3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2

Details

Name
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
Synonyms
  • 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II
  • 3-beta-HSD adrenal and gonadal type
  • 3-beta-HSD II
  • HSDB3B
Gene Name
HSD3B2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036946|3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
MGWSCLVTGAGGLLGQRIVRLLVEEKELKEIRALDKAFRPELREEFSKLQNRTKLTVLEG
DILDEPFLKRACQDVSVVIHTACIIDVFGVTHRESIMNVNVKGTQLLLEACVQASVPVFI
YTSSIEVAGPNSYKEIIQNGHEEEPLENTWPTPYPYSKKLAEKAVLAANGWNLKNGDTLY
TCALRPTYIYGEGGPFLSASINEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRALR
DPKKAPSVRGQFYYISDDTPHQSYDNLNYILSKEFGLRLDSRWSLPLTLMYWIGFLLEVV
SFLLSPIYSYQPPFNRHTVTLSNSVFTFSYKKAQRDLAYKPLYSWEEAKQKTVEWVGSLV
DRHKETLKSKTQ
Number of residues
372
Molecular Weight
42051.845
Theoretical pI
8.17
GO Classification
Functions
3-beta-hydroxy-delta5-steroid dehydrogenase activity / steroid delta-isomerase activity
Processes
androgen biosynthetic process / glucocorticoid biosynthetic process / mineralocorticoid biosynthetic process / small molecule metabolic process / steroid biosynthetic process / steroid metabolic process
Components
endoplasmic reticulum / endoplasmic reticulum membrane / integral component of membrane / mitochondrial inner membrane / mitochondrial intermembrane space / mitochondrial membrane / smooth endoplasmic reticulum membrane
General Function
Steroid delta-isomerase activity
Specific Function
3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.
Pfam Domain Function
Transmembrane Regions
287-307
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0009908|3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2)
ATGGGCTGGAGCTGCCTTGTGACAGGAGCAGGAGGGCTTCTGGGTCAGAGGATCGTCCGC
CTGTTGGTGGAAGAGAAGGAACTGAAGGAGATCAGGGCCTTGGACAAGGCCTTCAGACCA
GAATTGAGAGAGGAATTTTCTAAGCTCCAGAACAGGACCAAGCTGACTGTACTTGAAGGA
GACATTCTGGATGAGCCATTCCTGAAAAGAGCCTGCCAGGACGTCTCGGTCGTCATCCAC
ACCGCCTGTATCATTGATGTCTTTGGTGTCACTCACAGAGAGTCCATCATGAATGTCAAT
GTGAAAGGTACCCAGCTACTGTTGGAGGCCTGTGTCCAAGCCAGTGTGCCAGTCTTCATC
TACACCAGTAGCATAGAGGTAGCCGGGCCCAACTCCTACAAGGAAATCATCCAGAACGGC
CACGAAGAAGAGCCTCTGGAAAACACATGGCCCACTCCATACCCGTACAGCAAAAAGCTT
GCTGAGAAGGCTGTGCTGGCGGCTAATGGGTGGAATCTAAAAAATGGTGATACCTTGTAC
ACTTGTGCGTTAAGACCCACATATATCTATGGGGAAGGAGGCCCATTCCTTTCTGCCAGT
ATAAATGAGGCCCTGAACAACAATGGGATCCTGTCAAGTGTTGGAAAGTTCTCTACAGTC
AACCCAGTCTATGTTGGCAACGTGGCCTGGGCCCACATTCTGGCCTTGAGGGCTCTGCGG
GACCCCAAGAAGGCCCCAAGTGTCCGAGGTCAATTCTATTACATCTCAGATGACACGCCT
CACCAAAGCTATGATAACCTTAATTACATCCTGAGCAAAGAGTTTGGCCTCCGCCTTGAT
TCCAGATGGAGCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCTGCTGGAAGTAGTG
AGCTTCCTACTCAGCCCAATTTACTCCTATCAACCCCCCTTCAACCGCCACACAGTCACA
TTATCAAATAGTGTGTTCACCTTCTCTTACAAGAAGGCTCAGCGAGATCTGGCGTATAAG
CCACTCTACAGCTGGGAGGAAGCCAAGCAGAAAACCGTGGAGTGGGTTGGTTCCCTTGTG
GACCGGCACAAGGAGACCCTGAAGTCCAAGACTCAGTGA
Chromosome Location
1
Locus
1p13.1
External Identifiers
ResourceLink
UniProtKB IDP26439
UniProtKB Entry Name3BHS2_HUMAN
GenBank Protein ID184401
GenBank Gene IDM67466
GenAtlas IDHSD3B2
HGNC IDHGNC:5218
General References
  1. Lachance Y, Luu-The V, Verreault H, Dumont M, Rheaume E, Leblanc G, Labrie F: Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) gene: adrenal and gonadal specificity. DNA Cell Biol. 1991 Dec;10(10):701-11. [PubMed:1741954]
  2. Rheaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu-The V, Simard J, Labrie F: Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads. Mol Endocrinol. 1991 Aug;5(8):1147-57. [PubMed:1944309]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005]
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  6. Russell AJ, McCartin S, Corcao G, Burridge SM, McBride MW, McNicol AM, Hawes CS, Mason JI, Sutcliffe RG: Variation in the expression of human 3 beta-hydroxysteroid dehydrogenase. Endocr Res. 1995 Feb-May;21(1-2):485-94. [PubMed:7588414]
  7. Rheaume E, Simard J, Morel Y, Mebarki F, Zachmann M, Forest MG, New MI, Labrie F: Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene. Nat Genet. 1992 Jul;1(4):239-45. [PubMed:1363812]
  8. Carbunaru G, Prasad P, Scoccia B, Shea P, Hopwood N, Ziai F, Chang YT, Myers SE, Mason JI, Pang S: The hormonal phenotype of Nonclassic 3 beta-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females is associated with insulin-resistant polycystic ovary syndrome and is not a variant of inherited HSD3B2 deficiency. J Clin Endocrinol Metab. 2004 Feb;89(2):783-94. [PubMed:14764797]
  9. Simard J, Rheaume E, Sanchez R, Laflamme N, de Launoit Y, Luu-The V, van Seters AP, Gordon RD, Bettendorf M, Heinrich U, et al.: Molecular basis of congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency. Mol Endocrinol. 1993 May;7(5):716-28. [PubMed:8316254]
  10. Sanchez R, Mebarki F, Rheaume E, Laflamme N, Forest MG, Bey-Omard F, David M, Morel Y, Labrie F, Simard J: Functional characterization of the novel L108W and P186L mutations detected in the type II 3 beta-hydroxysteroid dehydrogenase gene of a male pseudohermaphrodite with congenital adrenal hyperplasia. Hum Mol Genet. 1994 Sep;3(9):1639-45. [PubMed:7833923]
  11. Sanchez R, Rheaume E, Laflamme N, Rosenfield RL, Labrie F, Simard J: Detection and functional characterization of the novel missense mutation Y254D in type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene of a female patient with nonsalt-losing 3 beta HSD deficiency. J Clin Endocrinol Metab. 1994 Mar;78(3):561-7. [PubMed:8126127]
  12. Rheaume E, Sanchez R, Simard J, Chang YT, Wang J, Pang S, Labrie F: Molecular basis of congenital adrenal hyperplasia in two siblings with classical nonsalt-losing 3 beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 1994 Oct;79(4):1012-8. [PubMed:7962268]
  13. Mendonca BB, Russell AJ, Vasconcelos-Leite M, Arnhold IJ, Bloise W, Wajchenberg BL, Nicolau W, Sutcliffe RG, Wallace AM: Mutation in 3 beta-hydroxysteroid dehydrogenase type II associated with pseudohermaphroditism in males and premature pubarche or cryptic expression in females. J Mol Endocrinol. 1994 Feb;12(1):119-22. [PubMed:8185809]
  14. Russell AJ, Wallace AM, Forest MG, Donaldson MD, Edwards CR, Sutcliffe RG: Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss. J Mol Endocrinol. 1994 Apr;12(2):225-37. [PubMed:8060486]
  15. Rheaume E, Sanchez R, Mebarki F, Gagnon E, Carel JC, Chaussain JL, Morel Y, Labrie F, Simard J: Identification and characterization of the G15D mutation found in a male patient with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency: alteration of the putative NAD-binding domain of type II 3 beta-HSD. Biochemistry. 1995 Mar 7;34(9):2893-900. [PubMed:7893703]
  16. Katsumata N, Tanae A, Yasunaga T, Horikawa R, Tanaka T, Hibi I: A novel missense mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene in a family with classical salt-wasting congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency. Hum Mol Genet. 1995 Apr;4(4):745-6. [PubMed:7633426]
  17. Tajima T, Fujieda K, Nakae J, Shinohara N, Yoshimoto M, Baba T, Kinoshita E, Igarashi Y, Oomura T: Molecular analysis of type II 3 beta-hydroxysteroid dehydrogenase gene in Japanese patients with classical 3 beta-hydroxysteroid dehydrogenase deficiency. Hum Mol Genet. 1995 May;4(5):969-71. [PubMed:7633460]
  18. Mebarki F, Sanchez R, Rheaume E, Laflamme N, Simard J, Forest MG, Bey-Omar F, David M, Labrie F, Morel Y: Nonsalt-losing male pseudohermaphroditism due to the novel homozygous N100S mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene. J Clin Endocrinol Metab. 1995 Jul;80(7):2127-34. [PubMed:7608265]
  19. Nayak S, Lee PA, Witchel SF: Variants of the type II 3beta-hydroxysteroid dehydrogenase gene in children with premature pubic hair and hyperandrogenic adolescents. Mol Genet Metab. 1998 Jul;64(3):184-92. [PubMed:9719627]
  20. Moisan AM, Ricketts ML, Tardy V, Desrochers M, Mebarki F, Chaussain JL, Cabrol S, Raux-Demay MC, Forest MG, Sippell WG, Peter M, Morel Y, Simard J: New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. J Clin Endocrinol Metab. 1999 Dec;84(12):4410-25. [PubMed:10599696]
  21. Marui S, Castro M, Latronico AC, Elias LL, Arnhold IJ, Moreira AC, Mendonca BB: Mutations in the type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature pubarche in girls. Clin Endocrinol (Oxf). 2000 Jan;52(1):67-75. [PubMed:10651755]
  22. Alos N, Moisan AM, Ward L, Desrochers M, Legault L, Leboeuf G, Van Vliet G, Simard J: A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-wasting 3beta-hydroxysteroid dehydrogenase deficiency in 46,XX and 46,XY French-Canadians: evaluation of gonadal function after puberty. J Clin Endocrinol Metab. 2000 May;85(5):1968-74. [PubMed:10843183]
  23. Pang S, Wang W, Rich B, David R, Chang YT, Carbunaru G, Myers SE, Howie AF, Smillie KJ, Mason JI: A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2002 Jun;87(6):2556-63. [PubMed:12050213]
  24. Welzel M, Wustemann N, Simic-Schleicher G, Dorr HG, Schulze E, Shaikh G, Clayton P, Grotzinger J, Holterhus PM, Riepe FG: Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2008 Apr;93(4):1418-25. doi: 10.1210/jc.2007-1874. Epub 2008 Feb 5. [PubMed:18252794]
  25. Rabbani B, Mahdieh N, Haghi Ashtiani MT, Setoodeh A, Rabbani A: In silico structural, functional and pathogenicity evaluation of a novel mutation: an overview of HSD3B2 gene mutations. Gene. 2012 Jul 25;503(2):215-21. doi: 10.1016/j.gene.2012.04.080. Epub 2012 May 8. [PubMed:22579964]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB01108Trilostaneapproved, investigational, vet_approved, withdrawnyesinhibitorDetails
DB00603Medroxyprogesterone acetateapproved, investigationalunknowninhibitorDetails
DB01285Corticotropinapproved, investigational, vet_approvedunknowninducerDetails
DB09070Tiboloneapproved, investigationalyessubstrateDetails