Canmetcon

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COMPOUND IDENTIFICATION

General description

Accession Number FDB011828
Name Genistein
Version 1.0
Creation Date 2010-08-10 16:28:32
Update Date 2010-08-20 13:35:16
Description Genistein is a phenolic compound belonging to the isoflavonoid group. Isoflavonoids are found mainly in soybean. Genistein and daidzein (another isoflavonoid) represent the major phytochemicals found in this plant. Health benefits (e.g. reduced risk for certain cancers and diseases of old age) associated to soya products consumption have been observed in East Asian populations and several epidemiological studies. This association has been linked to the action of isoflavonoids. With a chemical structure similar to the hormone 17-beta-estradiol, soy isoflavones are able to interact with the estrogen receptor. They also possess numerous biological activities. (1)
Synonyms
  • 4',5,7-Trihydroxyisoflavone
  • 5,7,4'-Trihydroxyisoflavone
  • 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4-benzopyrone
  • 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-Benzopyran-4-one
  • 5,7-Dihydroxy-3-(4-hydroxyphenyl)chromen-4-one
  • Bonistein
  • Differenol A
  • Genestein
  • Genisteol
  • Genisterin
  • Prunetol
  • Sophoricol
Chemical IUPAC Name 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one

Chemical information

Structure Structure
Chemical Formula C15H10O5
InChI Identifier InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H
InChI Key InChIKey=TZBJGXHYKVUXJN-UHFFFAOYSA-N
Isomeric SMILES OC1=CC=C(C=C1)C1=COC2=C(C(O)=CC(O)=C2)C1=O
Canonical SMILES OC1=CC=C(C=C1)C1=COC2=C(C(O)=CC(O)=C2)C1=O
Average Molecular Weight 270.2369
Monoisotopic Molecular Weight 270.052823430

Chemical taxonomy

Type Natural compound
Family Plant metabolite
Kingdom Organic
Super Class Alcohols
Class Polyphenols
Sub-class Isoflavonoids
Sub-structures
  • phenol or hydroxyhetarene
  • oxo(het)arene
  • aromatic compound
  • heterocyclic compound

Physico-chemical properties

Property Value Source
State Solid BioSpider
Physical Description Prisms (EtOH aq.) DFC
Mass Composition C66.67%; H3.73%; O29.60% [JChem] Calculated from structure
Melting Point 301-302° C DFC
Boiling Point Not Available Not Available
Experimental Water Solubility Not Available Not Available
Predicted Water Solubility 1.23e-01 g/l Calculated from structure
Experimental LogP/Hydrophobicity Not Available Not Available
Predicted LogP/Hydrophobicity 3.04 [aLOGPs]
3.08 [JChem]
Calculated from structure
Predicted LogS -3.34 [aLOGPs] Calculated from structure
Experimental pKa Not Available Not Available
Predicted acidic pKa 8.79 [JChem] Calculated from structure
Predicted basic pKa -5.35 [JChem] Calculated from structure
Isoelectric Point Not Available Not Available
Charge Not Available Not Available
Optical Rotation Not Available Not Available
Spectroscopic UV Data [neutral] lmax 261 (e 38500) (MeOH) (Derep) DFC
Density Not Available Not Available
Refractive Index Not Available Not Available

Linkouts

CAS Registry Number 446-72-0
DFC GZR02
EAFUS Not Available
DrugBank DB01645
HMDB HMDB03217
KEGG compound C06563
Pubchem compound 5280961
Pubchem substance 10318994
ChEBI 28088
Phenol-Explorer 396
Dr. Duke GENISTEIN
BIGG Not Available
KNApSAcK C00002526
Wikipedia Genistein
PDB Not Available

FOOD COMPOSITION

Food contents

Food name Content range
(ppm)
Content
(mg/100 g FW)
Analytical method Citations
Soy, flour - 42.83 After hydrolysis (9)
Soybean, roasted (soy nut) - 36.26 After hydrolysis (9)
Soybean, sprout, raw - 30.76 After hydrolysis (9)
Soybean, green (edamame) - 14.4 After hydrolysis (9)
Soy, tofu - 11.23 After hydrolysis (9)
Soy, tempe - 10.72 After hydrolysis (9)
Soy, flour - 51.4 After hydrolysis (10)
Soy, flour - 50.1 After hydrolysis (10)
Soy, flour - 46.3 After hydrolysis (10)
Soy, flour - 50.6 After hydrolysis (10)
Soy, Hypocotyl 242-247 - Unspecified (11)
Soy, Cotyledon 28-59 - Unspecified (11)

BIOLOGICAL EFFECTS

Biological effects overview

Health benefits
  • Post-menopausal conditions improvement (osteoporosis) (1)
  • Cancer chemoprevention (breast cancer, prostate cancer, endometrial cancer) (1)
  • Cardiovascular disease prevention (atherosclerosis, coronary heart disease) (1)
Adverse effects Not Available
Mechanisms of action
  • Post menopausal conditions improvement: Phytoestrogenic activity and estrogen receptor modulation (1,6)
  • Cancer prevention: Stimulates p53, antioxidant enzymes activities, BRCA2, caspase-3 and apoptosis, chloride efflux; Increases TGFb concentrations; Suppresses activation of NF-kappa B, matrix metalloproteinases, lipogenesis, COX-2; Inhibits signal transduction enzymes, tyrosine protein kinases, MAP kinase, ribosomal s6 kinase, DNA topoisomerase II activity (1,6)
  • Cardiovascular diseases prevention: Diminution of platelet agregation and thrombogenesis; Reduction of blood cholesterol level, blood lipids, LDL oxidation, homocysteine, blood pressure (1,6)
Bioactivities
  • anti-estrogenic (1,6)
  • anti-oxidant (1,6)
  • anti-platelet aggregation (1,6)
  • anti-thrombosis (1,6)
  • cancer cell growth inhibition (1,6)
  • estrogenic (1,6)
  • selective estrogen receptor modulator (SERM) (1,6)

METABOLISM

Metabolism overview

Biosynthesis Isoflavones are synthesized by a branch of the phenylpropanoid pathway of secondary metabolism. Isoflavone synthase (IFS) catalyzes the oxidation of naringenin to genistein. Conversion of naringenin to genistein occurs in two steps. In the first step naringenin is converted to a 2-hydroxyisoflavanone. This conversion requires NADPH, oxygen and cytochrome P-450. In the second step 2-hydroxyisoflavanone is converted to genistein by dehydration, this does not require NADPH or oxygen. (3,4)
Absorption Soy isoflavones (genistein, daidzein, and their glucosides) are absorbed in the small intestine after deglycosylation. A part of deglycosylation is catalyzed by colon microflora, but most of it is carried out by the enterocyte brush border enzyme lactase phlorizin hydrolase (LPH). Some studies also suggest that a small portion of the glycosides could be absorbed from the gut. (2,7)
Distribution Not Available
Metabolism After deglycosylation and absorption through the small intestine, the aglycone genistein is carried via the blood to the liver where it is converted into glucuronides and sulfates. The proportion of aglycone found in blood decreases with time owing to further conjugation: most of the absorbed genistein is found conjugated in plasma. The aglycone was initially thought to be the active form, however conjugated forms could exert biological activities as well. (1,2,7)
Excretion Most absorbed isoflavones are excreted as conjugates into the urine, but a smaller percentage undergoes enterohepatic recycling. (5)

Bioavailability / Pharmacokinetic values

Cmax
(μM)
tmax
(h)
t1/2
(h)
AUC
(μM x h)
Urinary Excretion
(% ± SD)
Fecal Excretion
(% ± SD)
Citations

4.09 ± 0.94

8.00 ± 0.68

5.74 ± 1.27

Not calculated

22 ± 4

-

(12)

0.8 ± 0.1

8.2 ± 1.0

16.6 ± 5.3

20 ± 5

(Calculation based on two studies)

18 ± 3

-

(13)

0.8 ± 0.1

7.3 ± 0.2

17.8 ± 2.7

21 ± 4

(Calculation based on two studies)

20 ± 2

-

(13)

0.53 ± 0.33

(Aglycones)

Varying, some subjects lack 2nd peak

-

8.3 ± 4.2

(Aglycones)

-

-

(14)

0.57 ± 0.29

(Glucosides)

Varying, some subjects lack 2nd peak

-

8.9 ± 4.7

(Glucosides)

-

-

(14)

* These data have been adapted from “Table 1 Summary of Human Studies Measuring Isoflavone Bioavailability via Plasma, Urine, or Feces” in Nielsen and Williamson: Review of the factors affecting bioavailability of soy isoflavones in humans. Nutrition and Cancer. 2007;57(1):1-10. (2)

Metabolites

Name HMDB_ID Citations
Dihydrogenistein HMDB05897 (7)
6'-Hydroxy-O-demethyl-angolensin Not Available (7)
Genistein 7-glucuronide-4′-sulfate Not Available (8)
Genistein 4′,7-diglucuronide Not Available (8)
Genistein 7-glucuronide Not Available (8)
Genistein 4'-glucuronide Not Available (8)
Genistein 4′,7-disulfate Not Available (8)
Genistein 7-sulfate Not Available (8)
Genistein 4′-sulfate Not Available (8)

Pathways

Pathway Database Pathway ID Pathway Name Organism
MetaCyc PWY-2083 Isoflavonoid biosynthesis II Core eudicotyledons
KEGG map00943 Isoflavonoid biosynthesis Not Available

Metabolic enzymes

Enzyme Pathway name and links Type Pathway
1. 2-Hydroxyisoflavanone dehydratase
  • Isoflavonoid biosynthesis II (MetaCyc: PWY-2083)
  • Isoflavonoid biosynthesis (KEGG: map00943)
Biosynthesis in plants
2. UDP-glucuronosyltransferase 1-6 precursor
Metabolism
3. UDP-sulfotransferase
Metabolism

Targets

Target Pathway name and links Type Pathway
1. DNA topoisomerase 2-alpha
2. Estrogen receptor beta
3. Protein tyrosine kinase 2 beta

Transporters

Transporter Reference

METABOLIC ENZYME, TARGET AND TRANSPORTER DETAILS

Enzyme 1
Enzyme 1 Name Putative uncharacterized protein
Enzyme 1 Synonyms
  1. 2-hydroxyisoflavanone dehydratase
Enzyme 1 Gene Name HIDH
Enzyme 1 Protein Sequence >Putative uncharacterized protein
  MAKEIVKELLPLIRVYKDGSVERLLSSENVAASPEDPQTGVSSKDIVIADNPYVSARIFLPKSHHTNNKL
  PIFLYFHGGAFCVESAFSFFVHRYLNILASEANIIAISVDFRLLPHHPIPAAYEDGWTTLKWIASHANNT
  NTTNPEPWLLNHADFTKVYVGGETSGANIAHNLLLRAGNESLPGDLKILGGLLCCPFFWGSKPIGSEAVE
  GHEQSLAMKVWNFACPDAPGGIDNPWINPCVPGAPSLATLACSKLLVTITGKDEFRDRDILYHHTVEQSG
  WQGELQLFDAGDEEHAFQLFKPETHLAKAMIKRLASFLV
Enzyme 1 Number of Residues 319
Enzyme 1 Molecular Weight 35137.7
Enzyme 1 Theoretical pI 6.14
Enzyme 1 GO Classification
Function
  • catalytic activity
  • hydrolase activity
Process
  • physiological process
  • metabolism
Component Not Available
Enzyme 1 General Function Lipid transport and metabolism
Enzyme 1 Specific Function Not Available
Enzyme 1 Pathways Not Available
Enzyme 1 Reactions Not Available
Enzyme 1 Pfam Domain Function
Enzyme 1 Signals None
Enzyme 1 Transmembrane Regions None
Enzyme 1 Essentiality Essential
Enzyme 1 GenBank ID Protein 255644388
Enzyme 1 UniProtKB/Swiss-Prot ID Q5NUF3
Enzyme 1 UniProtKB/Swiss-Prot Entry Name Q5NUF3_SOYBN
Enzyme 1 PDB ID Not Available
Enzyme 1 Cellular Location
  • Cytoplasmic
Enzyme 1 Gene Sequence >960 bp
  ATGGCGAAGGAGATAGTGAAAGAGCTTCTTCCTCTAATTCGAGTGTACAAGGATGGCAGCGTGGAGCGTC
  TTCTAAGCTCTGAAAACGTGGCAGCCTCCCCTGAAGATCCCCAAACTGGAGTCTCATCCAAAGACATAGT
  CATCGCAGACAACCCCTACGTCTCCGCTCGCATTTTCCTTCCCAAATCCCACCACACTAACAACAAACTC
  CCCATCTTCCTCTACTTCCACGGTGGCGCCTTTTGCGTCGAATCCGCCTTCTCCTTTTTCGTCCACCGCT
  ATCTCAACATCTTGGCCTCAGAAGCCAACATAATAGCCATCTCCGTCGACTTCAGACTCCTCCCACACCA
  CCCTATCCCTGCTGCCTACGAAGACGGTTGGACCACCCTCAAATGGATTGCTTCCCACGCCAACAACACC
  AACACCACCAACCCGGAGCCATGGCTACTCAACCACGCCGACTTCACCAAAGTCTACGTAGGAGGTGAAA
  CCAGCGGTGCTAACATCGCACACAACCTGCTTTTGCGTGCAGGTAACGAATCCCTCCCCGGGGATCTGAA
  AATATTGGGTGGATTACTATGCTGCCCCTTCTTCTGGGGCTCGAAGCCAATTGGGTCGGAGGCTGTTGAG
  GGGCACGAGCAGAGTTTGGCCATGAAGGTCTGGAACTTTGCCTGCCCTGATGCCCCCGGTGGAATCGATA
  ACCCCTGGATCAACCCCTGTGTTCCTGGGGCACCCTCTTTGGCCACTCTTGCCTGCTCTAAGTTGCTCGT
  TACTATCACTGGCAAAGACGAGTTCAGAGACAGAGATATTCTCTACCACCACACCGTTGAGCAAAGTGGC
  TGGCAAGGTGAACTTCAACTCTTTGATGCTGGCGATGAGGAGCATGCTTTCCAGCTCTTCAAGCCTGAGA
  CTCATCTTGCTAAAGCCATGATCAAACGCTTGGCTTCTTTTCTGGTTTGA
  
Enzyme 1 GenBank Gene ID BT097440
Enzyme 1 GeneCard ID HIDH
Enzyme 1 GenAtlas ID Not Available
Enzyme 1 HGNC ID Not Available
Enzyme 1 Chromosome Location Not Available
Enzyme 1 Locus Not Available
Enzyme 1 SNPs Not Available
Enzyme 1 General References
  1. Akashi T, Aoki T, Ayabe S: Molecular and biochemical characterization of 2-hydroxyisoflavanone dehydratase. Involvement of carboxylesterase-like proteins in leguminous isoflavone biosynthesis. Plant Physiol. 2005 Mar;137(3):882-91. Epub 2005 Feb 25. [PubMed]
Enzyme 2
Enzyme 2 Name UDP-glucuronosyltransferase 1-6 precursor
Enzyme 2 Synonyms
  1. UDP- glucuronosyltransferase 1A6
  2. UDPGT
  3. UGT1*6
  4. UGT1-06
  5. UGT1.6
  6. UGT- 1F
  7. UGT1F
  8. Phenol-metabolizing UDP-glucuronosyltransferase
Enzyme 2 Gene Name UGT1A6
Enzyme 2 Protein Sequence >UDP-glucuronosyltransferase 1-6 precursor
  MACLLRSFQRISAGVFFLALWGMVVGDKLLVVPQDGSHWLSMKDIVEVLSDRGHEIVVVV
  PEVNLLLKESKYYTRKIYPVPYDQEELKNRYQSFGNNHFAERSFLTAPQTEYRNNMIVIG
  LYFINCQSLLQDRDTLNFFKESKFDALFTDPALPCGVILAEYLGLPSVYLFRGFPCSLEH
  TFSRSPDPVSYIPRCYTKFSDHMTFSQRVANFLVNLLEPYLFYCLFSKYEELASAVLKRD
  VDIITLYQKVSVWLLRYDFVLEYPRPVMPNMVFIGGINCKKRKDLSQEFEAYINASGEHG
  IVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLL
  GHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSE
  DLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDL
  TWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Enzyme 2 Number of Residues 532
Enzyme 2 Molecular Weight 60751
Enzyme 2 Theoretical pI 8.55
Enzyme 2 GO Classification
Function
  • catalytic activity
  • transferase activity
  • transferase activity, transferring glycosyl groups
  • transferase activity, transferring hexosyl groups
Process
  • metabolism
  • physiological process
Component Not Available
Enzyme 2 General Function Carbohydrate transport and metabolism
Enzyme 2 Specific Function UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols
Enzyme 2 Pathways
Enzyme 2 Reactions
  • UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside
Enzyme 2 Pfam Domain Function
Enzyme 2 Signals
  • 1-26
Enzyme 2 Transmembrane Regions
  • 490-506
Enzyme 2 Essentiality Not Available
Enzyme 2 GenBank ID Protein 340141
Enzyme 2 UniProtKB/Swiss-Prot ID P19224
Enzyme 2 UniProtKB/Swiss-Prot Entry Name UD16_HUMAN
Enzyme 2 PDB ID Not Available
Enzyme 2 Cellular Location Not Available
Enzyme 2 Gene Sequence >861 bp
  ATGGCCTGCCTCCTTCGCTCATTTCAGAGAATTTCTGCAGGGGTTTTCTTCTTAGCACTT
  TGGGGCATGGTTGTAGGTGACAAGCTGCTGGTGGTCCCTCAGGACGGAAGCCACTGGCTT
  AGTATGAAGGATATAGTTGAGGTTCTCAGTGACCGGGGTCATGAGATTGTAGTGGTGGTG
  CCTGAAGTTAATTTGCTTTTGAAAGAATCCAAATACTACACAAGAAAAATCTATCCAGTG
  CCGTATGACCAAGAAGAGCTGAAGAACCGTTACCAATCATTTGGAAACAATCACTTTGCT
  GAGCGATCATTCCTAACTGCTCCTCAGACAGAGTACAGGAATAACATGATTGTTATTGGC
  CTGTACTTCATCAACTGCCAGAGCCTCCTGCAGGACAGGGACACCCTGAACTTCTTTAAG
  GAGAGCAAGTTTGATGCTCTTTTCACAGACCCAGCCTTACCCTGTGGGGTGATCCTGGCT
  GAGTATTTGGGCCTACCATCTGTGTACCTCTTCAGGGGTTTTCCGTGTTCCCTGGAGCAT
  ACATTCAGCAGAAGCCCAGACCCTGTGTCCTACATTCCCAGGTGCTACACAAAGTTTTCA
  GACCACATGACTTTTTCCCAACGAGTGGCCAACTTCCTTGTTAATTTGTTGGAGCCCTAT
  CTATTTTATTGTCTGTTTTCAAAGTATGAAGAACTCGCATCAGCTGTCCTCAAGAGAGAT
  GTGGATATAATCACCTTATATCAGAAGGTCTCTGTTTGGCTGTTAAGATATGACTTTGTG
  CTTGAATATCCTAGGCCGGTCATGCCCAACATGGTCTTCATTGGAGGTATCAACTGTAAG
  AAGAGGAAAGACTTGTCTCAG
Enzyme 2 GenBank Gene ID M84130
Enzyme 2 GeneCard ID UGT1A6
Enzyme 2 GenAtlas ID UGT1A6
Enzyme 2 HGNC ID HGNC:12538
Enzyme 2 Chromosome Location Not Available
Enzyme 2 Locus Not Available
Enzyme 2 SNPs SNPJam Report
Enzyme 2 General References
  1. Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS: A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem. 1992 Feb 15;267(5):3257-61. [PubMed]
  2. Harding D, Fournel-Gigleux S, Jackson MR, Burchell B: Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8381-5. [PubMed]
  3. Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC: Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. Pharmacogenetics. 2001 Jun;11(4):357-68. [PubMed]
  4. Munzel PA, Lehmkoster T, Bruck M, Ritter JK, Bock KW: Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6. Arch Biochem Biophys. 1998 Feb 1;350(1):72-8. [PubMed]
  5. Ciotti M, Marrone A, Potter C, Owens IS: Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications. Pharmacogenetics. 1997 Dec;7(6):485-95. [PubMed]

Molecular Targets

Target 1
Target 1 Name DNA topoisomerase 2-alpha
Target 1 Synonyms
  1. DNA topoisomerase II, alpha isozyme
  2. EC 5.99.1.3
Target 1 Gene Name TOP2A
Target 1 Protein Sequence >DNA topoisomerase 2-alpha
  MEVSPLQPVNENMQVNKIKKNEDAKKRLSVERIYQKKTQLEHILLRPDTYIGSVELVTQQ
  MWVYDEDVGINYREVTFVPGLYKIFDEILVNAADNKQRDPKMSCIRVTIDPENNLISIWN
  NGKGIPVVEHKVEKMYVPALIFGQLLTSSNYDDDEKKVTGGRNGYGAKLCNIFSTKFTVE
  TASREYKKMFKQTWMDNMGRAGEMELKPFNGEDYTCITFQPDLSKFKMQSLDKDIVALMV
  RRAYDIAGSTKDVKVFLNGNKLPVKGFRSYVDMYLKDKLDETGNSLKVIHEQVNHRWEVC
  LTMSEKGFQQISFVNSIATSKGGRHVDYVADQIVTKLVDVVKKKNKGGVAVKAHQVKNHM
  WIFVNALIENPTFDSQTKENMTLQPKSFGSTCQLSEKFIKAAIGCGIVESILNWVKFKAQ
  VQLNKKCSAVKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAVSGLGVVGRDK
  YGVFPLRGKILNVREASHKQIMENAEINNIIKIVGLQYKKNYEDEDSLKTLRYGKIMIMT
  DQDQDGSHIKGLLINFIHHNWPSLLRHRFLEEFITPIVKVSKNKQEMAFYSLPEFEEWKS
  STPNHKKWKVKYYKGLGTSTSKEAKEYFADMKRHRIQFKYSGPEDDAAISLAFSKKQIDD
  RKEWLTNFMEDRRQRKLLGLPEDYLYGQTTTYLTYNDFINKELILFSNSDNERSIPSMVD
  GLKPGQRKVLFTCFKRNDKREVKVAQLAGSVAEMSSYHHGEMSLMMTIINLAQNFVGSNN
  LNLLQPIGQFGTRLHGGKDSASPRYIFTMLSSLARLLFPPKDDHTLKFLYDDNQRVEPEW
  YIPIIPMVLINGAEGIGTGWSCKIPNFDVREIVNNIRRLMDGEEPLPMLPSYKNFKGTIE
  ELAPNQYVISGEVAILNSTTIEISELPVRTWTQTYKEQVLEPMLNGTEKTPPLITDYREY
  HTDTTVKFVVKMTEEKLAEAERVGLHKVFKLQTSLTCNSMVLFDHVGCLKKYDTVLDILR
  DFFELRLKYYGLRKEWLLGMLGAESAKLNNQARFILEKIDGKIIIENKPKKELIKVLIQR
  GYDSDPVKAWKEAQQKVPDEEENEESDNEKETEKSDSVTDSGPTFNYLLDMPLWYLTKEK
  KDELCRLRNEKEQELDTLKRKSPSDLWKEDLATFIEELEAVEAKEKQDEQVGLPGKGGKA
  KGKKTQMAEVLPSPRGQRVIPRITIEMKAEAEKKNKKKIKNENTEGSPQEDGVELEGLKQ
  RLEKKQKREPGTKTKKQTTLAFKPIKKGKKRNPWSDSESDRSSDESNFDVPPRETEPRRA
  ATKTKFTMDLDSDEDFSDFDEKTDDEDFVPSDASPPKTKTSPKLSNKELKPQKSVVSDLE
  ADDVKGSVPLSSSPPATHFPDETEITNPVPKKNVTVKKTAAKSQSSTSTTGAKKRAAPKG
  TKRDPALNSGVSQKPDPAKTKNRRKRKPSTSDDSDSNFEKIVSKAVTSKKSKGESDDFHM
  DFDSAVAPRAKSVRAKKPIKYLEESDEDDLF
Target 1 Number of Residues 1556
Target 1 Molecular Weight 174387
Target 1 Theoretical pI 9.17
Target 1 GO Classification
Function
  • DNA topoisomerase (ATP-hydrolyzing) activity
  • DNA topoisomerase activity
  • DNA topoisomerase (ATP-hydrolyzing) activity
  • nucleic acid binding
  • DNA binding
  • binding
  • nucleotide binding
  • purine nucleotide binding
  • adenyl nucleotide binding
  • ATP binding
Process
  • DNA topological change
  • physiological process
  • metabolism
  • cellular metabolism
  • nucleobase, nucleoside, nucleotide and nucleic acid metabolism
  • DNA metabolism
Component Not Available
Target 1 General Function Replication, recombination and repair
Target 1 Specific Function Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks
Target 1 Pathways Not Available
Target 1 Reactions
  • ATP-dependent breakage, passage and rejoining of double-stranded DNA INHIBITOR Coumermycin A1; GRI22222X; Nalidixic acid; Novobiocin; Ciprofloxacin
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 292830
Target 1 UniProtKB/Swiss-Prot ID P11388
Target 1 UniProtKB/Swiss-Prot Entry Name TOP2A_HUMAN
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Cytoplasm. Nucleus
  • nucleoplasm. Generally located in the nucleoplasm
Target 1 Gene Sequence >4596 bp
  ATGGAAGTGTCACCATTGCAGCCTGTAAATGAAAATATGCAAGTCAACAAAATAAAGAAA
  AATGAAGATGCTAAGAAAAGACTGTCTGTTGAAAGAATCTATCAAAAGAAAACACAATTG
  GAACATATTTTGCTCCGCCCAGACACCTACATTGGTTCTGTGGAATTAGTGACCCAGCAA
  ATGTGGGTTTACGATGAAGATGTTGGCATTAACTATAGGGAAGTCACTTTTGTTCCTGGT
  TTGTACAAAATCTTTGATGAGATTCTAGTTAATGCTGCGGACAACAAACAAAGGGACCCA
  AAAATGTCTTGTATTAGAGTCACAATTGATCCGGAAAACAATTTAATTAGTATATGGAAT
  AATGGAAAAGGTATTCCTGTTGTTGAACACAAAGTTGAAAAGATGTATGTCCCAGCTCTC
  ATATTTGGACAGCTCCTAACTTCTAGTAACTATGATGATGATGAAAAGAAAGTGACAGGT
  GGTCGAAATGGCTATGGAGCCAAATTGTGTAACATATTCAGTACCAAATTTACTGTGGAA
  ACAGCCAGTAGAGAATACAAGAAAATGTTCAAACAGACATGGATGGATAATATGGGAAGA
  GCTGGTGAGATGGAACTCAAGCCCTTCAATGGAGAAGATTATACATGTATCACCTTTCAG
  CCTGATTTGTCTAAGTTTAAAATGCAAAGCCTGGACAAAGATATTGTTGCACTAATGGTC
  AGAAGAGCATATGATATTGCTGGATCCACCAAAGATGTCAAAGTCTTTCTTAATGGAAAT
  AAACTGCCAGTAAAAGGATTTCGTAGTTATGTGGACATGTATTTGAAGGACAAGTTGGAT
  GAAACTGGTAACTCCTTGAAAGTAATACATGAACAAGTAAACCACAGGTGGGAAGTGTGT
  TTAACTATGAGTGAAAAAGGCTTTCAGCAAATTAGCTTTGTCAACAGCATTGCTACATCC
  AAGGGTGGCAGACATGTTGATTATGTAGCTGATCAGATTGTGACTAAACTTGTTGATGTT
  GTGAAGAAGAAGAACAAGGGTGGTGTTGCAGTAAAAGCACATCAGGTGAAAAATCACATG
  TGGATTTTTGTAAATGCCTTAATTGAAAACCCAACCTTTGACTCTCAGACAAAAGAAAAC
  ATGACTTTACAACCCAAGAGCTTTGGATCAACATGCCAATTGAGTGAAAAATTTATCAAA
  GCTGCCATTGGCTGTGGTATTGTAGAAAGCATACTAAACTGGGTGAAGTTTAAGGCCCAA
  GTCCAGTTAAACAAGAAGTGTTCAGCTGTAAAACATAATAGAATCAAGGGAATTCCCAAA
  CTCGATGATGCCAATGATGCAGGGGGCCGAAACTCCACTGAGTGTACGCTTATCCTGACT
  GAGGGAGATTCAGCCAAAACTTTGGCTGTTTCAGGCCTTGGTGTGGTTGGGAGAGACAAA
  TATGGGGTTTTCCCTCTTAGAGGAAAAATACTCAATGTTCGAGAAGCTTCTCATAAGCAG
  ATCATGGAAAATGCTGAGATTAACAATATCATCAAGATTGTGGGTCTTCAGTACAAGAAA
  AACTATGAAGATGAAGATTCATTGAAGACGCTTCGTTATGGGAAGATAATGATTATGACA
  GATCAGGACCAAGATGGTTCCCACATCAAAGGCTTGCTGATTAATTTTATCCATCACAAC
  TGGCCCTCTCTTCTGCGACATCGTTTTCTGGAGGAATTTATCACTCCCATTGTAAAGGTA
  TCTAAAAACAAGCAAGAAATGGCATTTTACAGCCTTCCTGAATTTGAAGAGTGGAAGAGT
  TCTACTCCAAATCATAAAAAATGGAAAGTCAAATATTACAAAGGTTTGGGCACCAGCACA
  TCAAAGGAAGCTAAAGAATACTTTGCAGATATGAAAAGACATCGTATCCAGTTCAAATAT
  TCTGGTCCTGAAGATGATGCTGCTATCAGCCTGGCCTTTAGCAAAAAACAGATAGATGAT
  CGAAAGGAATGGTTAACTAATTTCATGGAGGATAGAAGACAACGAAAGTTACTTGGGCTT
  CCTGAGGATTACTTGTATGGACAAACTACCACATATCTGACATATAATGACTTCATCAAC
  AAGGAACTTATCTTGTTCTCAAATTCTGATAACGAGAGATCTATCCCTTCTATGGTGGAT
  GGTTTGAAACCAGGTCAGAGAAAGGTTTTGTTTACTTGCTTCAAACGGAATGACAAGCGA
  GAAGTAAAGGTTGCCCAATTAGCTGGATCAGTGGCTGAAATGTCTTCTTATCATCATGGT
  GAGATGTCACTAATGATGACCATTATCAATTTGGCTCAGAATTTTGTGGGTAGCAATAAT
  CTAAACCTCTTGCAGCCCATTGGTCAGTTTGGTACCAGGCTACATGGTGGCAAGGATTCT
  GCTAGTCCACGATACATCTTTACAATGCTCAGCTCTTTGGCTCGATTGTTATTTCCACCA
  AAAGATGATCACACGTTGAAGTTTTTATATGATGACAACCAGCGTGTTGAGCCTGAATGG
  TACATTCCTATTATTCCCATGGTGCTGATAAATGGTGCTGAAGGAATCGGTACTGGGTGG
  TCCTGCAAAATCCCCAACTTTGATGTGCGTGAAATTGTAAATAACATCAGGCGTTTGATG
  GATGGAGAAGAACCTTTGCCAATGCTTCCAAGTTACAAGAACTTCAAGGGTACTATTGAA
  GAACTGGCTCCAAATCAATATGTGATTAGTGGTGAAGTAGCTATTCTTAATTCTACAACC
  ATTGAAATCTCAGAGCTTCCCGTCAGAACATGGACCCAGACATACAAAGAACAAGTTCTA
  GAACCCATGTTGAATGGCACCGAGAAGACACCTCCTCTCATAACAGACTATAGGGAATAC
  CATACAGATACCACTGTGAAATTTGTTGTGAAGATGACTGAAGAAAAACTGGCAGAGGCA
  GAGAGAGTTGGACTACACAAAGTCTTCAAACTCCAAACTAGTCTCACATGCAACTCTATG
  GTGCTTTTTGACCACGTAGGCTGTTTAAAGAAATATGACACGGTGTTGGATATTCTAAGA
  GACTTTTTTGAACTCAGACTTAAATATTATGGATTAAGAAAAGAATGGCTCCTAGGAATG
  CTTGGTGCTGAATCTGCTAAACTGAATAATCAGGCTCGCTTTATCTTAGAGAAAATAGAT
  GGCAAAATAATCATTGAAAATAAGCCTAAGAAAGAATTAATTAAAGTTCTGATTCAGAGG
  GGATATGATTCGGATCCTGTGAAGGCCTGGAAAGAAGCCCAGCAAAAGGTTCCAGATGAA
  GAAGAAAATGAAGAGAGTGACAACGAAAAGGAAACTGAAAAGAGTGACTCCGTAACAGAT
  TCTGGACCAACCTTCAACTATCTTCTTGATATGCCCCTTTGGTATTTAACCAAGGAAAAG
  AAAGATGAACTCTGCAGGCTAAGAAATGAAAAAGAACAAGAGCTGGACACATTAAAAAGA
  AAGAGTCCATCAGATTTGTGGAAAGAAGACTTGGCTACATTTATTGAAGAATTGGAGGCT
  GTTGAAGCCAAGGAAAAACAAGATGAACAAGTCGGACTTCCTGGGAAAGGGGGGAAGGCC
  AAGGGGAAAAAAACACAAATGGCTGAAGTTTTGCCTTCTCCGCGTGGTCAAAGAGTCATT
  CCACGAATAACCATAGAAATGAAAGCAGAGGCAGAAAAGAAAAATAAAAAGAAAATTAAG
  AATGAAAATACTGAAGGAAGCCCTCAAGAAGATGGTGTGGAACTAGAAGGCCTAAAACAA
  AGATTAGAAAAGAAACAGAAAAGAGAACCAGGTACAAAGACAAAGAAACAAACTACATTG
  GCATTTAAGCCAATCAAAAAAGGAAAGAAGAGAAATCCCTGGCCTGATTCAGAATCAGAT
  AGGAGCAGTGACGAAAGTAATTTTGATGTCCCTCCACGAGAAACAGAGCCACGGAGAGCA
  GCAACAAAAACAAAATTCACAATGGATTTGGATTCAGATGAAGATTTCTCAGATTTTGAT
  GAAAAAACTGATGATGAAGATTTTGTCCCATCAGATGCTAGTCCACCTAAGACCAAAACT
  TCCCCAAAACTTAGTAACAAAGAACTGAAACCACAGAAAAGTGTCGTGTCAGACCTTGAA
  GCTGATGATGTTAAGGGCAGTGTACCACTGTCTTCAAGCCCTCCTGCTACACATTTCCCA
  GATGAAACTGAAATTACAAACCCAGTTCCTAAAAAGAATGTGACAGTGAAGAAGACAGCA
  GCAAAAAGTCAGTCTTCCACCTCCACTACCGGTGCCAAAAAAAGGGCTGCCCCAAAAGGA
  ACTAAAAGGGATCCAGCTTTGAATTCTGGTGTCTCTCAAAAGCCTGATCCTGCCAAAACC
  AAGAATCGCCGCAAAAGGAAGCCATCCACTTCTGATGATTCTGACTCTAATTTTGAGAAA
  ATTGTTTCGAAAGCAGTCACAAGCAAGAAATCCAAGGGGGAGAGTGATGACTTCCATATG
  GACTTTGACTCAGCTGTGGCTCCTCGGGCAAAATCTGTACGGGCAAAGAAACCTATAAAG
  TACCTGGAAGAGTCAGATGAAGATGATCTGTTTTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID TOP2A
Target 1 GenAtlas ID TOP2A
Target 1 HGNC ID HGNC:11989
Target 1 Chromosome Location 17
Target 1 Locus 17q21-q22
Target 1 SNPs SNPJam Report
Target 1 General References
  1. Sng JH, Heaton VJ, Bell M, Maini P, Austin CA, Fisher LM: Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication. Biochim Biophys Acta. 1999 Mar 19;1444(3):395-406. [PubMed]
  2. Escargueil AE, Plisov SY, Filhol O, Cochet C, Larsen AK: Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. J Biol Chem. 2000 Nov 3;275(44):34710-8. [PubMed]
  3. Mirski SE, Bielawski JC, Cole SP: Identification of functional nuclear export sequences in human topoisomerase IIalpha and beta. Biochem Biophys Res Commun. 2003 Jul 11;306(4):905-11. [PubMed]
  4. Hinds M, Deisseroth K, Mayes J, Altschuler E, Jansen R, Ledley FD, Zwelling LA: Identification of a point mutation in the topoisomerase II gene from a human leukemia cell line containing an amsacrine-resistant form of topoisomerase II. Cancer Res. 1991 Sep 1;51(17):4729-31. [PubMed]
  5. Bugg BY, Danks MK, Beck WT, Suttle DP: Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7654-8. [PubMed]
  6. Tsai-Pflugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC: Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177-81. [PubMed]
  7. Wasserman RA, Austin CA, Fisher LM, Wang JC: Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. Cancer Res. 1993 Aug 1;53(15):3591-6. [PubMed]
  8. Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP: Structural organization of the human TOP2A and TOP2B genes. Gene. 1998 Oct 23;221(2):255-66. [PubMed]
Target 2
Target 2 Name Estrogen receptor beta
Target 2 Synonyms
  1. ER-beta
Target 2 Gene Name ESR2
Target 2 Protein Sequence >Estrogen receptor beta
  MDIKNSPSSLNSPSSYNCSQSILPLEHGSIYIPSSYVDSHHEYPAMTFYSPAVMNYSIPS
  NVTNLEGGPGRQTTSPNVLWPTPGHLSPLVVHRQLSHLYAEPQKSPWCEARSLEHTLPVN
  RETLKRKVSGNRCASPVTGPGSKRDAHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGH
  NDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMVKCGSRRERCGYRLVRRQRSADEQLH
  CAGKAKRSGGHAPRVRELLLDALSPEQLVLTLLEAEPPHVLISRPSAPFTEASMMMSLTK
  LADKELVHMISWAKKIPGFVELSLFDQVRLLESCWMEVLMMGLMWRSIDHPGKLIFAPDL
  VLDRDEGKCVEGILEIFDMLLATTSRFRELKLQHKEYLCVKAMILLNSSMYPLVTATQDA
  DSSRKLAHLLNAVTDALVWVIAKSGISSQQQSMRLANLLMLLSHVRHASNKGMEHLLNMK
  CKNVVPVYDLLLEMLNAHVLRGCKSSITGSECSPAEDSKSKEGSQNPQSQ
Target 2 Number of Residues 538
Target 2 Molecular Weight 59217
Target 2 Theoretical pI 8.55
Target 2 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 2 General Function Involved in transcription factor activity
Target 2 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 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 2911152
Target 2 UniProtKB/Swiss-Prot ID Q92731
Target 2 UniProtKB/Swiss-Prot Entry Name ESR2_HUMAN
Target 2 PDB ID 1QKM
Target 2 PDB File Show
Target 2 Cellular Location
  • Nucleus
Target 2 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 2 GenBank Gene ID
Target 2 GeneCard ID ESR2
Target 2 GenAtlas ID ESR2
Target 2 HGNC ID HGNC:3468
Target 2 Chromosome Location 14
Target 2 Locus 14q23.2
Target 2 SNPs SNPJam Report
Target 2 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]
  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]
  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]
  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]
  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]
  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]
  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]
  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]
  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]
  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]
  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
Target 3 Name Protein tyrosine kinase 2 beta
Target 3 Synonyms
  1. Focal adhesion kinase 2
  2. FADK 2
  3. Proline-rich tyrosine kinase 2
  4. Cell adhesion kinase beta
  5. CAK beta
  6. Calcium-dependent tyrosine kinase
  7. CADTK
  8. Related adhesion focal tyrosine kinase
  9. RAFTK
Target 3 Gene Name PTK2B
Target 3 Protein Sequence >Protein tyrosine kinase 2 beta
  MSGVSEPLSRVKLGTLRRPEGPAEPMVVVPVDVEKEDVRILKVCFYSNSFNPGKNFKLVK
  CTVQTEIREIITSILLSGRIGPNIRLAECYGLRLKHMKSDEIHWLHPQMTVGEVQDKYEC
  LHVEAEWRYDLQIRYLPEDFMESLKEDRTTLLYFYQQLRNDYMQRYASKVSEGMALQLGC
  LELRRFFKDMPHNALDKKSNFELLEKEVGLDLFFPKQMQENLKPKQFRKMIQQTFQQYAS
  LREEECVMKFFNTLAGFANIDQETYRCELIQGWNITVDLVIGPKGIRQLTSQDAKPTCLA
  EFKQIRSIRCLPLEEGQAVLQLGIEGAPQALSIKTSSLAEAENMADLIDGYCRLQGEHQG
  SLIIHPRKDGEKRNSLPQIPMLNLEARRSHLSESCSIESDIYAEIPDETLRRPGGPQYGI
  AREDVVLNRILGEGFFGEVYEGVYTNHKGEKINVAVKTCKKDCTLDNKEKFMSEAVIMKN
  LDHPHIVKLIGIIEEEPTWIIMELYPYGELGHYLERNKNSLKVLTLVLYSLQICKAMAYL
  ESINCVHRDIAVRNILVASPECVKLGDFGLSRYIEDEDYYKASVTRLPIKWMSPESINFR
  RFTTASDVWMFAVCMWEILSFGKQPFFWLENKDVIGVLEKGDRLPKPDLCPPVLYTLMTR
  CWDYDPSDRPRFTELVCSLSDVYQMEKDIAMEQERNARYRTPKILEPTAFQEPPPKPSRP
  KYRPPPQTNLLAPKLQFQVPEGLCASSPTLTSPMEYPSPVNSLHTPPLHRHNVFKRHSMR
  EEDFIQPSSREEAQQLWEAEKVKMRQILDKQQKQMVEDYQWLRQEEKSLDPMVYMNDKSP
  LTPEKEVGYLEFTGPPQKPPRLGAQSIQPTANLDRTDDLVYLNVMELVRAVLELKNELCQ
  LPPEGYVVVVKNVGLTLRKLIGSVDDLLPSLPSSSRTEIEGTQKLLNKDLAELINKMRLA
  QQNAVTSLSEECKRQMLTASHTLAVDAKNLLDAVDQAKVLANLAHPPAE
Target 3 Number of Residues 1009
Target 3 Molecular Weight 115876
Target 3 Theoretical pI 6.16
Target 3 GO Classification
Function
  • ATP binding
  • adenyl nucleotide binding
  • binding
  • catalytic activity
  • kinase activity
  • nucleotide binding
  • protein kinase activity
  • protein-tyrosine kinase activity
  • purine nucleotide binding
  • transferase activity
  • transferase activity, transferring phosphorus-containing groups
Process
  • biopolymer metabolism
  • biopolymer modification
  • macromolecule metabolism
  • metabolism
  • physiological process
  • protein amino acid phosphorylation
  • protein modification
Component
  • cytoskeleton
  • intracellular non-membrane-bound organelle
  • non-membrane-bound organelle
  • organelle
Target 3 General Function Not Available
Target 3 Specific Function Involved in calcium induced regulation of ion channel and activation of the map kinase signaling pathway. May represent an important signaling intermediate between neuropeptide activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. Interacts with the SH2 domain of Grb2. May phosphorylate the voltage-gated potassium channel protein Kv1.2. Its activation is highly correlated with the stimulation of c-Jun N-terminal kinase activity. Involved in osmotic stress-dependent SNCA 'Tyr-125' phosphorylation
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 Not Available
Target 3 GenBank ID Protein 988305
Target 3 UniProtKB/Swiss-Prot ID Q14289
Target 3 UniProtKB/Swiss-Prot Entry Name FAK2_HUMAN
Target 3 PDB ID Not Available
Target 3 Cellular Location Not Available
Target 3 Gene Sequence >3030 bp
  ATGTCTGGGGTGTCCGAGCCCCTGAGCCGAGTAAAGTTGGGCACATTACGCCGGCCTGAA
  GGCCCTGCAGAGCCCATGGTGGTGGTACCAGTAGATGTGGAAAAGGAGGACGTGCGTATC
  CTCAAGGTCTGCTTCTATAGCAACAGCTTCAATCCTGGGAAGAACTTCAAACTGGTCAAA
  TGCACTGTCCAGACGGAGATCCGGGAGATCATCACCTCCATCCTGCTGAGCGGGCGGATC
  GGGCCCAACATCCGGTTGGCTGAGTGCTATGGGCTGAGGCTGAAGCACATGAAGTCCGAT
  GAGATCCACTGGCTGCACCCACAGATGACGGTGGGTGAGGTGCAGGACAAGTATGAGTGT
  CTGCACGTGGAAGCCGAGTGGAGGTATGACCTTCAAATCCGCTACTTGCCAGAAGACTTC
  ATGGAGAGCCTGAAGGAGGACAGGACCACGCTGCTCTATTTTTACCAACAGCTCCGGAAC
  GACTACATGCAGCGCTACGCCAGCAAGGTCAGCGAGGGCATGGCCCTGCAGCTGGGCTGC
  CTGGAGCTCAGGCGGTTCTTCAAGGATATGCCCCACAATGCACTTGACAAGAAGTCCAAC
  TTCGAGCTCCTAGAAAAGGAAGTGGGGCTGGACTTGTTTTTCCCAAAGCAGATGCAGGAG
  AACTTAAAGCCCAAACAGTTCCGGAAGATGATCCAGCAGACCTTCCAGCAGTACGCCTCG
  CTCAGGGAGGAGGAGTGCGTCATGAAGTTCTTCAACACTCTCGCCGGCTTCGCCAACATC
  GACCAGGAGACCTACCGCTGTGAACTCATTCAAGGATGGAACATTACTGTGGACCTGGTC
  ATTGGCCCTAAAGGGATCCGCCAGCTGACTAGTCAGGACGCAAAGCCCACCTGCCTGGCC
  GAGTTCAAGCAGATCAGGTCCATCAGGTGCCTCCCGCTGGAGGAGGGCCAGGCAGTACTT
  CAGCTGGGCATTGAAGGTGCCCCCCAGGCCTTGTCCATCAAAACCTCATCCCTAGCAGAG
  GCTGAGAACATGGCTGACCTCATAGACGGCTACTGCCGGCTGCAGGGTGAGCACCAAGGC
  TCTCTCATCATCCATCCTAGGAAAGATGGTGAGAAGCGGAACAGCCTGCCCCAGATCCCC
  ATGCTAAACCTGGAGGCCCGGCGGTCCCACCTCTCAGAGAGCTGCAGCATAGAGTCAGAC
  ATCTACGCAGAGATTCCCGACGAAACCCTGCGAAGGCCCGGAGGTCCACAGTATGGCATT
  GCCCGTGAAGATGTGGTCCTGAATCGTATTCTTGGGGAAGGCTTTTTTGGGGAGGTCTAT
  GAAGGTGTCTACACAAATCACAAAGGGGAGAAAATCAATGTAGCTGTCAAGACCTGCAAG
  AAAGACTGCACTCTGGACAACAAGGAGAAGTTCATGAGCGAGGCAGTGATCATGAAGAAC
  CTCGACCACCCGCACATCGTGAAGCTGATCGGCATCATTGAAGAGGAGCCCACCTGGATC
  ATCATGGAATTGTATCCCTATGGGGAGCTGGGCCACTACCTGGAGCGGAACAAGAACTCC
  CTGAAGGTGCTCACCCTCGTGCTGTACTCACTGCAGATATGCAAAGCCATGGCCTACCTG
  GAGAGCATCAACTGCGTGCACAGGGACATTGCTGTCCGGAACATCCTGGTGGCCTCCCCT
  GAGTGTGTGAAGCTGGGGGACTTTGGTCTTTCCCGGTACATTGAGGACGAGGACTATTAC
  AAAGCCTCTGTGACTCGTCTCCCCATCAAATGGATGTCCCCAGAGTCCATTAACTTCCGA
  CGCTTCACGACAGCCAGTGACGTCTGGATGTTCGCCGTGTGCATGTGGGAGATCCTGAGC
  TTTGGGAAGCAGCCCTTCTTCTGGCTGGAGAACAAGGATGTCATCGGGGTGCTGGAGAAA
  GGAGACCGGCTGCCCAAGCCTGATCTCTGTCCACCGGTCCTTTATACCCTCATGACCCGC
  TGCTGGGACTACGACCCCAGTGACCGGCCCCGCTTCACCGAGCTGGTGTGCAGCCTCAGT
  GACGTTTATCAGATGGAGAAGGACATTGCCATGGAGCAAGAGAGGAATGCTCGCTACCGA
  ACCCCCAAAATCTTGGAGCCCACAGCCTTCCAGGAACCCCCACCCAAGCCCAGCCGACCT
  AAGTACAGACCCCCTCCGCAAACCAACCTCCTGGCTCCAAAGCTGCAGTTCCAGGTTCCT
  GAGGGTCTGTGTGCCAGCTCTCCTACGCTCACCAGCCCTATGGAGTATCCATCTCCCGTT
  AACTCACTGCACACCCCACCTCTCCACCGGCACAATGTCTTCAAACGCCACAGCATGCGG
  GAGGAGGACTTCATCCAACCCAGCAGCCGAGAAGAGGCCCAGCAGCTGTGGGAGGCTGAA
  AAGGTCAAAATGCGGCAAATCCTGGACAAACAGCAGAAGCAGATGGTGGAGGACTACCAG
  TGGCTCAGGCAGGAGGAGAAGTCCCTGGACCCCATGGTTTATATGAATGATAAGTCCCCA
  TTGACGCCAGAGAAGGAGGTCGGCTACCTGGAGTTCACAGGGCCCCCACAGAAGCCCCCG
  AGGCTGGGCGCACAGTCCATCCAGCCCACAGCTAACCTGGACCGGACCGATGACCTGGTG
  TACCTCAATGTCATGGAGCTGGTGCGGGCCGTGCTGGAGCTCAAGAATGAGCTCTGTCAG
  CTGCCCCCCGAGGGCTACGTGGTGGTGGTGAAGAATGTGGGGCTGACCCTGCGGAAGCTC
  ATCGGGAGCGTGGATGATCTCCTGCCTTCCTTGCCGTCATCTTCACGGACAGAGATCGAG
  GGCACCCAGAAACTGCTCAACAAAGACCTGGCAGAGCTCATCAACAAGATGCGGCTGGCG
  CAGCAGAACGCCGTGACCTCCCTGAGTGAGGAGTGCAAGAGGCAGATGCTGACGGCTTCA
  CACACCCTGGCTGTGGACGCCAAGAACCTGCTCGACGCTGTGGACCAGGCCAAGGTTCTG
  GCCAATCTGGCCCACCCACCTGCAGAGTGA
Target 3 GenBank Gene ID U33284
Target 3 GeneCard ID PTK2B
Target 3 GenAtlas ID PTK2B
Target 3 HGNC ID HGNC:9612
Target 3 Chromosome Location 8
Target 3 Locus 8p21.1
Target 3 SNPs SNPJam Report
Target 3 General References
  1. Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J: Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature. 1995 Aug 31;376(6543):737-45. [PubMed]
  2. Herzog H, Nicholl J, Hort YJ, Sutherland GR, Shine J: Molecular cloning and assignment of FAK2, a novel human focal adhesion kinase, to 8p11.2-p22 by nonisotopic in situ hybridization. Genomics. 1996 Mar 15;32(3):484-6. [PubMed]
  3. Sasaki H, Nagura K, Ishino M, Tobioka H, Kotani K, Sasaki T: Cloning and characterization of cell adhesion kinase beta, a novel protein-tyrosine kinase of the focal adhesion kinase subfamily. J Biol Chem. 1995 Sep 8;270(36):21206-19. [PubMed]
  4. Avraham S, London R, Fu Y, Ota S, Hiregowdara D, Li J, Jiang S, Pasztor LM, White RA, Groopman JE, et al.: Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain. J Biol Chem. 1995 Nov 17;270(46):27742-51. [PubMed]
  5. Li X, Hunter D, Morris J, Haskill JS, Earp HS: A calcium-dependent tyrosine kinase splice variant in human monocytes. Activation by a two-stage process involving adherence and a subsequent intracellular signal. J Biol Chem. 1998 Apr 17;273(16):9361-4. [PubMed]
  6. Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J: Identification of a new Pyk2 target protein with Arf-GAP activity. Mol Cell Biol. 1999 Mar;19(3):2338-50. [PubMed]
  7. Benzing T, Gerke P, Hopker K, Hildebrandt F, Kim E, Walz G: Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2. Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9784-9. Epub 2001 Aug 7. [PubMed]
  8. Salomon AR, Ficarro SB, Brill LM, Brinker A, Phung QT, Ericson C, Sauer K, Brock A, Horn DM, Schultz PG, Peters EC: Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):443-8. Epub 2003 Jan 9. [PubMed]

FILES

Structure files

MOL Show
SDF Show
PDB Show
2D Structure
3D Structure
Experimental PDB ID
Experimental PDB File
Experimental PDB Structure

Spectrum files

Experimental 1H NMR Show Spectrum
Download FID (Bruker)
Predicted 1H NMR Show Spectrum
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Experimental 13C NMR Not Available
Predicted 13C NMR Show Spectrum
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Experimental HSQC NMR Show Spectrum
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Simplified TOCSY Not Available
Mass Not Available
BMRB Not Available

REFERENCES

    General

  1. McCue P, Shetty K: Health benefits of soy isoflavonoids and strategies for enhancement: a review. Crit Rev Food Sci Nutr. 2004;44(5):361-7. [Pubmed]
  2. Nielsen IL, Williamson G: Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr Cancer. 2007;57(1):1-10. [Pubmed]
  3. Jung W, Yu O, Lau SM, O’Keefe DP, Odell J, Fader G, McGonigle B: Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes. Nat Biotechnol. 2000 Feb;18(2):208-12. [Pubmed]
  4. Kochs G, Grisebach H: Enzymic synthesis of isoflavones. Eur J Biochem. 1986 Mar 3;155(2):311-8. [Pubmed]
  5. Shelnutt SR et al.: Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein in men and women after consumption of a soy beverage. The American Journal of Clinical Nutrition. 2002;76(3): 588-94. [Pubmed]
  6. Messina MJ: Legumes and soybeans: overview of their nutritional profiles and health effects. The American Journal of Clinical Nutritio. 1999;70(3):439S-450S. [Pubmed]
  7. Metabolites

  8. Joannou GE et al.: A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. The Journal of Steroid Biochemistry and Molecular Biology. 1995;54(3-4):167-84. [Pubmed]
  9. Hosoda K et al.: Identification and quantification of daidzein-7-glucuronide-4'-sulfate, genistein-7-glucuronide-4'-sulfate and genistein-4',7-diglucuronide as major metabolites in human plasma after administration of kinako. Analytical and Bioanalytical Chemistry. 2010;397(4):1563-72. [Pubmed]
  10. Food composition

  11. Neveu V, Perez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, Knox C, Eisner R, Cruz J, Wishart D, Scalbert A. (2010) Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database, doi: 10.1093/database/bap024 (Version 1.5.2, available at http://www.phenol-explorer.eu). [Pubmed]
  12. Umphress S.T., Murphy S.P., Franke A.A., Custer L.J., Blitz C.L. (2005) Isoflavone content of foods with soy additives. Journal of Food Composition and Analysis 18:533-50 On-line
  13. “Dr. Duke's Phytochemical and Ethnobotanical Databases” (http://www.ars-grin.gov/duke/)
  14. Pharmacokinetics

  15. King RA and Bursill DB: Plasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. The American Journal of Clinical Nutrition. 1998;67(5):867-72. [Pubmed]
  16. Richelle M et al.: Hydrolysis of isoflavone glycosides to aglycones by beta-glycosidase does not alter plasma and urine isoflavone pharmacokinetics in postmenopausal women. The Journal of Nutrition. 2002;132(9):2587-92. [Pubmed]
  17. Zubik L and Meydani M: Bioavailability of soybean isoflavones from aglycone and glucoside forms in American women,” The American Journal of Clinical Nutrition. 2003;77(6):1459-65. [Pubmed]
  18. Synthesis reference