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Protein

Aromatase

Gene

CYP19A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the formation of aromatic C18 estrogens from C19 androgens.

Catalytic activityi

Testosterone + 3 [reduced NADPH--hemoprotein reductase] + 3 O2 = 17-beta-estradiol + formate + 4 H2O + 3 [oxidized NADPH--hemoprotein reductase].1 Publication
Androst-4-ene-3,17-dione + 3 [reduced NADPH--hemoprotein reductase] + 3 O2 = estrone + formate + 4 H2O + 3 [oxidized NADPH--hemoprotein reductase].1 Publication

Cofactori

Kineticsi

  1. KM=0.46 µM for androstenedione1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei309Substrate1
    Binding sitei374Substrate; via amide nitrogen1
    Metal bindingi437Iron (heme axial ligand)1

    GO - Molecular functioni

    • aromatase activity Source: UniProtKB
    • electron carrier activity Source: UniProtKB
    • heme binding Source: UniProtKB
    • iron ion binding Source: InterPro
    • 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 Source: UniProtKB
    • oxygen binding Source: ProtInc
    • steroid hydroxylase activity Source: Reactome

    GO - Biological processi

    Keywordsi

    Molecular functionMonooxygenase, Oxidoreductase
    LigandHeme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06413-MONOMER.
    BRENDAi1.14.14.14. 2681.
    ReactomeiR-HSA-193144. Estrogen biosynthesis.
    R-HSA-211976. Endogenous sterols.
    SABIO-RKiP11511.
    SIGNORiP11511.

    Chemistry databases

    SwissLipidsiSLP:000001716.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aromatase (EC:1.14.14.141 Publication)
    Alternative name(s):
    CYPXIX
    Cytochrome P-450AROM
    Cytochrome P450 19A1
    Estrogen synthase
    Gene namesi
    Name:CYP19A1
    Synonyms:ARO1, CYAR, CYP19
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:2594. CYP19A1.

    Subcellular locationi

    GO - Cellular componenti

    • endoplasmic reticulum Source: LIFEdb
    • endoplasmic reticulum membrane Source: Reactome
    • membrane Source: ProtInc

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Aromatase excess syndrome (AEXS)
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females.
    See also OMIM:139300
    Aromatase deficiency (AROD)4 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries.
    See also OMIM:613546
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_072784192R → H in AROD; strongly reduced aromatase activity; 81% reduction of androstenedione metabolism compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs765057534Ensembl.1
    Natural variantiVAR_016962365R → Q in AROD; 0.4% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs80051519Ensembl.1
    Natural variantiVAR_016963375R → C in AROD. 1 PublicationCorresponds to variant dbSNP:rs121434536Ensembl.1
    Natural variantiVAR_016964435R → C in AROD; 1.1% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs121434534Ensembl.1
    Natural variantiVAR_016965437C → Y in AROD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs78310315Ensembl.1

    Keywords - Diseasei

    Disease mutation, Pseudohermaphroditism

    Organism-specific databases

    DisGeNETi1588.
    MalaCardsiCYP19A1.
    MIMi139300. phenotype.
    613546. phenotype.
    OpenTargetsiENSG00000137869.
    Orphaneti91. Aromatase deficiency.
    178345. Aromatase excess syndrome.
    PharmGKBiPA27091.

    Chemistry databases

    ChEMBLiCHEMBL1978.
    DrugBankiDB02342. 2-Methoxyestradiol.
    DB00357. Aminoglutethimide.
    DB01217. Anastrozole.
    DB05338. atamestane-plus-toremifene.
    DB00443. Betamethasone.
    DB04794. Bifonazole.
    DB06719. Buserelin.
    DB00389. Carbimazole.
    DB00269. Chlorotrianisene.
    DB00856. Chlorphenesin.
    DB00882. Clomifene.
    DB00257. Clotrimazole.
    DB04839. Cyproterone acetate.
    DB01406. Danazol.
    DB05804. dehydroepiandrosterone sulfate.
    DB01234. Dexamethasone.
    DB00255. Diethylstilbestrol.
    DB02901. Dihydrotestosterone.
    DB00917. Dinoprostone.
    DB00858. Drostanolone.
    DB01127. Econazole.
    DB00974. Edetic Acid.
    DB00292. Etomidate.
    DB00926. Etretinate.
    DB00990. Exemestane.
    DB01026. Ketoconazole.
    DB01006. Letrozole.
    DB01227. Levomethadyl Acetate.
    DB00367. Levonorgestrel.
    DB00358. Mefloquine.
    DB01065. Melatonin.
    DB00333. Methadone.
    DB06710. Methyltestosterone.
    DB01110. Miconazole.
    DB05749. MPI-674.
    DB08804. Nandrolone decanoate.
    DB00984. Nandrolone phenpropionate.
    DB00184. Nicotine.
    DB09389. Norgestrel.
    DB01229. Paclitaxel.
    DB00481. Raloxifene.
    DB05875. substance P.
    DB06147. Sulfathiazole.
    DB00675. Tamoxifen.
    DB00857. Terbinafine.
    DB00894. Testolactone.
    DB00624. Testosterone.
    DB01007. Tioconazole.
    DB00072. Trastuzumab.
    DB00197. Troglitazone.
    GuidetoPHARMACOLOGYi1362.

    Polymorphism and mutation databases

    BioMutaiCYP19A1.
    DMDMi117293.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000519551 – 503AromataseAdd BLAST503

    Post-translational modificationi

    Phosphorylated in vitro by PKA and PKG/PRKG1. These phosphorylations inhibit the catalytic activity as measured by estrone synthesis from androstenedione (36% decrease for PKA and 30% for PKG/PRKG1).1 Publication

    Proteomic databases

    PaxDbiP11511.
    PeptideAtlasiP11511.
    PRIDEiP11511.

    PTM databases

    iPTMnetiP11511.
    PhosphoSitePlusiP11511.

    Expressioni

    Tissue specificityi

    Widely expressed, including in adult and fetal brain, placenta, skin fibroblasts, adipose tissue and gonads.4 Publications

    Gene expression databases

    BgeeiENSG00000137869.
    CleanExiHS_CYP19A1.
    ExpressionAtlasiP11511. baseline and differential.
    GenevisibleiP11511. HS.

    Organism-specific databases

    HPAiCAB000355.
    HPA051194.

    Interactioni

    Protein-protein interaction databases

    BioGridi107960. 7 interactors.
    IntActiP11511. 1 interactor.
    MINTiMINT-4054553.
    STRINGi9606.ENSP00000260433.

    Chemistry databases

    BindingDBiP11511.

    Structurei

    Secondary structure

    1503
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi54 – 56Combined sources3
    Helixi57 – 68Combined sources12
    Helixi70 – 80Combined sources11
    Beta strandi83 – 97Combined sources15
    Helixi100 – 108Combined sources9
    Helixi110 – 112Combined sources3
    Helixi119 – 125Combined sources7
    Beta strandi130 – 132Combined sources3
    Helixi138 – 151Combined sources14
    Helixi155 – 172Combined sources18
    Helixi173 – 177Combined sources5
    Beta strandi183 – 185Combined sources3
    Helixi187 – 203Combined sources17
    Helixi210 – 227Combined sources18
    Helixi232 – 236Combined sources5
    Helixi238 – 240Combined sources3
    Helixi242 – 267Combined sources26
    Turni270 – 275Combined sources6
    Helixi278 – 287Combined sources10
    Turni288 – 290Combined sources3
    Helixi293 – 324Combined sources32
    Helixi326 – 339Combined sources14
    Turni340 – 342Combined sources3
    Helixi347 – 349Combined sources3
    Turni350 – 352Combined sources3
    Helixi354 – 366Combined sources13
    Beta strandi373 – 376Combined sources4
    Beta strandi381 – 383Combined sources3
    Beta strandi386 – 388Combined sources3
    Beta strandi393 – 396Combined sources4
    Helixi398 – 401Combined sources4
    Turni402 – 404Combined sources3
    Helixi415 – 418Combined sources4
    Turni424 – 426Combined sources3
    Helixi433 – 435Combined sources3
    Helixi440 – 455Combined sources16
    Beta strandi458 – 463Combined sources6
    Turni468 – 470Combined sources3
    Beta strandi473 – 481Combined sources9
    Beta strandi483 – 485Combined sources3
    Beta strandi490 – 494Combined sources5

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1TQAmodel-A53-495[»]
    3EQMX-ray2.90A1-503[»]
    3S79X-ray2.75A1-503[»]
    3S7SX-ray3.21A1-503[»]
    4GL5X-ray3.48A1-503[»]
    4GL7X-ray3.90A1-503[»]
    4KQ8X-ray3.29A45-503[»]
    5JKVX-ray2.75A1-503[»]
    5JKWX-ray3.00A1-503[»]
    5JL6X-ray3.00A1-503[»]
    5JL7X-ray3.10A1-503[»]
    5JL9X-ray3.10A1-503[»]
    ProteinModelPortaliP11511.
    SMRiP11511.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11511.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiKOG0157. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00840000129915.
    HOGENOMiHOG000111912.
    HOVERGENiHBG050750.
    InParanoidiP11511.
    KOiK07434.
    OMAiMRRIMLD.
    OrthoDBiEOG091G056R.
    PhylomeDBiP11511.
    TreeFamiTF352039.

    Family and domain databases

    InterProiView protein in InterPro
    IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    PfamiView protein in Pfam
    PF00067. p450. 1 hit.
    PRINTSiPR00463. EP450I.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiView protein in PROSITE
    PS00086. CYTOCHROME_P450. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P11511-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MVLEMLNPIH YNITSIVPEA MPAATMPVLL LTGLFLLVWN YEGTSSIPGP
    60 70 80 90 100
    GYCMGIGPLI SHGRFLWMGI GSACNYYNRV YGEFMRVWIS GEETLIISKS
    110 120 130 140 150
    SSMFHIMKHN HYSSRFGSKL GLQCIGMHEK GIIFNNNPEL WKTTRPFFMK
    160 170 180 190 200
    ALSGPGLVRM VTVCAESLKT HLDRLEEVTN ESGYVDVLTL LRRVMLDTSN
    210 220 230 240 250
    TLFLRIPLDE SAIVVKIQGY FDAWQALLIK PDIFFKISWL YKKYEKSVKD
    260 270 280 290 300
    LKDAIEVLIA EKRRRISTEE KLEECMDFAT ELILAEKRGD LTRENVNQCI
    310 320 330 340 350
    LEMLIAAPDT MSVSLFFMLF LIAKHPNVEE AIIKEIQTVI GERDIKIDDI
    360 370 380 390 400
    QKLKVMENFI YESMRYQPVV DLVMRKALED DVIDGYPVKK GTNIILNIGR
    410 420 430 440 450
    MHRLEFFPKP NEFTLENFAK NVPYRYFQPF GFGPRGCAGK YIAMVMMKAI
    460 470 480 490 500
    LVTLLRRFHV KTLQGQCVES IQKIHDLSLH PDETKNMLEM IFTPRNSDRC

    LEH
    Length:503
    Mass (Da):57,883
    Last modified:January 23, 2007 - v3
    Checksum:i9BD9B28651D9A69A
    GO
    Isoform 2 (identifier: P11511-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         210-218: ESAIVVKIQ → GTEIFTLTS
         219-503: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:218
    Mass (Da):24,518
    Checksum:i9C15EFD1B411087C
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti496N → S in AAA35557 (PubMed:2973313).Curated1
    Sequence conflicti496N → S in CAA31929 (PubMed:2973313).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02342839W → R2 PublicationsCorresponds to variant dbSNP:rs2236722Ensembl.1
    Natural variantiVAR_072784192R → H in AROD; strongly reduced aromatase activity; 81% reduction of androstenedione metabolism compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs765057534Ensembl.1
    Natural variantiVAR_023429201T → M2 PublicationsCorresponds to variant dbSNP:rs28757184Ensembl.1
    Natural variantiVAR_018406264R → C 1.6 fold decrease in affinity for androstenedione substrate; slightly affects PKA-mediated reduction in catalytic activity as measured in vitro by estrone synthesis from androstenedione (49% decrease compared with 36% for the wild-type protein); no effect on PKG/PRKG1-mediated reduction in catalytic activity in vitro. 6 PublicationsCorresponds to variant dbSNP:rs700519Ensembl.1
    Natural variantiVAR_077526264R → H 2.5 fold decrease in affinity for androstenedione substrate; slightly affects PKA-mediated reduction in catalytic activity as measured by estrone synthesis from androstenedione in vitro (28% decrease compared with 36% for the wild-type protein) and PKG/PRKG1-mediated reduction in catalytic activity in vitro (15% decrease compared with 30% for the wild-type protein). 1 PublicationCorresponds to variant dbSNP:rs2304462Ensembl.1
    Natural variantiVAR_016962365R → Q in AROD; 0.4% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs80051519Ensembl.1
    Natural variantiVAR_016963375R → C in AROD. 1 PublicationCorresponds to variant dbSNP:rs121434536Ensembl.1
    Natural variantiVAR_054152375R → L1 Publication1
    Natural variantiVAR_016964435R → C in AROD; 1.1% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs121434534Ensembl.1
    Natural variantiVAR_016965437C → Y in AROD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs78310315Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_055583210 – 218ESAIVVKIQ → GTEIFTLTS in isoform 2. 1 Publication9
    Alternative sequenceiVSP_055584219 – 503Missing in isoform 2. 1 PublicationAdd BLAST285

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M22246 mRNA. Translation: AAA35557.1.
    X13589 mRNA. Translation: CAA31929.1.
    M18856 mRNA. Translation: AAA35556.1.
    J04127 mRNA. Translation: AAA52132.1.
    Y07508 mRNA. Translation: CAA68807.1.
    M30804
    , M30796, M30797, M30798, M30800, M30801, M30802, M30803 Genomic DNA. Translation: AAA35728.1.
    AY957953 Genomic DNA. Translation: AAX44046.1.
    AC012169 Genomic DNA. No translation available.
    AC020891 Genomic DNA. No translation available.
    BC035714 mRNA. Translation: AAH35714.1.
    BC107785 mRNA. Translation: AAI07786.1.
    M28420 mRNA. Translation: AAA52141.1.
    CCDSiCCDS10139.1. [P11511-1]
    PIRiA34451. O4HU19.
    RefSeqiNP_000094.2. NM_000103.3. [P11511-1]
    NP_001334177.1. NM_001347248.1. [P11511-1]
    NP_001334178.1. NM_001347249.1. [P11511-1]
    NP_001334179.1. NM_001347250.1. [P11511-1]
    NP_001334180.1. NM_001347251.1. [P11511-1]
    NP_001334181.1. NM_001347252.1. [P11511-1]
    NP_001334182.1. NM_001347253.1. [P11511-1]
    NP_001334183.1. NM_001347254.1. [P11511-1]
    NP_001334184.1. NM_001347255.1. [P11511-1]
    NP_001334185.1. NM_001347256.1. [P11511-1]
    NP_112503.1. NM_031226.2. [P11511-1]
    UniGeneiHs.260074.

    Genome annotation databases

    EnsembliENST00000396402; ENSP00000379683; ENSG00000137869. [P11511-1]
    ENST00000396404; ENSP00000379685; ENSG00000137869. [P11511-1]
    ENST00000405913; ENSP00000383930; ENSG00000137869. [P11511-2]
    ENST00000557858; ENSP00000452627; ENSG00000137869. [P11511-2]
    ENST00000559878; ENSP00000453149; ENSG00000137869. [P11511-1]
    GeneIDi1588.
    KEGGihsa:1588.
    UCSCiuc001zyz.5. human. [P11511-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiCP19A_HUMAN
    AccessioniPrimary (citable) accession number: P11511
    Secondary accession number(s): Q16731
    , Q3B764, Q58FA0, Q8IYJ7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: January 23, 2007
    Last modified: August 30, 2017
    This is version 195 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families