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
- Functionselectron transfer activity / steroid hydroxylase activityProcessesandrogen 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
- p450 (PF00067)
- 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
Resource Link UniProtKB ID P11511 UniProtKB Entry Name CP19A_HUMAN GenBank Protein ID 179002 GenBank Gene ID M22246 GeneCard ID CYP19A1 GenAtlas ID CYP19A1 HGNC ID HGNC:2594 PDB ID(s) 3EQM, 3S79, 3S7S, 4GL5, 4GL7, 4KQ8, 5JKV, 5JKW, 5JL6, 5JL7, 5JL9 KEGG ID hsa:1588 IUPHAR/Guide To Pharmacology ID 1362 NCBI Gene ID 1588 - General References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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-Entity Type Aromatase (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Aminoglutethimide approved, investigational yes target inhibitor Details Anastrozole approved, investigational yes target inhibitor Details Exemestane approved, investigational yes target inhibitor Details Letrozole approved, investigational yes target antagonist Details Testolactone approved, investigational yes target inhibitor Details MPI-674 investigational unknown target Details Letrozole approved, investigational unknown enzyme inhibitor Details Diethylstilbestrol approved, investigational, withdrawn unknown enzyme inhibitor Details Testosterone approved, investigational unknown enzyme substrate Details Danazol approved unknown enzyme inhibitor Details Stanolone illicit, investigational unknown enzyme substrate Details Betamethasone approved, vet_approved unknown enzyme substrateinhibitor Details Bifonazole approved, investigational unknown enzyme inhibitor Details Buserelin approved, investigational unknown enzyme inducer Details Econazole approved no enzyme inhibitor Details Etretinate withdrawn unknown enzyme inhibitor Details Exemestane approved, investigational unknown enzyme inhibitor Details Mefloquine approved, investigational unknown enzyme inhibitor Details Melatonin approved, nutraceutical, vet_approved unknown enzyme inhibitor Details Methadone approved unknown enzyme substrate Details Paclitaxel approved, vet_approved unknown enzyme inhibitor Details Raloxifene approved, investigational unknown enzyme inhibitor Details Tamoxifen approved unknown enzyme inhibitor Details Tioconazole approved unknown enzyme inhibitor Details Troglitazone approved, investigational, withdrawn unknown enzyme inhibitor Details 2-Methoxyestradiol investigational unknown target Details Drostanolone illicit unknown enzyme inhibitor Details Edetic acid approved, vet_approved unknown enzyme substrate Details Carbimazole approved, investigational unknown enzyme inhibitor Details Chlorphenesin approved, experimental unknown enzyme inducer Details Chlorotrianisene investigational, withdrawn unknown enzyme inducer Details Prasterone sulfate investigational unknown enzyme inducer Details Endostatin investigational unknown enzyme substrate Details Nandrolone decanoate approved, illicit unknown enzyme inducer Details Sar9, Met (O2)11-Substance P investigational unknown enzyme inhibitor Details Sulfathiazole approved, vet_approved, withdrawn unknown enzyme inducer Details Nicotine approved unknown target inhibitor Details Norgestrel approved unknown enzyme inhibitor Details Glyphosate experimental unknown target Details Estrone approved unknown target Details Naringenin experimental unknown target inhibitor Details Miconazole approved, investigational, vet_approved unknown enzyme inhibitor Details Edetate disodium anhydrous approved, vet_approved unknown enzyme modulator Details Testosterone undecanoate approved, investigational unknown enzyme substrate Details Testosterone enanthate approved unknown enzyme substrate Details Testosterone cypionate approved unknown enzyme substrate Details Methyltestosterone approved unknown enzyme substrateinducer Details Cyproterone acetate approved, investigational unknown enzyme inhibitor Details Ketoconazole approved, investigational unknown enzyme inhibitor Details Edetate calcium disodium anhydrous approved unknown enzyme modulator Details Levoketoconazole approved, investigational no enzyme inhibitor Details Mitapivat approved, investigational unknown target inhibitor Details Estradiol approved, investigational, vet_approved unknown enzyme product of Details Carbendazim investigational no enzyme regulator Details Androstenedione experimental, illicit yes target inhibitor Details alpha-Naphthoflavone experimental yes target inhibitor Details Biochanin A investigational yes target inhibitor Details Apigenin experimental yes target inhibitor Details Chrysin experimental yes target inhibitor Details Boldione experimental yes target inhibitor Details Flavone approved, experimental yes target inhibitor Details 5-deoxyflavanone experimental yes target inhibitor Details Formestane approved, investigational, withdrawn yes target inhibitor Details Dextromethorphan approved yes target inhibitor Details Liarozole investigational yes target inhibitor Details Fadrozole investigational yes target inhibitor Details Vorozole experimental yes target inhibitor Details