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Cytochrome P450 3A4 (EC 1.14.13.-) (1,8-cineole 2-exo-monooxygenase) (EC (Albendazole monooxygenase) (EC (Albendazole sulfoxidase) (CYPIIIA3) (CYPIIIA4) (Cholesterol 25-hydroxylase) (EC (Cytochrome P450 3A3) (Cytochrome P450 HLp) (Cytochrome P450 NF-25) (Cytochrome P450-PCN1) (Nifedipine oxidase) (Quinine 3-monooxygenase) (EC (Taurochenodeoxycholate 6-alpha-hydroxylase) (EC

 CP3A4_HUMAN             Reviewed;         503 AA.
P08684; P05184; Q16757; Q9UK50;
01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 4.
05-DEC-2018, entry version 212.
RecName: Full=Cytochrome P450 3A4;
AltName: Full=1,8-cineole 2-exo-monooxygenase;
EC= {ECO:0000269|PubMed:11159812};
AltName: Full=Albendazole monooxygenase;
AltName: Full=Albendazole sulfoxidase;
AltName: Full=CYPIIIA3;
AltName: Full=CYPIIIA4;
AltName: Full=Cholesterol 25-hydroxylase {ECO:0000305|PubMed:21576599};
EC=1.14.14.- {ECO:0000269|PubMed:21576599};
AltName: Full=Cytochrome P450 3A3;
AltName: Full=Cytochrome P450 HLp;
AltName: Full=Cytochrome P450 NF-25;
AltName: Full=Cytochrome P450-PCN1;
AltName: Full=Nifedipine oxidase;
AltName: Full=Quinine 3-monooxygenase;
EC= {ECO:0000269|PubMed:11159812};
AltName: Full=Taurochenodeoxycholate 6-alpha-hydroxylase;
EC=1.14.14.- {ECO:0000269|PubMed:11159812};
Name=CYP3A4; Synonyms=CYP3A3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
PubMed=3460094; DOI=10.1073/pnas.83.14.5311;
Molowa D.T., Schuetz E.G., Wrighton S.A., Watkins P.B., Kremers P.,
Mendez-Picon G., Parker G.A., Guzelian P.S.;
"Complete cDNA sequence of a cytochrome P-450 inducible by
glucocorticoids in human liver.";
Proc. Natl. Acad. Sci. U.S.A. 83:5311-5315(1986).
PubMed=3267210; DOI=10.1089/dna.1988.7.79;
Gonzalez F.J., Schmid B.J., Umeno M., McBride O.W., Hardwick J.P.,
Meyer U.A., Gelboin H.V., Idle J.R.;
"Human P450PCN1: sequence, chromosome localization, and direct
evidence through cDNA expression that P450PCN1 is nifedipine
DNA 7:79-86(1988).
PubMed=3464943; DOI=10.1073/pnas.83.21.8064;
Beaune P.H., Umbenhauer D.R., Bork R.W., Lloyd R.S., Guengerich F.P.;
"Isolation and sequence determination of a cDNA clone related to human
cytochrome P-450 nifedipine oxidase.";
Proc. Natl. Acad. Sci. U.S.A. 83:8064-8068(1986).
PubMed=2563251; DOI=10.1007/BF00293896;
Spurr N.K., Gough A.C., Stevenson K., Wolf C.R.;
"The human cytochrome P450 CYP3 locus: assignment to chromosome 7q22-
Hum. Genet. 81:171-174(1989).
Bork R.W., Muto T., Beaune P.H., Srivastava P.K., Lloyd R.S.,
Guengerich F.P.;
"Characterization of mRNA species related to human liver cytochrome P-
450 nifedipine oxidase and the regulation of catalytic activity.";
J. Biol. Chem. 264:910-919(1989).
Chen Q., Wu J., Yu Y.;
"Establishment of transgenic cell line CHL-3A4 and its metabolic
Zhonghua Yu Fang Yi Xue Za Zhi 32:281-284(1998).
PubMed=11266076; DOI=10.1097/00008571-200103000-00002;
Gellner K., Eiselt R., Hustert E., Arnold H., Koch I., Haberl M.,
Deglmann C.J., Burk O., Buntefuss D., Escher S., Bishop C.,
Koebe H.-G., Brinkmann U., Klenk H.-P., Kleine K., Meyer U.A.,
Wojnowski L.;
"Genomic organization of the human CYP3A locus: identification of a
new, inducible CYP3A gene.";
Pharmacogenetics 11:111-121(2001).
Hsieh K.-P., Lin Y.-Y., Cheng C.-L., Lai M.-L., Lin M.-S.,
Siest J.-P., Huang J.-D.;
"Novel mutations of CYP3A4 in Chinese.";
Drug Metab. Dispos. 29:268-273(2001).
Zhuge J., Qian Y., Xie H., Yu Y.;
"Sequence of a new human cytochrome P450-3A4 cDNA.";
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
Komori M., Hashizume T., Ohi H., Miura T., Kitada M., Nagashima K.,
Kamataki T.;
"Cytochrome P-450 in human liver microsomes: high-performance liquid
chromatographic isolation of three forms and their characterization.";
J. Biochem. 104:912-916(1988).
PubMed=3898085; DOI=10.1073/pnas.82.18.6310;
Watkins P.B., Wrighton S.A., Maurel P., Schuetz E.G., Mendez-Picon G.,
Parker G.A., Guzelian P.S.;
"Identification of an inducible form of cytochrome P-450 in human
Proc. Natl. Acad. Sci. U.S.A. 82:6310-6314(1985).
Aoyama T., Yamano S., Waxman D.J., Lapenson D.P., Meyer U.A.,
Fischer V., Tyndale R., Inaba T., Kalow W., Gelboin H.V.,
Gonzalez F.J.;
"Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product
that is differentially expressed in adult human liver. cDNA and
deduced amino acid sequence and distinct specificities of cDNA-
expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and
J. Biol. Chem. 264:10388-10395(1989).
Shimada T., Yamazaki H., Mimura M., Inui Y., Guengerich F.P.;
"Interindividual variations in human liver cytochrome P-450 enzymes
involved in the oxidation of drugs, carcinogens and toxic chemicals:
studies with liver microsomes of 30 Japanese and 30 Caucasians.";
J. Pharmacol. Exp. Ther. 270:414-423(1994).
Kolars J.C., Lown K.S., Schmiedlin-Ren P., Ghosh M., Fang C.,
Wrighton S.A., Merion R.M., Watkins P.B.;
"CYP3A gene expression in human gut epithelium.";
Pharmacogenetics 4:247-259(1994).
PubMed=9088578; DOI=10.1046/j.1365-2125.1997.00556.x;
Zhang H., Coville P.F., Walker R.J., Miners J.O., Birkett D.J.,
Wanwimolruk S.;
"Evidence for involvement of human CYP3A in the 3-hydroxylation of
Br. J. Clin. Pharmacol. 43:245-252(1997).
Zhao X.J., Kawashiro T., Ishizaki T.;
"Mutual inhibition between quinine and etoposide by human liver
microsomes. Evidence for cytochrome P4503A4 involvement in their major
metabolic pathways.";
Drug Metab. Dispos. 26:188-191(1998).
Miyazawa M., Shindo M., Shimada T.;
"Oxidation of 1,8-cineole, the monoterpene cyclic ether originated
from eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and
human liver microsomes.";
Drug Metab. Dispos. 29:200-205(2001).
PubMed=11726664; DOI=10.1074/jbc.M109175200;
Finta C., Zaphiropoulos P.G.;
"Intergenic mRNA molecules resulting from trans-splicing.";
J. Biol. Chem. 277:5882-5890(2002).
PubMed=19094056; DOI=10.1111/j.1471-4159.2008.05720.x;
Dauchy S., Dutheil F., Weaver R.J., Chassoux F., Daumas-Duport C.,
Couraud P.O., Scherrmann J.M., De Waziers I., Decleves X.;
"ABC transporters, cytochromes P450 and their main transcription
factors: expression at the human blood-brain barrier.";
J. Neurochem. 107:1518-1528(2008).
PubMed=18545703; DOI=10.1371/journal.pone.0002337;
Agarwal V., Kommaddi R.P., Valli K., Ryder D., Hyde T.M.,
Kleinman J.E., Strobel H.W., Ravindranath V.;
"Drug metabolism in human brain: high levels of cytochrome P4503A43 in
brain and metabolism of anti-anxiety drug alprazolam to its active
PLoS ONE 3:E2337-E2337(2008).
PubMed=19103148; DOI=10.1016/j.abb.2008.12.001;
Pabarcus M.K., Hoe N., Sadeghi S., Patterson C., Wiertz E.,
Correia M.A.;
"CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor
receptor, AMFR) and CHIP E3 ligases.";
Arch. Biochem. Biophys. 483:66-74(2009).
PubMed=19359404; DOI=10.1124/dmd.109.027011;
Dutheil F., Dauchy S., Diry M., Sazdovitch V., Cloarec O.,
Mellottee L., Bieche I., Ingelman-Sundberg M., Flinois J.P.,
de Waziers I., Beaune P., Decleves X., Duyckaerts C., Loriot M.A.;
"Xenobiotic-metabolizing enzymes and transporters in the normal human
brain: regional and cellular mapping as a basis for putative roles in
cerebral function.";
Drug Metab. Dispos. 37:1528-1538(2009).
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).
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).
PubMed=15258162; DOI=10.1074/jbc.C400293200;
Yano J.K., Wester M.R., Schoch G.A., Griffin K.J., Stout C.D.,
Johnson E.F.;
"The structure of human microsomal cytochrome P450 3A4 determined by
X-ray crystallography to 2.05-A resolution.";
J. Biol. Chem. 279:38091-38094(2004).
PubMed=15256616; DOI=10.1126/science.1099736;
Williams P.A., Cosme J., Vinkovic D.M., Ward A., Angove H.C.,
Day P.J., Vonrhein C., Tickle I.J., Jhoti H.;
"Crystal structures of human cytochrome P450 3A4 bound to metyrapone
and progesterone.";
Science 305:683-686(2004).
PubMed=10668853; DOI=10.1067/mcp.2000.104391;
Sata F., Sapone A., Elizondo G., Stocker P., Miller V.P., Zheng W.,
Raunio H., Crespi C.L., Gonzalez F.J.;
"CYP3A4 allelic variants with amino acid substitutions in exons 7 and
12: evidence for an allelic variant with altered catalytic activity.";
Clin. Pharmacol. Ther. 67:48-56(2000).
VARIANTS GLN-162; SER-189; PRO-293; THR-445 AND SER-467, AND
Dai D., Tang J., Rose R., Hodgson E., Bienstock R.J.,
Mohrenweiser H.W., Goldstein J.A.;
"Identification of variants of CYP3A4 and characterization of their
abilities to metabolize testosterone and chlorpyrifos.";
J. Pharmacol. Exp. Ther. 299:825-831(2001).
VARIANTS ASP-56; GLN-130; ILE-170; HIS-174; MET-363; PHE-373 AND
PubMed=11470997; DOI=10.1097/00008571-200107000-00008;
Eiselt R., Domanski T.L., Zibat A., Mueller R., Presecan-Siedel E.,
Hustert E., Zanger U.M., Brockmoller J., Klenk H.-P., Meyer U.A.,
Khan K.K., He Y.-A., Halpert J.R., Wojnowski L.;
"Identification and functional characterization of eight CYP3A4
protein variants.";
Pharmacogenetics 11:447-458(2001).
VARIANTS PRO-15; GLN-162; HIS-174; SER-185 AND PHE-373.
PubMed=11875366; DOI=10.1097/00008571-200203000-00006;
Lamba J.K., Lin Y.S., Thummel K., Daly A., Watkins P.B., Strom S.,
Zhang J., Schuetz E.G.;
"Common allelic variants of cytochrome P4503A4 and their prevalence in
different populations.";
Pharmacogenetics 12:121-132(2002).
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).
-!- 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 performs a variety
of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole
sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-
hydroxylation) of structurally unrelated compounds, including
steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-
exo-monooxygenase. The enzyme also hydroxylates etoposide
(PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol.
May catalyze 25-hydroxylation of cholesterol in vitro
(PubMed:21576599). {ECO:0000269|PubMed:11159812,
Reaction=O2 + quinine + reduced [NADPH--hemoprotein reductase] =
3-hydroxyquinine + H(+) + H2O + oxidized [NADPH--hemoprotein
reductase]; Xref=Rhea:RHEA:20149, Rhea:RHEA-COMP:11964,
Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
ChEBI:CHEBI:58234, ChEBI:CHEBI:137041; EC=;
Reaction=O2 + reduced [NADPH--hemoprotein reductase] +
taurochenodeoxycholate = H(+) + H2O + oxidized [NADPH--
hemoprotein reductase] + taurohyocholate; Xref=Rhea:RHEA:17857,
Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:9407,
ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58874;
Reaction=lithocholate + O2 + reduced [NADPH--hemoprotein
reductase] = H(+) + H2O + hyodeoxycholate + oxidized [NADPH--
hemoprotein reductase]; Xref=Rhea:RHEA:23644, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29744,
ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58875;
Reaction=albendazole + O2 + reduced [NADPH--hemoprotein reductase]
= albendazole S-oxide + H(+) + H2O + oxidized [NADPH--
hemoprotein reductase]; Xref=Rhea:RHEA:55924, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16664,
ChEBI:CHEBI:16959, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
Reaction=fenbendazole + O2 + reduced [NADPH--hemoprotein
reductase] = fenbendazole S-oxide + H(+) + H2O + oxidized
[NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:55928, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35812,
ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77092;
Reaction=1,8-cineole + O2 + reduced [NADPH--hemoprotein reductase]
= 2-exo-hydroxy-1,8-cineole + H(+) + H2O + oxidized [NADPH--
hemoprotein reductase]; Xref=Rhea:RHEA:32895, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16271,
ChEBI:CHEBI:27961, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
EC=; Evidence={ECO:0000269|PubMed:11159812};
Reaction=cholesterol + O2 + reduced [NADPH--hemoprotein reductase]
= 25-hydroxycholesterol + H(+) + H2O + oxidized [NADPH--
hemoprotein reductase]; Xref=Rhea:RHEA:50256, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113,
ChEBI:CHEBI:42977, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
Name=heme; Xref=ChEBI:CHEBI:30413;
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
membrane protein. Microsome membrane
{ECO:0000269|PubMed:21576599}; Single-pass membrane protein.
-!- TISSUE SPECIFICITY: Expressed in prostate and liver. According to
some authors, it is not expressed in brain (PubMed:19094056).
According to others, weak levels of expression are measured in
some brain locations (PubMed:19359404 and PubMed:18545703). Also
expressed in epithelium of the small intestine and large
intestine, bile duct, nasal mucosa, kidney, adrenal cortex,
epithelium of the gastric mucosa with intestinal metaplasia,
gallbladder, intercalated ducts of the pancreas, chief cells of
the parathyroid and the corpus luteum of the ovary (at protein
level). {ECO:0000269|PubMed:18545703, ECO:0000269|PubMed:19094056,
ECO:0000269|PubMed:19359404, ECO:0000269|PubMed:2732228,
ECO:0000269|PubMed:7894497, ECO:0000269|PubMed:8035341}.
-!- INDUCTION: By glucocorticoids. Also induced to high levels in
liver and other tissues by various foreign compounds, including
drugs, pesticides, and carcinogens.
-!- PTM: Polyubiquitinated in the presence of AMFR and UBE2G1 and also
STUB1/CHIP and UBE2D1 (in vitro). {ECO:0000269|PubMed:19103148}.
-!- MISCELLANEOUS: Chimeric transcripts, characterized by CYP3A43 exon
1 joined at canonical splice sites to distinct sets of CYP3A4
exons, have been detected. All are possibly produced by trans-
splicing. The chimeric transcripts exist in 3 different
combinations: CYP3A43 exon 1 joined in frame to CYP3A4 exons 2-13,
CYP3A43 exon 1 joined in frame to CYP3A4 exons 4-13 and CYP3A43
exon 1 joined in frame to CYP3A4 exon 7-13. The longest chimeric
isoform (CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6-
beta-hydroxylase activity, while a shorter isoform (CYP3A43 exon 1
joined to CYP3A4 exons 4-13) does not. All chimeric transcripts
are expressed at very low levels in the liver (PubMed:11726664).
-!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee;
Note=CYP3A4 alleles;
-!- WEB RESOURCE: Name=Wikipedia; Note=CYP3A4 entry;
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; D00003; BAA00001.1; -; mRNA.
EMBL; M13785; AAA35742.1; -; mRNA.
EMBL; M18907; AAA35745.1; -; mRNA.
EMBL; M14096; AAA35744.1; -; mRNA.
EMBL; X12387; CAA30944.1; -; mRNA.
EMBL; J04449; AAA35747.1; -; mRNA.
EMBL; AF182273; AAF13598.1; -; mRNA.
EMBL; AF280107; AAG32290.1; -; Genomic_DNA.
EMBL; AF209389; AAF21034.1; -; Genomic_DNA.
CCDS; CCDS5674.1; -.
PIR; A29410; A29410.
PIR; A29815; A29815.
RefSeq; NP_001189784.1; NM_001202855.2.
RefSeq; NP_059488.2; NM_017460.5.
UniGene; Hs.728751; -.
PDB; 1TQN; X-ray; 2.05 A; A=24-503.
PDB; 1W0E; X-ray; 2.80 A; A=25-503.
PDB; 1W0F; X-ray; 2.65 A; A=25-503.
PDB; 1W0G; X-ray; 2.74 A; A=25-503.
PDB; 2J0D; X-ray; 2.75 A; A/B=25-503.
PDB; 2V0M; X-ray; 2.80 A; A/B/C/D=25-503.
PDB; 3NXU; X-ray; 2.00 A; A/B=25-503.
PDB; 3TJS; X-ray; 2.25 A; A=23-503.
PDB; 3UA1; X-ray; 2.15 A; A=23-503.
PDB; 4D6Z; X-ray; 1.93 A; A=23-503.
PDB; 4D75; X-ray; 2.25 A; A=23-503.
PDB; 4D78; X-ray; 2.80 A; A=23-503.
PDB; 4D7D; X-ray; 2.76 A; A=23-503.
PDB; 4I3Q; X-ray; 2.60 A; A=23-503.
PDB; 4I4G; X-ray; 2.72 A; A=23-503.
PDB; 4I4H; X-ray; 2.90 A; A=23-503.
PDB; 4K9T; X-ray; 2.50 A; A=23-503.
PDB; 4K9U; X-ray; 2.85 A; A=23-503.
PDB; 4K9V; X-ray; 2.60 A; A=23-503.
PDB; 4K9W; X-ray; 2.40 A; A/B/C/D=23-503.
PDB; 4K9X; X-ray; 2.76 A; A=23-503.
PDB; 4NY4; X-ray; 2.95 A; A=25-503.
PDB; 5A1P; X-ray; 2.50 A; A=23-503.
PDB; 5A1R; X-ray; 2.45 A; A=23-503.
PDB; 5G5J; X-ray; 2.60 A; A=21-503.
PDB; 5TE8; X-ray; 2.70 A; A/B/C=23-503.
PDB; 5VC0; X-ray; 2.70 A; A=21-503.
PDB; 5VCC; X-ray; 1.70 A; A=21-503.
PDB; 5VCD; X-ray; 1.95 A; A=21-503.
PDB; 5VCE; X-ray; 2.20 A; A=21-503.
PDB; 5VCG; X-ray; 2.20 A; A=21-503.
PDB; 6BCZ; X-ray; 2.23 A; A=21-503.
PDB; 6BD5; X-ray; 2.50 A; A=21-503.
PDB; 6BD6; X-ray; 2.50 A; A=21-503.
PDB; 6BD7; X-ray; 2.42 A; A=21-503.
PDB; 6BD8; X-ray; 2.38 A; A=21-503.
PDB; 6BDH; X-ray; 2.25 A; A=21-503.
PDB; 6BDI; X-ray; 2.57 A; A=21-503.
PDB; 6BDK; X-ray; 2.67 A; A=21-503.
PDB; 6BDM; X-ray; 2.60 A; A=21-503.
PDBsum; 1TQN; -.
PDBsum; 1W0E; -.
PDBsum; 1W0F; -.
PDBsum; 1W0G; -.
PDBsum; 2J0D; -.
PDBsum; 2V0M; -.
PDBsum; 3NXU; -.
PDBsum; 3TJS; -.
PDBsum; 3UA1; -.
PDBsum; 4D6Z; -.
PDBsum; 4D75; -.
PDBsum; 4D78; -.
PDBsum; 4D7D; -.
PDBsum; 4I3Q; -.
PDBsum; 4I4G; -.
PDBsum; 4I4H; -.
PDBsum; 4K9T; -.
PDBsum; 4K9U; -.
PDBsum; 4K9V; -.
PDBsum; 4K9W; -.
PDBsum; 4K9X; -.
PDBsum; 4NY4; -.
PDBsum; 5A1P; -.
PDBsum; 5A1R; -.
PDBsum; 5G5J; -.
PDBsum; 5TE8; -.
PDBsum; 5VC0; -.
PDBsum; 5VCC; -.
PDBsum; 5VCD; -.
PDBsum; 5VCE; -.
PDBsum; 5VCG; -.
PDBsum; 6BCZ; -.
PDBsum; 6BD5; -.
PDBsum; 6BD6; -.
PDBsum; 6BD7; -.
PDBsum; 6BD8; -.
PDBsum; 6BDH; -.
PDBsum; 6BDI; -.
PDBsum; 6BDK; -.
PDBsum; 6BDM; -.
ProteinModelPortal; P08684; -.
SMR; P08684; -.
BioGrid; 107948; 17.
IntAct; P08684; 2.
STRING; 9606.ENSP00000337915; -.
BindingDB; P08684; -.
DrugBank; DB05812; Abiraterone.
DrugBank; DB01418; Acenocoumarol.
DrugBank; DB00316; Acetaminophen.
DrugBank; DB00819; Acetazolamide.
DrugBank; DB00546; Adinazolam.
DrugBank; DB00518; Albendazole.
DrugBank; DB00240; Alclometasone.
DrugBank; DB00041; Aldesleukin.
DrugBank; DB00802; Alfentanil.
DrugBank; DB00346; Alfuzosin.
DrugBank; DB01246; Alimemazine.
DrugBank; DB09026; Aliskiren.
DrugBank; DB01431; Allylestrenol.
DrugBank; DB00918; Almotriptan.
DrugBank; DB06203; Alogliptin.
DrugBank; DB00969; Alosetron.
DrugBank; DB00404; Alprazolam.
DrugBank; DB06403; Ambrisentan.
DrugBank; DB06742; Ambroxol.
DrugBank; DB00357; Aminoglutethimide.
DrugBank; DB01424; Aminophenazone.
DrugBank; DB01223; Aminophylline.
DrugBank; DB01118; Amiodarone.
DrugBank; DB00321; Amitriptyline.
DrugBank; DB00381; Amlodipine.
DrugBank; DB00701; Amprenavir.
DrugBank; DB01217; Anastrozole.
DrugBank; DB01435; Antipyrine.
DrugBank; DB06605; Apixaban.
DrugBank; DB05676; Apremilast.
DrugBank; DB00673; Aprepitant.
DrugBank; DB00278; Argatroban.
DrugBank; DB01238; Aripiprazole.
DrugBank; DB06413; Armodafinil.
DrugBank; DB01169; Arsenic trioxide.
DrugBank; DB06697; Artemether.
DrugBank; DB06216; Asenapine.
DrugBank; DB00637; Astemizole.
DrugBank; DB01072; Atazanavir.
DrugBank; DB00289; Atomoxetine.
DrugBank; DB01076; Atorvastatin.
DrugBank; DB06237; Avanafil.
DrugBank; DB06626; Axitinib.
DrugBank; DB00719; Azatadine.
DrugBank; DB00972; Azelastine.
DrugBank; DB04957; Azimilide.
DrugBank; DB00207; Azithromycin.
DrugBank; DB04975; Banoxantrone.
DrugBank; DB08903; Bedaquiline.
DrugBank; DB00865; Benzphetamine.
DrugBank; DB06770; Benzyl alcohol.
DrugBank; DB00443; Betamethasone.
DrugBank; DB00307; Bexarotene.
DrugBank; DB01393; Bezafibrate.
DrugBank; DB01128; Bicalutamide.
DrugBank; DB04794; Bifonazole.
DrugBank; DB00612; Bisoprolol.
DrugBank; DB08873; Boceprevir.
DrugBank; DB00188; Bortezomib.
DrugBank; DB00559; Bosentan.
DrugBank; DB06616; Bosutinib.
DrugBank; DB08870; Brentuximab vedotin.
DrugBank; DB09128; Brexpiprazole.
DrugBank; DB01194; Brinzolamide.
DrugBank; DB01558; Bromazepam.
DrugBank; DB01200; Bromocriptine.
DrugBank; DB00835; Brompheniramine.
DrugBank; DB01222; Budesonide.
DrugBank; DB00297; Bupivacaine.
DrugBank; DB00921; Buprenorphine.
DrugBank; DB01156; Bupropion.
DrugBank; DB00490; Buspirone.
DrugBank; DB01008; Busulfan.
DrugBank; DB06772; Cabazitaxel.
DrugBank; DB00248; Cabergoline.
DrugBank; DB08875; Cabozantinib.
DrugBank; DB00201; Caffeine.
DrugBank; DB04886; Calanolide A.
DrugBank; DB00136; Calcitriol.
DrugBank; DB08907; Canagliflozin.
DrugBank; DB06774; Capsaicin.
DrugBank; DB00564; Carbamazepine.
DrugBank; DB00748; Carbinoxamine.
DrugBank; DB06016; Cariprazine.
DrugBank; DB01136; Carvedilol.
DrugBank; DB00520; Caspofungin.
DrugBank; DB01333; Cefradine.
DrugBank; DB00482; Celecoxib.
DrugBank; DB04846; Celiprolol.
DrugBank; DB00567; Cephalexin.
DrugBank; DB09063; Ceritinib.
DrugBank; DB00439; Cerivastatin.
DrugBank; DB00185; Cevimeline.
DrugBank; DB06777; Chenodeoxycholic acid.
DrugBank; DB00446; Chloramphenicol.
DrugBank; DB00475; Chlordiazepoxide.
DrugBank; DB00608; Chloroquine.
DrugBank; DB01114; Chlorphenamine.
DrugBank; DB00856; Chlorphenesin.
DrugBank; DB00477; Chlorpromazine.
DrugBank; DB00356; Chlorzoxazone.
DrugBank; DB00169; Cholecalciferol.
DrugBank; DB01410; Ciclesonide.
DrugBank; DB01166; Cilostazol.
DrugBank; DB00501; Cimetidine.
DrugBank; DB01012; Cinacalcet.
DrugBank; DB00537; Ciprofloxacin.
DrugBank; DB00604; Cisapride.
DrugBank; DB00215; Citalopram.
DrugBank; DB01211; Clarithromycin.
DrugBank; DB00283; Clemastine.
DrugBank; DB04920; Clevidipine.
DrugBank; DB01190; Clindamycin.
DrugBank; DB00349; Clobazam.
DrugBank; DB00845; Clofazimine.
DrugBank; DB00636; Clofibrate.
DrugBank; DB00882; Clomifene.
DrugBank; DB01242; Clomipramine.
DrugBank; DB01068; Clonazepam.
DrugBank; DB00575; Clonidine.
DrugBank; DB00758; Clopidogrel.
DrugBank; DB00628; Clorazepate.
DrugBank; DB01559; Clotiazepam.
DrugBank; DB00257; Clotrimazole.
DrugBank; DB00363; Clozapine.
DrugBank; DB09065; Cobicistat.
DrugBank; DB05239; Cobimetinib.
DrugBank; DB00907; Cocaine.
DrugBank; DB00318; Codeine.
DrugBank; DB01394; Colchicine.
DrugBank; DB00872; Conivaptan.
DrugBank; DB00286; Conjugated Equine Estrogens.
DrugBank; DB01380; Cortisone acetate.
DrugBank; DB08865; Crizotinib.
DrugBank; DB00924; Cyclobenzaprine.
DrugBank; DB00531; Cyclophosphamide.
DrugBank; DB00091; Cyclosporine.
DrugBank; DB00987; Cytarabine.
DrugBank; DB08912; Dabrafenib.
DrugBank; DB09102; Daclatasvir.
DrugBank; DB01764; Dalfopristin.
DrugBank; DB01406; Danazol.
DrugBank; DB01219; Dantrolene.
DrugBank; DB06292; Dapagliflozin.
DrugBank; DB00250; Dapsone.
DrugBank; DB00496; Darifenacin.
DrugBank; DB01264; Darunavir.
DrugBank; DB09183; Dasabuvir.
DrugBank; DB01254; Dasatinib.
DrugBank; DB00694; Daunorubicin.
DrugBank; DB01609; Deferasirox.
DrugBank; DB11921; Deflazacort.
DrugBank; DB00705; Delavirdine.
DrugBank; DB01151; Desipramine.
DrugBank; DB06700; Desvenlafaxine.
DrugBank; DB01234; Dexamethasone.
DrugBank; DB04856; Dexloxiglumide.
DrugBank; DB00514; Dextromethorphan.
DrugBank; DB00647; Dextropropoxyphene.
DrugBank; DB00829; Diazepam.
DrugBank; DB00586; Diclofenac.
DrugBank; DB00485; Dicloxacillin.
DrugBank; DB00255; Diethylstilbestrol.
DrugBank; DB01396; Digitoxin.
DrugBank; DB00390; Digoxin.
DrugBank; DB01551; Dihydrocodeine.
DrugBank; DB00320; Dihydroergotamine.
DrugBank; DB00343; Diltiazem.
DrugBank; DB01093; Dimethyl sulfoxide.
DrugBank; DB00280; Disopyramide.
DrugBank; DB00822; Disulfiram.
DrugBank; DB01248; Docetaxel.
DrugBank; DB00204; Dofetilide.
DrugBank; DB00757; Dolasetron.
DrugBank; DB08930; Dolutegravir.
DrugBank; DB01184; Domperidone.
DrugBank; DB00843; Donepezil.
DrugBank; DB00869; Dorzolamide.
DrugBank; DB01142; Doxepin.
DrugBank; DB00997; Doxorubicin.
DrugBank; DB00254; Doxycycline.
DrugBank; DB00470; Dronabinol.
DrugBank; DB04855; Dronedarone.
DrugBank; DB01395; Drospirenone.
DrugBank; DB01126; Dutasteride.
DrugBank; DB01127; Econazole.
DrugBank; DB00625; Efavirenz.
DrugBank; DB00216; Eletriptan.
DrugBank; DB09039; Eliglustat.
DrugBank; DB09101; Elvitegravir.
DrugBank; DB00584; Enalapril.
DrugBank; DB08899; Enzalutamide.
DrugBank; DB00751; Epinastine.
DrugBank; DB00668; Epinephrine.
DrugBank; DB00700; Eplerenone.
DrugBank; DB00153; Ergocalciferol.
DrugBank; DB01049; Ergoloid mesylate.
DrugBank; DB01253; Ergonovine.
DrugBank; DB00696; Ergotamine.
DrugBank; DB00530; Erlotinib.
DrugBank; DB00199; Erythromycin.
DrugBank; DB01175; Escitalopram.
DrugBank; DB09119; Eslicarbazepine acetate.
DrugBank; DB00736; Esomeprazole.
DrugBank; DB01215; Estazolam.
DrugBank; DB00783; Estradiol.
DrugBank; DB01196; Estramustine.
DrugBank; DB00655; Estrone.
DrugBank; DB04574; Estrone sulfate.
DrugBank; DB00402; Eszopiclone.
DrugBank; DB00898; Ethanol.
DrugBank; DB00977; Ethinyl Estradiol.
DrugBank; DB00593; Ethosuximide.
DrugBank; DB01466; Ethylmorphine.
DrugBank; DB00294; Etonogestrel.
DrugBank; DB00773; Etoposide.
DrugBank; DB01628; Etoricoxib.
DrugBank; DB06414; Etravirine.
DrugBank; DB01590; Everolimus.
DrugBank; DB00990; Exemestane.
DrugBank; DB00973; Ezetimibe.
DrugBank; DB00426; Famciclovir.
DrugBank; DB00949; Felbamate.
DrugBank; DB01023; Felodipine.
DrugBank; DB01039; Fenofibrate.
DrugBank; DB00813; Fentanyl.
DrugBank; DB06702; Fesoterodine.
DrugBank; DB01216; Finasteride.
DrugBank; DB08868; Fingolimod.
DrugBank; DB04908; Flibanserin.
DrugBank; DB00301; Flucloxacillin.
DrugBank; DB00196; Fluconazole.
DrugBank; DB00180; Flunisolide.
DrugBank; DB01544; Flunitrazepam.
DrugBank; DB00324; Fluorometholone.
DrugBank; DB00472; Fluoxetine.
DrugBank; DB00690; Flurazepam.
DrugBank; DB00499; Flutamide.
DrugBank; DB08906; Fluticasone furoate.
DrugBank; DB00588; Fluticasone Propionate.
DrugBank; DB01095; Fluvastatin.
DrugBank; DB00176; Fluvoxamine.
DrugBank; DB01319; Fosamprenavir.
DrugBank; DB06717; Fosaprepitant.
DrugBank; DB01320; Fosphenytoin.
DrugBank; DB00947; Fulvestrant.
DrugBank; DB00674; Galantamine.
DrugBank; DB00317; Gefitinib.
DrugBank; DB01241; Gemfibrozil.
DrugBank; DB01067; Glipizide.
DrugBank; DB01016; Glyburide.
DrugBank; DB08909; Glycerol Phenylbutyrate.
DrugBank; DB00889; Granisetron.
DrugBank; DB00365; Grepafloxacin.
DrugBank; DB00400; Griseofulvin.
DrugBank; DB01170; Guanethidine.
DrugBank; DB01018; Guanfacine.
DrugBank; DB01218; Halofantrine.
DrugBank; DB00502; Haloperidol.
DrugBank; DB01159; Halothane.
DrugBank; DB01355; Hexobarbital.
DrugBank; DB05381; Histamine.
DrugBank; DB01275; Hydralazine.
DrugBank; DB00956; Hydrocodone.
DrugBank; DB00769; Hydrocortamate.
DrugBank; DB00741; Hydrocortisone.
DrugBank; DB00327; Hydromorphone.
DrugBank; DB06789; Hydroxyprogesterone caproate.
DrugBank; DB09053; Ibrutinib.
DrugBank; DB11737; Icotinib.
DrugBank; DB09054; Idelalisib.
DrugBank; DB01181; Ifosfamide.
DrugBank; DB04946; Iloperidone.
DrugBank; DB00619; Imatinib.
DrugBank; DB00458; Imipramine.
DrugBank; DB00724; Imiquimod.
DrugBank; DB05039; Indacaterol.
DrugBank; DB00808; Indapamide.
DrugBank; DB00224; Indinavir.
DrugBank; DB00332; Ipratropium bromide.
DrugBank; DB01029; Irbesartan.
DrugBank; DB00762; Irinotecan.
DrugBank; DB06636; Isavuconazonium.
DrugBank; DB00951; Isoniazid.
DrugBank; DB00883; Isosorbide Dinitrate.
DrugBank; DB01020; Isosorbide Mononitrate.
DrugBank; DB00270; Isradipine.
DrugBank; DB01167; Itraconazole.
DrugBank; DB09083; Ivabradine.
DrugBank; DB08820; Ivacaftor.
DrugBank; DB00602; Ivermectin.
DrugBank; DB04845; Ixabepilone.
DrugBank; DB09570; Ixazomib.
DrugBank; DB01321; Josamycin.
DrugBank; DB01221; Ketamine.
DrugBank; DB01587; Ketazolam.
DrugBank; DB06738; Ketobemidone.
DrugBank; DB01026; Ketoconazole.
DrugBank; DB00448; Lansoprazole.
DrugBank; DB01259; Lapatinib.
DrugBank; DB06685; Laquinimod.
DrugBank; DB09078; Lenvatinib.
DrugBank; DB00528; Lercanidipine.
DrugBank; DB01006; Letrozole.
DrugBank; DB01002; Levobupivacaine.
DrugBank; DB06282; Levocetirizine.
DrugBank; DB01137; Levofloxacin.
DrugBank; DB01227; Levomethadyl Acetate.
DrugBank; DB08918; Levomilnacipran.
DrugBank; DB00367; Levonorgestrel.
DrugBank; DB13139; Levosalbutamol.
DrugBank; DB00451; Levothyroxine.
DrugBank; DB00281; Lidocaine.
DrugBank; DB08882; Linagliptin.
DrugBank; DB00589; Lisuride.
DrugBank; DB08827; Lomitapide.
DrugBank; DB01206; Lomustine.
DrugBank; DB00836; Loperamide.
DrugBank; DB01601; Lopinavir.
DrugBank; DB00455; Loratadine.
DrugBank; DB04871; Lorcaserin.
DrugBank; DB00678; Losartan.
DrugBank; DB00227; Lovastatin.
DrugBank; DB08933; Luliconazole.
DrugBank; DB09280; Lumacaftor.
DrugBank; DB06708; Lumefantrine.
DrugBank; DB08815; Lurasidone.
DrugBank; DB08932; Macitentan.
DrugBank; DB04835; Maraviroc.
DrugBank; DB00643; Mebendazole.
DrugBank; DB00603; Medroxyprogesterone acetate.
DrugBank; DB00358; Mefloquine.
DrugBank; DB00814; Meloxicam.
DrugBank; DB01071; Mequitazine.
DrugBank; DB04817; Metamizole.
DrugBank; DB00333; Methadone.
DrugBank; DB04833; Methaqualone.
DrugBank; DB00703; Methazolamide.
DrugBank; DB00763; Methimazole.
DrugBank; DB00553; Methoxsalen.
DrugBank; DB01028; Methoxyflurane.
DrugBank; DB09543; Methyl salicylate.
DrugBank; DB00353; Methylergometrine.
DrugBank; DB00959; Methylprednisolone.
DrugBank; DB06710; Methyltestosterone.
DrugBank; DB00916; Metronidazole.
DrugBank; DB01011; Metyrapone.
DrugBank; DB00379; Mexiletine.
DrugBank; DB06148; Mianserin.
DrugBank; DB01388; Mibefradil.
DrugBank; DB01110; Miconazole.
DrugBank; DB00683; Midazolam.
DrugBank; DB00834; Mifepristone.
DrugBank; DB08893; Mirabegron.
DrugBank; DB00370; Mirtazapine.
DrugBank; DB00648; Mitotane.
DrugBank; DB01204; Mitoxantrone.
DrugBank; DB00745; Modafinil.
DrugBank; DB00471; Montelukast.
DrugBank; DB00295; Morphine.
DrugBank; DB00688; Mycophenolate mofetil.
DrugBank; DB00607; Nafcillin.
DrugBank; DB09049; Naloxegol.
DrugBank; DB01183; Naloxone.
DrugBank; DB00731; Nateglinide.
DrugBank; DB01149; Nefazodone.
DrugBank; DB00220; Nelfinavir.
DrugBank; DB09048; Netupitant.
DrugBank; DB00238; Nevirapine.
DrugBank; DB00622; Nicardipine.
DrugBank; DB02701; Nicotinamide.
DrugBank; DB00184; Nicotine.
DrugBank; DB01115; Nifedipine.
DrugBank; DB04868; Nilotinib.
DrugBank; DB06712; Nilvadipine.
DrugBank; DB00393; Nimodipine.
DrugBank; DB00401; Nisoldipine.
DrugBank; DB01595; Nitrazepam.
DrugBank; DB01054; Nitrendipine.
DrugBank; DB00435; Nitric Oxide.
DrugBank; DB00717; Norethisterone.
DrugBank; DB01059; Norfloxacin.
DrugBank; DB00957; Norgestimate.
DrugBank; DB09389; Norgestrel.
DrugBank; DB00540; Nortriptyline.
DrugBank; DB00334; Olanzapine.
DrugBank; DB09074; Olaparib.
DrugBank; DB00768; Olopatadine.
DrugBank; DB00338; Omeprazole.
DrugBank; DB00904; Ondansetron.
DrugBank; DB04911; Oritavancin.
DrugBank; DB01083; Orlistat.
DrugBank; DB01173; Orphenadrine.
DrugBank; DB09330; Osimertinib.
DrugBank; DB04938; Ospemifene.
DrugBank; DB00842; Oxazepam.
DrugBank; DB00776; Oxcarbazepine.
DrugBank; DB00239; Oxiconazole.
DrugBank; DB01062; Oxybutynin.
DrugBank; DB00497; Oxycodone.
DrugBank; DB01192; Oxymorphone.
DrugBank; DB01229; Paclitaxel.
DrugBank; DB09073; Palbociclib.
DrugBank; DB01267; Paliperidone.
DrugBank; DB00377; Palonosetron.
DrugBank; DB06603; Panobinostat.
DrugBank; DB00213; Pantoprazole.
DrugBank; DB00617; Paramethadione.
DrugBank; DB01384; Paramethasone.
DrugBank; DB08439; Parecoxib.
DrugBank; DB00910; Paricalcitol.
DrugBank; DB09297; Paritaprevir.
DrugBank; DB06589; Pazopanib.
DrugBank; DB00082; Pegvisomant.
DrugBank; DB00738; Pentamidine.
DrugBank; DB00312; Pentobarbital.
DrugBank; DB08883; Perampanel.
DrugBank; DB01186; Pergolide.
DrugBank; DB01074; Perhexiline.
DrugBank; DB04930; Permethrin.
DrugBank; DB00850; Perphenazine.
DrugBank; DB00454; Pethidine.
DrugBank; DB03783; Phenacetin.
DrugBank; DB00780; Phenelzine.
DrugBank; DB01174; Phenobarbital.
DrugBank; DB00925; Phenoxybenzamine.
DrugBank; DB00946; Phenprocoumon.
DrugBank; DB00812; Phenylbutazone.
DrugBank; DB00252; Phenytoin.
DrugBank; DB01085; Pilocarpine.
DrugBank; DB00337; Pimecrolimus.
DrugBank; DB01100; Pimozide.
DrugBank; DB01132; Pioglitazone.
DrugBank; DB01621; Pipotiazine.
DrugBank; DB04977; Plitidepsin.
DrugBank; DB01179; Podofilox.
DrugBank; DB08910; Pomalidomide.
DrugBank; DB08901; Ponatinib.
DrugBank; DB01263; Posaconazole.
DrugBank; DB05478; Pradefovir Mesylate.
DrugBank; DB01411; Pranlukast.
DrugBank; DB01708; Prasterone.
DrugBank; DB06209; Prasugrel.
DrugBank; DB00175; Pravastatin.
DrugBank; DB01588; Prazepam.
DrugBank; DB01058; Praziquantel.
DrugBank; DB00860; Prednisolone.
DrugBank; DB00635; Prednisone.
DrugBank; DB01087; Primaquine.
DrugBank; DB00794; Primidone.
DrugBank; DB01032; Probenecid.
DrugBank; DB00433; Prochlorperazine.
DrugBank; DB00396; Progesterone.
DrugBank; DB01131; Proguanil.
DrugBank; DB00420; Promazine.
DrugBank; DB01182; Propafenone.
DrugBank; DB00818; Propofol.
DrugBank; DB09396; Propoxyphene napsylate.
DrugBank; DB00571; Propranolol.
DrugBank; DB00339; Pyrazinamide.
DrugBank; DB00545; Pyridostigmine.
DrugBank; DB01589; Quazepam.
DrugBank; DB01224; Quetiapine.
DrugBank; DB01103; Quinacrine.
DrugBank; DB00908; Quinidine.
DrugBank; DB00468; Quinine.
DrugBank; DB01369; Quinupristin.
DrugBank; DB01129; Rabeprazole.
DrugBank; DB00481; Raloxifene.
DrugBank; DB00980; Ramelteon.
DrugBank; DB00863; Ranitidine.
DrugBank; DB00243; Ranolazine.
DrugBank; DB00234; Reboxetine.
DrugBank; DB08896; Regorafenib.
DrugBank; DB00912; Repaglinide.
DrugBank; DB02709; Resveratrol.
DrugBank; DB01256; Retapamulin.
DrugBank; DB00615; Rifabutin.
DrugBank; DB04934; Rifalazil.
DrugBank; DB01045; Rifampicin.
DrugBank; DB01201; Rifapentine.
DrugBank; DB01220; Rifaximin.
DrugBank; DB08864; Rilpivirine.
DrugBank; DB06155; Rimonabant.
DrugBank; DB08931; Riociguat.
DrugBank; DB00734; Risperidone.
DrugBank; DB00503; Ritonavir.
DrugBank; DB06228; Rivaroxaban.
DrugBank; DB00989; Rivastigmine.
DrugBank; DB00533; Rofecoxib.
DrugBank; DB09291; Rolapitant.
DrugBank; DB01301; Rolitetracycline.
DrugBank; DB06176; Romidepsin.
DrugBank; DB00268; Ropinirole.
DrugBank; DB00296; Ropivacaine.
DrugBank; DB01098; Rosuvastatin.
DrugBank; DB05271; Rotigotine.
DrugBank; DB00778; Roxithromycin.
DrugBank; DB12332; Rucaparib.
DrugBank; DB06201; Rufinamide.
DrugBank; DB01698; Rutin.
DrugBank; DB08877; Ruxolitinib.
DrugBank; DB06654; Safinamide.
DrugBank; DB01001; Salbutamol.
DrugBank; DB00938; Salmeterol.
DrugBank; DB01232; Saquinavir.
DrugBank; DB06335; Saxagliptin.
DrugBank; DB01037; Selegiline.
DrugBank; DB11362; Selexipag.
DrugBank; DB06144; Sertindole.
DrugBank; DB01104; Sertraline.
DrugBank; DB01236; Sevoflurane.
DrugBank; DB01105; Sibutramine.
DrugBank; DB00203; Sildenafil.
DrugBank; DB06207; Silodosin.
DrugBank; DB06290; Simeprevir.
DrugBank; DB00641; Simvastatin.
DrugBank; DB00877; Sirolimus.
DrugBank; DB01261; Sitagliptin.
DrugBank; DB06268; Sitaxentan.
DrugBank; DB01591; Solifenacin.
DrugBank; DB09143; Sonidegib.
DrugBank; DB00398; Sorafenib.
DrugBank; DB06145; Spiramycin.
DrugBank; DB01323; St. John's Wort.
DrugBank; DB00708; Sufentanil.
DrugBank; DB00359; Sulfadiazine.
DrugBank; DB01015; Sulfamethoxazole.
DrugBank; DB00259; Sulfanilamide.
DrugBank; DB01138; Sulfinpyrazone.
DrugBank; DB00263; Sulfisoxazole.
DrugBank; DB01268; Sunitinib.
DrugBank; DB00864; Tacrolimus.
DrugBank; DB00820; Tadalafil.
DrugBank; DB00675; Tamoxifen.
DrugBank; DB00706; Tamsulosin.
DrugBank; DB01349; Tasosartan.
DrugBank; DB05521; Telaprevir.
DrugBank; DB00976; Telithromycin.
DrugBank; DB00231; Temazepam.
DrugBank; DB00853; Temozolomide.
DrugBank; DB06287; Temsirolimus.
DrugBank; DB00444; Teniposide.
DrugBank; DB00857; Terbinafine.
DrugBank; DB00342; Terfenadine.
DrugBank; DB04905; Tesmilifene.
DrugBank; DB00624; Testosterone.
DrugBank; DB00759; Tetracycline.
DrugBank; DB00277; Theophylline.
DrugBank; DB00599; Thiopental.
DrugBank; DB04572; Thiotepa.
DrugBank; DB00906; Tiagabine.
DrugBank; DB08816; Ticagrelor.
DrugBank; DB00208; Ticlopidine.
DrugBank; DB00911; Tinidazole.
DrugBank; DB01007; Tioconazole.
DrugBank; DB01409; Tiotropium.
DrugBank; DB00932; Tipranavir.
DrugBank; DB08895; Tofacitinib.
DrugBank; DB08811; Tofisopam.
DrugBank; DB01036; Tolterodine.
DrugBank; DB06212; Tolvaptan.
DrugBank; DB00273; Topiramate.
DrugBank; DB01030; Topotecan.
DrugBank; DB00539; Toremifene.
DrugBank; DB05109; Trabectedin.
DrugBank; DB00193; Tramadol.
DrugBank; DB08911; Trametinib.
DrugBank; DB00752; Tranylcypromine.
DrugBank; DB05773; Trastuzumab emtansine.
DrugBank; DB00656; Trazodone.
DrugBank; DB00755; Tretinoin.
DrugBank; DB00620; Triamcinolone.
DrugBank; DB00897; Triazolam.
DrugBank; DB00347; Trimethadione.
DrugBank; DB00440; Trimethoprim.
DrugBank; DB00726; Trimipramine.
DrugBank; DB00197; Troglitazone.
DrugBank; DB01361; Troleandomycin.
DrugBank; DB06267; Udenafil.
DrugBank; DB08867; Ulipristal.
DrugBank; DB00580; Valdecoxib.
DrugBank; DB00313; Valproic Acid.
DrugBank; DB05294; Vandetanib.
DrugBank; DB03701; Vanoxerine.
DrugBank; DB00862; Vardenafil.
DrugBank; DB08881; Vemurafenib.
DrugBank; DB11581; Venetoclax.
DrugBank; DB00285; Venlafaxine.
DrugBank; DB00661; Verapamil.
DrugBank; DB09082; Vilanterol.
DrugBank; DB06684; Vilazodone.
DrugBank; DB00570; Vinblastine.
DrugBank; DB00541; Vincristine.
DrugBank; DB00309; Vindesine.
DrugBank; DB00361; Vinorelbine.
DrugBank; DB08828; Vismodegib.
DrugBank; DB00582; Voriconazole.
DrugBank; DB09068; Vortioxetine.
DrugBank; DB00682; Warfarin.
DrugBank; DB01392; Yohimbine.
DrugBank; DB00549; Zafirlukast.
DrugBank; DB00943; Zalcitabine.
DrugBank; DB00962; Zaleplon.
DrugBank; DB00495; Zidovudine.
DrugBank; DB00744; Zileuton.
DrugBank; DB00246; Ziprasidone.
DrugBank; DB00425; Zolpidem.
DrugBank; DB04828; Zomepirac.
DrugBank; DB00909; Zonisamide.
DrugBank; DB01198; Zopiclone.
GuidetoPHARMACOLOGY; 1337; -.
SwissLipids; SLP:000001201; -.
iPTMnet; P08684; -.
PhosphoSitePlus; P08684; -.
BioMuta; CYP3A4; -.
DMDM; 116241312; -.
PaxDb; P08684; -.
PeptideAtlas; P08684; -.
PRIDE; P08684; -.
ProteomicsDB; 52154; -.
Ensembl; ENST00000336411; ENSP00000337915; ENSG00000160868.
GeneID; 1576; -.
KEGG; hsa:1576; -.
CTD; 1576; -.
DisGeNET; 1576; -.
EuPathDB; HostDB:ENSG00000160868.14; -.
GeneCards; CYP3A4; -.
HGNC; HGNC:2637; CYP3A4.
HPA; CAB033671; -.
HPA; HPA072245; -.
MalaCards; CYP3A4; -.
MIM; 124010; gene.
neXtProt; NX_P08684; -.
OpenTargets; ENSG00000160868; -.
Orphanet; 241043; Tacrolimus dose selection.
PharmGKB; PA130; -.
eggNOG; KOG0158; Eukaryota.
eggNOG; COG2124; LUCA.
GeneTree; ENSGT00940000153111; -.
HOGENOM; HOG000039127; -.
HOVERGEN; HBG108567; -.
InParanoid; P08684; -.
KO; K17689; -.
OrthoDB; EOG091G0JNC; -.
PhylomeDB; P08684; -.
TreeFam; TF105087; -.
BioCyc; MetaCyc:HS08544-MONOMER; -.
BRENDA;; 2681.
BRENDA;; 2681.
Reactome; R-HSA-211981; Xenobiotics.
Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
Reactome; R-HSA-9027307; Biosynthesis of maresin-like SPMs.
SABIO-RK; P08684; -.
SIGNOR; P08684; -.
ChiTaRS; CYP3A4; human.
EvolutionaryTrace; P08684; -.
GeneWiki; CYP3A4; -.
GenomeRNAi; 1576; -.
PRO; PR:P08684; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000160868; Expressed in 163 organ(s), highest expression level in jejunal mucosa.
CleanEx; HS_CYP3A4; -.
ExpressionAtlas; P08684; baseline and differential.
Genevisible; P08684; HS.
GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:ProtInc.
GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
GO; GO:0034875; F:caffeine oxidase activity; IDA:BHF-UCL.
GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
GO; GO:0101020; F:estrogen 16-alpha-hydroxylase activity; IDA:BHF-UCL.
GO; GO:0020037; F:heme binding; IEA:InterPro.
GO; GO:0005506; F:iron ion binding; IDA:BHF-UCL.
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; IEA:InterPro.
GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
GO; GO:0005496; F:steroid binding; IDA:BHF-UCL.
GO; GO:0008395; F:steroid hydroxylase activity; IMP:BHF-UCL.
GO; GO:0050649; F:testosterone 6-beta-hydroxylase activity; IMP:BHF-UCL.
GO; GO:0070576; F:vitamin D 24-hydroxylase activity; IDA:BHF-UCL.
GO; GO:0030343; F:vitamin D3 25-hydroxylase activity; IDA:BHF-UCL.
GO; GO:0009822; P:alkaloid catabolic process; IDA:BHF-UCL.
GO; GO:0008209; P:androgen metabolic process; TAS:BHF-UCL.
GO; GO:0042737; P:drug catabolic process; IDA:BHF-UCL.
GO; GO:0017144; P:drug metabolic process; IDA:BHF-UCL.
GO; GO:0042738; P:exogenous drug catabolic process; IDA:BHF-UCL.
GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL.
GO; GO:0002933; P:lipid hydroxylation; IDA:BHF-UCL.
GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome.
GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL.
GO; GO:0055114; P:oxidation-reduction process; IDA:BHF-UCL.
GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL.
GO; GO:0006706; P:steroid catabolic process; IMP:BHF-UCL.
GO; GO:0008202; P:steroid metabolic process; IDA:BHF-UCL.
GO; GO:0042359; P:vitamin D metabolic process; IC: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; IPR008072; Cyt_P450_E_CYP3A.
InterPro; IPR002402; Cyt_P450_E_grp-II.
InterPro; IPR036396; Cyt_P450_sf.
Pfam; PF00067; p450; 1.
PRINTS; PR00464; EP450II.
PRINTS; PR00385; P450.
SUPFAM; SSF48264; SSF48264; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Direct protein sequencing;
Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Polymorphism;
Reference proteome; Steroid metabolism; Sterol metabolism;
Transmembrane; Transmembrane helix; Ubl conjugation.
INIT_MET 1 1 Removed. {ECO:0000269|PubMed:3243766,
CHAIN 2 503 Cytochrome P450 3A4.
TRANSMEM 2 22 Helical. {ECO:0000255}.
METAL 442 442 Iron (heme axial ligand).
VARIANT 15 15 L -> P (in allele CYP3A4*14;
VARIANT 56 56 G -> D (in allele CYP3A4*7;
VARIANT 96 96 K -> E (in dbSNP:rs3091339).
VARIANT 118 118 I -> V (in allele CYP3A4*4;
VARIANT 130 130 R -> Q (in allele CYP3A4*8;
VARIANT 162 162 R -> Q (in allele CYP3A4*15;
VARIANT 170 170 V -> I (in allele CYP3A4*9;
VARIANT 174 174 D -> H (in allele CYP3A4*10;
VARIANT 185 185 T -> S (in allele CYP3A4*16;
VARIANT 189 189 F -> S (in allele CYP3A4*17; exhibits
lower turnover numbers for testosterone
and chlorpyrifos; dbSNP:rs4987161).
VARIANT 218 218 P -> R (in allele CYP3A4*5;
VARIANT 222 222 S -> P (in allele CYP3A4*2; exhibits a
lower intrinsic clearance toward
nifedipine; dbSNP:rs55785340).
VARIANT 252 252 S -> A (in dbSNP:rs3208363).
VARIANT 293 293 L -> P (in allele CYP3A4*18; exhibits
higher turnover numbers for testosterone
and chlorpyrifos; dbSNP:rs28371759).
VARIANT 349 349 T -> N (in dbSNP:rs10250778).
VARIANT 363 363 T -> M (in allele CYP3A4*11; unstable
form; dbSNP:rs67784355).
VARIANT 373 373 L -> F (in allele CYP3A4*12; has an
altered testosterone hydroxylase
activity; dbSNP:rs12721629).
VARIANT 416 416 P -> L (in allele CYP3A4*13; lack of
expression; dbSNP:rs4986909).
VARIANT 431 431 I -> T (in dbSNP:rs1041988).
VARIANT 445 445 M -> T (in allele CYP3A4*3;
VARIANT 467 467 P -> S (in allele CYP3A4*19;
CONFLICT 3 3 L -> V (in Ref. 5; AAA35747).
CONFLICT 12 12 W -> R (in Ref. 9; AAF13598).
CONFLICT 72 72 W -> C (in Ref. 5; AAA35747).
CONFLICT 92 92 T -> L (in Ref. 1; BAA00001/AAA35742).
CONFLICT 106 106 R -> E (in Ref. 1; BAA00001/AAA35742).
CONFLICT 164 164 A -> R (in Ref. 1; BAA00001/AAA35742).
CONFLICT 187 187 T -> S (in Ref. 1; BAA00001/AAA35742).
CONFLICT 193 193 I -> V (in Ref. 1; BAA00001/AAA35742).
CONFLICT 203 203 F -> L (in Ref. 1; BAA00001/AAA35742).
CONFLICT 224 225 TV -> I (in Ref. 5; AAA35747).
CONFLICT 279 279 Q -> HK (in Ref. 1; BAA00001/AAA35742).
CONFLICT 307 307 Y -> C (in Ref. 9; AAF13598).
CONFLICT 392 392 V -> W (in Ref. 1; BAA00001/AAA35742, 3;
AAA35744, 4; CAA30944 and 5; AAA35747).
HELIX 23 26 {ECO:0000244|PDB:5TE8}.
HELIX 28 31 {ECO:0000244|PDB:5VCD}.
HELIX 32 36 {ECO:0000244|PDB:5VCC}.
TURN 45 47 {ECO:0000244|PDB:5VCC}.
HELIX 50 55 {ECO:0000244|PDB:5VCC}.
HELIX 57 68 {ECO:0000244|PDB:5VCC}.
STRAND 70 76 {ECO:0000244|PDB:5VCC}.
STRAND 79 84 {ECO:0000244|PDB:5VCC}.
HELIX 87 94 {ECO:0000244|PDB:5VCC}.
TURN 95 101 {ECO:0000244|PDB:5VCC}.
HELIX 112 116 {ECO:0000244|PDB:5VCC}.
TURN 118 120 {ECO:0000244|PDB:5VCC}.
HELIX 123 133 {ECO:0000244|PDB:5VCC}.
HELIX 134 137 {ECO:0000244|PDB:5VCC}.
HELIX 139 164 {ECO:0000244|PDB:5VCC}.
TURN 165 167 {ECO:0000244|PDB:5VCC}.
HELIX 172 189 {ECO:0000244|PDB:5VCC}.
TURN 195 197 {ECO:0000244|PDB:5VCC}.
HELIX 202 207 {ECO:0000244|PDB:5VCC}.
STRAND 209 212 {ECO:0000244|PDB:4K9T}.
STRAND 215 217 {ECO:0000244|PDB:6BDM}.
HELIX 218 225 {ECO:0000244|PDB:5VCC}.
HELIX 227 229 {ECO:0000244|PDB:5VCC}.
HELIX 230 235 {ECO:0000244|PDB:5VCC}.
HELIX 243 260 {ECO:0000244|PDB:5VCC}.
HELIX 271 278 {ECO:0000244|PDB:5VCC}.
STRAND 284 286 {ECO:0000244|PDB:2V0M}.
HELIX 292 323 {ECO:0000244|PDB:5VCC}.
HELIX 325 338 {ECO:0000244|PDB:5VCC}.
HELIX 340 342 {ECO:0000244|PDB:5VCC}.
HELIX 347 351 {ECO:0000244|PDB:5VCC}.
HELIX 354 366 {ECO:0000244|PDB:5VCC}.
STRAND 369 371 {ECO:0000244|PDB:4K9W}.
STRAND 373 376 {ECO:0000244|PDB:5VCC}.
STRAND 381 383 {ECO:0000244|PDB:5VCC}.
STRAND 386 388 {ECO:0000244|PDB:5VCC}.
STRAND 393 396 {ECO:0000244|PDB:5VCC}.
HELIX 398 402 {ECO:0000244|PDB:5VCC}.
TURN 405 407 {ECO:0000244|PDB:5VCC}.
STRAND 408 410 {ECO:0000244|PDB:5VCC}.
HELIX 416 419 {ECO:0000244|PDB:5VCC}.
TURN 421 423 {ECO:0000244|PDB:5VCC}.
HELIX 424 426 {ECO:0000244|PDB:5VCC}.
TURN 429 431 {ECO:0000244|PDB:5VCC}.
HELIX 438 440 {ECO:0000244|PDB:5VCE}.
HELIX 445 462 {ECO:0000244|PDB:5VCC}.
STRAND 463 467 {ECO:0000244|PDB:5VCC}.
STRAND 469 471 {ECO:0000244|PDB:5VCC}.
STRAND 479 482 {ECO:0000244|PDB:5VCC}.
STRAND 485 487 {ECO:0000244|PDB:5VCC}.
STRAND 490 495 {ECO:0000244|PDB:5VCC}.
SEQUENCE 503 AA; 57343 MW; 38ED122BF89F74F7 CRC64;

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