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Identification
HMDB Protein ID HMDBP00847
Secondary Accession Numbers
  • 6128
  • HMDBP07055
Name Estradiol 17-beta-dehydrogenase 1
Synonyms
  1. 17-beta-HSD 1
  2. 17-beta-hydroxysteroid dehydrogenase type 1
  3. 20 alpha-hydroxysteroid dehydrogenase
  4. 20-alpha-HSD
  5. E2DH
  6. Placental 17-beta-hydroxysteroid dehydrogenase
Gene Name HSD17B1
Protein Type Unknown
Biological Properties
General Function Involved in estradiol 17-beta-dehydrogenase activity
Specific Function Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
Pathways
  • 17-Beta Hydroxysteroid Dehydrogenase III Deficiency
  • Androgen and Estrogen Metabolism
  • Aromatase deficiency
  • estrogen biosynthesis
  • Estrone Metabolism
  • Steroid hormone biosynthesis
Reactions
Estradiol + NAD(P)(+) → Estrone + NAD(P)H details
Estradiol + NAD → Estrone + NADH + Hydrogen Ion details
Estradiol + NADP → Estrone + NADPH + Hydrogen Ion details
Estriol + NAD → 16b-Hydroxyestrone + NADH + Hydrogen Ion details
Estriol + NADP → 16b-Hydroxyestrone + NADPH + Hydrogen Ion details
11beta,17beta-Dihydroxy-4-androsten-3-one + NAD → 11b-Hydroxyandrost-4-ene-3,17-dione + NADH + Hydrogen Ion details
11beta,17beta-Dihydroxy-4-androsten-3-one + NADP → 11b-Hydroxyandrost-4-ene-3,17-dione + NADPH + Hydrogen Ion details
GO Classification
Biological Process
small molecule metabolic process
estrogen biosynthetic process
Cellular Component
cytosol
Component
cell part
intracellular part
cytoplasm
Function
binding
catalytic activity
oxidoreductase activity
steroid dehydrogenase activity
steroid dehydrogenase activity, acting on the ch-oh group of donors, nad or nadp as acceptor
estradiol 17-beta-dehydrogenase activity
Molecular Function
estradiol 17-beta-dehydrogenase activity
nucleotide binding
Process
metabolic process
primary metabolic process
oxidation reduction
lipid metabolic process
steroid metabolic process
steroid biosynthetic process
estrogen biosynthetic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 17
Locus 17q11-q21
SNPs HSD17B1
Gene Sequence
>987 bp
ATGGCCCGCACCGTGGTGCTCATCACCGGCTGTTCCTCGGGCATCGGCCTGCACTTGGCC
GTACGTCTGGCTTCAGATCCATCCCAGAGCTTCAAAGTGTATGCCACGTTGAGGGACCTG
AAAACACAGGGCCGGCTGTGGGAGGCGGCCCGGGCCCTGGCATGCCCTCCGGGATCCCTG
GAGACGTTGCAGCTGGACGTAAGGGACTCAAAATCCGTGGCCGCTGCCCGGGAACGCGTG
ACTGAGGGCCGCGTGGACGTGCTGGTGTGTAACGCAGGCCTGGGCCTGCTGGGGCCGCTG
GAGGCGCTGGGGGAGGACGCCGTGGCCTCTGTGCTGGACGTGAATGTAGTAGGGACTGTG
CGGATGCTGCAGGCCTTCCTGCCAGACATGAAGAGGCGCGGTTCGGGACGCGTGTTGGTG
ACCGGGAGCGTGGGAGGATTGATGGGGCTGCCTTTCAATGACGTTTATTGCGCCAGCAAG
TTCGCGCTCGAAGGCTTATGCGAGAGTCTGGCGGTTCTGCTGCTGCCCTTTGGGGTCCAC
TTGAGCCTGATCGAGTGCGGCCCAGTGCACACCGCCTTCATGGAGAAGGTGTTGGGCAGC
CCAGAGGAGGTGCTGGACCGCACGGACATCCACACCTTCCACCGCTTCTACCAATACCTC
GCCCACAGCAAGCAAGTCTTTCGCGAGGCGGCGCAGAACCCTGAGGAGGTGGCGGAGGTC
TTCCTCACCGCTTTGCGCGCCCCGAAGCCGACCCTGCGCTACTTCACCACCGAGCGCTTC
CTGCCCCTGCTGCGGATGCGCCTGGACGACCCCAGCGGCTCCAACTACGTCACCGCCATG
CACCGGGAAGTGTTCGGCGACGTTCCGGCAAAGGCCGAGGCTGGGGCCGAGGCTGGGGGC
GGGGCCGGGCCTGGGGCAGAGGACGAGGCCGGGCGCAGTGCGGTGGGGGACCCTGAGCTC
GGCGATCCTCCGGCCGCCCCGCAGTAA
Protein Properties
Number of Residues 328
Molecular Weight 34949.715
Theoretical pI 5.69
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Estradiol 17-beta-dehydrogenase 1
MARTVVLITGCSSGIGLHLAVRLASDPSQSFKVYATLRDLKTQGRLWEAARALACPPGSL
ETLQLDVRDSKSVAAARERVTEGRVDVLVCNAGLGLLGPLEALGEDAVASVLDVNVVGTV
RMLQAFLPDMKRRGSGRVLVTGSVGGLMGLPFNDVYCASKFALEGLCESLAVLLLPFGVH
LSLIECGPVHTAFMEKVLGSPEEVLDRTDIHTFHRFYQYLAHSKQVFREAAQNPEEVAEV
FLTALRAPKPTLRYFTTERFLPLLRMRLDDPSGSNYVTAMHREVFGDVPAKAEAGAEAGG
GAGPGAEDEAGRSAVGDPELGDPPAAPQ
GenBank ID Protein 23365
UniProtKB/Swiss-Prot ID P14061
UniProtKB/Swiss-Prot Entry Name DHB1_HUMAN
PDB IDs
GenBank Gene ID X13440
GeneCard ID HSD17B1
GenAtlas ID HSD17B1
HGNC ID HGNC:5210
References
General References
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  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. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. 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 ]
  22. 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 ]