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Identification
HMDB Protein ID HMDBP00698
Secondary Accession Numbers
  • 5971
  • HMDBP04887
Name 3-oxo-5-alpha-steroid 4-dehydrogenase 2
Synonyms
  1. 5 alpha-SR2
  2. S5AR 2
  3. SR type 2
  4. Steroid 5-alpha-reductase 2
  5. Type II 5-alpha reductase
Gene Name SRD5A2
Protein Type Enzyme
Biological Properties
General Function Involved in 3-oxo-5-alpha-steroid 4-dehydrogenase activity
Specific Function Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Pathways
  • Prostate cancer
  • Steroid hormone biosynthesis
Reactions
A 3-oxo-5-alpha-steroid + NADP → a 3-oxo-Delta(4)-steroid + NADPH details
Androstanedione + Acceptor → Androstenedione + Reduced acceptor details
Dihydrotestosterone + Acceptor → Testosterone + Reduced acceptor details
GO Classification
Biological Process
small molecule metabolic process
cell-cell signaling
cell differentiation
male gonad development
androgen biosynthetic process
Cellular Component
endoplasmic reticulum membrane
integral to membrane
Component
membrane
cell part
intracellular part
cytoplasm
membrane part
intrinsic to membrane
integral to membrane
Function
oxidoreductase activity, acting on the ch-ch group of donors
catalytic activity
steroid dehydrogenase activity, acting on the ch-ch group of donors
3-oxo-5-alpha-steroid 4-dehydrogenase activity
oxidoreductase activity
steroid dehydrogenase activity
Molecular Function
sterol 5-alpha reductase activity
3-oxo-5-alpha-steroid 4-dehydrogenase activity
cholestenone 5-alpha-reductase activity
Process
metabolic process
primary metabolic process
oxidation reduction
lipid metabolic process
steroid metabolic process
Cellular Location
  1. Multi-pass membrane protein (Potential)
  2. Endoplasmic reticulum membrane
  3. Multi-pass membrane protein
  4. Microsome membrane
Gene Properties
Chromosome Location 2
Locus 2p23
SNPs SRD5A2
Gene Sequence
>765 bp
ATGCAGGTTCAGTGCCAGCAGAGCCCAGTGCTGGCAGGCAGCGCCACTTTGGTCGCCCTT
GGGGCACTGGCCTTGTACGTCGCGAAGCCCTCCGGCTACGGGAAGCACACGGAGAGCCTG
AAGCCGGCGGCTACCCGCCTGCCAGCCCGCGCCGCCTGGTTCCTGCAGGAGCTGCCTTCC
TTCGCGGTGCCCGCGGGGATCCTCGCCCGGCAGCCCCTCTCCCTCTTCGGGCCACCTGGG
ACGGTACTTCTGGGCCTCTTCTGCGTACATTACTTCCACAGGACATTTGTGTACTCACTG
CTCAATCGAGGGAGGCCTTATCCAGCTATACTCATTCTCAGAGGCACTGCCTTCTGCACT
GGAAATGGAGTCCTTCAAGGCTACTATCTGATTTACTGTGCTGAATACCCTGATGGGTGG
TACACAGACATACGGTTTAGCTTGGGTGTCTTCTTATTTATTTTGGGAATGGGAATAAAC
ATTCATAGTGACTATATATTGCGCCAGCTCAGGAAGCCTGGAGAAATCAGCTACAGGATT
CCACAAGGTGGCTTGTTTACGTATGTTTCTGGAGCCAATTTCCTCGGTGAGATCATTGAA
TGGATCGGCTATGCCCTGGCCACTTGGTCCCTCCCAGCACTTGCATTTGCATTTTTCTCA
CTTTGTTTCCTTGGGCTGCGAGCTTTTCACCACCATAGGTTCTACCTCAAGATGTTTGAG
GACTACCCCAAATCTCGGAAAGCCCTTATTCCATTCATCTTTTAA
Protein Properties
Number of Residues 254
Molecular Weight 28407.035
Theoretical pI 9.395
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>3-oxo-5-alpha-steroid 4-dehydrogenase 2
MQVQCQQSPVLAGSATLVALGALALYVAKPSGYGKHTESLKPAATRLPARAAWFLQELPS
FAVPAGILARQPLSLFGPPGTVLLGLFCVHYFHRTFVYSLLNRGRPYPAILILRGTAFCT
GNGVLQGYYLIYCAEYPDGWYTDIRFSLGVFLFILGMGINIHSDYILRQLRKPGEISYRI
PQGGLFTYVSGANFLGEIIEWIGYALATWSLPALAFAFFSLCFLGLRAFHHHRFYLKMFE
DYPKSRKALIPFIF
GenBank ID Protein 338469
UniProtKB/Swiss-Prot ID P31213
UniProtKB/Swiss-Prot Entry Name S5A2_HUMAN
PDB IDs Not Available
GenBank Gene ID M74047
GeneCard ID SRD5A2
GenAtlas ID SRD5A2
HGNC ID HGNC:11285
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. 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 ]
  3. Andersson S, Berman DM, Jenkins EP, Russell DW: Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature. 1991 Nov 14;354(6349):159-61. [PubMed:1944596 ]
  4. Labrie F, Sugimoto Y, Luu-The V, Simard J, Lachance Y, Bachvarov D, Leblanc G, Durocher F, Paquet N: Structure of human type II 5 alpha-reductase gene. Endocrinology. 1992 Sep;131(3):1571-3. [PubMed:1505484 ]
  5. Thigpen AE, Davis DL, Milatovich A, Mendonca BB, Imperato-McGinley J, Griffin JE, Francke U, Wilson JD, Russell DW: Molecular genetics of steroid 5 alpha-reductase 2 deficiency. J Clin Invest. 1992 Sep;90(3):799-809. [PubMed:1522235 ]
  6. Boudon C, Lobaccaro JM, Lumbroso S, Ogur G, Ocal G, Belon C, Sultan C: A new deletion of the 5 alpha-reductase type 2 gene in a Turkish family with 5 alpha-reductase deficiency. Clin Endocrinol (Oxf). 1995 Aug;43(2):183-8. [PubMed:7554313 ]
  7. Cai LQ, Zhu YS, Katz MD, Herrera C, Baez J, DeFillo-Ricart M, Shackleton CH, Imperato-McGinley J: 5 alpha-reductase-2 gene mutations in the Dominican Republic. J Clin Endocrinol Metab. 1996 May;81(5):1730-5. [PubMed:8626825 ]
  8. Hochberg Z, Chayen R, Reiss N, Falik Z, Makler A, Munichor M, Farkas A, Goldfarb H, Ohana N, Hiort O: Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5 alpha-reductase 2 deficiency. J Clin Endocrinol Metab. 1996 Aug;81(8):2821-7. [PubMed:8768837 ]
  9. Anwar R, Gilbey SG, New JP, Markham AF: Male pseudohermaphroditism resulting from a novel mutation in the human steroid 5 alpha-reductase type 2 gene (SRD5A2). Mol Pathol. 1997 Feb;50(1):51-2. [PubMed:9208814 ]
  10. Nordenskjold A, Magnus O, Aagenaes O, Knudtzon J: Homozygous mutation (A228T) in the 5alpha-reductase type 2 gene in a boy with 5alpha-reductase deficiency: genotype-phenotype correlations. Am J Med Genet. 1998 Nov 16;80(3):269-72. [PubMed:9843052 ]
  11. Nordenskjold A, Ivarsson SA: Molecular characterization of 5 alpha-reductase type 2 deficiency and fertility in a Swedish family. J Clin Endocrinol Metab. 1998 Sep;83(9):3236-8. [PubMed:9745434 ]
  12. Makridakis NM, Ross RK, Pike MC, Crocitto LE, Kolonel LN, Pearce CL, Henderson BE, Reichardt JK: Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA. Lancet. 1999 Sep 18;354(9183):975-8. [PubMed:10501358 ]
  13. Vilchis F, Mendez JP, Canto P, Lieberman E, Chavez B: Identification of missense mutations in the SRD5A2 gene from patients with steroid 5alpha-reductase 2 deficiency. Clin Endocrinol (Oxf). 2000 Mar;52(3):383-7. [PubMed:10718838 ]
  14. Chavez B, Valdez E, Vilchis F: Uniparental disomy in steroid 5alpha-reductase 2 deficiency. J Clin Endocrinol Metab. 2000 Sep;85(9):3147-50. [PubMed:10999800 ]
  15. Pearce CL, Makridakis NM, Ross RK, Pike MC, Kolonel LN, Henderson BE, Reichardt JK: Steroid 5-alpha reductase type II V89L substitution is not associated with risk of prostate cancer in a multiethnic population study. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):417-8. [PubMed:11927504 ]
  16. Sasaki G, Ogata T, Ishii T, Kosaki K, Sato S, Homma K, Takahashi T, Hasegawa T, Matsuo N: Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients. J Clin Endocrinol Metab. 2003 Jul;88(7):3431-6. [PubMed:12843198 ]
  17. Loukola A, Chadha M, Penn SG, Rank D, Conti DV, Thompson D, Cicek M, Love B, Bivolarevic V, Yang Q, Jiang Y, Hanzel DK, Dains K, Paris PL, Casey G, Witte JS: Comprehensive evaluation of the association between prostate cancer and genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2. Eur J Hum Genet. 2004 Apr;12(4):321-32. [PubMed:14560315 ]
  18. Fernandez-Cancio M, Rodo J, Andaluz P, Martinez de Osaba MJ, Rodriguez-Hierro F, Esteban C, Carrascosa A, Audi L: Clinical, biochemical and morphologic diagnostic markers in an infant male pseudohermaphrodite patient with compound heterozygous mutations (G115D/R246W) in SRD5A2 gene. Horm Res. 2004;62(5):259-64. Epub 2004 Nov 2. [PubMed:15528927 ]
  19. Nicoletti A, Baldazzi L, Balsamo A, Barp L, Pirazzoli P, Gennari M, Radetti G, Cacciari E, Cicognani A: SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects. Clin Endocrinol (Oxf). 2005 Oct;63(4):375-80. [PubMed:16181229 ]
  20. Hackel C, Oliveira LE, Ferraz LF, Tonini MM, Silva DN, Toralles MB, Stuchi-Perez EG, Guerra-Junior G: New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2. J Mol Med (Berl). 2005 Jul;83(7):569-76. Epub 2005 Mar 16. [PubMed:15770495 ]
  21. Bahceci M, Ersay AR, Tuzcu A, Hiort O, Richter-Unruh A, Gokalp D: A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads to severe male pseudohermaphroditism in a Turkish family. Urology. 2005 Aug;66(2):407-10. [PubMed:16098368 ]