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Identification
HMDB Protein ID HMDBP04404
Secondary Accession Numbers
  • 9995
  • HMDBP09116
Name 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
Synonyms
  1. 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II
  2. 3-beta-HSD II
  3. 3-beta-hydroxy-5-ene steroid dehydrogenase
  4. 3-beta-hydroxy-Delta(5)-steroid dehydrogenase
  5. Delta-5-3-ketosteroid isomerase
  6. Progesterone reductase
  7. Steroid Delta-isomerase
  8. Hydroxy-delta-5-steroid dehydrogenase, 3 beta-and steroid delta-isomerase 2, isoform CRA_a
  9. 3-beta-HSD adrenal and gonadal type
Gene Name HSD3B2
Protein Type Unknown
Biological Properties
General Function Involved in 3-beta-hydroxy-delta5-steroid dehydrogenase 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.
Pathways
  • 11-beta-hydroxylase deficiency (CYP11B1)
  • 17-alpha-hydroxylase deficiency (CYP17)
  • 21-hydroxylase deficiency (CYP21)
  • 3-Beta-Hydroxysteroid Dehydrogenase Deficiency
  • Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency
  • Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency
  • Apparent mineralocorticoid excess syndrome
  • Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH
  • Corticosterone methyl oxidase I deficiency (CMO I)
  • Corticosterone methyl oxidase II deficiency - CMO II
  • steroid biosynthesis
  • Steroid hormone biosynthesis
  • Steroidogenesis
Reactions
A 3-beta-hydroxy-Delta(5)-steroid + NAD → a 3-oxo-Delta(5)-steroid + NADH details
A 3-oxo-Delta(5)-steroid → a 3-oxo-Delta(4)-steroid details
Dehydroepiandrosterone + NAD → Androstenedione + NADH + Hydrogen Ion details
Pregnenolone + NAD → Progesterone + NADH + Hydrogen Ion details
Testosterone + Hydrogen Ion + NADH → 5-Androstenediol + NAD details
Hydrocortisone + Hydrogen Ion + NADH → 11b,17a,21-Trihydroxypreg-nenolone + NAD details
17a-Hydroxypregnenolone + NAD → 17-Hydroxyprogesterone + NADH + Hydrogen Ion details
21-Hydroxypregnenolone + NAD → Deoxycorticosterone + NADH + Hydrogen Ion details
16a-Hydroxyandrost-4-ene-3,17-dione + Hydrogen Ion + NADH → 16a-Hydroxydehydroisoandrosterone + NAD details
Cortexolone + Hydrogen Ion + NADH → 17alpha,21-Dihydroxypregnenolone + NAD details
GO Classification
Biological Process
small molecule metabolic process
androgen biosynthetic process
glucocorticoid biosynthetic process
mineralocorticoid biosynthetic process
Cellular Component
integral to membrane
mitochondrial inner membrane
mitochondrial intermembrane space
smooth endoplasmic reticulum membrane
Function
binding
catalytic activity
oxidoreductase activity, acting on the ch-oh group of donors, nad or nadp as acceptor
intramolecular oxidoreductase activity, transposing c=c bonds
oxidoreductase activity, acting on ch-oh group of donors
oxidoreductase activity
isomerase activity
intramolecular oxidoreductase activity
steroid delta-isomerase activity
steroid dehydrogenase activity
steroid dehydrogenase activity, acting on the ch-oh group of donors, nad or nadp as acceptor
3-beta-hydroxy-delta5-steroid dehydrogenase activity
Molecular Function
3-beta-hydroxy-delta5-steroid dehydrogenase activity
nucleotide binding
steroid delta-isomerase activity
Process
metabolic process
cellular lipid metabolism
primary metabolism
lipid metabolism
primary metabolic process
physiological process
metabolism
lipid metabolic process
steroid metabolism
steroid biosynthesis
steroid metabolic process
steroid biosynthetic process
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Mitochondrion membrane
  3. Single-pass membrane protein
  4. Single-pass membrane protein
Gene Properties
Chromosome Location 1
Locus 1p13.1
SNPs HSD3B2
Gene Sequence
>1119 bp
ATGGGCTGGAGCTGCCTTGTGACAGGAGCAGGAGGGCTTCTGGGTCAGAGGATCGTCCGC
CTGTTGGTGGAAGAGAAGGAACTGAAGGAGATCAGGGCCTTGGACAAGGCCTTCAGACCA
GAATTGAGAGAGGAATTTTCTAAGCTCCAGAACAGGACCAAGCTGACTGTACTTGAAGGA
GACATTCTGGATGAGCCATTCCTGAAAAGAGCCTGCCAGGACGTCTCGGTCGTCATCCAC
ACCGCCTGTATCATTGATGTCTTTGGTGTCACTCACAGAGAGTCCATCATGAATGTCAAT
GTGAAAGGTACCCAGCTACTGTTGGAGGCCTGTGTCCAAGCCAGTGTGCCAGTCTTCATC
TACACCAGTAGCATAGAGGTAGCCGGGCCCAACTCCTACAAGGAAATCATCCAGAACGGC
CACGAAGAAGAGCCTCTGGAAAACACATGGCCCACTCCATACCCGTACAGCAAAAAGCTT
GCTGAGAAGGCTGTGCTGGCGGCTAATGGGTGGAATCTAAAAAATGGTGATACCTTGTAC
ACTTGTGCGTTAAGACCCACATATATCTATGGGGAAGGAGGCCCATTCCTTTCTGCCAGT
ATAAATGAGGCCCTGAACAACAATGGGATCCTGTCAAGTGTTGGAAAGTTCTCTACAGTC
AACCCAGTCTATGTTGGCAACGTGGCCTGGGCCCACATTCTGGCCTTGAGGGCTCTGCGG
GACCCCAAGAAGGCCCCAAGTGTCCGAGGTCAATTCTATTACATCTCAGATGACACGCCT
CACCAAAGCTATGATAACCTTAATTACATCCTGAGCAAAGAGTTTGGCCTCCGCCTTGAT
TCCAGATGGAGCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCTGCTGGAAGTAGTG
AGCTTCCTACTCAGCCCAATTTACTCCTATCAACCCCCCTTCAACCGCCACACAGTCACA
TTATCAAATAGTGTGTTCACCTTCTCTTACAAGAAGGCTCAGCGAGATCTGGCGTATAAG
CCACTCTACAGCTGGGAGGAAGCCAAGCAGAAAACCGTGGAGTGGGTTGGTTCCCTTGTG
GACCGGCACAAGGAGACCCTGAAGTCCAAGACTCAGTGA
Protein Properties
Number of Residues 372
Molecular Weight 42051.845
Theoretical pI 8.025
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
MGWSCLVTGAGGLLGQRIVRLLVEEKELKEIRALDKAFRPELREEFSKLQNRTKLTVLEG
DILDEPFLKRACQDVSVVIHTACIIDVFGVTHRESIMNVNVKGTQLLLEACVQASVPVFI
YTSSIEVAGPNSYKEIIQNGHEEEPLENTWPTPYPYSKKLAEKAVLAANGWNLKNGDTLY
TCALRPTYIYGEGGPFLSASINEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRALR
DPKKAPSVRGQFYYISDDTPHQSYDNLNYILSKEFGLRLDSRWSLPLTLMYWIGFLLEVV
SFLLSPIYSYQPPFNRHTVTLSNSVFTFSYKKAQRDLAYKPLYSWEEAKQKTVEWVGSLV
DRHKETLKSKTQ
GenBank ID Protein 124297709
UniProtKB/Swiss-Prot ID P26439
UniProtKB/Swiss-Prot Entry Name 3BHS2_HUMAN
PDB IDs Not Available
GenBank Gene ID M67466
GeneCard ID HSD3B2
GenAtlas ID HSD3B2
HGNC ID HGNC:5218
References
General References
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  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 ]
  4. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16899-903. Epub 2002 Dec 11. [PubMed:12477932 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. 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 ]
  22. 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 ]
  23. 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 ]
  24. 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 ]