CP3A7_HUMAN
ID CP3A7_HUMAN Reviewed; 503 AA.
AC P24462; A4D288; Q9H241;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Cytochrome P450 3A7 {ECO:0000303|PubMed:17178770};
DE EC=1.14.14.1 {ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847};
DE AltName: Full=CYPIIIA7;
DE AltName: Full=Cytochrome P450-HFLA {ECO:0000303|PubMed:2492179};
DE AltName: Full=P450HLp2 {ECO:0000303|PubMed:2492179};
GN Name=CYP3A7 {ECO:0000303|PubMed:17178770, ECO:0000312|HGNC:HGNC:2640};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal liver;
RX PubMed=2722762; DOI=10.1093/oxfordjournals.jbchem.a122632;
RA Komori M., Nishio K., Ohi H., Kitada M., Kamataki T.;
RT "Molecular cloning and sequence analysis of cDNA containing the entire
RT coding region for human fetal liver cytochrome P-450.";
RL J. Biochem. 105:161-163(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=11137287; DOI=10.1016/s0378-1119(00)00470-4;
RA Finta C., Zaphiropoulos P.G.;
RT "The human cytochrome P450 3A locus. Gene evolution by capture of
RT downstream exons.";
RL Gene 260:13-23(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11266076; DOI=10.1097/00008571-200103000-00002;
RA Gellner K., Eiselt R., Hustert E., Arnold H., Koch I., Haberl M.,
RA Deglmann C.J., Burk O., Buntefuss D., Escher S., Bishop C., Koebe H.-G.,
RA Brinkmann U., Klenk H.-P., Kleine K., Meyer U.A., Wojnowski L.;
RT "Genomic organization of the human CYP3A locus: identification of a new,
RT inducible CYP3A gene.";
RL Pharmacogenetics 11:111-121(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 1-30, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Fetal liver;
RX PubMed=2492179; DOI=10.1016/0003-9861(89)90575-4;
RA Wrighton S.A., Vandenbranden M.;
RT "Isolation and characterization of human fetal liver cytochrome P450HLp2: a
RT third member of the P450III gene family.";
RL Arch. Biochem. Biophys. 268:144-151(1989).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 282-503 (ISOFORM 1).
RC TISSUE=Fetal liver;
RX PubMed=2786707; DOI=10.1016/0003-9861(89)90213-0;
RA Komori M., Nishio K., Fujitani T., Ohi H., Kitada M., Mima S., Itahashi K.,
RA Kamataki T.;
RT "Isolation of a new human fetal liver cytochrome P450 cDNA clone: evidence
RT for expression of a limited number of forms of cytochrome P450 in human
RT fetal livers.";
RL Arch. Biochem. Biophys. 272:219-225(1989).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9555064; DOI=10.1016/s0304-4165(97)00156-6;
RA Ohmori S., Nakasa H., Asanome K., Kurose Y., Ishii I., Hosokawa M.,
RA Kitada M.;
RT "Differential catalytic properties in metabolism of endogenous and
RT exogenous substrates among CYP3A enzymes expressed in COS-7 cells.";
RL Biochim. Biophys. Acta 1380:297-304(1998).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=11093772; DOI=10.1124/mol.58.6.1341;
RA Marill J., Cresteil T., Lanotte M., Chabot G.G.;
RT "Identification of human cytochrome P450s involved in the formation of all-
RT trans-retinoic acid principal metabolites.";
RL Mol. Pharmacol. 58:1341-1348(2000).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=14559847;
RA Lee A.J., Conney A.H., Zhu B.T.;
RT "Human cytochrome P450 3A7 has a distinct high catalytic activity for the
RT 16alpha-hydroxylation of estrone but not 17beta-estradiol.";
RL Cancer Res. 63:6532-6536(2003).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=12865317; DOI=10.1210/en.2003-0192;
RA Lee A.J., Cai M.X., Thomas P.E., Conney A.H., Zhu B.T.;
RT "Characterization of the oxidative metabolites of 17beta-estradiol and
RT estrone formed by 15 selectively expressed human cytochrome p450
RT isoforms.";
RL Endocrinology 144:3382-3398(2003).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP MUTAGENESIS OF ASN-116; HIS-174; ASN-214; LYS-224; LYS-244 AND LYS-262.
RX PubMed=17178770; DOI=10.1124/dmd.106.011304;
RA Torimoto N., Ishii I., Toyama K., Hata M., Tanaka K., Shimomura H.,
RA Nakamura H., Ariyoshi N., Ohmori S., Kitada M.;
RT "Helices F-G are important for the substrate specificities of CYP3A7.";
RL Drug Metab. Dispos. 35:484-492(2007).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC steroid hormones and vitamins during embryogenesis (PubMed:9555064,
CC PubMed:11093772, PubMed:14559847, PubMed:12865317, PubMed:17178770).
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via cytochrome P450 reductase (NADPH--
CC hemoprotein reductase) (PubMed:9555064, PubMed:11093772,
CC PubMed:14559847, PubMed:12865317, PubMed:17178770). Catalyzes the
CC hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-
CC hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor
CC in the biosynthesis of androgen and estrogen steroid hormones
CC (PubMed:9555064, PubMed:17178770). Exhibits high catalytic activity for
CC the formation of hydroxyestrogens from estrone (E1), particularly D-
CC ring hydroxylated estrone at the C16-alpha position (PubMed:14559847,
CC PubMed:12865317). Mainly hydroxylates all trans-retinoic acid (atRA) to
CC 4-hydroxyretinoate and may play a role in atRA clearance during fetal
CC development (PubMed:11093772). Also involved in the oxidative
CC metabolism of xenobiotics including anticonvulsants (PubMed:9555064).
CC {ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:17178770,
CC ECO:0000269|PubMed:9555064}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:14559847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:11093772, ECO:0000305|PubMed:12865317,
CC ECO:0000305|PubMed:14559847};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + O2 + reduced [NADPH--
CC hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:47220, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:27771, ChEBI:CHEBI:28689, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:17178770,
CC ECO:0000269|PubMed:9555064};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47221;
CC Evidence={ECO:0000305|PubMed:17178770, ECO:0000305|PubMed:9555064};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dehydroepiandrosterone 3-sulfate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 16alpha-hydroxydehydroepiandrosterone 3-
CC sulfate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:47224, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:57905, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:87538; Evidence={ECO:0000269|PubMed:17178770,
CC ECO:0000269|PubMed:9555064};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47225;
CC Evidence={ECO:0000305|PubMed:17178770, ECO:0000305|PubMed:9555064};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + testosterone =
CC 6beta,17beta-dihydroxyandrost-4-en-3-one + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46296, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17347,
CC ChEBI:CHEBI:34477, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:9555064};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46297;
CC Evidence={ECO:0000305|PubMed:9555064};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2-
CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:14559847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209;
CC Evidence={ECO:0000305|PubMed:12865317, ECO:0000305|PubMed:14559847};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 4-
CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:47292, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:87602; Evidence={ECO:0000269|PubMed:14559847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293;
CC Evidence={ECO:0000305|PubMed:14559847};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] =
CC 16alpha-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:47204, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:14559847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47205;
CC Evidence={ECO:0000305|PubMed:12865317, ECO:0000305|PubMed:14559847};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:28744,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213;
CC Evidence={ECO:0000305|PubMed:12865317, ECO:0000305|PubMed:14559847};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 6beta-hydroxyestradiol-17beta + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:47216, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:16784,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47217;
CC Evidence={ECO:0000305|PubMed:12865317, ECO:0000305|PubMed:14559847};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-4-hydroxyretinoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51984, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134178;
CC Evidence={ECO:0000269|PubMed:11093772};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985;
CC Evidence={ECO:0000305|PubMed:11093772};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-18-hydroxyretinoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:55856, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:139258;
CC Evidence={ECO:0000269|PubMed:11093772};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55857;
CC Evidence={ECO:0000305|PubMed:11093772};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for estrone (16-alpha hydroxylation)
CC {ECO:0000269|PubMed:14559847};
CC KM=10 uM for estrone (2-hydroxylation) {ECO:0000269|PubMed:14559847};
CC KM=25.3 uM for estrone (4-hydroxylation)
CC {ECO:0000269|PubMed:14559847};
CC KM=33.5 uM for 17beta-estradiol (2-hydroxylation)
CC {ECO:0000269|PubMed:14559847};
CC KM=15 uM for all-trans-retinoate (4-hydroxylation)
CC {ECO:0000269|PubMed:11093772};
CC KM=5 uM for all-trans-retinoate (18-hydroxylation)
CC {ECO:0000269|PubMed:11093772};
CC KM=14.8 uM for 3beta-hydroxyandrost-5-en-17-one (16-alpha
CC hydroxylation) {ECO:0000269|PubMed:17178770};
CC KM=18.5 uM for 3beta-sulfooxy-androst-5-en-17-one (16-alpha
CC hydroxylation) {ECO:0000269|PubMed:17178770};
CC Vmax=1423 pmol/min/nmol enzyme toward estrone (16-alpha
CC hydroxylation) {ECO:0000269|PubMed:14559847};
CC Vmax=2109 pmol/min/nmol enzyme toward estrone (2-hydroxylation)
CC {ECO:0000269|PubMed:14559847};
CC Vmax=328 pmol/min/nmol enzyme toward estrone (4-hydroxylation)
CC {ECO:0000269|PubMed:14559847};
CC Vmax=616 pmol/min/nmol enzyme toward 17beta-estradiol (2-
CC hydroxylation) {ECO:0000269|PubMed:14559847};
CC Vmax=1869 pmol/min/nmol enzyme toward all-trans-retinoate (4-
CC hydroxylation) {ECO:0000269|PubMed:11093772};
CC Vmax=52 pmol/min/nmol enzyme toward all-trans-retinoate (18-
CC hydroxylation) {ECO:0000269|PubMed:11093772};
CC Vmax=20.8 nmol/min/nmol enzyme toward 3beta-hydroxyandrost-5-en-17-
CC one (16-alpha hydroxylation) {ECO:0000269|PubMed:17178770};
CC Vmax=6.5 nmol/min/nmol enzyme toward 3beta-sulfooxy-androst-5-en-17-
CC one (16-alpha hydroxylation) {ECO:0000269|PubMed:17178770};
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:17178770}.
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:11093772}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane {ECO:0000305|PubMed:2492179};
CC Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P24462-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P24462-2; Sequence=VSP_055577;
CC -!- TISSUE SPECIFICITY: Expressed in fetal liver (at protein level).
CC {ECO:0000269|PubMed:2492179}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP3A7 alleles;
CC URL="https://www.pharmvar.org/gene/CYP3A7";
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DR EMBL; D00408; BAA00310.1; -; mRNA.
DR EMBL; AF315325; AAG48618.1; -; mRNA.
DR EMBL; AF280107; AAG32289.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23867.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76637.1; -; Genomic_DNA.
DR EMBL; BC067436; AAH67436.1; -; mRNA.
DR CCDS; CCDS5673.1; -. [P24462-1]
DR PIR; JX0062; JX0062.
DR RefSeq; NP_000756.3; NM_000765.4. [P24462-1]
DR RefSeq; NP_001243426.2; NM_001256497.2. [P24462-2]
DR PDB; 7MK8; X-ray; 2.15 A; A/B=23-499.
DR PDBsum; 7MK8; -.
DR AlphaFoldDB; P24462; -.
DR SMR; P24462; -.
DR BioGRID; 107930; 5.
DR IntAct; P24462; 1.
DR STRING; 9606.ENSP00000480571; -.
DR BindingDB; P24462; -.
DR ChEMBL; CHEMBL3341582; -.
DR DrugBank; DB11703; Acalabrutinib.
DR DrugBank; DB00802; Alfentanil.
DR DrugBank; DB00404; Alprazolam.
DR DrugBank; DB13141; Ambroxol acefyllinate.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB14185; Aripiprazole lauroxil.
DR DrugBank; DB00637; Astemizole.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB00443; Betamethasone.
DR DrugBank; DB12267; Brigatinib.
DR DrugBank; DB01222; Budesonide.
DR DrugBank; DB00921; Buprenorphine.
DR DrugBank; DB00490; Buspirone.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00439; Cerivastatin.
DR DrugBank; DB00446; Chloramphenicol.
DR DrugBank; DB01114; Chlorpheniramine.
DR DrugBank; DB01166; Cilostazol.
DR DrugBank; DB00537; Ciprofloxacin.
DR DrugBank; DB00604; Cisapride.
DR DrugBank; DB00257; Clotrimazole.
DR DrugBank; DB09065; Cobicistat.
DR DrugBank; DB12483; Copanlisib.
DR DrugBank; DB08865; Crizotinib.
DR DrugBank; DB09102; Daclatasvir.
DR DrugBank; DB00250; Dapsone.
DR DrugBank; DB00705; Delavirdine.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB00514; Dextromethorphan.
DR DrugBank; DB11994; Diacerein.
DR DrugBank; DB00829; Diazepam.
DR DrugBank; DB00343; Diltiazem.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB08930; Dolutegravir.
DR DrugBank; DB01184; Domperidone.
DR DrugBank; DB11742; Ebastine.
DR DrugBank; DB00625; Efavirenz.
DR DrugBank; DB11979; Elagolix.
DR DrugBank; DB11574; Elbasvir.
DR DrugBank; DB00199; Erythromycin.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR DrugBank; DB00593; Ethosuximide.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB00813; Fentanyl.
DR DrugBank; DB01216; Finasteride.
DR DrugBank; DB13867; Fluticasone.
DR DrugBank; DB08906; Fluticasone furoate.
DR DrugBank; DB00588; Fluticasone propionate.
DR DrugBank; DB00176; Fluvoxamine.
DR DrugBank; DB12307; Foretinib.
DR DrugBank; DB06730; Gestodene.
DR DrugBank; DB13879; Glecaprevir.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB00502; Haloperidol.
DR DrugBank; DB00741; Hydrocortisone.
DR DrugBank; DB14538; Hydrocortisone aceponate.
DR DrugBank; DB14539; Hydrocortisone acetate.
DR DrugBank; DB14540; Hydrocortisone butyrate.
DR DrugBank; DB14541; Hydrocortisone cypionate.
DR DrugBank; DB14542; Hydrocortisone phosphate.
DR DrugBank; DB14543; Hydrocortisone probutate.
DR DrugBank; DB14544; Hydrocortisone valerate.
DR DrugBank; DB09054; Idelalisib.
DR DrugBank; DB04946; Iloperidone.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB00224; Indinavir.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB11757; Istradefylline.
DR DrugBank; DB01167; Itraconazole.
DR DrugBank; DB11951; Lemborexant.
DR DrugBank; DB00528; Lercanidipine.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB01227; Levacetylmethadol.
DR DrugBank; DB00281; Lidocaine.
DR DrugBank; DB06448; Lonafarnib.
DR DrugBank; DB01601; Lopinavir.
DR DrugBank; DB12130; Lorlatinib.
DR DrugBank; DB09212; Loxoprofen.
DR DrugBank; DB00643; Mebendazole.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB00333; Methadone.
DR DrugBank; DB00959; Methylprednisolone.
DR DrugBank; DB00916; Metronidazole.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB00683; Midazolam.
DR DrugBank; DB06595; Midostaurin.
DR DrugBank; DB11792; Mirodenafil.
DR DrugBank; DB16390; Mobocertinib.
DR DrugBank; DB09205; Moxisylyte.
DR DrugBank; DB11605; Myrrh.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB11691; Naldemedine.
DR DrugBank; DB00731; Nateglinide.
DR DrugBank; DB01149; Nefazodone.
DR DrugBank; DB00220; Nelfinavir.
DR DrugBank; DB00238; Nevirapine.
DR DrugBank; DB00401; Nisoldipine.
DR DrugBank; DB01054; Nitrendipine.
DR DrugBank; DB01059; Norfloxacin.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB09568; Omega-3-carboxylic acids.
DR DrugBank; DB00904; Ondansetron.
DR DrugBank; DB06412; Oxymetholone.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB00780; Phenelzine.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB13878; Pibrentasvir.
DR DrugBank; DB01100; Pimozide.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB05804; Prasterone sulfate.
DR DrugBank; DB01058; Praziquantel.
DR DrugBank; DB14631; Prednisolone phosphate.
DR DrugBank; DB00635; Prednisone.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB00571; Propranolol.
DR DrugBank; DB04216; Quercetin.
DR DrugBank; DB01224; Quetiapine.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00468; Quinine.
DR DrugBank; DB11853; Relugolix.
DR DrugBank; DB00409; Remoxipride.
DR DrugBank; DB13174; Rhein.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB01201; Rifapentine.
DR DrugBank; DB15305; Risdiplam.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB00938; Salmeterol.
DR DrugBank; DB01232; Saquinavir.
DR DrugBank; DB15685; Selpercatinib.
DR DrugBank; DB06731; Seproxetine.
DR DrugBank; DB00203; Sildenafil.
DR DrugBank; DB00877; Sirolimus.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB15569; Sotorasib.
DR DrugBank; DB01268; Sunitinib.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB12887; Tazemetostat.
DR DrugBank; DB06287; Temsirolimus.
DR DrugBank; DB00342; Terfenadine.
DR DrugBank; DB00624; Testosterone.
DR DrugBank; DB13943; Testosterone cypionate.
DR DrugBank; DB13944; Testosterone enanthate.
DR DrugBank; DB13946; Testosterone undecanoate.
DR DrugBank; DB00599; Thiopental.
DR DrugBank; DB00656; Trazodone.
DR DrugBank; DB00755; Tretinoin.
DR DrugBank; DB00620; Triamcinolone.
DR DrugBank; DB00897; Triazolam.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB13179; Troleandomycin.
DR DrugBank; DB11652; Tucatinib.
DR DrugBank; DB01586; Ursodeoxycholic acid.
DR DrugBank; DB00541; Vincristine.
DR DrugBank; DB00582; Voriconazole.
DR DrugBank; DB00962; Zaleplon.
DR DrugBank; DB15035; Zanubrutinib.
DR DrugCentral; P24462; -.
DR SwissLipids; SLP:000001324; -.
DR iPTMnet; P24462; -.
DR PhosphoSitePlus; P24462; -.
DR BioMuta; CYP3A7; -.
DR DMDM; 90110014; -.
DR MassIVE; P24462; -.
DR PaxDb; P24462; -.
DR PeptideAtlas; P24462; -.
DR PRIDE; P24462; -.
DR ProteomicsDB; 54205; -. [P24462-1]
DR Antibodypedia; 16242; 240 antibodies from 27 providers.
DR DNASU; 1551; -.
DR Ensembl; ENST00000336374.4; ENSP00000337450.2; ENSG00000160870.15. [P24462-1]
DR GeneID; 100861540; -.
DR GeneID; 1551; -.
DR KEGG; hsa:100861540; -.
DR KEGG; hsa:1551; -.
DR MANE-Select; ENST00000336374.4; ENSP00000337450.2; NM_000765.5; NP_000756.3.
DR UCSC; uc003uru.4; human. [P24462-1]
DR CTD; 100861540; -.
DR CTD; 1551; -.
DR DisGeNET; 100861540; -.
DR DisGeNET; 1551; -.
DR GeneCards; CYP3A7; -.
DR HGNC; HGNC:2640; CYP3A7.
DR HPA; ENSG00000160870; Tissue enriched (liver).
DR MIM; 605340; gene.
DR neXtProt; NX_P24462; -.
DR OpenTargets; ENSG00000160870; -.
DR OpenTargets; ENSG00000282301; -.
DR PharmGKB; PA122; -.
DR VEuPathDB; HostDB:ENSG00000160870; -.
DR eggNOG; KOG0158; Eukaryota.
DR GeneTree; ENSGT00950000182958; -.
DR HOGENOM; CLU_001570_5_2_1; -.
DR InParanoid; P24462; -.
DR OMA; ENHEWID; -.
DR OrthoDB; 467733at2759; -.
DR PhylomeDB; P24462; -.
DR TreeFam; TF105087; -.
DR BRENDA; 1.14.14.1; 2681.
DR PathwayCommons; P24462; -.
DR Reactome; R-HSA-211981; Xenobiotics.
DR SABIO-RK; P24462; -.
DR SignaLink; P24462; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 100861540; 2 hits in 148 CRISPR screens.
DR BioGRID-ORCS; 1551; 3 hits in 998 CRISPR screens.
DR GeneWiki; CYP3A7; -.
DR Pharos; P24462; Tclin.
DR PRO; PR:P24462; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P24462; protein.
DR Bgee; ENSG00000160870; Expressed in buccal mucosa cell and 133 other tissues.
DR Genevisible; P24462; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0062183; F:all-trans retinoic acid 18-hydroxylase activity; IEA:RHEA.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0101020; F:estrogen 16-alpha-hydroxylase activity; IDA:BHF-UCL.
DR GO; GO:0101021; F:estrogen 2-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0008401; F:retinoic acid 4-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0008395; F:steroid hydroxylase activity; IDA:BHF-UCL.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0002933; P:lipid hydroxylation; IDA:BHF-UCL.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
DR GO; GO:0042573; P:retinoic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0008202; P:steroid metabolic process; IDA:BHF-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR008072; Cyt_P450_E_CYP3A.
DR InterPro; IPR002402; Cyt_P450_E_grp-II.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00464; EP450II.
DR PRINTS; PR01689; EP450IICYP3A.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis.
FT CHAIN 1..503
FT /note="Cytochrome P450 3A7"
FT /id="PRO_0000051790"
FT BINDING 442
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250"
FT VAR_SEQ 500..503
FT /note="VSGA -> FVDMEPIHMDFLRSLAFQGPHLCFFWELLCPTIRSR (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:11137287"
FT /id="VSP_055577"
FT VARIANT 71
FT /note="V -> A (in dbSNP:rs45580339)"
FT /id="VAR_055564"
FT VARIANT 409
FT /note="T -> R (in dbSNP:rs2257401)"
FT /id="VAR_020124"
FT MUTAGEN 116
FT /note="N->S: Has no effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:17178770"
FT MUTAGEN 174
FT /note="H->D: Increases catalytic activity."
FT /evidence="ECO:0000269|PubMed:17178770"
FT MUTAGEN 214
FT /note="N->D: Increases catalytic activity."
FT /evidence="ECO:0000269|PubMed:17178770"
FT MUTAGEN 224
FT /note="K->T: Reduces affinity for substrate and catalytic
FT efficiency."
FT /evidence="ECO:0000269|PubMed:17178770"
FT MUTAGEN 244
FT /note="K->E: Reduces affinity for substrate and catalytic
FT efficiency."
FT /evidence="ECO:0000269|PubMed:17178770"
FT MUTAGEN 262
FT /note="K->E: Has no effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:17178770"
FT HELIX 32..36
FT /evidence="ECO:0007829|PDB:7MK8"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 57..68
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 70..76
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 87..94
FT /evidence="ECO:0007829|PDB:7MK8"
FT TURN 95..101
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 113..116
FT /evidence="ECO:0007829|PDB:7MK8"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 123..133
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 139..164
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 172..189
FT /evidence="ECO:0007829|PDB:7MK8"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 202..211
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 220..223
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 230..235
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 243..260
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 271..277
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 292..323
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 325..338
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 354..366
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 393..396
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 398..402
FT /evidence="ECO:0007829|PDB:7MK8"
FT TURN 405..407
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 416..419
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 421..426
FT /evidence="ECO:0007829|PDB:7MK8"
FT TURN 429..431
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:7MK8"
FT HELIX 445..462
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 463..467
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 484..487
FT /evidence="ECO:0007829|PDB:7MK8"
FT STRAND 490..495
FT /evidence="ECO:0007829|PDB:7MK8"
SQ SEQUENCE 503 AA; 57470 MW; 087CCEED9BAC314C CRC64;
MDLIPNLAVE TWLLLAVSLI LLYLYGTRTH GLFKKLGIPG PTPLPFLGNA LSFRKGYWTF
DMECYKKYRK VWGIYDCQQP MLAITDPDMI KTVLVKECYS VFTNRRPFGP VGFMKNAISI
AEDEEWKRIR SLLSPTFTSG KLKEMVPIIA QYGDVLVRNL RREAETGKPV TLKHVFGAYS
MDVITSTSFG VSIDSLNNPQ DPFVENTKKL LRFNPLDPFV LSIKVFPFLT PILEALNITV
FPRKVISFLT KSVKQIKEGR LKETQKHRVD FLQLMIDSQN SKDSETHKAL SDLELMAQSI
IFIFAGYETT SSVLSFIIYE LATHPDVQQK VQKEIDTVLP NKAPPTYDTV LQLEYLDMVV
NETLRLFPVA MRLERVCKKD VEINGMFIPK GVVVMIPSYV LHHDPKYWTE PEKFLPERFS
KKNKDNIDPY IYTPFGSGPR NCIGMRFALV NMKLALVRVL QNFSFKPCKE TQIPLKLRFG
GLLLTEKPIV LKAESRDETV SGA
