Corticosteroid 11-beta-dehydrogenase isozyme 1

Details

Name
Corticosteroid 11-beta-dehydrogenase isozyme 1
Synonyms
  • 1.1.1.146
  • 11-beta-HSD1
  • 11-beta-hydroxysteroid dehydrogenase 1
  • 11-DH
  • HSD11
  • HSD11L
  • SDR26C1
  • Short chain dehydrogenase/reductase family 26C member 1
Gene Name
HSD11B1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010089|Corticosteroid 11-beta-dehydrogenase isozyme 1
MAFMKKYLLPILGLFMAYYYYSANEEFRPEMLQGKKVIVTGASKGIGREMAYHLAKMGAH
VVVTARSKETLQKVVSHCLELGAASAHYIAGTMEDMTFAEQFVAQAGKLMGGLDMLILNH
ITNTSLNLFHDDIHHVRKSMEVNFLSYVVLTVAALPMLKQSNGSIVVVSSLAGKVAYPMV
AAYSASKFALDGFFSSIRKEYSVSRVNVSITLCVLGLIDTETAMKAVSGIVHMQAAPKEE
CALEIIKGGALRQEEVYYDSSLWTTLLIRNPCRKILEFLYSTSYNMDRFINK
Number of residues
292
Molecular Weight
32400.665
Theoretical pI
8.77
GO Classification
Functions
11-beta-hydroxysteroid dehydrogenase (NADP+) activity / 11-beta-hydroxysteroid dehydrogenase [NAD(P)] activity
Processes
glucocorticoid biosynthetic process / lung development / small molecule metabolic process / steroid metabolic process
Components
endoplasmic reticulum membrane / integral component of membrane / membrane
General Function
11-beta-hydroxysteroid dehydrogenase [nad(p)] activity
Specific Function
Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).
Pfam Domain Function
Transmembrane Regions
8-24
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0010090|Corticosteroid 11-beta-dehydrogenase isozyme 1 (HSD11B1)
ATGGCTTTTATGAAAAAATATCTCCTCCCCATTCTGGGGCTCTTCATGGCCTACTACTAC
TATTCTGCAAACGAGGAATTCAGACCAGAGATGCTCCAAGGAAAGAAAGTGATTGTCACA
GGGGCCAGCAAAGGGATCGGAAGAGAGATGGCTTATCATCTGGCGAAGATGGGAGCCCAT
GTGGTGGTGACAGCGAGGTCAAAAGAAACTCTACAGAAGGTGGTATCCCACTGCCTGGAG
CTTGGAGCAGCCTCAGCACACTACATTGCTGGCACCATGGAAGACATGACCTTCGCAGAG
CAATTTGTTGCCCAAGCAGGAAAGCTCATGGGAGGACTAGACATGCTCATTCTCAACCAC
ATCACCAACACTTCTTTGAATCTTTTTCATGATGATATTCACCATGTGCGCAAAAGCATG
GAAGTCAACTTCCTCAGTTACGTGGTCCTGACTGTAGCTGCCTTGCCCATGCTGAAGCAG
AGCAATGGAAGCATTGTTGTCGTCTCCTCTCTGGCTGGGAAAGTGGCTTATCCAATGGTT
GCTGCCTATTCTGCAAGCAAGTTTGCTTTGGATGGGTTCTTCTCCTCCATCAGAAAGGAA
TATTCAGTGTCCAGGGTCAATGTATCAATCACTCTCTGTGTTCTTGGCCTCATAGACACA
GAAACAGCCATGAAGGCAGTTTCTGGGATAGTCCATATGCAAGCAGCTCCAAAGGAGGAA
TGTGCCCTGGAGATCATCAAAGGGGGAGCTCTGCGCCAAGAAGAAGTGTATTATGACAGC
TCACTCTGGACCACTCTTCTGATCAGAAATCCATGCAGGAAGATCCTGGAATTTCTCTAC
TCAACGAGCTATAATATGGACAGATTCATAAACAAGTAG
Chromosome Location
1
Locus
1q32-q41
External Identifiers
ResourceLink
UniProtKB IDP28845
UniProtKB Entry NameDHI1_HUMAN
GenBank Protein ID179475
GenBank Gene IDM76665
GenAtlas IDHSD11B1
HGNC IDHGNC:5208
General References
  1. Tannin GM, Agarwal AK, Monder C, New MI, White PC: The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. J Biol Chem. 1991 Sep 5;266(25):16653-8. [PubMed:1885595]
  2. Draper N, Echwald SM, Lavery GG, Walker EA, Fraser R, Davies E, Sorensen TI, Astrup A, Adamski J, Hewison M, Connell JM, Pedersen O, Stewart PM: Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism. J Clin Endocrinol Metab. 2002 Nov;87(11):4984-90. [PubMed:12414862]
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  5. 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. [PubMed:15489334]
  6. Odermatt A, Arnold P, Stauffer A, Frey BM, Frey FJ: The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane. J Biol Chem. 1999 Oct 1;274(40):28762-70. [PubMed:10497248]
  7. Draper N, Walker EA, Bujalska IJ, Tomlinson JW, Chalder SM, Arlt W, Lavery GG, Bedendo O, Ray DW, Laing I, Malunowicz E, White PC, Hewison M, Mason PJ, Connell JM, Shackleton CH, Stewart PM: Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat Genet. 2003 Aug;34(4):434-9. [PubMed:12858176]
  8. Frick C, Atanasov AG, Arnold P, Ozols J, Odermatt A: Appropriate function of 11beta-hydroxysteroid dehydrogenase type 1 in the endoplasmic reticulum lumen is dependent on its N-terminal region sharing similar topological determinants with 50-kDa esterase. J Biol Chem. 2004 Jul 23;279(30):31131-8. Epub 2004 May 19. [PubMed:15152005]
  9. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  10. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  11. Hosfield DJ, Wu Y, Skene RJ, Hilgers M, Jennings A, Snell GP, Aertgeerts K: Conformational flexibility in crystal structures of human 11beta-hydroxysteroid dehydrogenase type I provide insights into glucocorticoid interconversion and enzyme regulation. J Biol Chem. 2005 Feb 11;280(6):4639-48. Epub 2004 Oct 28. [PubMed:15513927]
  12. Sorensen B, Winn M, Rohde J, Shuai Q, Wang J, Fung S, Monzon K, Chiou W, Stolarik D, Imade H, Pan L, Deng X, Chovan L, Longenecker K, Judge R, Qin W, Brune M, Camp H, Frevert EU, Jacobson P, Link JT: Adamantane sulfone and sulfonamide 11-beta-HSD1 Inhibitors. Bioorg Med Chem Lett. 2007 Jan 15;17(2):527-32. Epub 2006 Oct 7. [PubMed:17070044]
  13. Yuan C, St Jean DJ Jr, Liu Q, Cai L, Li A, Han N, Moniz G, Askew B, Hungate RW, Johansson L, Tedenborg L, Pyring D, Williams M, Hale C, Chen M, Cupples R, Zhang J, Jordan S, Bartberger MD, Sun Y, Emery M, Wang M, Fotsch C: The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25. [PubMed:17919905]
  14. Wang H, Ruan Z, Li JJ, Simpkins LM, Smirk RA, Wu SC, Hutchins RD, Nirschl DS, Van Kirk K, Cooper CB, Sutton JC, Ma Z, Golla R, Seethala R, Salyan ME, Nayeem A, Krystek SR Jr, Sheriff S, Camac DM, Morin PE, Carpenter B, Robl JA, Zahler R, Gordon DA, Hamann LG: Pyridine amides as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3168-72. doi: 10.1016/j.bmcl.2008.04.069. Epub 2008 May 1. [PubMed:18485702]
  15. Hale C, Veniant M, Wang Z, Chen M, McCormick J, Cupples R, Hickman D, Min X, Sudom A, Xu H, Matsumoto G, Fotsch C, St Jean DJ Jr, Wang M: Structural characterization and pharmacodynamic effects of an orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor. Chem Biol Drug Des. 2008 Jan;71(1):36-44. Epub 2007 Dec 7. [PubMed:18069989]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB02329CarbenoxoloneexperimentalunknowninhibitorDetails
DB03461Nicotinamide adenine dinucleotide phosphateexperimentalunknownDetails
DB038142-(N-morpholino)ethanesulfonic acidexperimentalunknownDetails
DB05064INCB13739investigationalunknownDetails
DB06992(3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanoneexperimentalunknownDetails
DB07017(5S)-2-{[(1S)-1-(4-Fluorophenyl)ethyl]amino}-5-(2-hydroxy-2-propanyl)-5-methyl-1,3-thiazol-4(5H)-oneexperimentalunknownDetails
DB07049(2R)-1-[(4-tert-butylphenyl)sulfonyl]-2-methyl-4-(4-nitrophenyl)piperazineexperimentalunknownDetails
DB070562-(6-{[(3-chloro-2-methylphenyl)sulfonyl]amino}pyridin-2-yl)-N,N-diethylacetamideexperimentalunknownDetails
DB07310(5S)-2-{[(1S)-1-(2-fluorophenyl)ethyl]amino}-5-methyl-5-(trifluoromethyl)-1,3-thiazol-4(5H)-oneexperimentalunknownDetails
DB07316N-{1-[(1-carbamoylcyclopropyl)methyl]piperidin-4-yl}-N-cyclopropyl-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]benzamideexperimentalunknownDetails
DB04652CorticosteroneexperimentalunknownDetails
DB07619N-cyclopropyl-N-(trans-4-pyridin-3-ylcyclohexyl)-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]benzamideexperimentalunknownDetails
DB076241-{[(3R)-3-methyl-4-({4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]phenyl}sulfonyl)piperazin-1-yl]methyl}cyclopropanecarboxamideexperimentalunknownDetails
DB07866(5S)-2-(Cyclooctylamino)-5-methyl-5-propyl-1,3-thiazol-4(5H)-oneexperimentalunknownDetails
DB082772-(2-CHLORO-4-FLUOROPHENOXY)-2-METHYL-N-[(1R,2S,3S,5S,7S)-5-(METHYLSULFONYL)-2-ADAMANTYL]PROPANAMIDEexperimentalunknownDetails
DB08280(1S,3R,4S,5S,7S)-4-{[2-(4-METHOXYPHENOXY)-2-METHYLPROPANOYL]AMINO}ADAMANTANE-1-CARBOXAMIDEexperimentalunknownDetails
DB08771(5R)-2-[(2-Fluorophenyl)amino]-5-isopropyl-1,3-thiazol-4(5H)-oneexperimentalunknownDetails
DB13751Glycyrrhizic acidapproved, experimentalyesantagonistDetails
DB00461NabumetoneapprovedunknownsubstrateDetails
DB00687Fludrocortisoneapproved, investigationalunknownsubstrateDetails
DB00635Prednisoneapproved, vet_approvedunknownsubstrateDetails
DB00741Hydrocortisoneapproved, vet_approvedunknownsubstrateDetails
DB01234Dexamethasoneapproved, investigational, vet_approvedunknownsubstrateDetails
DB00959Methylprednisoloneapproved, vet_approvedunknownDetails