Estradiol 17-beta-dehydrogenase 1

Details

Name
Estradiol 17-beta-dehydrogenase 1
Synonyms
  • 1.1.1.62
  • 17-beta-HSD 1
  • 17-beta-hydroxysteroid dehydrogenase type 1
  • 20 alpha-hydroxysteroid dehydrogenase
  • 20-alpha-HSD
  • E17KSR
  • E2DH
  • EDH17B1
  • EDH17B2
  • EDHB17
  • Placental 17-beta-hydroxysteroid dehydrogenase
  • SDR28C1
  • Short chain dehydrogenase/reductase family 28C member 1
Gene Name
HSD17B1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009997|Estradiol 17-beta-dehydrogenase 1
MARTVVLITGCSSGIGLHLAVRLASDPSQSFKVYATLRDLKTQGRLWEAARALACPPGSL
ETLQLDVRDSKSVAAARERVTEGRVDVLVCNAGLGLLGPLEALGEDAVASVLDVNVVGTV
RMLQAFLPDMKRRGSGRVLVTGSVGGLMGLPFNDVYCASKFALEGLCESLAVLLLPFGVH
LSLIECGPVHTAFMEKVLGSPEEVLDRTDIHTFHRFYQYLAHSKQVFREAAQNPEEVAEV
FLTALRAPKPTLRYFTTERFLPLLRMRLDDPSGSNYVTAMHREVFGDVPAKAEAGAEAGG
GAGPGAEDEAGRGAVGDPELGDPPAAPQ
Number of residues
328
Molecular Weight
34949.715
Theoretical pI
5.42
GO Classification
Functions
catalytic activity / estradiol 17-beta-dehydrogenase activity / testosterone dehydrogenase (NAD+) activity
Processes
bone development / cellular response to metal ion / estrogen biosynthetic process / estrogen metabolic process / small molecule metabolic process / steroid biosynthetic process / steroid metabolic process / testosterone biosynthetic process
Components
cytoplasm / cytosol / nuclear membrane / nucleoplasm
General Function
Testosterone dehydrogenase (nad+) activity
Specific Function
Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0009998|Estradiol 17-beta-dehydrogenase 1 (HSD17B1)
ATGGCCCGCACCGTGGTGCTCATCACCGGCTGTTCCTCGGGCATCGGCCTGCACTTGGCC
GTACGTCTGGCTTCAGATCCATCCCAGAGCTTCAAAGTGTATGCCACGTTGAGGGACCTG
AAAACACAGGGCCGGCTGTGGGAGGCGGCCCGGGCCCTGGCATGCCCTCCGGGATCCCTG
GAGACGTTGCAGCTGGACGTAAGGGACTCAAAATCCGTGGCCGCTGCCCGGGAACGCGTG
ACTGAGGGCCGCGTGGACGTGCTGGTGTGTAACGCAGGCCTGGGCCTGCTGGGGCCGCTG
GAGGCGCTGGGGGAGGACGCCGTGGCCTCTGTGCTGGACGTGAATGTAGTAGGGACTGTG
CGGATGCTGCAGGCCTTCCTGCCAGACATGAAGAGGCGCGGTTCGGGACGCGTGTTGGTG
ACCGGGAGCGTGGGAGGATTGATGGGGCTGCCTTTCAATGACGTTTATTGCGCCAGCAAG
TTCGCGCTCGAAGGCTTATGCGAGAGTCTGGCGGTTCTGCTGCTGCCCTTTGGGGTCCAC
TTGAGCCTGATCGAGTGCGGCCCAGTGCACACCGCCTTCATGGAGAAGGTGTTGGGCAGC
CCAGAGGAGGTGCTGGACCGCACGGACATCCACACCTTCCACCGCTTCTACCAATACCTC
GCCCACAGCAAGCAAGTCTTTCGCGAGGCGGCGCAGAACCCTGAGGAGGTGGCGGAGGTC
TTCCTCACCGCTTTGCGCGCCCCGAAGCCGACCCTGCGCTACTTCACCACCGAGCGCTTC
CTGCCCCTGCTGCGGATGCGCCTGGACGACCCCAGCGGCTCCAACTACGTCACCGCCATG
CACCGGGAAGTGTTCGGCGACGTTCCGGCAAAGGCCGAGGCTGGGGCCGAGGCTGGGGGC
GGGGCCGGGCCTGGGGCAGAGGACGAGGCCGGGCGCGGTGCGGTGGGGGACCCTGAGCTC
GGCGATCCTCCGGCCGCCCCGCAGTAA
Chromosome Location
17
Locus
17q11-q21
External Identifiers
ResourceLink
UniProtKB IDP14061
UniProtKB Entry NameDHB1_HUMAN
GenBank Protein ID23365
GenBank Gene IDX13440
GenAtlas IDHSD17B1
HGNC IDHGNC:5210
General References
  1. Peltoketo H, Isomaa V, Maentausta O, Vihko R: Complete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA. FEBS Lett. 1988 Oct 24;239(1):73-7. [PubMed:2846351]
  2. Luu The V, Labrie C, Zhao HF, Couet J, Lachance Y, Simard J, Leblanc G, Cote J, Berube D, Gagne R, et al.: Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5'-termini in human placenta. Mol Endocrinol. 1989 Aug;3(8):1301-9. [PubMed:2779584]
  3. Luu-The V, Labrie C, Simard J, Lachance Y, Zhao HF, Couet J, Leblanc G, Labrie F: Structure of two in tandem human 17 beta-hydroxysteroid dehydrogenase genes. Mol Endocrinol. 1990 Feb;4(2):268-75. [PubMed:2330005]
  4. Luu-The V, Labrie C, Zhao HF, Couet J, Lachance Y, Simard J, Cote J, Leblanc G, Lagace L, Berube D, et al.: Purification, cloning, complementary DNA structure, and predicted amino acid sequence of human estradiol 17 beta-dehydrogenase. Ann N Y Acad Sci. 1990;595:40-52. [PubMed:2197970]
  5. Peltoketo H, Isomaa V, Vihko R: Genomic organization and DNA sequences of human 17 beta-hydroxysteroid dehydrogenase genes and flanking regions. Localization of multiple Alu sequences and putative cis-acting elements. Eur J Biochem. 1992 Oct 1;209(1):459-66. [PubMed:1327779]
  6. 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]
  7. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [PubMed:16625196]
  8. 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]
  9. Burns DJ, Engel LL, Bethune JL: Amino acid composition and subunit structure. Human placental 17 -estradiol dehydrogenase. Biochemistry. 1972 Jul 4;11(14):2699-703. [PubMed:5045524]
  10. Nicolas JC, Harris JI: Human placental 17 -oestradiol dehydrogenase. Sequence of a tryptic peptide containing an essential cysteine. FEBS Lett. 1973 Jan 15;29(2):173-6. [PubMed:4719204]
  11. Murdock GL, Chin CC, Warren JC: Human placental estradiol 17 beta-dehydrogenase: sequence of a histidine-bearing peptide in the catalytic region. Biochemistry. 1986 Feb 11;25(3):641-6. [PubMed:3456799]
  12. Murdock GL, Chin CC, Offord RE, Bradshaw RA, Warren JC: Human placental estradiol 17 beta-dehydrogenase. Identification of a single histidine residue affinity-labeled by both 3-bromoacetoxyestrone and 12 beta-bromoacetoxy-4-estrene-3,17-dione. J Biol Chem. 1983 Oct 10;258(19):11460-4. [PubMed:6578212]
  13. Baker ME: Human placental 17 beta-hydroxysteroid dehydrogenase is homologous to NodG protein of Rhizobium meliloti. Mol Endocrinol. 1989 May;3(5):881-4. [PubMed:2547159]
  14. Ghosh D, Pletnev VZ, Zhu DW, Wawrzak Z, Duax WL, Pangborn W, Labrie F, Lin SX: Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 A resolution. Structure. 1995 May 15;3(5):503-13. [PubMed:7663947]
  15. Azzi A, Rehse PH, Zhu DW, Campbell RL, Labrie F, Lin SX: Crystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase complexed with 17 beta-estradiol. Nat Struct Biol. 1996 Aug;3(8):665-8. [PubMed:8756321]
  16. Breton R, Housset D, Mazza C, Fontecilla-Camps JC: The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors. Structure. 1996 Aug 15;4(8):905-15. [PubMed:8805577]
  17. Mazza C, Breton R, Housset D, Fontecilla-Camps JC: Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase. J Biol Chem. 1998 Apr 3;273(14):8145-52. [PubMed:9525918]
  18. Sawicki MW, Erman M, Puranen T, Vihko P, Ghosh D: Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):840-5. [PubMed:9927655]
  19. Han Q, Campbell RL, Gangloff A, Huang YW, Lin SX: Dehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid discrimination and enzyme-induced strain. J Biol Chem. 2000 Jan 14;275(2):1105-11. [PubMed:10625652]
  20. Qiu W, Campbell RL, Gangloff A, Dupuis P, Boivin RP, Tremblay MR, Poirier D, Lin SX: A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity. FASEB J. 2002 Nov;16(13):1829-31. Epub 2002 Sep 5. [PubMed:12223444]
  21. Gangloff A, Shi R, Nahoum V, Lin SX: Pseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase. FASEB J. 2003 Feb;17(2):274-6. Epub 2002 Dec 17. [PubMed:12490543]
  22. Shi R, Lin SX: Cofactor hydrogen bonding onto the protein main chain is conserved in the short chain dehydrogenase/reductase family and contributes to nicotinamide orientation. J Biol Chem. 2004 Apr 16;279(16):16778-85. Epub 2004 Feb 13. [PubMed:14966133]
  23. Normand T, Narod S, Labrie F, Simard J: Detection of polymorphisms in the estradiol 17 beta-hydroxysteroid dehydrogenase II gene at the EDH17B2 locus on 17q11-q21. Hum Mol Genet. 1993 Apr;2(4):479-83. [PubMed:8389226]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB02187EquilinexperimentalunknownDetails
DB02323EM-1745experimentalunknownDetails
DB01536Androstenedioneexperimental, illicityesinducerDetails
DB03461Nicotinamide adenine dinucleotide phosphateexperimentalunknownDetails
DB02901Stanoloneillicit, investigationalunknownDetails
DB01561Androstanedioneexperimental, illicitunknownDetails
DB13951Stanolone acetateexperimentalunknownDetails
DB01708Prasteroneapproved, investigational, nutraceuticalunknownsubstrateDetails