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Showing drug card for Estradiol (DB00783)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:31
Primary Accession Number DB00783
Secondary Accession Number
  • APRD00311
Name Estradiol
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Generally refers to the 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. In humans, it is produced primarily by the cyclic ovaries and the placenta. It is also produced by the adipose tissue of men and postmenopausal women. The 17-alpha-isomer of estradiol binds weakly to estrogen receptors (receptors, estrogen) and exhibits little estrogenic activity in estrogen-responsive tissues. Various isomers can be synthesized. [PubChem]
Synonyms
  1. 17-beta
  2. Beta-Estradiol
  3. Cis-Estradiol
  4. Cis-Oestradiol
  5. D-Estradiol
  6. D-Oestradiol
  7. Dihydrofollicular Hormone
  8. Dihydrofolliculin
  9. Dihydroxyesterin
  10. Dihydroxyestrin
  11. Dihydroxyoestrin
  12. Estradiol Cypionate
  13. Estradiol Valerate
  14. Estradiol-17beta
  15. estradiol
Brand Names
  1. Aerodiol
  2. Agofollin
  3. Alora
  4. Altrad
  5. Amnestrogen
  6. Aquadiol
  7. Bardiol
  8. Climaderm
  9. Climara
  10. Combipatch
  11. Compudose
  12. Compudose 200
  13. Compudose 365
  14. Corpagen
  15. Delestrogen
  16. Depo-Estradiol
  17. Dermestril
  18. Dihydromenformon
  19. Dihydrotheelin
  20. Dimenformon
  21. Dimenformon Prolongatum
  22. Diogyn
  23. Diogynets
  24. Divigel
  25. Elestrin
  26. Encore
  27. Esclim
  28. Estinyl
  29. Estrace
  30. Estraderm
  31. Estraderm Tts
  32. Estradurin
  33. Estrasorb
  34. Estreva
  35. Estrifam
  36. Estring
  37. Estring Vaginal Ring
  38. Estroclim
  39. Estroclim 50
  40. Estrofem 2
  41. Estrofem Forte
  42. Estrogel
  43. Estrogens, Esterified
  44. Estrovite
  45. Evamist
  46. Evorel
  47. Extrasorb
  48. Femestral
  49. Femestrol
  50. Feminone
  51. Femogen
  52. Fempatch
  53. Femring
  54. Femtrace
  55. Femtran
  56. Follicyclin
  57. Ginedisc
  58. Ginosedol
  59. Gynergon
  60. Gynestrel
  61. Gynodiol
  62. Gynoestryl
  63. Gynpolar
  64. Innofem
  65. Lamdiol
  66. Lynoral
  67. Macrodiol
  68. Macrol
  69. Menest
  70. Menorest
  71. Menostar
  72. Microdiol
  73. Nordicol
  74. Oestergon
  75. Oestradiol
  76. Oestradiol R
  77. Oestrogel
  78. Oestroglandol
  79. Oestrogynal
  80. Ovahormon
  81. Ovasterol
  82. Ovastevol
  83. Ovociclina
  84. Ovocyclin
  85. Ovocycline
  86. Ovocylin
  87. Perlatanol
  88. Primofol
  89. Profoliol
  90. Profoliol B
  91. Progynon
  92. Progynon Dh
  93. Progynon-Dh
  94. Ricifon
  95. Ritsifon
  96. Sandrena Gel
  97. Sisare Gel
  98. Sk-Estrogens
  99. Soldep
  100. Sotipox
  101. Syndiol
  102. Systen
  103. Tradelia
  104. Trial Sat
  105. Trocosone
  106. Vagifem
  107. Vivelle
  108. Zerella
  109. Zumenon
Brand Mixtures
  1. Alesse 21 Tablets (Ethinyl Estradiol + Levonorgestrel)
  2. Alesse 28 Tablets (Ethinyl Estradiol + Levonorgestrel)
  3. Brevicon 0.5/35 21 Tab (Ethinyl Estradiol + Norethindrone)
  4. Brevicon 0.5/35 28 Tab (Ethinyl Estradiol + Norethindrone)
  5. Brevicon 1/35 21 Tab (Ethinyl Estradiol + Norethindrone)
  6. Brevicon 1/35 28 Tab (Ethinyl Estradiol + Norethindrone)
  7. Calf-Oid Implant (Estradiol Benzoate + Progesterone)
  8. Climacteron Injection (Estradiol Benzoate + Estradiol Dienanthate + Testosterone Enanthate Benzilic Acid Hydrazone)
  9. Demulen 50 (21 Day Pack) (Ethinyl Estradiol + Ethynodiol Diacetate)
  10. Demulen 50 (28 Day Pack) (Ethinyl Estradiol + Ethynodiol Diacetate)
  11. Min-Ovral 21 Tab (Ethinyl Estradiol + Levonorgestrel)
  12. Min-Ovral 28 Tab (Ethinyl Estradiol + Levonorgestrel)
  13. Neo Mens Tab (Ethinyl Estradiol + Ethisterone)
  14. Ortho 10/11 Tablets (21 Day) (Ethinyl Estradiol + Norethindrone)
  15. Ortho 10/11 Tablets (28 Day) (Ethinyl Estradiol + Norethindrone)
  16. Ovral 21 Tab (Ethinyl Estradiol + Norgestrel (Norgestrel))
  17. Ovral 28tab (Ethinyl Estradiol + Norgestrel)
  18. Preven Tablets (Ethinyl Estradiol + Levonorgestrel)
  19. Synphasic 21 Tablets (Ethinyl Estradiol + Norethindrone)
  20. Synphasic-28 Tablets (Ethinyl Estradiol + Norethindrone)
  21. Tri-Cyclen Lo (Ethinyl Estradiol + Norgestimate)
  22. Triphasil 21 Tab (Ethinyl Estradiol + Levonorgestrel)
  23. Triphasil 28 Tab (Ethinyl Estradiol + Levonorgestrel)
  24. Triquilar 21 (Ethinyl Estradiol + Levonorgestrel)
Chemical IUPAC Name (8R,9S,13S,14S,17S)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
Chemical Formula C18H24O2
Chemical Structure Structure
CAS Registry Number 50-28-2
InChI Identifier InChI=1/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1
InChI Key VOXZDWNPVJITMN-ZBRFXRBCBJ
KEGG Drug D00105 Link Image
KEGG Compound C00951 Link Image
PubChem Compound 5757 Link Image
PubChem Substance 148536 Link Image
ChEBI ID 16469 Link Image
PharmGKB ID PA449503 Link Image
HET ID ECO Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02246969 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/estrogel.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Estradiol Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference A. Butenandt, C. Georgens, Z. Physiol. Chem.. 284, 129 (1937)
Average Molecular Weight 272.3820
Monoisotopic Molecular Weight 272.1776
State Solid
Melting Point 173-179 oC
Experimental Water Solubility 3.6 mg/L Source: PhysProp
Predicted Water Solubility 2.13e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4.2 Source: PhysProp
Predicted LogP 3.57 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.11 Calculated using ALOGPS
Experimental Caco2 Permeability -4.77 [ADME Research, USCD]
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES C[C@]12CC[C@H]3[C@@H](CCC4=C3C=CC(O)=C4)[C@@H]1CC[C@@H]2O
Canonical SMILES CC12CCC3C(CCC4=C3C=CC(O)=C4)C1CCC2O
Drug Category
  • Anti-menopausal Agents
  • Anticholesteremic Agents
  • Estrogens
ATC Codes
AHFS Codes
  • 68:16.04
Indication For the treatment of urogenital symptoms associated with post-menopausal atrophy of the vagina (such as dryness, burning, pruritus and dyspareunia) and/or the lower urinary tract (urinary urgency and dysuria).
Pharmacology Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level.
Mechanism of Action Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.
Absorption 43%
Toxicity Can cause nausea and vomiting, and withdrawal bleeding may occur in females.
Protein Binding >95%
Biotransformation Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450.
Half Life 36 hours
Dosage Forms
Form Route
Disc Transdermal
Gel Transdermal
Liquid Intramuscular
Patch Transdermal
Ring Intravaginal
Tablet Intravaginal
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Amobarbital The enzyme inducer decreases the effect of hormones
Aprobarbital The enzyme inducer decreases the effect of hormones
Butabarbital The enzyme inducer decreases the effect of hormones
Butalbital The enzyme inducer decreases the effect of hormones
Butethal The enzyme inducer decreases the effect of hormones
Ethotoin The enzyme inducer decreases the effect of hormones
Fosphenytoin The enzyme inducer decreases the effect of hormones
Griseofulvin The enzyme inducer decreases the effect of hormones
Heptabarbital The enzyme inducer decreases the effect of hormones
Hexobarbital The enzyme inducer decreases the effect of hormones
Mephenytoin The enzyme inducer decreases the effect of hormones
Methohexital The enzyme inducer decreases the effect of hormones
Methylphenobarbital The enzyme inducer decreases the effect of hormones
Pentobarbital The enzyme inducer decreases the effect of hormones
Phenobarbital The enzyme inducer decreases the effect of hormones
Phenytoin The enzyme inducer decreases the effect of hormones
Prednisolone The estrogenic agent increases the effect of corticosteroid
Prednisone The estrogenic agent increases the effect of corticosteroid
Primidone The enzyme inducer decreases the effect of hormones
Raloxifene Association not recommended
Secobarbital The enzyme inducer decreases the effect of hormones
Talbutal The enzyme inducer decreases the effect of hormones
Ursodeoxycholic acid Estrogens decreases the effect of ursodiol
Food Interactions
  • Take with food to decrease nausea.
Pathways Not Available
General References
  1. Pentikainen V, Erkkila K, Suomalainen L, Parvinen M, Dunkel L: Estradiol acts as a germ cell survival factor in the human testis in vitro. J Clin Endocrinol Metab. 2000 May;85(5):2057-67. [PubMed Link Image]
  2. Raman JD, Schlegel PN: Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9. [PubMed Link Image]
  3. Behl C, Widmann M, Trapp T, Holsboer F: 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun. 1995 Nov 13;216(2):473-82. [PubMed Link Image]
  4. Sharpe RM, Skakkebaek NE: Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993 May 29;341(8857):1392-5. [PubMed Link Image]
  5. Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER: Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 1997 Jul 10;337(2):91-5. [PubMed Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2A6 (CYP2A6)
  2. Cytochrome P450 1A2 (CYP1A2)
  3. Glucuronosyltransferase
Targets
  1. Estrogen receptor
  2. Sex hormone-binding globulin
  3. Estrogen receptor beta
  4. Orphan nuclear receptor PXR
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2A6 (CYP2A6)
Enzyme 1 Gene Name CYP2A6
Enzyme 1 SwissProt ID P11509 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P11509|CP2A6_HUMAN Cytochrome P450 2A6 (EC 1.14.14.1) 
MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMK
ISERYGPVFTIHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSN
GERAKQLRRFSIATLRDFGVGKRGIEERIQEEAGFLIDAHRGTGGANIDPTFFLSRTVSN
VISSIVFGDRFDYKDKEFLSLLRMMLGIFQFTSTSTGQLYEMFSSVMKHLPGPQQQAFQL
LQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFI
GGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYMEAVIHEIQ
RFGDVIPMSLARRVKKDTKFRDFFLPKGTEVYPMLGSVLRDPSFFSNPQDFNPQHFLNEK
GQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGF
ATIPRNYTMSFLPR
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 2 Gene Name CYP1A2
Enzyme 2 SwissProt ID P05177 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human). 
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Glucuronosyltransferase
Enzyme 3 Gene Name UGT1A1
Enzyme 3 SwissProt ID P22309 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P22309|UD11_HUMAN UDP-glucuronosyltransferase 1-1 precursor 
MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVL
APDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDS
AMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLE
FEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQR
EVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEH
GIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDL
LGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTS
EDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHD
LTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Drug Target 1 [top]
Target 1 ID 136
Target 1 Name Estrogen receptor
Target 1 Synonyms
  1. ER
  2. ER-alpha
  3. Estradiol receptor
Target 1 Gene Name ESR1
Target 1 Protein Sequence >Estrogen receptor 
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAY
EFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPF
LQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAK
ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQAC
RLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKR
SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINW
AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEG
MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLD
KITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLL
LEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
Target 1 Number of Residues 604
Target 1 Molecular Weight 66217
Target 1 Theoretical pI 8.14
Target 1 GO Classification
Function
ion binding
cation binding
transition metal ion binding
zinc ion binding
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 1 General Function Involved in transcription factor activity
Target 1 Specific Function Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 31234 Link Image
Target 1 UniProtKB/Swiss-Prot ID P03372 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ESR1_HUMAN Link Image
Target 1 PDB ID 1R5K Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Nucleus
Target 1 Gene Sequence >1788 bp 
ATGACCATGACCCTCCACACCAAAGCATCTGGGATGGCCCTACTGCATCAGATCCAAGGG
AACGAGCTGGAGCCCCTGAACCGTCCGCAGCTCAAGATCCCCCTGGAGCGGCCCCTGGGC
GAGGTGTACCTGGACAGCAGCAAGCCCGCCGTGTACAACTACCCCGAGGGCGCCGCCTAC
GAGTTCAACGCCGCGGCCGCCGCCAACGCGCAGGTCTACGGTCAGACCGGCCTCCCCTAC
GGCCCCGGGTCTGAGGCTGCGGCGTTCGGCTCCAACGGCCTGGGGGGTTTCCCCCCACTC
AACAGCGTGTCTCCGAGCCCGCTGATGCTACTGCACCCGCCGCCGCAGCTGTCGCCTTTC
CTGCAGCCCCACGGCCAGCAGGTGCCCTACTACCTGGAGAACGAGCCCAGCGGCTACACG
GTGCGCGAGGCCGGCCCGCCGGCATTCTACAGGCCAAATTCAGATAATCGACGCCAGGGT
GGCAGAGAAAGATTGGCCAGTACCAATGACAAGGGAAGTATGGCTATGGAATCTGCCAAG
GAGACTCGCTACTGTGCAGTGTGCAATGACTATGCTTCAGGCTACCATTATGGAGTCTGG
TCCTGTGAGGGCTGCAAGGCCTTCTTCAAGAGAAGTATTCAAGGACATAACGACTATATG
TGTCCAGCCACCAACCAGTGCACCATTGATAAAAACAGGAGGAAGAGCTGCCAGGCCTGC
CGGCTCCGCAAATGCTACGAAGTGGGAATGATGAAAGGTGGGATACGAAAAGACCGAAGA
GGAGGGAGAATGTTGAAACACAAGCGCCAGAGAGATGATGGGGAGGGCAGGGGTGAAGTG
GGGTCTGCTGGAGACATGAGAGCTGCCAACCTTTGGCCAAGCCCGCTCATGATCAAACGC
TCTAAGAAGAACAGCCTGGCCTTGTCCCTGACGGCCGACCAGATGGTCAGTGCCTTGTTG
GATGCTGAGCCCCCCATACTCTATTCCGAGTATGATCCTACCAGACCCTTCAGTGAAGCT
TCGATGATGGGCTTACTGACCAACCTGGCAGACAGGGAGCTGGTTCACATGATCAACTGG
GCGAAGAGGGTGCCAGGCTTTGTGGATTTGACCCTCCATGATCAGGTCCACCTTCTAGAA
TGTGCCTGGCTAGAGATCCTGATGATTGGTCTCGTCTGGCGCTCCATGGAGCACCCAGTG
AAGCTACTGTTTGCTCCTAACTTGCTCTTGGACAGGAACCAGGGAAAATGTGTAGAGGGC
ATGGTGGAGATCTTCGACATGCTGCTGGCTACATCATCTCGGTTCCGCATGATGAATCTG
CAGGGAGAGGAGTTTGTGTGCCTCAAATCTATTATTTTGCTTAATTCTGGAGTGTACACA
TTTCTGTCCAGCACCCTGAAGTCTCTGGAAGAGAAGGACCATATCCACCGAGTCCTGGAC
AAGATCACAGACACTTTGATCCACCTGATGGCCAAGGCAGGCCTGACCCTGCAGCAGCAG
CACCAGCGGCTGGCCCAGCTCCTCCTCATCCTCTCCCACATCAGGCACATGAGTAACAAA
GGCATGGAGCATCTGTACAGCATGAAGTGCAAGAACGTGGTGCCCCTCTATGACCTGCTG
CTGGAGATGCTGGACGCCCACCGCCTACATGCGCCCACTAGCCGTGGAGGGGCATCCGTG
GAGGAGACGGACCAAAGCCACTTGGCCACTGCGGGCTCTACTTCATCGCATTCCTTGCAA
AAGTATTACATCACGGGGGAGGCAGAGGGTTTCCCTGCCACAGTCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ESR1 Link Image
Target 1 GenAtlas ID ESR1 Link Image
Target 1 HGNC ID HGNC:3467 Link Image
Target 1 Chromosome Location 6
Target 1 Locus 6q25.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS: An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6947-52. [PubMed Link Image]
  2. Rogatsky I, Trowbridge JM, Garabedian MJ: Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex. J Biol Chem. 1999 Aug 6;274(32):22296-302. [PubMed Link Image]
  3. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem. 1999 Nov 26;274(48):34283-93. [PubMed Link Image]
  4. Schubert EL, Lee MK, Newman B, King MC: Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility. J Steroid Biochem Mol Biol. 1999 Nov;71(1-2):21-7. [PubMed Link Image]
  5. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. [PubMed Link Image]
  6. Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. [PubMed Link Image]
  7. Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ: Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8. Epub 2002 Nov 1. [PubMed Link Image]
  8. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed Link Image]
  9. Reese JC, Katzenellenbogen BS: Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation. J Biol Chem. 1992 May 15;267(14):9868-73. [PubMed Link Image]
  10. Schwabe JW, Neuhaus D, Rhodes D: Solution structure of the DNA-binding domain of the oestrogen receptor. Nature. 1990 Nov 29;348(6300):458-61. [PubMed Link Image]
  11. 2792078 Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P: The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 1989 Jul;8(7):1981-6.
  12. 3753802 Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J: Sequence and expression of human estrogen receptor complementary DNA. Science. 1986 Mar 7;231(4742):1150-4.
  13. 3754034 Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P: Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13-19;320(6058):134-9.
  14. 7476978 Joel PB, Traish AM, Lannigan DA: Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Mol Endocrinol. 1995 Aug;9(8):1041-52.
  15. 7539106 Arnold SF, Obourn JD, Jaffe H, Notides AC: Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. Mol Endocrinol. 1995 Jan;9(1):24-33.
  16. 7838153 Arnold SF, Obourn JD, Jaffe H, Notides AC: Serine 167 is the major estradiol-induced phosphorylation site on the human estrogen receptor. Mol Endocrinol. 1994 Sep;8(9):1208-14.
  17. 7916651 Pfeffer U, Fecarotta E, Castagnetta L, Vidali G: Estrogen receptor variant messenger RNA lacking exon 4 in estrogen-responsive human breast cancer cell lines. Cancer Res. 1993 Feb 15;53(4):741-3.
  18. 8221895 Schwabe JW, Chapman L, Finch JT, Rhodes D: The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements. Cell. 1993 Nov 5;75(3):567-78.
  19. 8600466 Pink JJ, Wu SQ, Wolf DM, Bilimoria MM, Jordan VC: A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7. Nucleic Acids Res. 1996 Mar 1;24(5):962-9.
  20. 8961262 McInerney EM, Ince BA, Shapiro DJ, Katzenellenbogen BS: A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action. Mol Endocrinol. 1996 Dec;10(12):1519-26.
  21. 9195227 Anderson TI, Wooster R, Laake K, Collins N, Warren W, Skrede M, Elles R, Tveit KM, Johnston SR, Dowsett M, Olsen AO, Moller P, Stratton MR, Borresen-Dale AL: Screening for ESR mutations in breast and ovarian cancer patients. Hum Mutat. 1997;9(6):531-6.
  22. 9338790 Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M: Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997 Oct 16;389(6652):753-8.
  23. 9600906 Tanenbaum DM, Wang Y, Williams SP, Sigler PB: Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003.
  24. 9619507 Maalouf GJ, Xu W, Smith TF, Mohr SC: Homology model for the ligand-binding domain of the human estrogen receptor. J Biomol Struct Dyn. 1998 Apr;15(5):841-51.
  25. 9875847 Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL: The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998 Dec 23;95(7):927-37.
Target 1 Drug References
  1. Garcia-Segura LM, Sanz A, Mendez P: Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection. Neuroendocrinology. 2006;84(4):275-9. Epub 2006 Nov 23. [PubMed Link Image]
  2. Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, d'Abusco AS, Scandurra R, Migliaccio S: Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):102-8. Epub 2006 Nov 27. [PubMed Link Image]
  3. Lehnes K, Winder AD, Alfonso C, Kasid N, Simoneaux M, Summe H, Morgan E, Iann MC, Duncan J, Eagan M, Tavaluc R, Evans CH Jr, Russell R, Wang A, Hu F, Stoica A: The effect of estradiol on in vivo tumorigenesis is modulated by the human epidermal growth factor receptor 2/phosphatidylinositol 3-kinase/Akt1 pathway. Endocrinology. 2007 Mar;148(3):1171-80. Epub 2006 Nov 30. [PubMed Link Image]
  4. Mukai H, Tsurugizawa T, Ogiue-Ikeda M, Murakami G, Hojo Y, Ishii H, Kimoto T, Kawato S: Local neurosteroid production in the hippocampus: influence on synaptic plasticity of memory. Neuroendocrinology. 2006;84(4):255-63. Epub 2006 Dec 1. [PubMed Link Image]
  5. Fritah A, Redeuilh G, Sabbah M: Molecular cloning and characterization of the human WISP-2/CCN5 gene promoter reveal its upregulation by oestrogens. J Endocrinol. 2006 Dec;191(3):613-24. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 756
Target 2 Name Sex hormone-binding globulin
Target 2 Synonyms
  1. ABP
  2. SBP
  3. SHBG
  4. Sex hormone-binding globulin precursor
  5. Sex steroid-binding protein
  6. TeBG
  7. Testis-specific androgen-binding protein
  8. Testosterone-estradiol- binding globulin
  9. Testosterone-estrogen-binding globulin
Target 2 Gene Name SHBG
Target 2 Protein Sequence >Sex hormone-binding globulin precursor 
MESRGPLATSRLLLLLLLLLLRHTRQGWALRPVLPTQSAHDPPAVHLSNGPGQEPIAVMT
FDLTKITKTSSSFEVRTWDPEGVIFYGDTNPKDDWFMLGLRDGRPEIQLHNHWAQLTVGA
GPRLDDGRWHQVEVKMEGDSVLLEVDGEEVLRLRQVSGPLTSKRHPIMRIALGGLLFPAS
NLRLPLVPALDGCLRRDSWLDKQAEISASAPTSLRSCDVESNPGIFLPPGTQAEFNLRDI
PQPHAEPWAFSLDLGLKQAAGSGHLLALGTPENPSWLSLHLQDQKVVLSSGSGPGLDLPL
VLGLPLQLKLSMSRVVLSQGSKMKALALPPLGLAPLLNLWAKPQGRLFLGALPGEDSSTS
FCLNGLWAQGQRLDVDQALNRSHEIWTHSCPQSPGNGTDASH
Target 2 Number of Residues 408
Target 2 Molecular Weight 43780
Target 2 Theoretical pI 6.70
Target 2 GO Classification Not Available
Target 2 General Function Involved in androgen binding
Target 2 Specific Function Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-29
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 296673 Link Image
Target 2 UniProtKB/Swiss-Prot ID P04278 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name SHBG_HUMAN Link Image
Target 2 PDB ID 1F5F Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Secreted protein. In testis, it is synthesized by the Sertoli cells, secreted into the lumen of the
Target 2 Gene Sequence >1209 bp 
ATGGAGAGCAGAGGCCCACTGGCTACCTCGCGCCTGCTGCTGTTGCTGCTGTTGCTACTA
CTGCGTCACACCCGCCAGGGATGGGCCCTGAGACCTGTTCTCCCCACCCAGAGTGCCCAC
GACCCTCCGGCTGTCCACCTCAGCAATGGCCCAGGACAAGAGCCTATCGCTGTCATGACC
TTTGACCTCACCAAGATCACAAAAACCTCCTCCTCCTTTGAGGTTCGAACCTGGGACCCA
GAGGGAGTGATTTTTTATGGGGATACCAACCCTAAGGATGACTGGTTTATGCTGGGACTT
CGAGACGGCAGGCCTGAGATCCAACTGCACAATCACTGGGCCCAGCTTACGGTGGGTGCT
GGACCACGGCTGGATGATGGGAGATGGCACCAGGTGGAAGTCAAGATGGAGGGGGACTCT
GTGCTGCTGGAGGTGGATGGGGAGGAGGTGCTGCGCCTGAGACAGGTCTCTGGGCCCCTG
ACCAGCAAACGCCATCCCATCATGAGGATTGCGCTTGGGGGGCTGCTCTTCCCCGCTTCC
AACCTTCGGTTGCCGCTGGTTCCTGCCCTGGATGGCTGCCTGCGCCGGGATTCCTGGCTG
GACAAACAGGCCGAGATCTCAGCATCTGCCCCCACTAGCCTCAGAAGCTGTGATGTAGAA
TCAAATCCCGGGATATTTCTCCCTCCAGGGACTCAGGCAGAATTCAATCTCCGAGACATT
CCCCAGCCTCATGCAGAGCCCTGGGCCTTCTCTTTGGACCTGGGACTCAAGCAGGCAGCA
GGCTCAGGCCACCTCCTTGCTCTTGGGACACCAGAGAACCCATCTTGGCTCAGTCTCCAC
CTCCAAGATCAAAAGGTGGTGTTGTCTTCTGGGTCGGGGCCAGGGCTGGATCTGCCCCTG
GTCTTGGGACTCCCTCTTCAGCTGAAGCTGAGTATGTCCAGGGTGGTCTTGAGCCAAGGG
TCGAAGATGAAGGCCCTTGCCCTGCCTCCCTTAGGCCTGGCTCCCCTCCTTAACCTCTGG
GCCAAGCCTCAAGGGCGTCTCTTCCTGGGGGCTTTACCAGGAGAAGACTCTTCCACCTCT
TTTTGCCTGAATGGCCTTTGGGCACAAGGTCAGAGGCTGGATGTGGACCAGGCCCTGAAC
AGAAGCCATGAGATCTGGACTCACAGCTGCCCCCAGAGCCCAGGCAATGGCACTGACGCT
TCCCATTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID SHBG Link Image
Target 2 GenAtlas ID SHBG Link Image
Target 2 HGNC ID HGNC:10839 Link Image
Target 2 Chromosome Location 17
Target 2 Locus 17p13-p12
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA: Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain. EMBO J. 2000 Feb 15;19(4):504-12. [PubMed Link Image]
  3. Grishkovskaya I, Avvakumov GV, Hammond GL, Catalano MG, Muller YA: Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation. J Biol Chem. 2002 Aug 30;277(35):32086-93. Epub 2002 Jun 13. [PubMed Link Image]
  4. Power SG, Bocchinfuso WP, Pallesen M, Warmels-Rodenhiser S, Van Baelen H, Hammond GL: Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain. J Clin Endocrinol Metab. 1992 Oct;75(4):1066-70. [PubMed Link Image]
  5. Gershagen S, Lundwall A, Fernlund P: Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis. Nucleic Acids Res. 1989 Nov 25;17(22):9245-58. [PubMed Link Image]
  6. Hammond GL, Underhill DA, Rykse HM, Smith CL: The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs. Mol Endocrinol. 1989 Nov;3(11):1869-76. [PubMed Link Image]
  7. Que BG, Petra PH: Characterization of a cDNA coding for sex steroid-binding protein of human plasma. FEBS Lett. 1987 Jul 27;219(2):405-9. [PubMed Link Image]
  8. Gershagen S, Fernlund P, Lundwall A: A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S. FEBS Lett. 1987 Aug 10;220(1):129-35. [PubMed Link Image]
  9. Walsh KA, Titani K, Takio K, Kumar S, Hayes R, Petra PH: Amino acid sequence of the sex steroid binding protein of human blood plasma. Biochemistry. 1986 Nov 18;25(23):7584-90. [PubMed Link Image]
  10. Hammond GL, Underhill DA, Smith CL, Goping IS, Harley MJ, Musto NA, Cheng CY, Bardin CW: The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain. FEBS Lett. 1987 May 4;215(1):100-4. [PubMed Link Image]
  11. 3702459 Hammond GL, Robinson PA, Sugino H, Ward DN, Finne J: Physicochemical characteristics of human sex hormone binding globulin: evidence for two identical subunits. J Steroid Biochem. 1986 Apr;24(4):815-24.
  12. 7714097 Hardy DO, Carino C, Catterall JF, Larrea F: Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects. J Clin Endocrinol Metab. 1995 Apr;80(4):1253-6.
Target 2 Drug References
  1. Campusano M C, Brusco G F, Campino J C, Rodriguez P L, Arteaga U E: [Assessment of androgenic decline in the elderly] Rev Med Chil. 2006 Sep;134(9):1123-8. Epub 2006 Dec 12. [PubMed Link Image]
  2. Kuba R, Pohanka M, Zakopcan J, Novotna I, Rektor I: Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia. 2006 Dec;47(12):2135-40. [PubMed Link Image]
  3. Bendlova B, Zavadilova J, Vankova M, Vejrazkova D, Lukasova P, Vcelak J, Hill M, Cibula D, Vondra K, Starka L, Vrbikova J: Role of D327N sex hormone-binding globulin gene polymorphism in the pathogenesis of polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2007 Apr;104(1-2):68-74. Epub 2007 Jan 26. [PubMed Link Image]
  4. Sablik Z, Samborska-Sablik A, Bolinska-Soltysiak H, Goch JH, Kula K: [Hyperandrogenism as a risk factor of coronary artery disease in young women] Pol Arch Med Wewn. 2006 Feb;115(2):118-24. [PubMed Link Image]
  5. Mohamad MJ, Mohammad MA, Karayyem M, Hairi A, Hader AA: Serum levels of sex hormones in men with acute myocardial infarction. Neuro Endocrinol Lett. 2007 Apr;28(2):182-6. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 869
Target 3 Name Estrogen receptor beta
Target 3 Synonyms
  1. ER-beta
Target 3 Gene Name ESR2
Target 3 Protein Sequence >Estrogen receptor beta 
MDIKNSPSSLNSPSSYNCSQSILPLEHGSIYIPSSYVDSHHEYPAMTFYSPAVMNYSIPS
NVTNLEGGPGRQTTSPNVLWPTPGHLSPLVVHRQLSHLYAEPQKSPWCEARSLEHTLPVN
RETLKRKVSGNRCASPVTGPGSKRDAHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGH
NDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMVKCGSRRERCGYRLVRRQRSADEQLH
CAGKAKRSGGHAPRVRELLLDALSPEQLVLTLLEAEPPHVLISRPSAPFTEASMMMSLTK
LADKELVHMISWAKKIPGFVELSLFDQVRLLESCWMEVLMMGLMWRSIDHPGKLIFAPDL
VLDRDEGKCVEGILEIFDMLLATTSRFRELKLQHKEYLCVKAMILLNSSMYPLVTATQDA
DSSRKLAHLLNAVTDALVWVIAKSGISSQQQSMRLANLLMLLSHVRHASNKGMEHLLNMK
CKNVVPVYDLLLEMLNAHVLRGCKSSITGSECSPAEDSKSKEGSQNPQSQ
Target 3 Number of Residues 538
Target 3 Molecular Weight 59217
Target 3 Theoretical pI 8.55
Target 3 GO Classification
Function
ion binding
cation binding
transition metal ion binding
zinc ion binding
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 3 General Function Involved in transcription factor activity
Target 3 Specific Function Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 2911152 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q92731 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ESR2_HUMAN Link Image
Target 3 PDB ID 1QKM Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Nucleus
Target 3 Gene Sequence >1593 bp 
ATGGATATAAAAAACTCACCATCTAGCCTTAATTCTCCTTCCTCCTACAACTGCAGTCAA
TCCATCTTACCCCTGGAGCACGGCTCCATATACATACCTTCCTCCTATGTAGACAGCCAC
CATGAATATCCAGCCATGACATTCTATAGCCCTGCTGTGATGAATTACAGCATTCCCAGC
AATGTCACTAACTTGGAAGGTGGGCCTGGTCGGCAGACCACAAGCCCAAATGTGTTGTGG
CCAACACCTGGGCACCTTTCTCCTTTAGTGGTCCATCGCCAGTTATCACATCTGTATGCG
GAACCTCAAAAGAGTCCCTGGTGTGAAGCAAGATCGCTAGAACACACCTTACCTGTAAAC
AGAGAGACACTGAAAAGGAAGGTTAGTGGGAACCGTTGCGCCAGCCCTGTTACTGGTCCA
GGTTCAAAGAGGGATGCTCACTTCTGCGCTGTCTGCAGCGATTACGCATCGGGATATCAC
TATGGAGTCTGGTCGTGTGAAGGATGTAAGGCCTTTTTTAAAAGAAGCATTCAAGGACAT
AATGATTATATTTGTCCAGCTACAAATCAGTGTACAATCGATAAAAACCGGCGCAAGAGC
TGCCAGGCCTGCCGACTTCGGAAGTGTTACGAAGTGGGAATGGTGAAGTGTGGCTCCCGG
AGAGAGAGATGTGGGTACCGCCTTGTGCGGAGACAGAGAAGTGCCGACGAGCAGCTGCAC
TGTGCCGGCAAGGCCAAGAGAAGTGGCGGCCACGCGCCCCGAGTGCGGGAGCTGCTGCTG
GACGCCCTGAGCCCCGAGCAGCTAGTGCTCACCCTCCTGGAGGCTGAGCCGCCCCATGTG
CTGATCAGCCGCCCCAGTGCGCCCTTCACCGAGGCCTCCATGATGATGTCCCTGACCAAG
TTGGCCGACAAGGAGTTGGTACACATGATCAGCTGGGCCAAGAAGATTCCCGGCTTTGTG
GAGCTCAGCCTGTTCGACCAAGTGCGGCTCTTGGAGAGCTGTTGGATGGAGGTGTTAATG
ATGGGGCTGATGTGGCGCTCAATTGACCACCCCGGCAAGCTCATCTTTGCTCCAGATCTT
GTTCTGGACAGGGATGAGGGGAAATGCGTAGAAGGAATTCTGGAAATCTTTGACATGCTC
CTGGCAACTACTTCAAGGTTTCGAGAGTTAAAACTCCAACACAAAGAATATCTCTGTGTC
AAGGCCATGATCCTGCTCAATTCCAGTATGTACCCTCTGGTCACAGCGACCCAGGATGCT
GACAGCAGCCGGAAGCTGGCTCACTTGCTGAACGCCGTGACCGATGCTTTGGTTTGGGTG
ATTGCCAAGAGCGGCATCTCCTCCCAGCAGCAATCCATGCGCCTGGCTAACCTCCTGATG
CTCCTGTCCCACGTCAGGCATGCGAGTAACAAGGGCATGGAACATCTGCTCAACATGAAG
TGCAAAAATGTGGTCCCAGTGTATGACCTGCTGCTGGAGATGCTGAATGCCCACGTGCTT
CGCGGGTGCAAGTCCTCCATCACGGGGTCCGAGTGCAGCCCGGCAGAGGACAGTAAAAGC
AAAGAGGGCTCCCAGAACCCACAGTCTCAGTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID ESR2 Link Image
Target 3 GenAtlas ID ESR2 Link Image
Target 3 HGNC ID HGNC:3468 Link Image
Target 3 Chromosome Location 14
Target 3 Locus 14q23.2
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Caira F, Antonson P, Pelto-Huikko M, Treuter E, Gustafsson JA: Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem. 2000 Feb 25;275(8):5308-17. [PubMed Link Image]
  2. Li LC, Yeh CC, Nojima D, Dahiya R: Cloning and characterization of human estrogen receptor beta promoter. Biochem Biophys Res Commun. 2000 Aug 28;275(2):682-9. [PubMed Link Image]
  3. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. [PubMed Link Image]
  4. Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ: Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8. Epub 2002 Nov 1. [PubMed Link Image]
  5. Mosselman S, Polman J, Dijkema R: ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996 Aug 19;392(1):49-53. [PubMed Link Image]
  6. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. [PubMed Link Image]
  7. Pace P, Taylor J, Suntharalingam S, Coombes RC, Ali S: Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha. J Biol Chem. 1997 Oct 10;272(41):25832-8. [PubMed Link Image]
  8. Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y, Muramatsu M: The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro. Biochem Biophys Res Commun. 1998 Feb 4;243(1):122-6. [PubMed Link Image]
  9. Moore JT, McKee DD, Slentz-Kesler K, Moore LB, Jones SA, Horne EL, Su JL, Kliewer SA, Lehmann JM, Willson TM: Cloning and characterization of human estrogen receptor beta isoforms. Biochem Biophys Res Commun. 1998 Jun 9;247(1):75-8. [PubMed Link Image]
  10. Ogawa S, Inoue S, Watanabe T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M: Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human. Nucleic Acids Res. 1998 Aug 1;26(15):3505-12. [PubMed Link Image]
  11. 9685228 Lu B, Leygue E, Dotzlaw H, Murphy LJ, Murphy LC, Watson PH: Estrogen receptor-beta mRNA variants in human and murine tissues. Mol Cell Endocrinol. 1998 Mar 16;138(1-2):199-203.
Target 3 Drug References
  1. Schmidt JW, Wollner D, Curcio J, Riedlinger J, Kim LS: Hormone replacement therapy in menopausal women: Past problems and future possibilities. Gynecol Endocrinol. 2006 Oct;22(10):564-77. [PubMed Link Image]
  2. Prewitt AK, Wilson ME: Changes in estrogen receptor-alpha mRNA in the mouse cortex during development. Brain Res. 2007 Feb 23;1134(1):62-9. Epub 2007 Jan 17. [PubMed Link Image]
  3. Vijayanathan V, Greenfield NJ, Thomas TJ, Ivanova MM, Tyulmenkov VV, Klinge CM, Gallo MA, Thomas T: Effects of estradiol and 4-hydroxytamoxifen on the conformation, thermal stability, and DNA recognition of estrogen receptor beta. Biochem Cell Biol. 2007 Feb;85(1):1-10. [PubMed Link Image]
  4. Elbeltagy K, Honda KI, Ozaki K, Misugi T, Tokuyama O, Kimura M, Kira Y, Ishiko O: In vitro effect of dehydroepiandrosterone sulfate on steroid receptors, aromatase, cyclooxygenase-2 expression, and steroid hormone production in preovulatory human granulosa cells. Fertil Steril. 2007 Jun 2;. [PubMed Link Image]
  5. Foresta C, Zuccarello D, Biagioli A, De Toni L, Prana E, Nicoletti V, Ambrosini G, Ferlin A: Oestrogen stimulates endothelial progenitor cells via oestrogen receptor-alpha. Clin Endocrinol (Oxf). 2007 Oct;67(4):520-5. Epub 2007 Jun 15. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 1284
Target 4 Name Orphan nuclear receptor PXR
Target 4 Synonyms
  1. Orphan nuclear receptor PAR1
  2. Pregnane X receptor
  3. SXR
  4. Steroid and xenobiotic receptor
Target 4 Gene Name NR1I2
Target 4 Protein Sequence >Orphan nuclear receptor PXR 
MEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQICRVCGDKATGYHFNVMTCEG
CKGFFRRAMKRNARLRCPFRKGACEITRKTRRQCQACRLRKCLESGMKKEMIMSDEAVEE
RRALIKRKKSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSS
GCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLL
PHMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTVFNAETGTWE
CGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHR
VVDQLQEQFAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIHPF
ATPLMQELFGITGS
Target 4 Number of Residues 441
Target 4 Molecular Weight 49762
Target 4 Theoretical pI 8.44
Target 4 GO Classification
Function
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 4 General Function Involved in transcription factor activity
Target 4 Specific Function Orphan receptor; its natural ligand is probably pregnane. Binds to a response element in the CYP3A4 and ABCB1/MDR1 genes promoter. Activates its expression in response to a wide variety of endobiotics and xenobiotics
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 3511138 Link Image
Target 4 UniProtKB/Swiss-Prot ID O75469 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name PXR_HUMAN Link Image
Target 4 PDB ID 1NRL Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Nucleus
Target 4 Gene Sequence >1305 bp 
CTGGAGGTGAGACCCAAAGAAAGCTGGAACCATGCTGACTTTGTACACTGTGAGGACACA
GAGTCTGTTCCTGGAAAGCCCAGTGTCAACGCAGATGAGGAAGTCGGAGGTCCCCAAATC
TGCCGTGTATGTGGGGACAAGGCCACTGGCTATCACTTCAATGTCATGACATGTGAAGGA
TGCAAGGGCTTTTTCAGGAGGGCCATGAAACGCAACGCCCGGCTGAGGTGCCCCTTCCGG
AAGGGCGCCTGCGAGATCACCCGGAAGACCCGGCGACAGTGCCAGGCCTGCCGCCTGCGC
AAGTGCCTGGAGAGCGGCATGAAGAAGGAGATGATCATGTCCGACGAGGCCGTGGAGGAG
AGGCGGGCCTTGATCAAGCGGAAGAAAAGTGAACGGACAGGGACTCAGCCACTGGGAGTG
CAGGGGCTGACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAA
ACCTTTGACACTACCTTCTCCCATTTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGT
GGCTGCGAGTTGCCAGAGTCTCTGCAGGCCCCATCGAGGGAAGAAGCTGCCAAGTGGAGC
CAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTGCGGGGGGAGGATGGC
AGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTG
CCCCACATGGCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTC
ATCTCCTACTTCAGGGACTTGCCCATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCT
TTCGAGCTGTGTCAACTGAGATTCAACACAGTGTTCAACGCGGAGACTGGAACCTGGGAG
TGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTCCAGCAACTTCTACTG
GAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTAT
GTGCTGATGCAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGC
GTGGTGGACCAGCTGCAGGAGCAATTCGCCATTACTCTGAAGTCCTACATTGAATGCAAT
CGGCCCCAGCCTGCTCATAGGTTCTTGTTCCTGAAGATCATGGCTATGCTCACCGAGCTC
CGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAGGACATACACCCCTTT
GCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID NR1I2 Link Image
Target 4 GenAtlas ID NR1I2 Link Image
Target 4 HGNC ID HGNC:7968 Link Image
Target 4 Chromosome Location 3
Target 4 Locus 3q12-q13.3
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, Kliewer SA, Redinbo MR: The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science. 2001 Jun 22;292(5525):2329-33. Epub 2001 Jun 14. [PubMed Link Image]
  2. Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Wrighton SA, Hancock M, Kim RB, Strom S, Thummel K, Russell CG, Hudson JR Jr, Schuetz EG, Boguski MS: The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics. 2001 Oct;11(7):555-72. [PubMed Link Image]
  3. Kawana K, Ikuta T, Kobayashi Y, Gotoh O, Takeda K, Kawajiri K: Molecular mechanism of nuclear translocation of an orphan nuclear receptor, SXR. Mol Pharmacol. 2003 Mar;63(3):524-31. [PubMed Link Image]
  4. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA: The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998 Sep 1;102(5):1016-23. [PubMed Link Image]
  5. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Backman M, Ohlsson R, Postlind H, Blomquist P, Berkenstam A: Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12208-13. [PubMed Link Image]
  6. Blumberg B, Sabbagh W Jr, Juguilon H, Bolado J Jr, van Meter CM, Ong ES, Evans RM: SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 1998 Oct 15;12(20):3195-205. [PubMed Link Image]
Target 4 Drug References
  1. Xue Y, Moore LB, Orans J, Peng L, Bencharit S, Kliewer SA, Redinbo MR: Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition. Mol Endocrinol. 2007 May;21(5):1028-38. Epub 2007 Feb 27. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.