ID CP19A_HUMAN Reviewed; 503 AA. AC P11511; Q16731; Q3B764; Q58FA0; Q8IYJ7; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 235. DE RecName: Full=Aromatase {ECO:0000303|PubMed:20385561}; DE EC=1.14.14.14 {ECO:0000269|PubMed:27702664, ECO:0000269|PubMed:2848247}; DE AltName: Full=CYPXIX; DE AltName: Full=Cytochrome P-450AROM; DE AltName: Full=Cytochrome P450 19A1 {ECO:0000303|PubMed:20385561}; DE AltName: Full=Estrogen synthase; GN Name=CYP19A1 {ECO:0000303|PubMed:24705274, GN ECO:0000312|HGNC:HGNC:2594}; Synonyms=ARO1, CYAR, CYP19; 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), AND SUBCELLULAR LOCATION. RC TISSUE=Placenta; RX PubMed=2973313; DOI=10.1016/s0006-291x(88)80903-3; RA Harada N.; RT "Cloning of a complete cDNA encoding human aromatase: immunochemical RT identification and sequence analysis."; RL Biochem. Biophys. Res. Commun. 156:725-732(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3390233; DOI=10.1089/dna.1988.7.27; RA Chen S., Besman M.J., Sparkes R.S., Zollman S., Klisak I., Mohandas T., RA Hall P.F., Shively J.E.; RT "Human aromatase: cDNA cloning, Southern blot analysis, and assignment of RT the gene to chromosome 15."; RL DNA 7:27-38(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CYS-264, FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=2848247; DOI=10.1073/pnas.85.23.8948; RA Corbin C.J., Graham-Lorence S., McPhaul M., Mason J.I., Mendelson C.R., RA Simpson E.R.; RT "Isolation of a full-length cDNA insert encoding human aromatase system RT cytochrome P-450 and its expression in nonsteroidogenic cells."; RL Proc. Natl. Acad. Sci. U.S.A. 85:8948-8952(1988). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=2541021; DOI=10.1016/0014-5793(89)81373-0; RA Toda K., Terashima M., Mitsuuchi Y., Yamasaki Y., Yokoyama Y., Nojima S., RA Ushiro H., Maeda T., Yamamoto Y., Sagara Y., Shizuta Y.; RT "Alternative usage of different poly(A) addition signals for two major RT species of mRNA encoding human aromatase P-450."; RL FEBS Lett. 247:371-376(1989). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2808431; DOI=10.1016/s0021-9258(19)47313-4; RA Means G.D., Mahendroo M.S., Corbin C.J., Mathis J.M., Powell F.E., RA Mendelson C.R., Simpson E.R.; RT "Structural analysis of the gene encoding human aromatase cytochrome P-450, RT the enzyme responsible for estrogen biosynthesis."; RL J. Biol. Chem. 264:19385-19391(1989). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=2691883; DOI=10.1210/mend-3-9-1477; RA Pompon D., Liu R.Y., Besman M.J., Wang P.L., Shively J.E., Chen S.; RT "Expression of human placental aromatase in Saccharomyces cerevisiae."; RL Mol. Endocrinol. 3:1477-1487(1989). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1371509; DOI=10.1016/s0021-9258(18)42900-6; RA Harada N., Ogawa H., Shozu M., Yamada K., Suhara K., Nishida E., Takagi Y.; RT "Biochemical and molecular genetic analyses on placental aromatase (P- RT 450AROM) deficiency."; RL J. Biol. Chem. 267:4781-4785(1992). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-39; MET-201 AND RP CYS-264. RG NIEHS SNPs program; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP MET-201. RC TISSUE=Ovary, and Placenta; 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 [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-503 (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Placenta; RX PubMed=3018730; DOI=10.1073/pnas.83.17.6387; RA Evans C.T., Ledesma D.B., Schulz T.Z., Simpson E.R., Mendelson C.R.; RT "Isolation and characterization of a complementary DNA specific for human RT aromatase-system cytochrome P-450 mRNA."; RL Proc. Natl. Acad. Sci. U.S.A. 83:6387-6391(1986). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-503 (ISOFORM 1), AND VARIANT CYS-264. RX PubMed=3653507; DOI=10.1016/0303-7207(87)90054-2; RA Simpson E.R., Evans C.T., Corbin C.J., Powell F.E., Ledesma D.B., RA Mendelson C.R.; RT "Sequencing of cDNA inserts encoding aromatase cytochrome P-450 (P- RT 450AROM)."; RL Mol. Cell. Endocrinol. 52:267-272(1987). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49, AND TISSUE SPECIFICITY. RX PubMed=2040633; DOI=10.1016/s0021-9258(18)99159-3; RA Mahendroo M.S., Means G.D., Mendelson C.R., Simpson E.R.; RT "Tissue-specific expression of human P-450AROM. The promoter responsible RT for expression in adipose tissue is different from that utilized in RT placenta."; RL J. Biol. Chem. 266:11276-11281(1991). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49, TISSUE SPECIFICITY, AND RP ALTERNATIVE PROMOTER USAGE. RX PubMed=7690033; DOI=10.1016/s0021-9258(19)36538-x; RA Mahendroo M.S., Mendelson C.R., Simpson E.R.; RT "Tissue-specific and hormonally controlled alternative promoters regulate RT aromatase cytochrome P450 gene expression in human adipose tissue."; RL J. Biol. Chem. 268:19463-19470(1993). RN [15] RP PRELIMINARY PROTEIN SEQUENCE OF N-TERMINUS. RC TISSUE=Placenta; RX PubMed=3964273; DOI=10.1016/0006-291x(86)90987-3; RA Chen S., Shively J.E., Nakajin S., Shinoda M., Hall P.F.; RT "Amino terminal sequence analysis of human placenta aromatase."; RL Biochem. Biophys. Res. Commun. 135:713-719(1986). RN [16] RP ALTERNATIVE PROMOTER USAGE, AND TISSUE SPECIFICITY. RX PubMed=8117272; DOI=10.1006/bbrc.1994.1163; RA Honda S., Harada N., Takagi Y.; RT "Novel exon 1 of the aromatase gene specific for aromatase transcripts in RT human brain."; RL Biochem. Biophys. Res. Commun. 198:1153-1160(1994). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY. RX PubMed=20385561; DOI=10.1074/jbc.m110.123711; RA Sohl C.D., Guengerich F.P.; RT "Kinetic analysis of the three-step steroid aromatase reaction of human RT cytochrome P450 19A1."; RL J. Biol. Chem. 285:17734-17743(2010). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY. RX PubMed=22773874; DOI=10.1074/jbc.m112.390047; RA Cheng Q., Sohl C.D., Yoshimoto F.K., Guengerich F.P.; RT "Oxidation of dihydrotestosterone by human cytochromes P450 19A1 and 3A4."; RL J. Biol. Chem. 287:29554-29567(2012). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH ANDROSTENEDIONE, AND RP HEME. RX PubMed=19129847; DOI=10.1038/nature07614; RA Ghosh D., Griswold J., Erman M., Pangborn W.; RT "Structural basis for androgen specificity and oestrogen synthesis in human RT aromatase."; RL Nature 457:219-223(2009). RN [20] RP VARIANTS AROD CYS-435 AND TYR-437. RX PubMed=8265607; DOI=10.1073/pnas.90.24.11673; RA Ito Y., Fisher C.R., Conte F.A., Grumbach M.M., Simpson E.R.; RT "Molecular basis of aromatase deficiency in an adult female with sexual RT infantilism and polycystic ovaries."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11673-11677(1993). RN [21] RP VARIANT AROD CYS-375. RX PubMed=8530621; DOI=10.1210/jcem.80.12.8530621; RA Morishima A., Grumbach M.M., Simpson E.R., Fisher C., Qin K.; RT "Aromatase deficiency in male and female siblings caused by a novel RT mutation and the physiological role of estrogens."; RL J. Clin. Endocrinol. Metab. 80:3689-3698(1995). RN [22] RP VARIANT AROD GLN-365. RX PubMed=9211678; DOI=10.1056/nejm199707103370204; RA Carani C., Qin K., Simoni M., Faustini-Fustini M., Serpente S., Boyd J., RA Korach K.S., Simpson E.R.; RT "Effect of testosterone and estradiol in a man with aromatase deficiency."; RL N. Engl. J. Med. 337:91-95(1997). RN [23] RP VARIANT CYS-264. RX PubMed=9352581; DOI=10.1097/00008571-199710000-00014; RA Watanabe J., Harada N., Suemasu K., Higashi Y., Gotoh O., Kawajiri K.; RT "Arginine-cysteine polymorphism at codon 264 of the human CYP19 gene does RT not affect aromatase activity."; RL Pharmacogenetics 7:419-424(1997). RN [24] RP VARIANTS ARG-39 AND CYS-264. RX PubMed=10956405; RX DOI=10.1002/1097-0215(20000720)89:4<325::aid-ijc2>3.0.co;2-3; RA Miyoshi Y., Iwao K., Ikeda N., Egawa C., Noguchi S.; RT "Breast cancer risk associated with polymorphism in CYP19 in Japanese RT women."; RL Int. J. Cancer 89:325-328(2000). RN [25] RP VARIANT [LARGE SCALE ANALYSIS] LEU-375. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). RN [26] RP VARIANT AROD HIS-192, AND CHARACTERIZATION OF VARIANT AROD HIS-192. RX PubMed=24705274; DOI=10.1016/j.mce.2014.03.008; RA Bouchoucha N., Samara-Boustani D., Pandey A.V., Bony-Trifunovic H., RA Hofer G., Aigrain Y., Polak M., Fluck C.E.; RT "Characterization of a novel CYP19A1 (aromatase) R192H mutation causing RT virilization of a 46,XX newborn, undervirilization of the 46,XY brother, RT but no virilization of the mother during pregnancies."; RL Mol. Cell. Endocrinol. 390:8-17(2014). RN [27] RP VARIANT PRO-314. RX PubMed=27657680; DOI=10.1038/gim.2016.142; RA Chen D.Y., Liu X.F., Lin X.J., Zhang D., Chai Y.C., Yu D.H., Sun C.L., RA Wang X.L., Zhu W.D., Chen Y., Sun L.H., Wang X.W., Shi F.X., Huang Z.W., RA Yang T., Wu H.; RT "A dominant variant in DMXL2 is linked to nonsyndromic hearing loss."; RL Genet. Med. 19:553-558(2017). RN [28] RP CHARACTERIZATION OF VARIANTS CYS-264 AND HIS-264, PHOSPHORYLATION, RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=27702664; DOI=10.1016/j.jsbmb.2016.09.022; RA Baravalle R., Di Nardo G., Bandino A., Barone I., Catalano S., Ando S., RA Gilardi G.; RT "Impact of R264C and R264H polymorphisms in human aromatase function."; RL J. Steroid Biochem. Mol. Biol. 167:23-32(2017). CC -!- FUNCTION: A cytochrome P450 monooxygenase that catalyzes the conversion CC of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and CC testosterone to the C18 estrogens, estrone and estradiol, respectively CC (PubMed:27702664, PubMed:2848247). Catalyzes three successive CC oxidations of C19 androgens: two conventional oxidations at C19 CC yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a CC third oxidative aromatization step that involves C1-beta hydrogen CC abstraction combined with cleavage of the C10-C19 bond to yield a CC phenolic A ring and formic acid (PubMed:20385561). Alternatively, the CC third oxidative reaction yields a 19-norsteroid and formic acid. CC Converts dihydrotestosterone to delta1,10-dehydro 19- CC nordihydrotestosterone and may play a role in homeostasis of this CC potent androgen (PubMed:22773874). Also displays 2-hydroxylase activity CC toward estrone (PubMed:22773874). 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 (CPR; NADPH-ferrihemoprotein reductase) CC (PubMed:20385561, PubMed:22773874). {ECO:0000269|PubMed:20385561, CC ECO:0000269|PubMed:22773874, ECO:0000269|PubMed:27702664, CC ECO:0000269|PubMed:2848247}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3 O2 + 3 reduced [NADPH--hemoprotein reductase] + testosterone CC = 17beta-estradiol + formate + 4 H(+) + 4 H2O + 3 oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38191, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, CC ChEBI:CHEBI:16469, ChEBI:CHEBI:17347, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; EC=1.14.14.14; CC Evidence={ECO:0000269|PubMed:2848247}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38192; CC Evidence={ECO:0000305|PubMed:2848247}; CC -!- CATALYTIC ACTIVITY: CC Reaction=androst-4-ene-3,17-dione + 3 O2 + 3 reduced CC [NADPH--hemoprotein reductase] = estrone + formate + 4 H(+) + 4 H2O + CC 3 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38195, CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, CC ChEBI:CHEBI:16422, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; EC=1.14.14.14; CC Evidence={ECO:0000269|PubMed:27702664, ECO:0000269|PubMed:2848247}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38196; CC Evidence={ECO:0000305|PubMed:27702664, ECO:0000305|PubMed:2848247}; CC -!- CATALYTIC ACTIVITY: CC Reaction=androst-4-ene-3,17-dione + O2 + reduced [NADPH--hemoprotein CC reductase] = 19-hydroxyandrost-4-ene-3,17-dione + H(+) + H2O + CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38199, 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:27576, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC Evidence={ECO:0000269|PubMed:20385561}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38200; CC Evidence={ECO:0000305|PubMed:20385561}; CC -!- CATALYTIC ACTIVITY: CC Reaction=19-hydroxyandrost-4-ene-3,17-dione + O2 + reduced CC [NADPH--hemoprotein reductase] = 19-oxo-androst-4-ene-3,17-dione + CC H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase]; CC Xref=Rhea:RHEA:38203, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, CC ChEBI:CHEBI:799, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:27576, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:20385561}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38204; CC Evidence={ECO:0000305|PubMed:20385561}; CC -!- CATALYTIC ACTIVITY: CC Reaction=19-oxo-androst-4-ene-3,17-dione + O2 + reduced CC [NADPH--hemoprotein reductase] = estrone + formate + 2 H(+) + H2O + CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38207, CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:799, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:15740, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:20385561}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38208; CC Evidence={ECO:0000305|PubMed:20385561}; 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:22773874}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; CC Evidence={ECO:0000305|PubMed:22773874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + O2 + reduced CC [NADPH--hemoprotein reductase] = 17beta,19-dihydroxy-3-oxo-5alpha- CC androstanone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; CC Xref=Rhea:RHEA:53200, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16330, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:137031; Evidence={ECO:0000269|PubMed:22773874}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53201; CC Evidence={ECO:0000305|PubMed:22773874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta,19-dihydroxy-3-oxo-5alpha-androstanone + O2 + reduced CC [NADPH--hemoprotein reductase] = 17beta-hydroxy-3,19-dioxo-5alpha- CC androstanone + H(+) + 2 H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:53204, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137031, CC ChEBI:CHEBI:137032; Evidence={ECO:0000269|PubMed:22773874}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53205; CC Evidence={ECO:0000305|PubMed:22773874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-hydroxy-3,19-dioxo-5alpha-androstanone + O2 + reduced CC [NADPH--hemoprotein reductase] = 17beta-hydroxy-3-oxo-19-nor-5alpha- CC androst-1-ene + formate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:53276, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:137032, ChEBI:CHEBI:137110; CC Evidence={ECO:0000269|PubMed:22773874}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53277; CC Evidence={ECO:0000305|PubMed:22773874}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000269|PubMed:19129847}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.46 uM for androst-4-ene-3,17-dione CC {ECO:0000269|PubMed:27702664}; CC KM=0.044 uM for androst-4-ene-3,17-dione (19-hydroxylation) CC {ECO:0000269|PubMed:20385561}; CC KM=21 uM for 19-hydroxyandrost-4-ene-3,17-dione CC {ECO:0000269|PubMed:20385561}; CC KM=18 uM for 19-oxo-androst-4-ene-3,17-dione CC {ECO:0000269|PubMed:20385561}; CC KM=2.7 uM for estrone (2-hydroxylation) CC {ECO:0000269|PubMed:22773874}; CC KM=3.8 uM for 17beta-hydroxy-5alpha-androstan-3-one CC (19-hydroxylation) {ECO:0000269|PubMed:22773874}; CC KM=3.2 uM for 17beta,19-dihydroxy-3-oxo-5alpha-androstanone CC {ECO:0000269|PubMed:22773874}; CC KM=7.6 uM for 17beta-hydroxy-3,19-dioxo-5alpha-androstanone CC {ECO:0000269|PubMed:22773874}; CC Note=kcat is 0.060 sec(-1) with androst-4-ene-3,17-dione as substrate CC (PubMed:20385561). kcat is 0.13 sec(-1) with CC 19-oxo-androst-4-ene-3,17-dione (PubMed:20385561). kcat is 0.42 CC sec(-1) with androst-4-ene-3,17-dione as substrate (PubMed:20385561). CC kcat is 0.046 min(-1) with estrone as substrate (PubMed:22773874). CC kcat is 0.27 min(-1) with 17beta-hydroxy-5alpha-androstan-3-one as CC substrate (PubMed:22773874). kcat is 0.32 min(-1) with CC 17beta,19-dihydroxy-3-oxo-5alpha-androstanone as substrate CC (PubMed:22773874). kcat is 0.77 min(-1) with CC 17beta-hydroxy-3,19-dioxo-5alpha-androstanone as substrate CC (PubMed:22773874). {ECO:0000269|PubMed:20385561, CC ECO:0000269|PubMed:22773874}; CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:20385561, CC ECO:0000269|PubMed:22773874}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:2973313}; Multi-pass membrane protein CC {ECO:0000305}. Microsome membrane {ECO:0000269|PubMed:2973313}; Multi- CC pass membrane protein {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11511-1; Sequence=Displayed; CC Name=2; CC IsoId=P11511-2; Sequence=VSP_055583, VSP_055584; CC -!- TISSUE SPECIFICITY: Widely expressed, including in adult and fetal CC brain, placenta, skin fibroblasts, adipose tissue and gonads. CC {ECO:0000269|PubMed:2040633, ECO:0000269|PubMed:3018730, CC ECO:0000269|PubMed:7690033, ECO:0000269|PubMed:8117272}. CC -!- PTM: Phosphorylated in vitro by PKA and PKG/PRKG1. These CC phosphorylations inhibit the catalytic activity as measured by estrone CC synthesis from androstenedione (36% decrease for PKA and 30% for CC PKG/PRKG1). {ECO:0000269|PubMed:27702664}. CC -!- DISEASE: Aromatase excess syndrome (AEXS) [MIM:139300]: An autosomal CC dominant disorder characterized by increased extraglandular CC aromatization of steroids that presents with heterosexual precocity in CC males and isosexual precocity in females. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Aromatase deficiency (AROD) [MIM:613546]: A rare disease in CC which fetal androgens are not converted into estrogens due to placental CC aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which CC spontaneously resolves after post-partum. At birth, female babies CC present with pseudohermaphroditism due to virilization of extern CC genital organs. In adult females, manifestations include delay of CC puberty, breast hypoplasia and primary amenorrhoea with multicystic CC ovaries. {ECO:0000269|PubMed:24705274, ECO:0000269|PubMed:8265607, CC ECO:0000269|PubMed:8530621, ECO:0000269|PubMed:9211678}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Aromatase entry; CC URL="https://en.wikipedia.org/wiki/Aromatase"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cyp19a1/"; 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; M22246; AAA35557.1; -; mRNA. DR EMBL; X13589; CAA31929.1; -; mRNA. DR EMBL; M18856; AAA35556.1; -; mRNA. DR EMBL; J04127; AAA52132.1; -; mRNA. DR EMBL; Y07508; CAA68807.1; -; mRNA. DR EMBL; M30804; AAA35728.1; -; Genomic_DNA. DR EMBL; M30796; AAA35728.1; JOINED; Genomic_DNA. DR EMBL; M30797; AAA35728.1; JOINED; Genomic_DNA. DR EMBL; M30798; AAA35728.1; JOINED; Genomic_DNA. DR EMBL; M30800; AAA35728.1; JOINED; Genomic_DNA. DR EMBL; M30801; AAA35728.1; JOINED; Genomic_DNA. DR EMBL; M30802; AAA35728.1; JOINED; Genomic_DNA. DR EMBL; M30803; AAA35728.1; JOINED; Genomic_DNA. DR EMBL; AY957953; AAX44046.1; -; Genomic_DNA. DR EMBL; AC012169; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC020891; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035714; AAH35714.1; -; mRNA. DR EMBL; BC107785; AAI07786.1; -; mRNA. DR EMBL; M28420; AAA52141.1; -; mRNA. DR CCDS; CCDS10139.1; -. [P11511-1] DR PIR; A34451; O4HU19. DR RefSeq; NP_000094.2; NM_000103.3. [P11511-1] DR RefSeq; NP_001334177.1; NM_001347248.1. [P11511-1] DR RefSeq; NP_001334178.1; NM_001347249.1. [P11511-1] DR RefSeq; NP_001334179.1; NM_001347250.1. [P11511-1] DR RefSeq; NP_001334180.1; NM_001347251.1. [P11511-1] DR RefSeq; NP_001334181.1; NM_001347252.1. [P11511-1] DR RefSeq; NP_001334182.1; NM_001347253.1. [P11511-1] DR RefSeq; NP_001334183.1; NM_001347254.1. [P11511-1] DR RefSeq; NP_001334184.1; NM_001347255.1. [P11511-1] DR RefSeq; NP_001334185.1; NM_001347256.1. [P11511-1] DR RefSeq; NP_112503.1; NM_031226.2. [P11511-1] DR PDB; 3EQM; X-ray; 2.90 A; A=1-503. DR PDB; 3S79; X-ray; 2.75 A; A=1-503. DR PDB; 3S7S; X-ray; 3.21 A; A=1-503. DR PDB; 4GL5; X-ray; 3.48 A; A=1-503. DR PDB; 4GL7; X-ray; 3.90 A; A=1-503. DR PDB; 4KQ8; X-ray; 3.29 A; A=45-503. DR PDB; 5JKV; X-ray; 2.75 A; A=1-503. DR PDB; 5JKW; X-ray; 3.00 A; A=1-503. DR PDB; 5JL6; X-ray; 3.00 A; A=1-503. DR PDB; 5JL7; X-ray; 3.10 A; A=1-503. DR PDB; 5JL9; X-ray; 3.10 A; A=1-503. DR PDBsum; 3EQM; -. DR PDBsum; 3S79; -. DR PDBsum; 3S7S; -. DR PDBsum; 4GL5; -. DR PDBsum; 4GL7; -. DR PDBsum; 4KQ8; -. DR PDBsum; 5JKV; -. DR PDBsum; 5JKW; -. DR PDBsum; 5JL6; -. DR PDBsum; 5JL7; -. DR PDBsum; 5JL9; -. DR AlphaFoldDB; P11511; -. DR SMR; P11511; -. DR BioGRID; 107960; 41. DR IntAct; P11511; 6. DR MINT; P11511; -. DR STRING; 9606.ENSP00000379683; -. DR BindingDB; P11511; -. DR ChEMBL; CHEMBL1978; -. DR DrugBank; DB02342; 2-Methoxyestradiol. DR DrugBank; DB00357; Aminoglutethimide. DR DrugBank; DB01217; Anastrozole. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB04794; Bifonazole. DR DrugBank; DB06719; Buserelin. DR DrugBank; DB13009; Carbendazim. DR DrugBank; DB00389; Carbimazole. DR DrugBank; DB00269; Chlorotrianisene. DR DrugBank; DB00856; Chlorphenesin. DR DrugBank; DB04839; Cyproterone acetate. DR DrugBank; DB01406; Danazol. DR DrugBank; DB00255; Diethylstilbestrol. DR DrugBank; DB00858; Drostanolone. DR DrugBank; DB01127; Econazole. DR DrugBank; DB14598; Edetate calcium disodium anhydrous. DR DrugBank; DB14600; Edetate disodium anhydrous. DR DrugBank; DB00974; Edetic acid. DR DrugBank; DB06423; Endostatin. DR DrugBank; DB00783; Estradiol. DR DrugBank; DB00655; Estrone. DR DrugBank; DB00926; Etretinate. DR DrugBank; DB00990; Exemestane. DR DrugBank; DB04539; Glyphosate. DR DrugBank; DB01026; Ketoconazole. DR DrugBank; DB01006; Letrozole. DR DrugBank; DB05667; Levoketoconazole. DR DrugBank; DB00358; Mefloquine. DR DrugBank; DB01065; Melatonin. DR DrugBank; DB00333; Methadone. DR DrugBank; DB06710; Methyltestosterone. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB16236; Mitapivat. DR DrugBank; DB05749; MPI-674. DR DrugBank; DB08804; Nandrolone decanoate. DR DrugBank; DB03467; Naringenin. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB09389; Norgestrel. DR DrugBank; DB01229; Paclitaxel. DR DrugBank; DB05804; Prasterone sulfate. DR DrugBank; DB00481; Raloxifene. DR DrugBank; DB05875; Sar9, Met (O2)11-Substance P. DR DrugBank; DB02901; Stanolone. DR DrugBank; DB06147; Sulfathiazole. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB00894; Testolactone. DR DrugBank; DB00624; Testosterone. DR DrugBank; DB13943; Testosterone cypionate. DR DrugBank; DB13944; Testosterone enanthate. DR DrugBank; DB13946; Testosterone undecanoate. DR DrugBank; DB01007; Tioconazole. DR DrugBank; DB00197; Troglitazone. DR DrugCentral; P11511; -. DR GuidetoPHARMACOLOGY; 1362; -. DR SwissLipids; SLP:000001716; -. DR iPTMnet; P11511; -. DR PhosphoSitePlus; P11511; -. DR BioMuta; CYP19A1; -. DR DMDM; 117293; -. DR MassIVE; P11511; -. DR PaxDb; 9606-ENSP00000379683; -. DR PeptideAtlas; P11511; -. DR ProteomicsDB; 52787; -. [P11511-1] DR ProteomicsDB; 71189; -. DR ABCD; P11511; 1 sequenced antibody. DR Antibodypedia; 4371; 769 antibodies from 41 providers. DR DNASU; 1588; -. DR Ensembl; ENST00000396402.6; ENSP00000379683.1; ENSG00000137869.16. [P11511-1] DR Ensembl; ENST00000396404.8; ENSP00000379685.4; ENSG00000137869.16. [P11511-1] DR Ensembl; ENST00000405913.7; ENSP00000383930.3; ENSG00000137869.16. [P11511-2] DR Ensembl; ENST00000557858.5; ENSP00000452627.1; ENSG00000137869.16. [P11511-2] DR Ensembl; ENST00000559878.5; ENSP00000453149.1; ENSG00000137869.16. [P11511-1] DR GeneID; 1588; -. DR KEGG; hsa:1588; -. DR MANE-Select; ENST00000396402.6; ENSP00000379683.1; NM_000103.4; NP_000094.2. DR UCSC; uc001zyz.5; human. [P11511-1] DR AGR; HGNC:2594; -. DR CTD; 1588; -. DR DisGeNET; 1588; -. DR GeneCards; CYP19A1; -. DR HGNC; HGNC:2594; CYP19A1. DR HPA; ENSG00000137869; Tissue enriched (placenta). DR MalaCards; CYP19A1; -. DR MIM; 107910; gene. DR MIM; 139300; phenotype. DR MIM; 613546; phenotype. DR neXtProt; NX_P11511; -. DR OpenTargets; ENSG00000137869; -. DR Orphanet; 91; Aromatase deficiency. DR Orphanet; 178345; Aromatase excess syndrome. DR PharmGKB; PA27091; -. DR VEuPathDB; HostDB:ENSG00000137869; -. DR eggNOG; KOG0157; Eukaryota. DR GeneTree; ENSGT00840000129915; -. DR HOGENOM; CLU_041874_0_0_1; -. DR InParanoid; P11511; -. DR OMA; PGLQCIG; -. DR OrthoDB; 5385594at2759; -. DR PhylomeDB; P11511; -. DR TreeFam; TF352039; -. DR BioCyc; MetaCyc:HS06413-MONOMER; -. DR BRENDA; 1.14.14.14; 2681. DR PathwayCommons; P11511; -. DR Reactome; R-HSA-193144; Estrogen biosynthesis. DR Reactome; R-HSA-211976; Endogenous sterols. DR Reactome; R-HSA-5579030; Defective CYP19A1 causes AEXS. DR SABIO-RK; P11511; -. DR SignaLink; P11511; -. DR SIGNOR; P11511; -. DR BioGRID-ORCS; 1588; 8 hits in 1156 CRISPR screens. DR ChiTaRS; CYP19A1; human. DR EvolutionaryTrace; P11511; -. DR GeneWiki; Aromatase; -. DR GenomeRNAi; 1588; -. DR Pharos; P11511; Tclin. DR PRO; PR:P11511; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P11511; Protein. DR Bgee; ENSG00000137869; Expressed in placenta and 102 other cell types or tissues. DR ExpressionAtlas; P11511; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0070330; F:aromatase activity; IDA:UniProtKB. DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR 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; TAS:UniProtKB. DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc. DR GO; GO:0008395; F:steroid hydroxylase activity; TAS:Reactome. DR GO; GO:0006710; P:androgen catabolic process; IDA:CAFA. DR GO; GO:0006703; P:estrogen biosynthetic process; TAS:Reactome. DR GO; GO:0030540; P:female genitalia development; IEA:Ensembl. DR GO; GO:0008585; P:female gonad development; IBA:GO_Central. DR GO; GO:0030879; P:mammary gland development; IEA:Ensembl. DR GO; GO:0002677; P:negative regulation of chronic inflammatory response; IEA:Ensembl. DR GO; GO:0010760; P:negative regulation of macrophage chemotaxis; IEA:Ensembl. DR GO; GO:2000866; P:positive regulation of estradiol secretion; IDA:CAFA. DR GO; GO:0060736; P:prostate gland growth; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IBA:GO_Central. DR GO; GO:0006694; P:steroid biosynthetic process; TAS:ProtInc. DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome. DR GO; GO:0006949; P:syncytium formation; TAS:ARUK-UCL. DR GO; GO:0061370; P:testosterone biosynthetic process; IEA:Ensembl. DR GO; GO:0060065; P:uterus development; IEA:Ensembl. DR CDD; cd20616; CYP19A1; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24291:SF43; AROMATASE; 1. DR PANTHER; PTHR24291; CYTOCHROME P450 FAMILY 4; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P11511; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disease variant; Endoplasmic reticulum; Heme; Iron; Lipid metabolism; KW Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; KW Pseudohermaphroditism; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1..503 FT /note="Aromatase" FT /id="PRO_0000051955" FT TRANSMEM 19..39 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 303..323 FT /note="Helical" FT /evidence="ECO:0000255" FT BINDING 309 FT /ligand="substrate" FT BINDING 374 FT /ligand="substrate" FT BINDING 437 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:0000269|PubMed:19129847, FT ECO:0007744|PDB:3EQM" FT VAR_SEQ 210..218 FT /note="ESAIVVKIQ -> GTEIFTLTS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055583" FT VAR_SEQ 219..503 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055584" FT VARIANT 39 FT /note="W -> R (in dbSNP:rs2236722)" FT /evidence="ECO:0000269|PubMed:10956405, ECO:0000269|Ref.8" FT /id="VAR_023428" FT VARIANT 192 FT /note="R -> H (in AROD; strongly reduced aromatase FT activity; 81% reduction of androstenedione metabolism FT compared to wild-type; dbSNP:rs765057534)" FT /evidence="ECO:0000269|PubMed:24705274" FT /id="VAR_072784" FT VARIANT 201 FT /note="T -> M (in dbSNP:rs28757184)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.8" FT /id="VAR_023429" FT VARIANT 264 FT /note="R -> C (1.6 fold decrease in affinity for FT androstenedione substrate; slightly affects PKA-mediated FT reduction in catalytic activity as measured in vitro by FT estrone synthesis from androstenedione (49% decrease FT compared with 36% for the wild-type protein); no effect on FT PKG/PRKG1-mediated reduction in catalytic activity in FT vitro; dbSNP:rs700519)" FT /evidence="ECO:0000269|PubMed:10956405, FT ECO:0000269|PubMed:27702664, ECO:0000269|PubMed:2848247, FT ECO:0000269|PubMed:3653507, ECO:0000269|PubMed:9352581, FT ECO:0000269|Ref.8" FT /id="VAR_018406" FT VARIANT 264 FT /note="R -> H (2.5 fold decrease in affinity for FT androstenedione substrate; slightly affects PKA-mediated FT reduction in catalytic activity as measured by estrone FT synthesis from androstenedione in vitro (28% decrease FT compared with 36% for the wild-type protein) and FT PKG/PRKG1-mediated reduction in catalytic activity in vitro FT (15% decrease compared with 30% for the wild-type protein); FT dbSNP:rs2304462)" FT /evidence="ECO:0000269|PubMed:27702664" FT /id="VAR_077526" FT VARIANT 314 FT /note="S -> P (found in deaf patients; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:27657680" FT /id="VAR_079486" FT VARIANT 365 FT /note="R -> Q (in AROD; 0.4% of wild-type activity; FT dbSNP:rs80051519)" FT /evidence="ECO:0000269|PubMed:9211678" FT /id="VAR_016962" FT VARIANT 375 FT /note="R -> C (in AROD; dbSNP:rs121434536)" FT /evidence="ECO:0000269|PubMed:8530621" FT /id="VAR_016963" FT VARIANT 375 FT /note="R -> L (in dbSNP:rs762631156)" FT /evidence="ECO:0000269|PubMed:18987736" FT /id="VAR_054152" FT VARIANT 435 FT /note="R -> C (in AROD; 1.1% of wild-type activity; FT dbSNP:rs121434534)" FT /evidence="ECO:0000269|PubMed:8265607" FT /id="VAR_016964" FT VARIANT 437 FT /note="C -> Y (in AROD; complete loss of activity; FT dbSNP:rs78310315)" FT /evidence="ECO:0000269|PubMed:8265607" FT /id="VAR_016965" FT CONFLICT 496 FT /note="N -> S (in Ref. 1; AAA35557/CAA31929)" FT /evidence="ECO:0000305" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 57..68 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 70..80 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 83..97 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 100..108 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 110..112 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 119..125 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 138..151 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 155..172 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 173..177 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:5JKW" FT HELIX 187..203 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 210..227 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 232..236 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 238..240 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 242..267 FT /evidence="ECO:0007829|PDB:3S79" FT TURN 270..275 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 278..287 FT /evidence="ECO:0007829|PDB:3S79" FT TURN 288..290 FT /evidence="ECO:0007829|PDB:3EQM" FT HELIX 293..324 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 326..339 FT /evidence="ECO:0007829|PDB:3S79" FT TURN 340..342 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 347..349 FT /evidence="ECO:0007829|PDB:3S79" FT TURN 350..352 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 354..366 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 373..376 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 381..383 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 386..388 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 393..396 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 398..401 FT /evidence="ECO:0007829|PDB:3S79" FT TURN 402..404 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 415..418 FT /evidence="ECO:0007829|PDB:3S79" FT TURN 424..426 FT /evidence="ECO:0007829|PDB:3S79" FT HELIX 433..435 FT /evidence="ECO:0007829|PDB:5JL6" FT HELIX 440..455 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 458..463 FT /evidence="ECO:0007829|PDB:3S79" FT TURN 468..470 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 473..481 FT /evidence="ECO:0007829|PDB:3S79" FT STRAND 483..485 FT /evidence="ECO:0007829|PDB:4KQ8" FT STRAND 490..494 FT /evidence="ECO:0007829|PDB:3S79" SQ SEQUENCE 503 AA; 57883 MW; 9BD9B28651D9A69A CRC64; MVLEMLNPIH YNITSIVPEA MPAATMPVLL LTGLFLLVWN YEGTSSIPGP GYCMGIGPLI SHGRFLWMGI GSACNYYNRV YGEFMRVWIS GEETLIISKS SSMFHIMKHN HYSSRFGSKL GLQCIGMHEK GIIFNNNPEL WKTTRPFFMK ALSGPGLVRM VTVCAESLKT HLDRLEEVTN ESGYVDVLTL LRRVMLDTSN TLFLRIPLDE SAIVVKIQGY FDAWQALLIK PDIFFKISWL YKKYEKSVKD LKDAIEVLIA EKRRRISTEE KLEECMDFAT ELILAEKRGD LTRENVNQCI LEMLIAAPDT MSVSLFFMLF LIAKHPNVEE AIIKEIQTVI GERDIKIDDI QKLKVMENFI YESMRYQPVV DLVMRKALED DVIDGYPVKK GTNIILNIGR MHRLEFFPKP NEFTLENFAK NVPYRYFQPF GFGPRGCAGK YIAMVMMKAI LVTLLRRFHV KTLQGQCVES IQKIHDLSLH PDETKNMLEM IFTPRNSDRC LEH //