vet_approvedunknowntargetDetails
Hydrocortisone valerateapproved, vet_approvedunknowntargetDetails
Fludrocortisoneapproved, investigationalunknownenzymesubstrateDetails
Hydrocortisoneapproved, vet_approvedunknownenzymesubstrateDetails
Dexamethasoneapproved, investigational, vet_approvedunknownenzymesubstrateDetails
Prednisolone phosphateapproved, vet_approvedunknownenzymesubstrateDetails
Dexamethasone acetateapproved, investigational, vet_approvedunknownenzymesubstrateDetails
CorticosteroneexperimentalnoenzymesubstrateDetails
Methylprednisoloneapproved, vet_approvedunknownenzymeDetails