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UniProtKB - P11511 (CP19A_HUMAN)

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Protein

Aromatase

Gene

CYP19A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

heme

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 transfer 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
    View the complete GO annotation on QuickGO ...

    GO - Biological processi

    View the complete GO annotation on QuickGO ...

    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
    R-HSA-5579030 Defective CYP19A1 causes Aromatase excess syndrome (AEXS)
    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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000137869.13
    HGNCiHGNC:2594 CYP19A1
    MIMi107910 gene
    neXtProtiNX_P11511

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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:rs80051519EnsemblClinVar.1
    Natural variantiVAR_016963375R → C in AROD. 1 PublicationCorresponds to variant dbSNP:rs121434536EnsemblClinVar.1
    Natural variantiVAR_016964435R → C in AROD; 1.1% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs121434534EnsemblClinVar.1
    Natural variantiVAR_016965437C → Y in AROD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs78310315EnsemblClinVar.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
    ProteomicsDBi52787

    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
    MINTiP11511
    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

    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

    Gene3Di1.10.630.10, 1 hit
    InterProiView protein in InterPro
    IPR001128 Cyt_P450
    IPR017972 Cyt_P450_CS
    IPR002401 Cyt_P450_E_grp-I
    IPR036396 Cyt_P450_sf
    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:rs2236722EnsemblClinVar.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:rs28757184EnsemblClinVar.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:rs700519EnsemblClinVar.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_079486314S → P Found in deaf patients; unknown pathological significance. 1 Publication1
    Natural variantiVAR_016962365R → Q in AROD; 0.4% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs80051519EnsemblClinVar.1
    Natural variantiVAR_016963375R → C in AROD. 1 PublicationCorresponds to variant dbSNP:rs121434536EnsemblClinVar.1
    Natural variantiVAR_054152375R → L1 Publication1
    Natural variantiVAR_016964435R → C in AROD; 1.1% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs121434534EnsemblClinVar.1
    Natural variantiVAR_016965437C → Y in AROD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs78310315EnsemblClinVar.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
    Hs.641200

    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: July 18, 2018
    This is version 202 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

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