Aromatase

UniProt P11511 Organism Homo sapiens Gene ARO1, CYAR, CYP19, CYP19A1 EC 1.14.14.14

Also known as: ARO1, CYAR, CYP19, CYP19A1

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. 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. 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. Also displays 2-hydroxylase activity toward estrone. 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).

Classification

Family (Pfam): PF00067 p450
InterPro: Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf, Cytochrome_P450_Monoox
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 11

3EQM X-ray 2.90A
3S79 X-ray 2.75A
3S7S X-ray 3.21A
4GL5 X-ray 3.48A
4GL7 X-ray 3.90A
4KQ8 X-ray 3.29A
5JKV X-ray 2.75A
5JKW X-ray 3.00A
5JL6 X-ray 3.00A
5JL7 X-ray 3.10A
5JL9 X-ray 3.10A

A predicted model is available from AlphaFold.

Gene Ontology · 19

Disease associations

aromatase excess syndrome MONDO:0007690
aromatase deficiency MONDO:0013301

Drugs targeting this protein · 6

EXEMESTANE inhibitor
ANASTROZOLE inhibitor
LETROZOLE inhibitor
TESTOLACTONE inhibitor
FADROZOLE HYDROCHLORIDE inhibitor
AMINOGLUTETHIMIDE inhibitor

Neighborhood · nearest proteins

Nearest neighbours of Aromatase: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

DmX-like protein 2 1 shared papers
Cytochrome P450 3A4 1 shared papers
DmX-like protein 2 1 shared papers
AP-4 complex subunit epsilon-1 1 shared papers
Dihydropyrimidine dehydrogenase [NADP(+)] 1 shared papers
Histone-lysine N-methyltransferase, H3 lysine-36 specific 1 shared papers
Adhesion G protein-coupled receptor A1 1 shared papers
Myosin-1 1 shared papers
Disks large homolog 5 1 shared papers
Collagen alpha-1(XVIII) chain 1 shared papers
Receptor-type tyrosine-protein phosphatase T 1 shared papers
Cadherin-related family member 2 1 shared papers

Literature · 27 cited papers

Impact of R264C and R264H polymorphisms in human aromatase function. J. Steroid Biochem. Mol. Biol. · 2017
A dominant variant in DMXL2 is linked to nonsyndromic hearing loss. Genet. Med. · 2017
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
Oxidation of dihydrotestosterone by human cytochromes P450 19A1 and 3A4. J. Biol. Chem. · 2012
Kinetic analysis of the three-step steroid aromatase reaction of human cytochrome P450 19A1. J. Biol. Chem. · 2010
Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature · 2009
DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature · 2008
Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Breast cancer risk associated with polymorphism in CYP19 in Japanese women. Int. J. Cancer · 2000
Arginine-cysteine polymorphism at codon 264 of the human CYP19 gene does not affect aromatase activity. Pharmacogenetics · 1997
Effect of testosterone and estradiol in a man with aromatase deficiency. N. Engl. J. Med. · 1997
… and 15 more in the literature graph

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