Aromatase

Details

Name
Aromatase
Synonyms
  • 1.14.14.14
  • ARO1
  • CYAR
  • CYP19
  • CYPXIX
  • Cytochrome P-450AROM
  • Cytochrome P450 19A1
  • Estrogen synthase
Gene Name
CYP19A1
UniProtKB Entry
P11511Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
electron transfer activity / steroid hydroxylase activity
Processes
androgen catabolic process / female genitalia development / female gonad development / mammary gland development / positive regulation of estradiol secretion / response to estradiol / syncytium formation / testosterone biosynthetic process / uterus development
General Function
A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (PubMed:27702664, PubMed:2848247). Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid (PubMed:20385561). Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen (PubMed:22773874). Also displays 2-hydroxylase activity toward estrone (PubMed:22773874). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20385561, PubMed:22773874)
Specific Function
aromatase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
19-39 303-323
Cellular Location
Endoplasmic reticulum 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
15q21.2
External Identifiers
ResourceLink
UniProtKB IDP11511
UniProtKB Entry NameCP19A_HUMAN
GenBank Protein ID179002
GenBank Gene IDM22246
GeneCard IDCYP19A1
GenAtlas IDCYP19A1
HGNC IDHGNC:2594
PDB ID(s)3EQM, 3S79, 3S7S, 4GL5, 4GL7, 4KQ8, 5JKV, 5JKW, 5JL6, 5JL7, 5JL9
KEGG IDhsa:1588
IUPHAR/Guide To Pharmacology ID1362
NCBI Gene ID1588
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Aromatase (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Aminoglutethimideapproved, investigationalyestargetinhibitorDetails
Anastrozoleapproved, investigationalyestargetinhibitorDetails
Exemestaneapproved, investigationalyestargetinhibitorDetails
Letrozoleapproved, investigationalyestargetantagonistDetails
Testolactoneapproved, investigationalyestargetinhibitorDetails
MPI-674investigationalunknowntargetDetails
Letrozoleapproved, investigationalunknownenzymeinhibitorDetails
Diethylstilbestrolapproved, investigational, withdrawnunknownenzymeinhibitorDetails
Testosteroneapproved, investigationalunknownenzymesubstrateDetails
DanazolapprovedunknownenzymeinhibitorDetails
Stanoloneillicit, investigationalunknownenzymesubstrateDetails
Betamethasoneapproved, vet_approvedunknownenzymesubstrateinhibitorDetails
Bifonazoleapproved, investigationalunknownenzymeinhibitorDetails
Buserelinapproved, investigationalunknownenzymeinducerDetails
EconazoleapprovednoenzymeinhibitorDetails
EtretinatewithdrawnunknownenzymeinhibitorDetails
Exemestaneapproved, investigationalunknownenzymeinhibitorDetails
Mefloquineapproved, investigationalunknownenzymeinhibitorDetails
Melatoninapproved, nutraceutical, vet_approvedunknownenzymeinhibitorDetails
MethadoneapprovedunknownenzymesubstrateDetails
Paclitaxelapproved, vet_approvedunknownenzymeinhibitorDetails
Raloxifeneapproved, investigationalunknownenzymeinhibitorDetails
TamoxifenapprovedunknownenzymeinhibitorDetails
TioconazoleapprovedunknownenzymeinhibitorDetails
Troglitazoneapproved, investigational, withdrawnunknownenzymeinhibitorDetails
2-MethoxyestradiolinvestigationalunknowntargetDetails
DrostanoloneillicitunknownenzymeinhibitorDetails
Edetic acidapproved, vet_approvedunknownenzymesubstrateDetails
Carbimazoleapproved, investigationalunknownenzymeinhibitorDetails
Chlorphenesinapproved, experimentalunknownenzymeinducerDetails
Chlorotrianiseneinvestigational, withdrawnunknownenzymeinducerDetails
Prasterone sulfateinvestigationalunknownenzymeinducerDetails
EndostatininvestigationalunknownenzymesubstrateDetails
Nandrolone decanoateapproved, illicitunknownenzymeinducerDetails
Sar9, Met (O2)11-Substance PinvestigationalunknownenzymeinhibitorDetails
Sulfathiazoleapproved, vet_approved, withdrawnunknownenzymeinducerDetails
NicotineapprovedunknowntargetinhibitorDetails
NorgestrelapprovedunknownenzymeinhibitorDetails
GlyphosateexperimentalunknowntargetDetails
EstroneapprovedunknowntargetDetails
NaringeninexperimentalunknowntargetinhibitorDetails
Miconazoleapproved, investigational, vet_approvedunknownenzymeinhibitorDetails
Edetate disodium anhydrousapproved, vet_approvedunknownenzymemodulatorDetails
Testosterone undecanoateapproved, investigationalunknownenzymesubstrateDetails
Testosterone enanthateapprovedunknownenzymesubstrateDetails
Testosterone cypionateapprovedunknownenzymesubstrateDetails
MethyltestosteroneapprovedunknownenzymesubstrateinducerDetails
Cyproterone acetateapproved, investigationalunknownenzymeinhibitorDetails
Ketoconazoleapproved, investigationalunknownenzymeinhibitorDetails
Edetate calcium disodium anhydrousapprovedunknownenzymemodulatorDetails
Levoketoconazoleapproved, investigationalnoenzymeinhibitorDetails
Mitapivatapproved, investigationalunknowntargetinhibitorDetails
Estradiolapproved, investigational, vet_approvedunknownenzymeproduct ofDetails
CarbendaziminvestigationalnoenzymeregulatorDetails
Androstenedioneexperimental, illicityestargetinhibitorDetails
alpha-NaphthoflavoneexperimentalyestargetinhibitorDetails
Biochanin AinvestigationalyestargetinhibitorDetails
ApigeninexperimentalyestargetinhibitorDetails
ChrysinexperimentalyestargetinhibitorDetails
BoldioneexperimentalyestargetinhibitorDetails
Flavoneapproved, experimentalyestargetinhibitorDetails
5-deoxyflavanoneexperimentalyestargetinhibitorDetails
Formestaneapproved, investigational, withdrawnyestargetinhibitorDetails
DextromethorphanapprovedyestargetinhibitorDetails
LiarozoleinvestigationalyestargetinhibitorDetails
FadrozoleinvestigationalyestargetinhibitorDetails
VorozoleexperimentalyestargetinhibitorDetails