Aromatase

Details

Name
Aromatase
Synonyms
  • 1.14.14.14
  • ARO1
  • CYAR
  • CYP19
  • CYPXIX
  • Cytochrome P-450AROM
  • Cytochrome P450 19A1
  • Estrogen synthase
Gene Name
CYP19A1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004098|Aromatase
MVLEMLNPIHYNITSIVPEAMPAATMPVLLLTGLFLLVWNYEGTSSIPGPGYCMGIGPLI
SHGRFLWMGIGSACNYYNRVYGEFMRVWISGEETLIISKSSSMFHIMKHNHYSSRFGSKL
GLQCIGMHEKGIIFNNNPELWKTTRPFFMKALSGPGLVRMVTVCAESLKTHLDRLEEVTN
ESGYVDVLTLLRRVMLDTSNTLFLRIPLDESAIVVKIQGYFDAWQALLIKPDIFFKISWL
YKKYEKSVKDLKDAIEVLIAEKRRRISTEEKLEECMDFATELILAEKRGDLTRENVNQCI
LEMLIAAPDTMSVSLFFMLFLIAKHPNVEEAIIKEIQTVIGERDIKIDDIQKLKVMENFI
YESMRYQPVVDLVMRKALEDDVIDGYPVKKGTNIILNIGRMHRLEFFPKPNEFTLENFAK
NVPYRYFQPFGFGPRGCAGKYIAMVMMKAILVTLLRRFHVKTLQGQCVESIQKIHDLSLH
PDETKNMLEMIFTPRNSDRCLEH
Number of residues
503
Molecular Weight
57882.48
Theoretical pI
7.56
GO Classification
Functions
aromatase activity / electron carrier activity / heme binding / iron ion binding / 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 / oxygen binding
Processes
androgen metabolic process / estrogen biosynthetic process / negative regulation of chronic inflammatory response / negative regulation of macrophage chemotaxis / prostate gland growth / small molecule metabolic process / steroid biosynthetic process / steroid metabolic process / sterol metabolic process / xenobiotic metabolic process
Components
endoplasmic reticulum / endoplasmic reticulum membrane / membrane
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0016675|Aromatase (CYP19A1)
ATGGTTTTGGAAATGCTGAACCCGATACATTATAACATCACCAGCATCGTGCCTGAAGCC
ATGCCTGCTGCCACCATGCCAGTCCTGCTCCTCACTGGCCTTTTTCTCTTGGTGTGGAAT
TATGAGGGCACATCCTCAATACCAGGTCCTGGCTACTGCATGGGAATTGGACCCCTCATC
TCCCACGGCAGATTCCTGTGGATGGGGATCGGCAGTGCCTGCAACTACTACAACCGGGTA
TATGGAGAATTCATGCGAGTCTGGATCTCTGGAGAGGAAACACTCATTATCAGCAAGTCC
TCAAGTATGTTCCACATAATGAAGCACAATCATTACAGCTCTCGATTCGGCAGCAAACTT
GGGCTGCAGTGCATCGGTATGCATGAGAAAGGCATCATATTTAACAACAATCCAGAGCTC
TGGAAAACAACTCGACCCTTCTTTATGAAAGCTCTGTCAGGCCCCGGCCTTGTTCGTATG
GTCACAGTCTGTGCTGAATCCCTCAAAACACATCTGGACAGGTTGGAGGAGGTGACCAAT
GAATCGGGCTATGTGGACGTGTTGACCCTTCTGCGTCGTGTCATGCTGGACACCTCTAAC
ACGCTCTTCTTGAGGATCCCTTTGGACGAAAGTGCTATCGTGGTTAAAATCCAAGGTTAT
TTTGATGCATGGCAAGCTCTCCTCATCAAACCAGACATCTTCTTTAAGATTTCTTGGCTA
TACAAAAAGTATGAGAAGTCTGTCAAGGATTTGAAAGATGCCATAGAAGTTCTGATAGCA
GAAAAAAGACGCAGGATTTCCACAGAAGAGAAACTGGAAGAATGTATGGACTTTGCCACT
GAGTTGATTTTAGCAGAGAAACGTGGTGACCTGACAAGAGAGAATGTGAACCAGTGCATA
TTGGAAATGCTGATCGCAGCTCCTGACACCATGTCTGTCTCTTTGTTCTTCATGCTATTT
CTCATTGCAAAGCACCCTAATGTTGAAGAGGCAATAATAAAGGAAATCCAGACTGTTATT
GGTGAGAGAGACATAAAGATTGATGATATACAAAAATTAAAAGTGATGGAAAACTTCATT
TATGAGAGCATGCGGTACCAGCCTGTCGTGGACTTGGTCATGCGCAAAGCCTTAGAAGAT
GATGTAATCGATGGCTACCCAGTGAAAAAGGGGACAAACATTATCCTGAATATTGGAAGG
ATGCACAGACTCGAGTTTTTCCCCAAACCCAATGAATTTACTCTTGAAAATTTTGCAAAG
AATGTTCCTTATAGGTACTTTCAGCCATTTGGCTTTGGGCCCCGTGGCTGTGCAGGAAAG
TACATCGCCATGGTGATGATGAAAGCCATCCTCGTTACACTTCTGAGACGATTCCACGTG
AAGACATTGCAAGGACAGTGTGTTGAGAGCATACAGAAGATACACGACTTGTCCTTGCAC
CCAGATGAGACTAAAAACATGCTGGAAATGATCTTTACCCCAAGAAACTCAGACAGGTGT
CTGGAACACTAG
Chromosome Location
15
Locus
15q21.1
External Identifiers
ResourceLink
UniProtKB IDP11511
UniProtKB Entry NameCP19A_HUMAN
GenBank Protein ID179002
GenBank Gene IDM22246
GenAtlas IDCYP19A1
HGNC IDHGNC:2594
General References
  1. Harada N: Cloning of a complete cDNA encoding human aromatase: immunochemical identification and sequence analysis. Biochem Biophys Res Commun. 1988 Oct 31;156(2):725-32. [PubMed:2973313]
  2. Chen SA, Besman MJ, Sparkes RS, Zollman S, Klisak I, Mohandas T, Hall PF, Shively JE: Human aromatase: cDNA cloning, Southern blot analysis, and assignment of the gene to chromosome 15. DNA. 1988 Jan-Feb;7(1):27-38. [PubMed:3390233]
  3. Corbin CJ, Graham-Lorence S, McPhaul M, Mason JI, Mendelson CR, Simpson ER: Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8948-52. [PubMed:2848247]
  4. Toda K, Terashima M, Mitsuuchi Y, Yamasaki Y, Yokoyama Y, Nojima S, Ushiro H, Maeda T, Yamamoto Y, Sagara Y, et al.: Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P-450. FEBS Lett. 1989 Apr 24;247(2):371-6. [PubMed:2541021]
  5. Means GD, Mahendroo MS, Corbin CJ, Mathis JM, Powell FE, Mendelson CR, Simpson ER: Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis. J Biol Chem. 1989 Nov 15;264(32):19385-91. [PubMed:2808431]
  6. Pompon D, Liu RY, Besman MJ, Wang PL, Shively JE, Chen S: Expression of human placental aromatase in Saccharomyces cerevisiae. Mol Endocrinol. 1989 Sep;3(9):1477-87. [PubMed:2691883]
  7. Harada N, Ogawa H, Shozu M, Yamada K, Suhara K, Nishida E, Takagi Y: Biochemical and molecular genetic analyses on placental aromatase (P-450AROM) deficiency. J Biol Chem. 1992 Mar 5;267(7):4781-5. [PubMed:1371509]
  8. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [PubMed:16572171]
  9. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  10. Evans CT, Ledesma DB, Schulz TZ, Simpson ER, Mendelson CR: Isolation and characterization of a complementary DNA specific for human aromatase-system cytochrome P-450 mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6387-91. [PubMed:3018730]
  11. Simpson ER, Evans CT, Corbin CJ, Powell FE, Ledesma DB, Mendelson CR: Sequencing of cDNA inserts encoding aromatase cytochrome P-450 (P-450AROM). Mol Cell Endocrinol. 1987 Aug;52(3):267-72. [PubMed:3653507]
  12. Mahendroo MS, Means GD, Mendelson CR, Simpson ER: Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. J Biol Chem. 1991 Jun 15;266(17):11276-81. [PubMed:2040633]
  13. Mahendroo MS, Mendelson CR, Simpson ER: Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem. 1993 Sep 15;268(26):19463-70. [PubMed:7690033]
  14. Chen S, Shively JE, Nakajin S, Shinoda M, Hall PF: Amino terminal sequence analysis of human placenta aromatase. Biochem Biophys Res Commun. 1986 Mar 28;135(3):713-9. [PubMed:3964273]
  15. Honda S, Harada N, Takagi Y: Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1153-60. [PubMed:8117272]
  16. Ghosh D, Griswold J, Erman M, Pangborn W: Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature. 2009 Jan 8;457(7226):219-23. doi: 10.1038/nature07614. [PubMed:19129847]
  17. Ito Y, Fisher CR, Conte FA, Grumbach MM, Simpson ER: Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11673-7. [PubMed:8265607]
  18. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K: Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995 Dec;80(12):3689-98. [PubMed:8530621]
  19. Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER: Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 1997 Jul 10;337(2):91-5. [PubMed:9211678]
  20. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. [PubMed:18987736]
  21. Bouchoucha N, Samara-Boustani D, Pandey AV, Bony-Trifunovic H, Hofer G, Aigrain Y, Polak M, Fluck CE: Characterization of a novel CYP19A1 (aromatase) R192H mutation causing virilization of a 46,XX newborn, undervirilization of the 46,XY brother, but no virilization of the mother during pregnancies. Mol Cell Endocrinol. 2014 Jun 5;390(1-2):8-17. doi: 10.1016/j.mce.2014.03.008. Epub 2014 Apr 4. [PubMed:24705274]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00357Aminoglutethimideapproved, investigationalyesinhibitorDetails
DB01217Anastrozoleapproved, investigationalyesinhibitorDetails
DB00990Exemestaneapproved, investigationalyesinhibitorDetails
DB01006Letrozoleapproved, investigationalyesantagonistDetails
DB00894Testolactoneapproved, investigationalyesinhibitorDetails
DB05749MPI-674investigationalunknownDetails
DB01217Anastrozoleapproved, investigationalunknowninhibitorDetails
DB01006Letrozoleapproved, investigationalunknownsubstrateinhibitorDetails
DB00255Diethylstilbestrolapproved, investigationalunknowninducerDetails
DB00624Testosteroneapproved, investigationalunknownsubstrateDetails
DB01406DanazolapprovedunknowninhibitorDetails
DB02901Stanoloneillicit, investigationalunknownsubstrateDetails
DB00443Betamethasoneapproved, vet_approvedunknownsubstrateinducerDetails
DB04794Bifonazoleapproved, investigationalunknowninhibitorDetails
DB06719Buserelinapproved, investigationalunknowninducerDetails
DB00882Clomifeneapproved, investigationalunknowninhibitorDetails
DB04839Cyproterone acetateapproved, investigationalunknowninhibitorDetails
DB01234Dexamethasoneapproved, investigational, vet_approvedunknowninducerDetails
DB00917DinoprostoneapprovedunknowninducerDetails
DB01127EconazoleapprovedunknowninhibitorDetails
DB00292EtomidateapprovedunknowninhibitorDetails
DB00926EtretinatewithdrawnunknowninhibitorDetails
DB00990Exemestaneapproved, investigationalunknowninhibitorDetails
DB01227Levacetylmethadolapproved, investigationalunknownsubstrateDetails
DB00367Levonorgestrelapproved, investigationalunknowninhibitorDetails
DB00358Mefloquineapproved, investigationalunknowninhibitorDetails
DB01065Melatoninapproved, nutraceutical, vet_approvedunknowninhibitorDetails
DB00333Methadoneapproved, illicitunknownsubstrateDetails
DB06710MethyltestosteroneapprovedunknowninducerDetails
DB00984Nandrolone phenpropionateapproved, illicit, investigationalunknownsubstrateDetails
DB01229Paclitaxelapproved, vet_approvedunknowninhibitorDetails
DB00481Raloxifeneapproved, investigationalunknowninhibitorDetails
DB00675TamoxifenapprovedunknowninhibitorDetails
DB00857Terbinafineapproved, investigational, vet_approvedunknowninhibitorDetails
DB01007TioconazoleapprovedunknowninhibitorDetails
DB00072Trastuzumabapproved, investigationalunknowninhibitorDetails
DB00197Troglitazoneinvestigational, withdrawnunknowninhibitorDetails
DB023422-MethoxyestradiolinvestigationalunknownDetails
DB00858DrostanoloneillicitunknowninhibitorDetails
DB00974Edetic Acidapproved, vet_approvedunknownsubstrateDetails
DB00389Carbimazoleapproved, investigationalunknowninhibitorDetails
DB00856Chlorphenesinapproved, experimentalunknowninducerDetails
DB00269Chlorotrianiseneinvestigational, withdrawnunknowninducerDetails
DB05804Prasterone sulfateinvestigationalunknowninducerDetails
DB06423EndostatininvestigationalunknownsubstrateDetails
DB08804Nandrolone decanoateapproved, illicitunknowninducerDetails
DB05875Sar9, Met (O2)11-Substance PinvestigationalunknowninhibitorDetails
DB06147Sulfathiazoleapproved, vet_approvedunknowninducerDetails
DB01026Ketoconazoleapproved, investigationalunknowninhibitorDetails
DB00184NicotineapprovedunknowninhibitorDetails
DB09389NorgestrelapprovedunknowninhibitorDetails
DB04539GlyphosateexperimentalunknownDetails
DB00655EstroneapprovedunknownDetails
DB03467NaringeninexperimentalunknowninhibitorDetails
DB13943Testosterone cypionateapprovedunknownsubstrateDetails
DB13944Testosterone enanthateapprovedunknownsubstrateDetails
DB13946Testosterone undecanoateapproved, investigationalunknownsubstrateDetails
DB13951Stanolone acetateexperimentalunknownsubstrateDetails
DB01110Miconazoleapproved, investigational, vet_approvedunknownDetails
DB14600Edetate disodium anhydrousapproved, vet_approvedunknownDetails