CP19A_HUMAN
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 03-AUG-2022, entry version 226.
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, ECO:0000312|HGNC:HGNC:2594};
GN 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 [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:38191, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.14; 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 [NADPH--
CC hemoprotein reductase] = estrone + formate + 4 H(+) + 4 H2O + 3
CC 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 [NADPH--
CC hemoprotein reductase] = 19-oxo-androst-4-ene-3,17-dione + H(+) + 2
CC H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38203,
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:27576, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC 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 [NADPH--
CC hemoprotein reductase] = estrone + formate + 2 H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38207, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:799, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC 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 [NADPH--
CC 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 (19-
CC 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 19-oxo-androst-4-ene-
CC 3,17-dione (PubMed:20385561). kcat is 0.42 sec(-1) with androst-4-
CC ene-3,17-dione as substrate (PubMed:20385561). kcat is 0.046 min(-1)
CC with estrone as substrate (PubMed:22773874). kcat is 0.27 min(-1)
CC with 17beta-hydroxy-5alpha-androstan-3-one as substrate
CC (PubMed:22773874). kcat is 0.32 min(-1) with 17beta,19-dihydroxy-3-
CC oxo-5alpha-androstanone as substrate (PubMed:22773874). kcat is 0.77
CC min(-1) with 17beta-hydroxy-3,19-dioxo-5alpha-androstanone as
CC substrate (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 ---------------------------------------------------------------------------
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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; 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; DB00655; Estrone.
DR DrugBank; DB00926; Etretinate.
DR DrugBank; DB00990; Exemestane.
DR DrugBank; DB04539; Glyphosate.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB01006; Letrozole.
DR DrugBank; DB00358; Mefloquine.
DR DrugBank; DB01065; Melatonin.
DR DrugBank; DB00333; Methadone.
DR DrugBank; DB06710; Methyltestosterone.
DR DrugBank; DB01110; Miconazole.
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; P11511; -.
DR PeptideAtlas; P11511; -.
DR PRIDE; P11511; -.
DR ProteomicsDB; 52787; -. [P11511-1]
DR ProteomicsDB; 71189; -.
DR ABCD; P11511; 1 sequenced antibody.
DR Antibodypedia; 4371; 674 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 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; VRPFFMK; -.
DR PhylomeDB; P11511; -.
DR TreeFam; TF352039; -.
DR BioCyc; MetaCyc:HS06413-MON; -.
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; 7 hits in 1070 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 100 other tissues.
DR ExpressionAtlas; P11511; baseline and differential.
DR Genevisible; P11511; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 Gene3D; 1.10.630.10; -; 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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
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 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 PKG/PRKG1-
FT mediated reduction in catalytic activity in vitro (15%
FT 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; unknown pathological
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
