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CP3A5_HUMAN
ID   CP3A5_HUMAN             Reviewed;         502 AA.
AC   P20815; A4D289; B7Z5I7; Q53WY8; Q75MV0; Q9HB56;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   03-AUG-2022, entry version 210.
DE   RecName: Full=Cytochrome P450 3A5 {ECO:0000303|PubMed:11502729};
DE            EC=1.14.14.1 {ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:2732228};
DE   AltName: Full=CYPIIIA5;
DE   AltName: Full=Cytochrome P450-PCN3 {ECO:0000303|PubMed:2732228};
GN   Name=CYP3A5 {ECO:0000303|PubMed:8569713, ECO:0000312|HGNC:HGNC:2638};
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), CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=2732228; DOI=10.1016/s0021-9258(18)81632-5;
RA   Aoyama T., Yamano S., Waxman D.J., Lapenson D.P., Meyer U.A., Fischer V.,
RA   Tyndale R., Inaba T., Kalow W., Gelboin H.V., Gonzalez F.J.;
RT   "Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is
RT   differentially expressed in adult human liver. cDNA and deduced amino acid
RT   sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for
RT   the metabolism of steroid hormones and cyclosporine.";
RL   J. Biol. Chem. 264:10388-10395(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RC   TISSUE=Liver;
RX   PubMed=2802615; DOI=10.1016/0003-9861(89)90449-9;
RA   Schuetz J.D., Molowa D.T., Guzelian P.S.;
RT   "Characterization of a cDNA encoding a new member of the glucocorticoid-
RT   responsive cytochromes P450 in human liver.";
RL   Arch. Biochem. Biophys. 274:355-365(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
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 GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Colon;
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   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-106.
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   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24, AND INDUCTION BY DEXAMETHASONE.
RX   PubMed=8569713;
RA   Schuetz J.D., Schuetz E.G., Thottassery J.V., Guzelian P.S., Strom S.,
RA   Sun D.;
RT   "Identification of a novel dexamethasone responsive enhancer in the human
RT   CYP3A5 gene and its activation in human and rat liver cells.";
RL   Mol. Pharmacol. 49:63-72(1996).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RX   PubMed=7811260; DOI=10.1006/bbrc.1994.2870;
RA   Jounaidi Y., Guzelian P.S., Maurel P., Vilarem M.J.;
RT   "Sequence of the 5'-flanking region of CYP3A5: comparative analysis with
RT   CYP3A4 and CYP3A7.";
RL   Biochem. Biophys. Res. Commun. 205:1741-1747(1994).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=10681376;
RA   Chen H., Howald W.N., Juchau M.R.;
RT   "Biosynthesis of all-trans-retinoic acid from all-trans-retinol: catalysis
RT   of all-trans-retinol oxidation by human P-450 cytochromes.";
RL   Drug Metab. Dispos. 28:315-322(2000).
RN   [12]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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   [13]
RP   TRANS-SPLICING.
RX   PubMed=11726664; DOI=10.1074/jbc.m109175200;
RA   Finta C., Zaphiropoulos P.G.;
RT   "Intergenic mRNA molecules resulting from trans-splicing.";
RL   J. Biol. Chem. 277:5882-5890(2002).
RN   [14]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, 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   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [16]
RP   VARIANT CYP3A5*2 ASN-398.
RX   PubMed=8619878; DOI=10.1006/bbrc.1996.0618;
RA   Jounaidi Y., Hyrailles V., Gervot L., Maurel P.;
RT   "Detection of CYP3A5 allelic variant: a candidate for the polymorphic
RT   expression of the protein?";
RL   Biochem. Biophys. Res. Commun. 221:466-470(1996).
RN   [17]
RP   VARIANT CYP3A5*4 ARG-200.
RX   PubMed=11502729;
RA   Chou F.C., Tzeng S.J., Huang J.D.;
RT   "Genetic polymorphism of cytochrome P450 3A5 in Chinese.";
RL   Drug Metab. Dispos. 29:1205-1209(2001).
RN   [18]
RP   VARIANTS CYS-28; THR-337 AND SER-446.
RX   PubMed=12893984; DOI=10.1097/00008571-200308000-00004;
RA   Lee S.J., Usmani K.A., Chanas B., Ghanayem B., Xi T., Hodgson E.,
RA   Mohrenweiser H.W., Goldstein J.A.;
RT   "Genetic findings and functional studies of human CYP3A5 single nucleotide
RT   polymorphisms in different ethnic groups.";
RL   Pharmacogenetics 13:461-472(2003).
RN   [19]
RP   VARIANTS TYR-30; GLU-277; THR-337 AND ASN-398.
RX   PubMed=15469410; DOI=10.1517/14622416.5.7.895;
RA   Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q.,
RA   McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
RT   "Genetic variation in eleven phase I drug metabolism genes in an ethnically
RT   diverse population.";
RL   Pharmacogenomics 5:895-931(2004).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC       steroid hormones and vitamins (PubMed:2732228, PubMed:10681376,
CC       PubMed:11093772, PubMed:12865317). Mechanistically, uses molecular
CC       oxygen inserting one oxygen atom into a substrate, and reducing the
CC       second into a water molecule, with two electrons provided by NADPH via
CC       cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the
CC       hydroxylation of carbon-hydrogen bonds (PubMed:12865317,
CC       PubMed:2732228, PubMed:10681376, PubMed:11093772). Exhibits high
CC       catalytic activity for the formation of catechol estrogens from 17beta-
CC       estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2
CC       (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid
CC       hormones testosterone, progesterone, and androstenedione
CC       (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-
CC       retinol to all-trans-retinal, a rate-limiting step for the biosynthesis
CC       of all-trans-retinoic acid (atRA) (PubMed:10681376). Further
CC       metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and
CC       may play a role in hepatic atRA clearance (PubMed:11093772). Also
CC       involved in the oxidative metabolism of xenobiotics, including calcium
CC       channel blocking drug nifedipine and immunosuppressive drug
CC       cyclosporine (PubMed:2732228). {ECO:0000269|PubMed:10681376,
CC       ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317,
CC       ECO:0000269|PubMed:2732228}.
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:2732228};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC         Evidence={ECO:0000305|PubMed:11093772, ECO:0000305|PubMed:12865317,
CC         ECO:0000305|PubMed:2732228};
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};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213;
CC         Evidence={ECO:0000305|PubMed:12865317};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase]
CC         = 4-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--
CC         hemoprotein reductase]; Xref=Rhea:RHEA:47280, Rhea:RHEA-COMP:11964,
CC         Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210, ChEBI:CHEBI:62845;
CC         Evidence={ECO:0000269|PubMed:12865317};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281;
CC         Evidence={ECO:0000305|PubMed:12865317};
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       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209;
CC         Evidence={ECO:0000305|PubMed:12865317};
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:12865317};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293;
CC         Evidence={ECO:0000305|PubMed:12865317};
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:2732228};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46297;
CC         Evidence={ECO:0000305|PubMed:2732228};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=androst-4-ene-3,17-dione + O2 + reduced [NADPH--hemoprotein
CC         reductase] = 6beta-hydroxyandrost-4-ene-3,17-dione + H(+) + H2O +
CC         oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47256,
CC         Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87571;
CC         Evidence={ECO:0000269|PubMed:2732228};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47257;
CC         Evidence={ECO:0000305|PubMed:2732228};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] =
CC         6beta-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:47252, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17026, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:62117; Evidence={ECO:0000269|PubMed:2732228};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47253;
CC         Evidence={ECO:0000305|PubMed:2732228};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein
CC         reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized [NADPH--
CC         hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA-COMP:11964,
CC         Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC         Evidence={ECO:0000269|PubMed:10681376};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093;
CC         Evidence={ECO:0000305|PubMed:10681376};
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   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=52.47 uM for 17beta-estradiol (2-hydroxylation)
CC         {ECO:0000269|PubMed:12865317};
CC         KM=46.03 uM for 17beta-estradiol (4-hydroxylation)
CC         {ECO:0000269|PubMed:12865317};
CC         KM=15.04 uM for estrone (2-hydroxylation)
CC         {ECO:0000269|PubMed:12865317};
CC         KM=27.75 uM for estrone (4-hydroxylation)
CC         {ECO:0000269|PubMed:12865317};
CC         KM=44 uM for all-trans-retinoate (4-hydroxylation)
CC         {ECO:0000269|PubMed:11093772};
CC         Vmax=627.4 pmol/min/nmol enzyme toward 17beta-estradiol (2-
CC         hydroxylation) {ECO:0000269|PubMed:12865317};
CC         Vmax=297.8 pmol/min/nmol enzyme toward 17beta-estradiol (4-
CC         hydroxylation) {ECO:0000269|PubMed:12865317};
CC         Vmax=102.6 pmol/min/nmol enzyme toward estrone (2-hydroxylation)
CC         {ECO:0000269|PubMed:12865317};
CC         Vmax=156.3 pmol/min/nmol enzyme toward estrone (4-hydroxylation)
CC         {ECO:0000269|PubMed:12865317};
CC         Vmax=1124 pmol/min/nmol enzyme toward all-trans-retinoate (4-
CC         hydroxylation) {ECO:0000269|PubMed:11093772};
CC   -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:12865317}.
CC   -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC       {ECO:0000269|PubMed:10681376}.
CC   -!- INTERACTION:
CC       P20815; P42858: HTT; NbExp=3; IntAct=EBI-3908011, EBI-466029;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC       membrane protein. Microsome membrane; Peripheral membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P20815-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P20815-2; Sequence=VSP_042734, VSP_042735;
CC   -!- INDUCTION: By glucocorticoids, such as dexamethesone.
CC       {ECO:0000269|PubMed:8569713}.
CC   -!- MISCELLANEOUS: Chimeric transcripts, characterized by CYP3A43 exon 1
CC       joined at canonical splice sites to distinct sets of CYP3A5 exons, have
CC       been detected. All are possibly produced by trans-splicing. The
CC       chimeric transcripts exist in 2 different combinations: CYP3A43 exon 1
CC       joined in frame to CYP3A5 exon 11-13 and CYP3A43 exon 1 joined in frame
CC       to CYP3A5 exon 12-13. All chimeric transcripts are expressed at very
CC       low levels in the liver (PubMed:11726664).
CC       {ECO:0000305|PubMed:11726664}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC       Note=CYP3A5 alleles;
CC       URL="https://www.pharmvar.org/gene/CYP3A5";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; J04813; AAA02993.1; -; mRNA.
DR   EMBL; AK299002; BAH12923.1; -; mRNA.
DR   EMBL; AC005020; AAS02016.1; -; Genomic_DNA.
DR   EMBL; CH236956; EAL23868.1; -; Genomic_DNA.
DR   EMBL; CH471091; EAW76638.1; -; Genomic_DNA.
DR   EMBL; CH471091; EAW76642.1; -; Genomic_DNA.
DR   EMBL; BC033862; AAH33862.1; -; mRNA.
DR   EMBL; AF280107; AAG32288.1; -; Genomic_DNA.
DR   EMBL; L35912; AAB00083.1; -; Genomic_DNA.
DR   EMBL; S74699; AAD14157.1; -; Genomic_DNA.
DR   EMBL; S74700; AAD14158.1; -; Genomic_DNA.
DR   CCDS; CCDS55134.1; -. [P20815-2]
DR   CCDS; CCDS5672.1; -. [P20815-1]
DR   PIR; A34101; A34101.
DR   PIR; A60558; A60558.
DR   RefSeq; NP_000768.1; NM_000777.4. [P20815-1]
DR   RefSeq; NP_001177413.1; NM_001190484.2. [P20815-2]
DR   PDB; 5VEU; X-ray; 2.91 A; A/B/C/D/E/F/G/H/I/J/K/L=24-497.
DR   PDBsum; 5VEU; -.
DR   AlphaFoldDB; P20815; -.
DR   SMR; P20815; -.
DR   BioGRID; 107949; 12.
DR   IntAct; P20815; 10.
DR   STRING; 9606.ENSP00000222982; -.
DR   BindingDB; P20815; -.
DR   ChEMBL; CHEMBL3019; -.
DR   DrugBank; DB11703; Acalabrutinib.
DR   DrugBank; DB00802; Alfentanil.
DR   DrugBank; DB00404; Alprazolam.
DR   DrugBank; DB06403; Ambrisentan.
DR   DrugBank; DB13141; Ambroxol acefyllinate.
DR   DrugBank; DB00288; Amcinonide.
DR   DrugBank; DB00321; Amitriptyline.
DR   DrugBank; DB00381; Amlodipine.
DR   DrugBank; DB00701; Amprenavir.
DR   DrugBank; DB01217; Anastrozole.
DR   DrugBank; DB06605; Apixaban.
DR   DrugBank; DB00714; Apomorphine.
DR   DrugBank; DB00278; Argatroban.
DR   DrugBank; DB01238; Aripiprazole.
DR   DrugBank; DB14185; Aripiprazole lauroxil.
DR   DrugBank; DB06413; Armodafinil.
DR   DrugBank; DB06697; Artemether.
DR   DrugBank; DB00637; Astemizole.
DR   DrugBank; DB11586; Asunaprevir.
DR   DrugBank; DB01076; Atorvastatin.
DR   DrugBank; DB06626; Axitinib.
DR   DrugBank; DB00972; Azelastine.
DR   DrugBank; DB04957; Azimilide.
DR   DrugBank; DB00394; Beclomethasone dipropionate.
DR   DrugBank; DB09231; Benidipine.
DR   DrugBank; DB00443; Betamethasone.
DR   DrugBank; DB14669; Betamethasone phosphate.
DR   DrugBank; DB00905; Bimatoprost.
DR   DrugBank; DB08873; Boceprevir.
DR   DrugBank; DB12267; Brigatinib.
DR   DrugBank; DB01222; Budesonide.
DR   DrugBank; DB00921; Buprenorphine.
DR   DrugBank; DB00490; Buspirone.
DR   DrugBank; DB06772; Cabazitaxel.
DR   DrugBank; DB09061; Cannabidiol.
DR   DrugBank; DB00564; Carbamazepine.
DR   DrugBank; DB14984; Casimersen.
DR   DrugBank; DB06119; Cenobamate.
DR   DrugBank; DB00439; Cerivastatin.
DR   DrugBank; DB06419; Cethromycin.
DR   DrugBank; DB00446; Chloramphenicol.
DR   DrugBank; DB00608; Chloroquine.
DR   DrugBank; DB01114; Chlorpheniramine.
DR   DrugBank; DB01166; Cilostazol.
DR   DrugBank; DB00501; Cimetidine.
DR   DrugBank; DB00537; Ciprofloxacin.
DR   DrugBank; DB00604; Cisapride.
DR   DrugBank; DB01211; Clarithromycin.
DR   DrugBank; DB01190; Clindamycin.
DR   DrugBank; DB11750; Clobetasol.
DR   DrugBank; DB01013; Clobetasol propionate.
DR   DrugBank; DB14652; Clocortolone acetate.
DR   DrugBank; DB00845; Clofazimine.
DR   DrugBank; DB00575; Clonidine.
DR   DrugBank; DB00758; Clopidogrel.
DR   DrugBank; DB13843; Cloprednol.
DR   DrugBank; DB09065; Cobicistat.
DR   DrugBank; DB12483; Copanlisib.
DR   DrugBank; DB14681; Cortisone.
DR   DrugBank; DB01380; Cortisone acetate.
DR   DrugBank; DB13003; Cortivazol.
DR   DrugBank; DB08865; Crizotinib.
DR   DrugBank; DB14635; Curcumin sulfate.
DR   DrugBank; DB00531; Cyclophosphamide.
DR   DrugBank; DB00091; Cyclosporine.
DR   DrugBank; DB09102; Daclatasvir.
DR   DrugBank; DB00250; Dapsone.
DR   DrugBank; DB01254; Dasatinib.
DR   DrugBank; DB00694; Daunorubicin.
DR   DrugBank; DB11921; Deflazacort.
DR   DrugBank; DB00705; Delavirdine.
DR   DrugBank; DB12161; Deutetrabenazine.
DR   DrugBank; DB01234; Dexamethasone.
DR   DrugBank; DB14649; Dexamethasone acetate.
DR   DrugBank; DB11487; Dexamethasone isonicotinate.
DR   DrugBank; DB04856; Dexloxiglumide.
DR   DrugBank; DB11994; Diacerein.
DR   DrugBank; DB00829; Diazepam.
DR   DrugBank; DB09095; Difluocortolone.
DR   DrugBank; DB00343; Diltiazem.
DR   DrugBank; DB00822; Disulfiram.
DR   DrugBank; DB02520; Ditiocarb.
DR   DrugBank; DB01248; Docetaxel.
DR   DrugBank; DB08930; Dolutegravir.
DR   DrugBank; DB01184; Domperidone.
DR   DrugBank; DB12301; Doravirine.
DR   DrugBank; DB04855; Dronedarone.
DR   DrugBank; DB01126; Dutasteride.
DR   DrugBank; DB11742; Ebastine.
DR   DrugBank; DB00625; Efavirenz.
DR   DrugBank; DB11979; Elagolix.
DR   DrugBank; DB11574; Elbasvir.
DR   DrugBank; DB15444; Elexacaftor.
DR   DrugBank; DB08899; Enzalutamide.
DR   DrugBank; DB00700; Eplerenone.
DR   DrugBank; DB00530; Erlotinib.
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; DB00655; Estrone.
DR   DrugBank; DB00977; Ethinylestradiol.
DR   DrugBank; DB00593; Ethosuximide.
DR   DrugBank; DB00773; Etoposide.
DR   DrugBank; DB01023; Felodipine.
DR   DrugBank; DB00574; Fenfluramine.
DR   DrugBank; DB12265; Fexinidazole.
DR   DrugBank; DB01216; Finasteride.
DR   DrugBank; DB00196; Fluconazole.
DR   DrugBank; DB01047; Fluocinonide.
DR   DrugBank; DB08971; Fluocortolone.
DR   DrugBank; DB00324; Fluorometholone.
DR   DrugBank; DB00472; Fluoxetine.
DR   DrugBank; DB08970; Fluprednidene.
DR   DrugBank; DB14634; Fluprednidene acetate.
DR   DrugBank; DB00499; Flutamide.
DR   DrugBank; DB13867; Fluticasone.
DR   DrugBank; DB08906; Fluticasone furoate.
DR   DrugBank; DB00588; Fluticasone propionate.
DR   DrugBank; DB01095; Fluvastatin.
DR   DrugBank; DB00176; Fluvoxamine.
DR   DrugBank; DB12307; Foretinib.
DR   DrugBank; DB00317; Gefitinib.
DR   DrugBank; DB06730; Gestodene.
DR   DrugBank; DB13879; Glecaprevir.
DR   DrugBank; DB01016; Glyburide.
DR   DrugBank; DB01218; Halofantrine.
DR   DrugBank; DB13728; Halometasone.
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; DB06789; Hydroxyprogesterone caproate.
DR   DrugBank; DB00557; Hydroxyzine.
DR   DrugBank; DB09053; Ibrutinib.
DR   DrugBank; DB11737; Icotinib.
DR   DrugBank; DB09054; Idelalisib.
DR   DrugBank; DB01181; Ifosfamide.
DR   DrugBank; DB04946; Iloperidone.
DR   DrugBank; DB00619; Imatinib.
DR   DrugBank; DB00224; Indinavir.
DR   DrugBank; DB00762; Irinotecan.
DR   DrugBank; DB11633; Isavuconazole.
DR   DrugBank; DB11757; Istradefylline.
DR   DrugBank; DB01167; Itraconazole.
DR   DrugBank; DB08820; Ivacaftor.
DR   DrugBank; DB01026; Ketoconazole.
DR   DrugBank; DB01259; Lapatinib.
DR   DrugBank; DB11951; Lemborexant.
DR   DrugBank; DB00528; Lercanidipine.
DR   DrugBank; DB12070; Letermovir.
DR   DrugBank; DB05667; Levoketoconazole.
DR   DrugBank; DB00367; Levonorgestrel.
DR   DrugBank; DB00281; Lidocaine.
DR   DrugBank; DB06448; Lonafarnib.
DR   DrugBank; DB16222; Loncastuximab tesirine.
DR   DrugBank; DB01601; Lopinavir.
DR   DrugBank; DB00455; Loratadine.
DR   DrugBank; DB12130; Lorlatinib.
DR   DrugBank; DB09212; Loxoprofen.
DR   DrugBank; DB00643; Mebendazole.
DR   DrugBank; DB14009; Medical Cannabis.
DR   DrugBank; DB00253; Medrysone.
DR   DrugBank; DB14659; Melengestrol acetate.
DR   DrugBank; DB00170; Menadione.
DR   DrugBank; DB09383; Meprednisone.
DR   DrugBank; DB09241; Methylene blue.
DR   DrugBank; DB00959; Methylprednisolone.
DR   DrugBank; DB14644; Methylprednisolone hemisuccinate.
DR   DrugBank; DB00916; Metronidazole.
DR   DrugBank; DB01388; Mibefradil.
DR   DrugBank; DB00683; Midazolam.
DR   DrugBank; DB06595; Midostaurin.
DR   DrugBank; DB00834; Mifepristone.
DR   DrugBank; DB11792; Mirodenafil.
DR   DrugBank; DB16390; Mobocertinib.
DR   DrugBank; DB00745; Modafinil.
DR   DrugBank; DB00764; Mometasone.
DR   DrugBank; DB14512; Mometasone furoate.
DR   DrugBank; DB09205; Moxisylyte.
DR   DrugBank; DB00688; Mycophenolate mofetil.
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; DB00622; Nicardipine.
DR   DrugBank; DB01115; Nifedipine.
DR   DrugBank; DB00401; Nisoldipine.
DR   DrugBank; DB01054; Nitrendipine.
DR   DrugBank; DB00540; Nortriptyline.
DR   DrugBank; DB00334; Olanzapine.
DR   DrugBank; DB09074; Olaparib.
DR   DrugBank; DB09568; Omega-3-carboxylic acids.
DR   DrugBank; DB00904; Ondansetron.
DR   DrugBank; DB11837; Osilodrostat.
DR   DrugBank; DB00776; Oxcarbazepine.
DR   DrugBank; DB01062; Oxybutynin.
DR   DrugBank; DB00497; Oxycodone.
DR   DrugBank; DB06412; Oxymetholone.
DR   DrugBank; DB01229; Paclitaxel.
DR   DrugBank; DB01267; Paliperidone.
DR   DrugBank; DB01384; Paramethasone.
DR   DrugBank; DB09297; Paritaprevir.
DR   DrugBank; DB00738; Pentamidine.
DR   DrugBank; DB08883; Perampanel.
DR   DrugBank; DB00780; Phenelzine.
DR   DrugBank; DB01174; Phenobarbital.
DR   DrugBank; DB00252; Phenytoin.
DR   DrugBank; DB13878; Pibrentasvir.
DR   DrugBank; DB05316; Pimavanserin.
DR   DrugBank; DB01100; Pimozide.
DR   DrugBank; DB08901; Ponatinib.
DR   DrugBank; DB12016; Ponesimod.
DR   DrugBank; DB15822; Pralsetinib.
DR   DrugBank; DB01058; Praziquantel.
DR   DrugBank; DB14633; Prednisolone hemisuccinate.
DR   DrugBank; DB14631; Prednisolone phosphate.
DR   DrugBank; DB00635; Prednisone.
DR   DrugBank; DB14646; Prednisone acetate.
DR   DrugBank; DB13208; Prednylidene.
DR   DrugBank; DB00396; Progesterone.
DR   DrugBank; DB00571; Propranolol.
DR   DrugBank; DB04216; Quercetin.
DR   DrugBank; DB01224; Quetiapine.
DR   DrugBank; DB01103; Quinacrine.
DR   DrugBank; DB00468; Quinine.
DR   DrugBank; DB11853; Relugolix.
DR   DrugBank; DB00409; Remoxipride.
DR   DrugBank; DB00206; Reserpine.
DR   DrugBank; DB13174; Rhein.
DR   DrugBank; DB01045; Rifampicin.
DR   DrugBank; DB01201; Rifapentine.
DR   DrugBank; DB00896; Rimexolone.
DR   DrugBank; DB15305; Risdiplam.
DR   DrugBank; DB00503; Ritonavir.
DR   DrugBank; DB06228; Rivaroxaban.
DR   DrugBank; DB06176; Romidepsin.
DR   DrugBank; DB12332; Rucaparib.
DR   DrugBank; DB06654; Safinamide.
DR   DrugBank; DB00938; Salmeterol.
DR   DrugBank; DB12543; Samidorphan.
DR   DrugBank; DB01232; Saquinavir.
DR   DrugBank; DB06335; Saxagliptin.
DR   DrugBank; DB15685; Selpercatinib.
DR   DrugBank; DB11689; Selumetinib.
DR   DrugBank; DB06731; Seproxetine.
DR   DrugBank; DB00203; Sildenafil.
DR   DrugBank; DB00641; Simvastatin.
DR   DrugBank; DB00877; Sirolimus.
DR   DrugBank; DB00398; Sorafenib.
DR   DrugBank; DB15569; Sotorasib.
DR   DrugBank; DB01268; Sunitinib.
DR   DrugBank; DB00864; Tacrolimus.
DR   DrugBank; DB00675; Tamoxifen.
DR   DrugBank; DB12887; Tazemetostat.
DR   DrugBank; DB09256; Tegafur.
DR   DrugBank; DB06287; Temsirolimus.
DR   DrugBank; DB11761; Tenapanor.
DR   DrugBank; DB00444; Teniposide.
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; DB11712; Tezacaftor.
DR   DrugBank; DB01041; Thalidomide.
DR   DrugBank; DB00599; Thiopental.
DR   DrugBank; DB08816; Ticagrelor.
DR   DrugBank; DB05773; Trastuzumab emtansine.
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; DB06267; Udenafil.
DR   DrugBank; DB13609; Umifenovir.
DR   DrugBank; DB01586; Ursodeoxycholic acid.
DR   DrugBank; DB11915; Valbenazine.
DR   DrugBank; DB00313; Valproic acid.
DR   DrugBank; DB00862; Vardenafil.
DR   DrugBank; DB00661; Verapamil.
DR   DrugBank; DB06652; Vicriviroc.
DR   DrugBank; DB00541; Vincristine.
DR   DrugBank; DB00582; Voriconazole.
DR   DrugBank; DB09068; Vortioxetine.
DR   DrugBank; DB00962; Zaleplon.
DR   DrugBank; DB15035; Zanubrutinib.
DR   DrugBank; DB00909; Zonisamide.
DR   DrugCentral; P20815; -.
DR   GuidetoPHARMACOLOGY; 1338; -.
DR   SwissLipids; SLP:000001325; -.
DR   iPTMnet; P20815; -.
DR   PhosphoSitePlus; P20815; -.
DR   BioMuta; CYP3A5; -.
DR   DMDM; 117157; -.
DR   jPOST; P20815; -.
DR   MassIVE; P20815; -.
DR   PaxDb; P20815; -.
DR   PeptideAtlas; P20815; -.
DR   PRIDE; P20815; -.
DR   ProteomicsDB; 53804; -. [P20815-1]
DR   ProteomicsDB; 53805; -. [P20815-2]
DR   Antibodypedia; 30428; 215 antibodies from 31 providers.
DR   DNASU; 1577; -.
DR   Ensembl; ENST00000222982.8; ENSP00000222982.4; ENSG00000106258.15. [P20815-1]
DR   Ensembl; ENST00000439761.3; ENSP00000401269.1; ENSG00000106258.15. [P20815-2]
DR   Ensembl; ENST00000646887.1; ENSP00000496704.1; ENSG00000106258.15. [P20815-2]
DR   GeneID; 1577; -.
DR   KEGG; hsa:1577; -.
DR   MANE-Select; ENST00000222982.8; ENSP00000222982.4; NM_000777.5; NP_000768.1.
DR   UCSC; uc003urq.4; human. [P20815-1]
DR   CTD; 1577; -.
DR   DisGeNET; 1577; -.
DR   GeneCards; CYP3A5; -.
DR   HGNC; HGNC:2638; CYP3A5.
DR   HPA; ENSG00000106258; Tissue enhanced (intestine, liver).
DR   MalaCards; CYP3A5; -.
DR   MIM; 605325; gene.
DR   neXtProt; NX_P20815; -.
DR   OpenTargets; ENSG00000106258; -.
DR   Orphanet; 241043; Tacrolimus dose selection.
DR   PharmGKB; PA131; -.
DR   VEuPathDB; HostDB:ENSG00000106258; -.
DR   eggNOG; KOG0158; Eukaryota.
DR   GeneTree; ENSGT00950000182958; -.
DR   HOGENOM; CLU_001570_5_2_1; -.
DR   InParanoid; P20815; -.
DR   OMA; KPWQSRR; -.
DR   OrthoDB; 467733at2759; -.
DR   PhylomeDB; P20815; -.
DR   TreeFam; TF105087; -.
DR   BRENDA; 1.14.14.1; 2681.
DR   PathwayCommons; P20815; -.
DR   Reactome; R-HSA-211981; Xenobiotics.
DR   Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR   SABIO-RK; P20815; -.
DR   SignaLink; P20815; -.
DR   UniPathway; UPA00912; -.
DR   BioGRID-ORCS; 1577; 8 hits in 1066 CRISPR screens.
DR   ChiTaRS; CYP3A5; human.
DR   GeneWiki; CYP3A5; -.
DR   GenomeRNAi; 1577; -.
DR   Pharos; P20815; Tclin.
DR   PRO; PR:P20815; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P20815; protein.
DR   Bgee; ENSG00000106258; Expressed in jejunal mucosa and 159 other tissues.
DR   ExpressionAtlas; P20815; baseline and differential.
DR   Genevisible; P20815; HS.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:ProtInc.
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: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:0016491; F:oxidoreductase activity; IDA:BHF-UCL.
DR   GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR   GO; GO:0008401; F:retinoic acid 4-hydroxylase activity; IDA:UniProtKB.
DR   GO; GO:0046222; P:aflatoxin metabolic process; TAS:Reactome.
DR   GO; GO:0009822; P:alkaloid catabolic process; 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; IDA:BHF-UCL.
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:0008202; P:steroid metabolic process; IDA:BHF-UCL.
DR   GO; GO:0042178; P:xenobiotic catabolic 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; Endoplasmic reticulum; Heme; Iron;
KW   Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Steroid metabolism.
FT   CHAIN           1..502
FT                   /note="Cytochrome P450 3A5"
FT                   /id="PRO_0000051787"
FT   BINDING         441
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   VAR_SEQ         107..140
FT                   /note="SLGPVGFMKSAISLAEDEEWKRIRSLLSPTFTSG -> ICATTSTIKMQTHS
FT                   VTMWLPPAVLQSQHGVCLFL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_042734"
FT   VAR_SEQ         141..502
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_042735"
FT   VARIANT         28
FT                   /note="R -> C (in allele CYP3A5*8; dbSNP:rs55817950)"
FT                   /evidence="ECO:0000269|PubMed:12893984"
FT                   /id="VAR_024731"
FT   VARIANT         30
FT                   /note="H -> Y (in dbSNP:rs28383468)"
FT                   /evidence="ECO:0000269|PubMed:15469410"
FT                   /id="VAR_024728"
FT   VARIANT         200
FT                   /note="Q -> R (in allele CYP3A5*4; dbSNP:rs56411402)"
FT                   /evidence="ECO:0000269|PubMed:11502729"
FT                   /id="VAR_024732"
FT   VARIANT         277
FT                   /note="D -> E (in dbSNP:rs28383477)"
FT                   /evidence="ECO:0000269|PubMed:15469410"
FT                   /id="VAR_024729"
FT   VARIANT         337
FT                   /note="A -> T (in allele CYP3A5*9; dbSNP:rs28383479)"
FT                   /evidence="ECO:0000269|PubMed:12893984,
FT                   ECO:0000269|PubMed:15469410"
FT                   /id="VAR_024730"
FT   VARIANT         371
FT                   /note="I -> V (in dbSNP:rs28365092)"
FT                   /id="VAR_029161"
FT   VARIANT         398
FT                   /note="T -> N (in allele CYP3A5*2; dbSNP:rs28365083)"
FT                   /evidence="ECO:0000269|PubMed:15469410,
FT                   ECO:0000269|PubMed:8619878"
FT                   /id="VAR_008365"
FT   VARIANT         446
FT                   /note="F -> S (in dbSNP:rs41279854)"
FT                   /evidence="ECO:0000269|PubMed:12893984"
FT                   /id="VAR_024733"
FT   VARIANT         488
FT                   /note="I -> T (in dbSNP:rs28365085)"
FT                   /id="VAR_029162"
FT   CONFLICT        305
FT                   /note="A -> P (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        318
FT                   /note="L -> F (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        324
FT                   /note="H -> D (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        377
FT                   /note="C -> G (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   HELIX           32..35
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   TURN            45..47
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           50..55
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           57..67
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          70..76
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          79..84
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           87..94
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   TURN            95..101
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           112..116
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   TURN            118..120
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           123..133
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           134..137
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           139..166
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           172..189
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           202..207
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           208..211
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           218..225
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           229..235
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           243..262
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          264..266
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           271..276
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           277..280
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          285..287
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           292..323
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           325..338
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           340..342
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           347..352
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           354..366
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          369..376
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          381..388
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          393..396
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           398..402
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   TURN            405..407
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          408..410
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           416..418
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          424..426
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   TURN            428..430
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   HELIX           444..459
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          462..465
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          478..481
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          484..486
FT                   /evidence="ECO:0007829|PDB:5VEU"
FT   STRAND          489..494
FT                   /evidence="ECO:0007829|PDB:5VEU"
SQ   SEQUENCE   502 AA;  57109 MW;  D5A2302E2633E717 CRC64;
     MDLIPNLAVE TWLLLAVSLV LLYLYGTRTH GLFKRLGIPG PTPLPLLGNV LSYRQGLWKF
     DTECYKKYGK MWGTYEGQLP VLAITDPDVI RTVLVKECYS VFTNRRSLGP VGFMKSAISL
     AEDEEWKRIR SLLSPTFTSG KLKEMFPIIA QYGDVLVRNL RREAEKGKPV TLKDIFGAYS
     MDVITGTSFG VNIDSLNNPQ DPFVESTKKF LKFGFLDPLF LSIILFPFLT PVFEALNVSL
     FPKDTINFLS KSVNRMKKSR LNDKQKHRLD FLQLMIDSQN SKETESHKAL SDLELAAQSI
     IFIFAGYETT SSVLSFTLYE LATHPDVQQK LQKEIDAVLP NKAPPTYDAV VQMEYLDMVV
     NETLRLFPVA IRLERTCKKD VEINGVFIPK GSMVVIPTYA LHHDPKYWTE PEEFRPERFS
     KKKDSIDPYI YTPFGTGPRN CIGMRFALMN MKLALIRVLQ NFSFKPCKET QIPLKLDTQG
     LLQPEKPIVL KVDSRDGTLS GE
 
 
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