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Cytochrome P450 1A2 (EC 1.14.14.1) (CYPIA2) (Cholesterol 25-hydroxylase) (Cytochrome P(3)450) (Cytochrome P450 4) (Cytochrome P450-P3)

 CP1A2_HUMAN             Reviewed;         515 AA.
P05177; Q16754; Q6NWU5; Q9BXX7; Q9UK49;
13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 3.
25-OCT-2017, entry version 187.
RecName: Full=Cytochrome P450 1A2;
EC=1.14.14.1 {ECO:0000269|PubMed:21576599};
AltName: Full=CYPIA2;
AltName: Full=Cholesterol 25-hydroxylase {ECO:0000305|PubMed:21576599};
AltName: Full=Cytochrome P(3)450;
AltName: Full=Cytochrome P450 4;
AltName: Full=Cytochrome P450-P3;
Name=CYP1A2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=3755823; DOI=10.1093/nar/14.16.6773;
Jaiswal A.K., Nebert D.W., Gonzalez F.J.;
"Human P3(450): cDNA and complete amino acid sequence.";
Nucleic Acids Res. 14:6773-6774(1986).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
PubMed=3462722; DOI=10.1073/pnas.83.18.6731;
Quattrochi L.C., Pendurthi U.R., Okino S.T., Potenza C., Tukey R.H.;
"Human cytochrome P-450 4 mRNA and gene: part of a multigene family
that contains Alu sequences in its mRNA.";
Proc. Natl. Acad. Sci. U.S.A. 83:6731-6735(1986).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2575218; DOI=10.1210/mend-3-9-1399;
Ikeya K., Jaiswal A.K., Owens R.A., Jones J.E., Nebert D.W.,
Kimura S.;
"Human CYP1A2: sequence, gene structure, comparison with the mouse and
rat orthologous gene, and differences in liver 1A2 mRNA expression.";
Mol. Endocrinol. 3:1399-1408(1989).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Liver;
PubMed=3681487;
Jaiswal A.K., Nebert D.W., McBride O.W., Gonzalez F.J.;
"Human P(3)450: cDNA and complete protein sequence, repetitive Alu
sequences in the 3' nontranslated region, and localization of gene to
chromosome 15.";
J. Exp. Pathol. 3:1-17(1987).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT VAL-314.
TISSUE=Liver;
Zhuge J., Qian Y., Xie H., Yu Y.;
"Sequence of a new human cytochrome P450-1A2 cDNA.";
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=11207026; DOI=10.1097/00008571-200102000-00001;
Corchero J., Pimprale S., Kimura S., Gonzalez F.J.;
"Organization of the CYP1A cluster on human chromosome 15:
implications for gene regulation.";
Pharmacogenetics 11:1-6(2001).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-73; ASN-104;
PHE-111; VAL-205; TRP-281 AND ILE-438.
NIEHS SNPs program;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[9]
PROTEIN SEQUENCE OF 2-19.
PubMed=3517618;
Wrighton S.A., Campanile C., Thomas P.E., Maines S.L., Watkins P.B.,
Parker G., Mendez-Picon G., Haniu M., Shively J.E., Levin W.,
Guzelian P.S.;
"Identification of a human liver cytochrome P-450 homologous to the
major isosafrole-inducible cytochrome P-450 in the rat.";
Mol. Pharmacol. 29:405-410(1986).
[10]
NUCLEOTIDE SEQUENCE [MRNA] OF 295-485.
TISSUE=Liver;
PubMed=3000715; DOI=10.1089/dna.1985.4.395;
Quattrochi L.C., Okino S.T., Pendurthi U.R., Tukey R.H.;
"Cloning and isolation of human cytochrome P-450 cDNAs homologous to
dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6.";
DNA 4:395-400(1985).
[11]
FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF
VARIANTS ASN-348; PHE-386; TYR-406 AND TRP-431.
PubMed=14725854; DOI=10.1016/j.abb.2003.11.019;
Zhou H., Josephy P.D., Kim D., Guengerich F.P.;
"Functional characterization of four allelic variants of human
cytochrome P450 1A2.";
Arch. Biochem. Biophys. 422:23-30(2004).
[12]
CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
PubMed=21576599; DOI=10.1194/jlr.M014084;
Honda A., Miyazaki T., Ikegami T., Iwamoto J., Maeda T., Hirayama T.,
Saito Y., Teramoto T., Matsuzaki Y.;
"Cholesterol 25-hydroxylation activity of CYP3A.";
J. Lipid Res. 52:1509-1516(2011).
[13]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[14]
X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 27-515 IN COMPLEX WITH THE
INHIBITOR ALPHA-NAPHTHOFLAVONE AND HEME.
PubMed=17311915; DOI=10.1074/jbc.M611692200;
Sansen S., Yano J.K., Reynald R.L., Schoch G.A., Griffin K.J.,
Stout C.D., Johnson E.F.;
"Adaptations for the oxidation of polycyclic aromatic hydrocarbons
exhibited by the structure of human P450 1A2.";
J. Biol. Chem. 282:14348-14355(2007).
[15]
VARIANT LEU-21.
PubMed=9884316;
Huang J.D., Guo W.C., Lai M.D., Guo Y.L., Lambert G.H.;
"Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in
Chinese.";
Drug Metab. Dispos. 27:98-101(1999).
[16]
VARIANTS ASN-348; PHE-386; TYR-406 AND TRP-431.
PubMed=11295848; DOI=10.1002/humu.49;
Chevalier D., Cauffiez C., Allorge D., Lo-Guidice J.-M., Lhermitte M.,
Lafitte J.-J., Broly F.;
"Five novel natural allelic variants-951A->C, 1042G->A (D348N),
1156A->T (I386F), 1217G->A (C406Y) and 1291C->T (C431Y)-of the human
CYP1A2 gene in a French Caucasian population.";
Hum. Mutat. 17:355-356(2001).
[17]
VARIANTS MET-83; GLN-168; LEU-186; CYS-212; SER-299 AND ILE-438.
PubMed=14563787; DOI=10.1124/jpet.103.055798;
Murayama N., Soyama A., Saito Y., Nakajima Y., Komamura K., Ueno K.,
Kamakura S., Kitakaze M., Kimura H., Goto Y., Saitoh O., Katoh M.,
Ohnuma T., Kawai M., Sugai K., Ohtsuki T., Suzuki C., Minami N.,
Ozawa S., Sawada J.;
"Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic
activities of the naturally occurring variant enzymes.";
J. Pharmacol. Exp. Ther. 308:300-306(2004).
[18]
VARIANTS CYS-18; ARG-298; VAL-314 AND TRP-431.
PubMed=15469410; DOI=10.1517/14622416.5.7.895;
Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q.,
McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
"Genetic variation in eleven phase I drug metabolism genes in an
ethnically diverse population.";
Pharmacogenomics 5:895-931(2004).
[19]
VARIANTS ARG-42; GLN-377 AND HIS-456.
PubMed=15770072; DOI=10.2133/dmpk.20.24;
Soyama A., Saito Y., Hanioka N., Maekawa K., Komamura K., Kamakura S.,
Kitakaze M., Tomoike H., Ueno K., Goto Y., Kimura H., Katoh M.,
Sugai K., Saitoh O., Kawai M., Ohnuma T., Ohtsuki T., Suzuki C.,
Minami N., Kamatani N., Ozawa S., Sawada J.;
"Single nucleotide polymorphisms and haplotypes of CYP1A2 in a
Japanese population.";
Drug Metab. Pharmacokinet. 20:24-33(2005).
[20]
VARIANT CYS-18.
PubMed=15643613; DOI=10.1002/humu.20134;
Jiang Z., Dalton T.P., Jin L., Wang B., Tsuneoka Y., Shertzer H.G.,
Deka R., Nebert D.W.;
"Toward the evaluation of function in genetic variability:
characterizing human SNP frequencies and establishing BAC-transgenic
mice carrying the human CYP1A1_CYP1A2 locus.";
Hum. Mutat. 25:196-206(2005).
[21]
EFFECT OF CAFFEINE METABOLISM ON RISKS OF MYOCARDIAL INFARCTION.
PubMed=16522833; DOI=10.1001/jama.295.10.1135;
Cornelis M.C., El-Sohemy A., Kabagambe E.K., Campos H.;
"Coffee, CYP1A2 genotype, and risk of myocardial infarction.";
JAMA 295:1135-1141(2006).
-!- FUNCTION: Cytochromes P450 are a group of heme-thiolate
monooxygenases. In liver microsomes, this enzyme is involved in an
NADPH-dependent electron transport pathway. It oxidizes a variety
of structurally unrelated compounds, including steroids, fatty
acids, and xenobiotics. Most active in catalyzing 2-hydroxylation.
Caffeine is metabolized primarily by cytochrome CYP1A2 in the
liver through an initial N3-demethylation. Also acts in the
metabolism of aflatoxin B1 and acetaminophen. Participates in the
bioactivation of carcinogenic aromatic and heterocyclic amines.
Catalizes the N-hydroxylation of heterocyclic amines and the O-
deethylation of phenacetin. {ECO:0000269|PubMed:14725854}.
-!- CATALYTIC ACTIVITY: RH + [reduced NADPH--hemoprotein reductase] +
O(2) = ROH + [oxidized NADPH--hemoprotein reductase] + H(2)O.
{ECO:0000269|PubMed:21576599}.
-!- COFACTOR:
Name=heme; Xref=ChEBI:CHEBI:30413;
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=4 uM for 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole
{ECO:0000269|PubMed:14725854};
KM=21 uM for 2-amino-3-methylimidazo[4,5-f]quinoline
{ECO:0000269|PubMed:14725854};
KM=26 uM for 2-amino-2,4-dimethylimidazo[4,5-f]quinoline
{ECO:0000269|PubMed:14725854};
KM=27 uM for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
{ECO:0000269|PubMed:14725854};
KM=71 uM for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
{ECO:0000269|PubMed:14725854};
KM=25 uM for phenacetin {ECO:0000269|PubMed:14725854};
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
membrane protein. Microsome membrane
{ECO:0000269|PubMed:21576599}; Peripheral membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P05177-1; Sequence=Displayed;
Name=2;
IsoId=P05177-2; Sequence=VSP_017123;
-!- TISSUE SPECIFICITY: Liver.
-!- INDUCTION: By nicotine, omeprazole, phenobarbital, primidone and
rifampicin.
-!- POLYMORPHISM: The CYP1A2*1F allele which is quite common (40 to
50%) is due to a substitution of a base in the non-coding region
of the CYP1A2 gene and has the effect of decreasing the enzyme
inducibility. Individuals who are homozygous for the CYP1A2*1F
allele are 'slow' caffeine metabolizers. Thus for these individual
increased intake of caffeine seems to be associated with a
concomitant increase in the risk of non-fatal myocardial
infraction (MI).
-!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee;
Note=CYP1A2 alleles;
URL="http://www.cypalleles.ki.se/cyp1a2.htm";
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/cyp1a2/";
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EMBL; Z00036; CAA77335.1; -; mRNA.
EMBL; L00389; AAA35738.1; -; Genomic_DNA.
EMBL; L00384; AAA35738.1; JOINED; Genomic_DNA.
EMBL; L00385; AAA35738.1; JOINED; Genomic_DNA.
EMBL; L00386; AAA35738.1; JOINED; Genomic_DNA.
EMBL; L00388; AAA35738.1; JOINED; Genomic_DNA.
EMBL; L00387; AAA35738.1; JOINED; Genomic_DNA.
EMBL; M31667; AAA52163.1; -; Genomic_DNA.
EMBL; M31664; AAA52163.1; JOINED; Genomic_DNA.
EMBL; M31665; AAA52163.1; JOINED; Genomic_DNA.
EMBL; M31666; AAA52163.1; JOINED; Genomic_DNA.
EMBL; M12078; AAA52154.1; -; mRNA.
EMBL; AF182274; AAF13599.1; -; mRNA.
EMBL; AF253322; AAK25728.1; -; Genomic_DNA.
EMBL; DQ022432; AAY26399.1; -; Genomic_DNA.
EMBL; BC067424; AAH67424.1; -; mRNA.
EMBL; BC067425; AAH67425.1; -; mRNA.
EMBL; BC067426; AAH67426.1; -; mRNA.
EMBL; BC067427; AAH67427.1; -; mRNA.
EMBL; BC067428; AAH67428.1; -; mRNA.
EMBL; M55053; AAA52146.1; -; mRNA.
CCDS; CCDS32293.1; -. [P05177-2]
PIR; S16718; O4HU4.
RefSeq; NP_000752.2; NM_000761.4. [P05177-2]
UniGene; Hs.1361; -.
PDB; 2HI4; X-ray; 1.95 A; A=27-515.
PDBsum; 2HI4; -.
ProteinModelPortal; P05177; -.
SMR; P05177; -.
BioGrid; 107924; 7.
STRING; 9606.ENSP00000342007; -.
BindingDB; P05177; -.
ChEMBL; CHEMBL3356; -.
DrugBank; DB07453; 2-PHENYL-4H-BENZO[H]CHROMEN-4-ONE.
DrugBank; DB05812; Abiraterone.
DrugBank; DB01418; Acenocoumarol.
DrugBank; DB00316; Acetaminophen.
DrugBank; DB00787; Aciclovir.
DrugBank; DB06594; Agomelatine.
DrugBank; DB00518; Albendazole.
DrugBank; DB00523; Alitretinoin.
DrugBank; DB00918; Almotriptan.
DrugBank; DB00969; Alosetron.
DrugBank; DB00357; Aminoglutethimide.
DrugBank; DB01424; Aminophenazone.
DrugBank; DB01223; Aminophylline.
DrugBank; DB01118; Amiodarone.
DrugBank; DB00321; Amitriptyline.
DrugBank; DB00381; Amlodipine.
DrugBank; DB00261; Anagrelide.
DrugBank; DB01217; Anastrozole.
DrugBank; DB01435; Antipyrine.
DrugBank; DB06605; Apixaban.
DrugBank; DB00714; Apomorphine.
DrugBank; DB00673; Aprepitant.
DrugBank; DB06413; Armodafinil.
DrugBank; DB06216; Asenapine.
DrugBank; DB01072; Atazanavir.
DrugBank; DB00572; Atropine.
DrugBank; DB06626; Axitinib.
DrugBank; DB00972; Azelastine.
DrugBank; DB00207; Azithromycin.
DrugBank; DB06769; Bendamustine.
DrugBank; DB06770; Benzyl alcohol.
DrugBank; DB06732; beta-Naphthoflavone.
DrugBank; DB00195; Betaxolol.
DrugBank; DB00188; Bortezomib.
DrugBank; DB01558; Bromazepam.
DrugBank; DB01200; Bromocriptine.
DrugBank; DB00297; Bupivacaine.
DrugBank; DB00921; Buprenorphine.
DrugBank; DB01156; Bupropion.
DrugBank; DB00201; Caffeine.
DrugBank; DB06774; Capsaicin.
DrugBank; DB00564; Carbamazepine.
DrugBank; DB00389; Carbimazole.
DrugBank; DB00262; Carmustine.
DrugBank; DB01136; Carvedilol.
DrugBank; DB00477; Chlorpromazine.
DrugBank; DB00356; Chlorzoxazone.
DrugBank; DB01166; Cilostazol.
DrugBank; DB00501; Cimetidine.
DrugBank; DB01012; Cinacalcet.
DrugBank; DB00568; Cinnarizine.
DrugBank; DB00537; Ciprofloxacin.
DrugBank; DB00604; Cisapride.
DrugBank; DB00215; Citalopram.
DrugBank; DB01211; Clarithromycin.
DrugBank; DB01407; Clenbuterol.
DrugBank; DB04920; Clevidipine.
DrugBank; DB01013; Clobetasol propionate.
DrugBank; DB00882; Clomifene.
DrugBank; DB01242; Clomipramine.
DrugBank; DB00575; Clonidine.
DrugBank; DB00758; Clopidogrel.
DrugBank; DB00257; Clotrimazole.
DrugBank; DB00363; Clozapine.
DrugBank; DB00286; Conjugated Equine Estrogens.
DrugBank; DB05219; Crisaborole.
DrugBank; DB00924; Cyclobenzaprine.
DrugBank; DB00851; Dacarbazine.
DrugBank; DB04816; Dantron.
DrugBank; DB06292; Dapagliflozin.
DrugBank; DB01254; Dasatinib.
DrugBank; DB00694; Daunorubicin.
DrugBank; DB00705; Delavirdine.
DrugBank; DB01151; Desipramine.
DrugBank; DB00967; Desloratadine.
DrugBank; DB01191; Dexfenfluramine.
DrugBank; DB00633; Dexmedetomidine.
DrugBank; DB00829; Diazepam.
DrugBank; DB00586; Diclofenac.
DrugBank; DB00917; Dinoprostone.
DrugBank; DB01075; Diphenhydramine.
DrugBank; DB00822; Disulfiram.
DrugBank; DB01184; Domperidone.
DrugBank; DB00988; Dopamine.
DrugBank; DB01142; Doxepin.
DrugBank; DB00476; Duloxetine.
DrugBank; DB00974; Edetic Acid.
DrugBank; DB00625; Efavirenz.
DrugBank; DB06210; Eltrombopag.
DrugBank; DB00467; Enoxacin.
DrugBank; DB00494; Entacapone.
DrugBank; DB00668; Epinephrine.
DrugBank; DB00696; Ergotamine.
DrugBank; DB00530; Erlotinib.
DrugBank; DB00199; Erythromycin.
DrugBank; DB00783; Estradiol.
DrugBank; DB00655; Estrone.
DrugBank; DB04574; Estrone sulfate.
DrugBank; DB00898; Ethanol.
DrugBank; DB00773; Etoposide.
DrugBank; DB01628; Etoricoxib.
DrugBank; DB00196; Fluconazole.
DrugBank; DB04841; Flunarizine.
DrugBank; DB01544; Flunitrazepam.
DrugBank; DB00544; Fluorouracil.
DrugBank; DB00472; Fluoxetine.
DrugBank; DB00623; Fluphenazine.
DrugBank; DB00499; Flutamide.
DrugBank; DB01095; Fluvastatin.
DrugBank; DB00176; Fluvoxamine.
DrugBank; DB00998; Frovatriptan.
DrugBank; DB01241; Gemfibrozil.
DrugBank; DB01645; Genistein.
DrugBank; DB08909; Glycerol Phenylbutyrate.
DrugBank; DB00365; Grepafloxacin.
DrugBank; DB00400; Griseofulvin.
DrugBank; DB05708; GTS-21.
DrugBank; DB00629; Guanabenz.
DrugBank; DB00502; Haloperidol.
DrugBank; DB01094; Hesperetin.
DrugBank; DB01355; Hexobarbital.
DrugBank; DB11737; Icotinib.
DrugBank; DB04946; Iloperidone.
DrugBank; DB00619; Imatinib.
DrugBank; DB00458; Imipramine.
DrugBank; DB00724; Imiquimod.
DrugBank; DB01306; Insulin Aspart.
DrugBank; DB09456; Insulin Beef.
DrugBank; DB01307; Insulin Detemir.
DrugBank; DB00047; Insulin Glargine.
DrugBank; DB01309; Insulin Glulisine.
DrugBank; DB00030; Insulin Human.
DrugBank; DB00046; Insulin Lispro.
DrugBank; DB00071; Insulin Pork.
DrugBank; DB00033; Interferon gamma-1b.
DrugBank; DB01029; Irbesartan.
DrugBank; DB00951; Isoniazid.
DrugBank; DB09570; Ixazomib.
DrugBank; DB01026; Ketoconazole.
DrugBank; DB00448; Lansoprazole.
DrugBank; DB01097; Leflunomide.
DrugBank; DB01002; Levobupivacaine.
DrugBank; DB01137; Levofloxacin.
DrugBank; DB00281; Lidocaine.
DrugBank; DB00978; Lomefloxacin.
DrugBank; DB01601; Lopinavir.
DrugBank; DB04871; Lorcaserin.
DrugBank; DB00678; Losartan.
DrugBank; DB01283; Lumiracoxib.
DrugBank; DB00772; Malathion.
DrugBank; DB00934; Maprotiline.
DrugBank; DB00737; Meclizine.
DrugBank; DB01065; Melatonin.
DrugBank; DB00170; Menadione.
DrugBank; DB00532; Mephenytoin.
DrugBank; DB01357; Mestranol.
DrugBank; DB00333; Methadone.
DrugBank; DB00763; Methimazole.
DrugBank; DB01403; Methotrimeprazine.
DrugBank; DB00553; Methoxsalen.
DrugBank; DB01028; Methoxyflurane.
DrugBank; DB00379; Mexiletine.
DrugBank; DB06148; Mianserin.
DrugBank; DB01388; Mibefradil.
DrugBank; DB01110; Miconazole.
DrugBank; DB00834; Mifepristone.
DrugBank; DB00370; Mirtazapine.
DrugBank; DB01171; Moclobemide.
DrugBank; DB00745; Modafinil.
DrugBank; DB00461; Nabumetone.
DrugBank; DB00607; Nafcillin.
DrugBank; DB00788; Naproxen.
DrugBank; DB01149; Nefazodone.
DrugBank; DB00220; Nelfinavir.
DrugBank; DB00238; Nevirapine.
DrugBank; DB06803; Niclosamide.
DrugBank; DB00184; Nicotine.
DrugBank; DB01115; Nifedipine.
DrugBank; DB06712; Nilvadipine.
DrugBank; DB00401; Nisoldipine.
DrugBank; DB00435; Nitric Oxide.
DrugBank; DB00325; Nitroprusside.
DrugBank; DB00368; Norepinephrine.
DrugBank; DB01059; Norfloxacin.
DrugBank; DB00540; Nortriptyline.
DrugBank; DB05990; Obeticholic acid.
DrugBank; DB01165; Ofloxacin.
DrugBank; DB00334; Olanzapine.
DrugBank; DB00338; Omeprazole.
DrugBank; DB00904; Ondansetron.
DrugBank; DB01173; Orphenadrine.
DrugBank; DB09330; Osimertinib.
DrugBank; DB00526; Oxaliplatin.
DrugBank; DB01303; Oxtriphylline.
DrugBank; DB06412; Oxymetholone.
DrugBank; DB00377; Palonosetron.
DrugBank; DB00213; Pantoprazole.
DrugBank; DB00715; Paroxetine.
DrugBank; DB06589; Pazopanib.
DrugBank; DB00487; Pefloxacin.
DrugBank; DB00008; Peginterferon alfa-2a.
DrugBank; DB00022; Peginterferon alfa-2b.
DrugBank; DB00738; Pentamidine.
DrugBank; DB00806; Pentoxifylline.
DrugBank; DB00850; Perphenazine.
DrugBank; DB03783; Phenacetin.
DrugBank; DB01174; Phenobarbital.
DrugBank; DB00191; Phentermine.
DrugBank; DB00388; Phenylephrine.
DrugBank; DB00397; Phenylpropanolamine.
DrugBank; DB01100; Pimozide.
DrugBank; DB01621; Pipotiazine.
DrugBank; DB08910; Pomalidomide.
DrugBank; DB01058; Praziquantel.
DrugBank; DB01087; Primaquine.
DrugBank; DB00794; Primidone.
DrugBank; DB00396; Progesterone.
DrugBank; DB01131; Proguanil.
DrugBank; DB00420; Promazine.
DrugBank; DB01182; Propafenone.
DrugBank; DB00818; Propofol.
DrugBank; DB00571; Propranolol.
DrugBank; DB00339; Pyrazinamide.
DrugBank; DB00908; Quinidine.
DrugBank; DB00468; Quinine.
DrugBank; DB01129; Rabeprazole.
DrugBank; DB00980; Ramelteon.
DrugBank; DB00863; Ranitidine.
DrugBank; DB01367; Rasagiline.
DrugBank; DB02709; Resveratrol.
DrugBank; DB00615; Rifabutin.
DrugBank; DB01045; Rifampicin.
DrugBank; DB08864; Rilpivirine.
DrugBank; DB00740; Riluzole.
DrugBank; DB00503; Ritonavir.
DrugBank; DB00953; Rizatriptan.
DrugBank; DB00533; Rofecoxib.
DrugBank; DB00268; Ropinirole.
DrugBank; DB00296; Ropivacaine.
DrugBank; DB00412; Rosiglitazone.
DrugBank; DB05271; Rotigotine.
DrugBank; DB00778; Roxithromycin.
DrugBank; DB12332; Rucaparib.
DrugBank; DB00418; Secobarbital.
DrugBank; DB01037; Selegiline.
DrugBank; DB01104; Sertraline.
DrugBank; DB06290; Simeprevir.
DrugBank; DB06819; Sodium phenylbutyrate.
DrugBank; DB00398; Sorafenib.
DrugBank; DB00428; Streptozocin.
DrugBank; DB06820; Sulconazole.
DrugBank; DB00605; Sulindac.
DrugBank; DB00382; Tacrine.
DrugBank; DB00675; Tamoxifen.
DrugBank; DB01079; Tegaserod.
DrugBank; DB00976; Telithromycin.
DrugBank; DB01405; Temafloxacin.
DrugBank; DB00300; Tenofovir.
DrugBank; DB00857; Terbinafine.
DrugBank; DB01041; Thalidomide.
DrugBank; DB01412; Theobromine.
DrugBank; DB00277; Theophylline.
DrugBank; DB00730; Thiabendazole.
DrugBank; DB00679; Thioridazine.
DrugBank; DB01623; Thiothixene.
DrugBank; DB00208; Ticlopidine.
DrugBank; DB01007; Tioconazole.
DrugBank; DB00697; Tizanidine.
DrugBank; DB01056; Tocainide.
DrugBank; DB00539; Toremifene.
DrugBank; DB00752; Tranylcypromine.
DrugBank; DB00384; Triamterene.
DrugBank; DB00831; Trifluoperazine.
DrugBank; DB08867; Ulipristal.
DrugBank; DB00577; Valaciclovir.
DrugBank; DB00313; Valproic Acid.
DrugBank; DB08881; Vemurafenib.
DrugBank; DB00661; Verapamil.
DrugBank; DB00682; Warfarin.
DrugBank; DB00549; Zafirlukast.
DrugBank; DB00744; Zileuton.
DrugBank; DB00246; Ziprasidone.
DrugBank; DB00315; Zolmitriptan.
DrugBank; DB00425; Zolpidem.
GuidetoPHARMACOLOGY; 1319; -.
SwissLipids; SLP:000001202; -.
iPTMnet; P05177; -.
PhosphoSitePlus; P05177; -.
BioMuta; CYP1A2; -.
DMDM; 117144; -.
MaxQB; P05177; -.
PaxDb; P05177; -.
PeptideAtlas; P05177; -.
PRIDE; P05177; -.
Ensembl; ENST00000343932; ENSP00000342007; ENSG00000140505. [P05177-2]
GeneID; 1544; -.
KEGG; hsa:1544; -.
UCSC; uc002ayr.2; human. [P05177-1]
CTD; 1544; -.
DisGeNET; 1544; -.
EuPathDB; HostDB:ENSG00000140505.6; -.
GeneCards; CYP1A2; -.
HGNC; HGNC:2596; CYP1A2.
HPA; CAB016531; -.
MalaCards; CYP1A2; -.
MIM; 108330; gene.
MIM; 124060; gene+phenotype.
neXtProt; NX_P05177; -.
OpenTargets; ENSG00000140505; -.
Orphanet; 284121; Toxixity or absent response to clozapine.
PharmGKB; PA27093; -.
eggNOG; KOG0156; Eukaryota.
eggNOG; COG2124; LUCA.
GeneTree; ENSGT00900000140831; -.
HOVERGEN; HBG106944; -.
InParanoid; P05177; -.
KO; K07409; -.
OMA; YTNGLNM; -.
OrthoDB; EOG091G0BT8; -.
PhylomeDB; P05177; -.
TreeFam; TF105095; -.
BioCyc; MetaCyc:HS06728-MONOMER; -.
BRENDA; 1.14.14.1; 2681.
BRENDA; 1.14.99.38; 2681.
Reactome; R-HSA-156581; Methylation.
Reactome; R-HSA-211957; Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2.
Reactome; R-HSA-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
Reactome; R-HSA-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
SABIO-RK; P05177; -.
EvolutionaryTrace; P05177; -.
GeneWiki; CYP1A2; -.
GenomeRNAi; 1544; -.
PRO; PR:P05177; -.
Proteomes; UP000005640; Chromosome 15.
Bgee; ENSG00000140505; -.
CleanEx; HS_CYP1A2; -.
Genevisible; P05177; HS.
GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
GO; GO:0034875; F:caffeine oxidase activity; IDA:BHF-UCL.
GO; GO:0032451; F:demethylase activity; IDA:UniProtKB.
GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB.
GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
GO; GO:0020037; F:heme binding; IDA:UniProtKB.
GO; GO:0005506; F:iron ion binding; IEA:InterPro.
GO; GO:0004497; F:monooxygenase activity; IDA:BHF-UCL.
GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL.
GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IMP:UniProtKB.
GO; GO:0019825; F:oxygen binding; TAS:Reactome.
GO; GO:0009820; P:alkaloid metabolic process; IDA:BHF-UCL.
GO; GO:0045333; P:cellular respiration; IEA:Ensembl.
GO; GO:0071276; P:cellular response to cadmium ion; IEA:Ensembl.
GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEA:Ensembl.
GO; GO:0042737; P:drug catabolic process; IMP:BHF-UCL.
GO; GO:0017144; P:drug metabolic process; IDA:BHF-UCL.
GO; GO:0019373; P:epoxygenase P450 pathway; TAS:Reactome.
GO; GO:0042738; P:exogenous drug catabolic process; IDA:BHF-UCL.
GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL.
GO; GO:0050665; P:hydrogen peroxide biosynthetic process; IEA:Ensembl.
GO; GO:0030324; P:lung development; IEA:Ensembl.
GO; GO:0032259; P:methylation; TAS:Reactome.
GO; GO:0032787; P:monocarboxylic acid metabolic process; IDA:BHF-UCL.
GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL.
GO; GO:0097267; P:omega-hydroxylase P450 pathway; TAS:Reactome.
GO; GO:0055114; P:oxidation-reduction process; IDA:BHF-UCL.
GO; GO:0071615; P:oxidative deethylation; IDA:BHF-UCL.
GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL.
GO; GO:0006778; P:porphyrin-containing compound metabolic process; IEA:Ensembl.
GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
GO; GO:0006706; P:steroid catabolic process; IMP:BHF-UCL.
GO; GO:0009403; P:toxin biosynthetic process; IDA:BHF-UCL.
GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
Gene3D; 1.10.630.10; -; 1.
InterPro; IPR001128; Cyt_P450.
InterPro; IPR017972; Cyt_P450_CS.
InterPro; IPR002401; Cyt_P450_E_grp-I.
InterPro; IPR008066; Cyt_P450_E_grp-I_CYP1.
InterPro; IPR036396; Cyt_P450_sf.
Pfam; PF00067; p450; 1.
PRINTS; PR00463; EP450I.
PRINTS; PR01683; EP450ICYP1A.
PRINTS; PR00385; P450.
SUPFAM; SSF48264; SSF48264; 1.
PROSITE; PS00086; CYTOCHROME_P450; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome;
Direct protein sequencing; Endoplasmic reticulum; Glycoprotein; Heme;
Iron; Lipid metabolism; Membrane; Metal-binding; Microsome;
Monooxygenase; Oxidoreductase; Polymorphism; Reference proteome;
Steroid metabolism; Sterol metabolism.
INIT_MET 1 1 Removed. {ECO:0000269|PubMed:3517618}.
CHAIN 2 515 Cytochrome P450 1A2.
/FTId=PRO_0000051651.
METAL 458 458 Iron (heme axial ligand).
BINDING 226 226 Substrate. {ECO:0000305}.
CARBOHYD 69 69 O-linked (GlcNAc) serine. {ECO:0000250}.
VAR_SEQ 510 510 R -> RL (in isoform 2).
{ECO:0000303|PubMed:15489334,
ECO:0000303|Ref.5}.
/FTId=VSP_017123.
VARIANT 18 18 S -> C (in dbSNP:rs17861152).
{ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:15643613}.
/FTId=VAR_023196.
VARIANT 21 21 F -> L (in allele CYP1A2*2;
dbSNP:rs56160784).
{ECO:0000269|PubMed:9884316}.
/FTId=VAR_008349.
VARIANT 42 42 P -> R (in allele CYP1A2*15).
{ECO:0000269|PubMed:15770072}.
/FTId=VAR_025182.
VARIANT 73 73 G -> R (in dbSNP:rs45565238).
{ECO:0000269|Ref.7}.
/FTId=VAR_025183.
VARIANT 83 83 T -> M (in allele CYP1A2*9).
{ECO:0000269|PubMed:14563787}.
/FTId=VAR_020848.
VARIANT 104 104 D -> N (in dbSNP:rs34067076).
{ECO:0000269|Ref.7}.
/FTId=VAR_025184.
VARIANT 111 111 L -> F (in dbSNP:rs45442197).
{ECO:0000269|Ref.7}.
/FTId=VAR_025185.
VARIANT 168 168 E -> Q (in allele CYP1A2*10).
{ECO:0000269|PubMed:14563787}.
/FTId=VAR_020849.
VARIANT 186 186 F -> L (in allele CYP1A2*11; drastic
reduction in O-deethylation of phenacetin
and 7-ethoxyresorufin; has a Vmax of
approximately 5% of that of the wild-type
and 5-fold lower Km value).
{ECO:0000269|PubMed:14563787}.
/FTId=VAR_020850.
VARIANT 205 205 F -> V (in dbSNP:rs45540640).
{ECO:0000269|Ref.7}.
/FTId=VAR_025186.
VARIANT 212 212 S -> C (in allele CYP1A2*12).
{ECO:0000269|PubMed:14563787}.
/FTId=VAR_020851.
VARIANT 281 281 R -> W (in dbSNP:rs45468096).
{ECO:0000269|Ref.7}.
/FTId=VAR_025187.
VARIANT 298 298 S -> R (in dbSNP:rs17861157).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024709.
VARIANT 299 299 G -> S (in allele CYP1A2*13;
dbSNP:rs35796837).
{ECO:0000269|PubMed:14563787}.
/FTId=VAR_020852.
VARIANT 314 314 I -> V (in dbSNP:rs28399418).
{ECO:0000269|PubMed:15469410,
ECO:0000269|Ref.5}.
/FTId=VAR_024710.
VARIANT 348 348 D -> N (in allele CYP1A2*3; increases N-
hydroxylation activity of heterocyclic
amines; reduces phenacetin O-deethylation
activity; dbSNP:rs56276455).
{ECO:0000269|PubMed:11295848,
ECO:0000269|PubMed:14725854}.
/FTId=VAR_020793.
VARIANT 377 377 R -> Q (in allele CYP1A2*16).
{ECO:0000269|PubMed:15770072}.
/FTId=VAR_025188.
VARIANT 386 386 I -> F (in allele CYP1A2*4; increases
catalytic efficiency of N-hydroxylation
towards some heterocyclic amines and
reduces towards others; reduces catalytic
efficiency of phenacetin O-deethylation
due to a high decrease in the affinity
for phenacetin).
{ECO:0000269|PubMed:11295848,
ECO:0000269|PubMed:14725854}.
/FTId=VAR_020794.
VARIANT 406 406 C -> Y (in allele CYP1A2*5; increases N-
hydroxylation activity of heterocyclic
amines; reduces catalytic efficiency of
phenacetin O-deethylation;
dbSNP:rs55889066).
{ECO:0000269|PubMed:11295848,
ECO:0000269|PubMed:14725854}.
/FTId=VAR_020795.
VARIANT 431 431 R -> W (in allele CYP1A2*6; not detected
when expressed in heterologous system as
it may be critical for maintenance of
protein tertiary structure;
dbSNP:rs28399424).
{ECO:0000269|PubMed:11295848,
ECO:0000269|PubMed:14725854,
ECO:0000269|PubMed:15469410}.
/FTId=VAR_020796.
VARIANT 438 438 T -> I (in allele CYP1A2*14;
dbSNP:rs45486893).
{ECO:0000269|PubMed:14563787,
ECO:0000269|Ref.7}.
/FTId=VAR_020853.
VARIANT 456 456 R -> H (in allele CYP1A2*8).
{ECO:0000269|PubMed:15770072}.
/FTId=VAR_025189.
VARIANT 457 457 R -> W (in dbSNP:rs34151816).
/FTId=VAR_055563.
CONFLICT 79 79 R -> S (in Ref. 2; AAA35738).
{ECO:0000305}.
CONFLICT 81 81 G -> D (in Ref. 8; AAH67427).
{ECO:0000305}.
CONFLICT 170 170 K -> M (in Ref. 5; AAF13599).
{ECO:0000305}.
CONFLICT 311 311 V -> L (in Ref. 10; AAA52154).
{ECO:0000305}.
CONFLICT 450 451 LF -> MLV (in Ref. 10; AAA52154).
{ECO:0000305}.
CONFLICT 492 492 T -> I (in Ref. 5; AAF13599).
{ECO:0000305}.
CONFLICT 511 511 R -> LP (in Ref. 2; AAA35738).
{ECO:0000305}.
TURN 49 51 {ECO:0000244|PDB:2HI4}.
HELIX 54 57 {ECO:0000244|PDB:2HI4}.
HELIX 61 72 {ECO:0000244|PDB:2HI4}.
STRAND 74 80 {ECO:0000244|PDB:2HI4}.
STRAND 83 88 {ECO:0000244|PDB:2HI4}.
HELIX 91 98 {ECO:0000244|PDB:2HI4}.
TURN 99 101 {ECO:0000244|PDB:2HI4}.
HELIX 102 104 {ECO:0000244|PDB:2HI4}.
HELIX 112 115 {ECO:0000244|PDB:2HI4}.
TURN 123 125 {ECO:0000244|PDB:2HI4}.
HELIX 131 146 {ECO:0000244|PDB:2HI4}.
TURN 147 149 {ECO:0000244|PDB:2HI4}.
HELIX 160 181 {ECO:0000244|PDB:2HI4}.
HELIX 188 205 {ECO:0000244|PDB:2HI4}.
HELIX 206 208 {ECO:0000244|PDB:2HI4}.
HELIX 214 220 {ECO:0000244|PDB:2HI4}.
HELIX 221 223 {ECO:0000244|PDB:2HI4}.
HELIX 224 227 {ECO:0000244|PDB:2HI4}.
HELIX 235 237 {ECO:0000244|PDB:2HI4}.
HELIX 240 244 {ECO:0000244|PDB:2HI4}.
HELIX 248 273 {ECO:0000244|PDB:2HI4}.
HELIX 283 293 {ECO:0000244|PDB:2HI4}.
HELIX 305 308 {ECO:0000244|PDB:2HI4}.
HELIX 310 335 {ECO:0000244|PDB:2HI4}.
HELIX 337 350 {ECO:0000244|PDB:2HI4}.
TURN 351 353 {ECO:0000244|PDB:2HI4}.
HELIX 359 361 {ECO:0000244|PDB:2HI4}.
HELIX 366 379 {ECO:0000244|PDB:2HI4}.
STRAND 394 396 {ECO:0000244|PDB:2HI4}.
STRAND 399 401 {ECO:0000244|PDB:2HI4}.
STRAND 406 410 {ECO:0000244|PDB:2HI4}.
HELIX 411 416 {ECO:0000244|PDB:2HI4}.
TURN 418 420 {ECO:0000244|PDB:2HI4}.
HELIX 429 432 {ECO:0000244|PDB:2HI4}.
STRAND 437 440 {ECO:0000244|PDB:2HI4}.
HELIX 442 445 {ECO:0000244|PDB:2HI4}.
HELIX 454 456 {ECO:0000244|PDB:2HI4}.
HELIX 461 478 {ECO:0000244|PDB:2HI4}.
STRAND 480 482 {ECO:0000244|PDB:2HI4}.
STRAND 496 498 {ECO:0000244|PDB:2HI4}.
STRAND 507 510 {ECO:0000244|PDB:2HI4}.
SEQUENCE 515 AA; 58294 MW; 23AEFEEBDF6806AB CRC64;
MALSQSVPFS ATELLLASAI FCLVFWVLKG LRPRVPKGLK SPPEPWGWPL LGHVLTLGKN
PHLALSRMSQ RYGDVLQIRI GSTPVLVLSR LDTIRQALVR QGDDFKGRPD LYTSTLITDG
QSLTFSTDSG PVWAARRRLA QNALNTFSIA SDPASSSSCY LEEHVSKEAK ALISRLQELM
AGPGHFDPYN QVVVSVANVI GAMCFGQHFP ESSDEMLSLV KNTHEFVETA SSGNPLDFFP
ILRYLPNPAL QRFKAFNQRF LWFLQKTVQE HYQDFDKNSV RDITGALFKH SKKGPRASGN
LIPQEKIVNL VNDIFGAGFD TVTTAISWSL MYLVTKPEIQ RKIQKELDTV IGRERRPRLS
DRPQLPYLEA FILETFRHSS FLPFTIPHST TRDTTLNGFY IPKKCCVFVN QWQVNHDPEL
WEDPSEFRPE RFLTADGTAI NKPLSEKMML FGMGKRRCIG EVLAKWEIFL FLAILLQQLE
FSVPPGVKVD LTPIYGLTMK HARCEHVQAR RFSIN


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U1557p CLIA 21-OHase,CYP21,CYP21A1,CYP21A3,Cytochrome P450 21,Cytochrome P450 XXI,Cytochrome P-450c21,Cytochrome P450-C21,Pig,Steroid 21-hydroxylase,Sus scrofa 96T
U1557r CLIA 21-OHase,Cyp21,Cyp21a1,Cytochrome P450 21,Cytochrome P450 XXI,Cytochrome P-450c21,Cytochrome P450-C21,Rat,Rattus norvegicus,Steroid 21-hydroxylase 96T


 

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