Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P11511 (CP19A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aromatase

EC=1.14.14.14
Alternative name(s):
CYPXIX
Cytochrome P-450AROM
Cytochrome P450 19A1
Estrogen synthase
Gene names
Name:CYP19A1
Synonyms:ARO1, CYAR, CYP19
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the formation of aromatic C18 estrogens from C19 androgens.

Catalytic activity

Testosterone + 3 O2 + 3 reduced flavoproteins = 17-beta-estradiol + formate + 4 H2O + 3 oxidized flavoproteins.

Androst-4-ene-3,17-dione + 3 O2 + 3 reduced flavoproteins = estrone + formate + 4 H2O + 3 oxidized flavoproteins.

Cofactor

Heme group.

Subcellular location

Membrane; Peripheral membrane protein.

Tissue specificity

Brain, placenta and gonads. Ref.10 Ref.12 Ref.13 Ref.15

Involvement in disease

Aromatase excess syndrome (AEXS) [MIM:139300]: An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Aromatase deficiency (AROD) [MIM:613546]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.18 Ref.19

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Pseudohermaphroditism
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processandrogen metabolic process

Inferred from electronic annotation. Source: Ensembl

estrogen biosynthetic process

Traceable author statement. Source: Reactome

prostate gland growth

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid biosynthetic process

Traceable author statement Ref.3. Source: ProtInc

steroid metabolic process

Traceable author statement. Source: Reactome

sterol metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum

Inferred from direct assay. Source: LIFEdb

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

membrane

Traceable author statement Ref.3. Source: ProtInc

   Molecular_functionaromatase activity

Inferred from direct assay Ref.16. Source: UniProtKB

electron carrier activity

Traceable author statement Ref.3. Source: UniProtKB

heme binding

Inferred from direct assay Ref.16. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. 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

Traceable author statement Ref.7. Source: UniProtKB

oxygen binding

Traceable author statement Ref.3. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 503503Aromatase
PRO_0000051955

Sites

Metal binding4371Iron (heme axial ligand)
Binding site3091Substrate
Binding site3741Substrate; via amide nitrogen

Natural variations

Natural variant391W → R. Ref.8
Corresponds to variant rs2236722 [ dbSNP | Ensembl ].
VAR_023428
Natural variant2011T → M. Ref.8 Ref.9
Corresponds to variant rs28757184 [ dbSNP | Ensembl ].
VAR_023429
Natural variant2641R → C. Ref.3 Ref.8 Ref.11
Corresponds to variant rs700519 [ dbSNP | Ensembl ].
VAR_018406
Natural variant3651R → Q in AROD; 0.4% of wild-type activity. Ref.19
VAR_016962
Natural variant3751R → C in AROD. Ref.18
VAR_016963
Natural variant3751R → L. Ref.20
VAR_054152
Natural variant4351R → C in AROD; 1.1% of wild-type activity. Ref.17
VAR_016964
Natural variant4371C → Y in AROD; complete loss of activity. Ref.17
VAR_016965

Experimental info

Sequence conflict4961N → S in AAA35557. Ref.1
Sequence conflict4961N → S in CAA31929. Ref.1

Secondary structure

............................................................................. 503
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11511 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 9BD9B28651D9A69A

FASTA50357,883
        10         20         30         40         50         60 
MVLEMLNPIH YNITSIVPEA MPAATMPVLL LTGLFLLVWN YEGTSSIPGP GYCMGIGPLI 

        70         80         90        100        110        120 
SHGRFLWMGI GSACNYYNRV YGEFMRVWIS GEETLIISKS SSMFHIMKHN HYSSRFGSKL 

       130        140        150        160        170        180 
GLQCIGMHEK GIIFNNNPEL WKTTRPFFMK ALSGPGLVRM VTVCAESLKT HLDRLEEVTN 

       190        200        210        220        230        240 
ESGYVDVLTL LRRVMLDTSN TLFLRIPLDE SAIVVKIQGY FDAWQALLIK PDIFFKISWL 

       250        260        270        280        290        300 
YKKYEKSVKD LKDAIEVLIA EKRRRISTEE KLEECMDFAT ELILAEKRGD LTRENVNQCI 

       310        320        330        340        350        360 
LEMLIAAPDT MSVSLFFMLF LIAKHPNVEE AIIKEIQTVI GERDIKIDDI QKLKVMENFI 

       370        380        390        400        410        420 
YESMRYQPVV DLVMRKALED DVIDGYPVKK GTNIILNIGR MHRLEFFPKP NEFTLENFAK 

       430        440        450        460        470        480 
NVPYRYFQPF GFGPRGCAGK YIAMVMMKAI LVTLLRRFHV KTLQGQCVES IQKIHDLSLH 

       490        500 
PDETKNMLEM IFTPRNSDRC LEH 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of a complete cDNA encoding human aromatase: immunochemical identification and sequence analysis."
Harada N.
Biochem. Biophys. Res. Commun. 156:725-732(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]"Human aromatase: cDNA cloning, Southern blot analysis, and assignment of the gene to chromosome 15."
Chen S., Besman M.J., Sparkes R.S., Zollman S., Klisak I., Mohandas T., Hall P.F., Shively J.E.
DNA 7:27-38(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells."
Corbin C.J., Graham-Lorence S., McPhaul M., Mason J.I., Mendelson C.R., Simpson E.R.
Proc. Natl. Acad. Sci. U.S.A. 85:8948-8952(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CYS-264.
[4]"Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P-450."
Toda K., Terashima M., Mitsuuchi Y., Yamasaki Y., Yokoyama Y., Nojima S., Ushiro H., Maeda T., Yamamoto Y., Sagara Y., Shizuta Y.
FEBS Lett. 247:371-376(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[5]"Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis."
Means G.D., Mahendroo M.S., Corbin C.J., Mathis J.M., Powell F.E., Mendelson C.R., Simpson E.R.
J. Biol. Chem. 264:19385-19391(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Expression of human placental aromatase in Saccharomyces cerevisiae."
Pompon D., Liu R.Y., Besman M.J., Wang P.L., Shively J.E., Chen S.
Mol. Endocrinol. 3:1477-1487(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[7]"Biochemical and molecular genetic analyses on placental aromatase (P-450AROM) deficiency."
Harada N., Ogawa H., Shozu M., Yamada K., Suhara K., Nishida E., Takagi Y.
J. Biol. Chem. 267:4781-4785(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]NIEHS SNPs program
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-39; MET-201 AND CYS-264.
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-201.
Tissue: Placenta.
[10]"Isolation and characterization of a complementary DNA specific for human aromatase-system cytochrome P-450 mRNA."
Evans C.T., Ledesma D.B., Schulz T.Z., Simpson E.R., Mendelson C.R.
Proc. Natl. Acad. Sci. U.S.A. 83:6387-6391(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-503, TISSUE SPECIFICITY.
Tissue: Placenta.
[11]"Sequencing of cDNA inserts encoding aromatase cytochrome P-450 (P-450AROM)."
Simpson E.R., Evans C.T., Corbin C.J., Powell F.E., Ledesma D.B., Mendelson C.R.
Mol. Cell. Endocrinol. 52:267-272(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-503, VARIANT CYS-264.
[12]"Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta."
Mahendroo M.S., Means G.D., Mendelson C.R., Simpson E.R.
J. Biol. Chem. 266:11276-11281(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49, TISSUE SPECIFICITY.
[13]"Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue."
Mahendroo M.S., Mendelson C.R., Simpson E.R.
J. Biol. Chem. 268:19463-19470(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49, TISSUE SPECIFICITY, ALTERNATIVE PROMOTER USAGE.
[14]"Amino terminal sequence analysis of human placenta aromatase."
Chen S., Shively J.E., Nakajin S., Shinoda M., Hall P.F.
Biochem. Biophys. Res. Commun. 135:713-719(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PRELIMINARY PROTEIN SEQUENCE OF N-TERMINUS.
Tissue: Placenta.
[15]"Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain."
Honda S., Harada N., Takagi Y.
Biochem. Biophys. Res. Commun. 198:1153-1160(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE PROMOTER USAGE, TISSUE SPECIFICITY.
[16]"Structural basis for androgen specificity and oestrogen synthesis in human aromatase."
Ghosh D., Griswold J., Erman M., Pangborn W.
Nature 457:219-223(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH ANDROSTENEDIONE, HEME.
[17]"Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries."
Ito Y., Fisher C.R., Conte F.A., Grumbach M.M., Simpson E.R.
Proc. Natl. Acad. Sci. U.S.A. 90:11673-11677(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AROD CYS-435 AND TYR-437.
[18]"Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens."
Morishima A., Grumbach M.M., Simpson E.R., Fisher C., Qin K.
J. Clin. Endocrinol. Metab. 80:3689-3698(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AROD CYS-375.
[19]"Effect of testosterone and estradiol in a man with aromatase deficiency."
Carani C., Qin K., Simoni M., Faustini-Fustini M., Serpente S., Boyd J., Korach K.S., Simpson E.R.
N. Engl. J. Med. 337:91-95(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AROD GLN-365.
[20]"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome."
Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. expand/collapse author list , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K.
Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-375.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , M30796, M30797, M30798, M30800, M30801, M30802, M30803 Genomic DNA. Translation: AAA35728.1.
AY957953 Genomic DNA. Translation: AAX44046.1.
BC107785 mRNA. Translation: AAI07786.1.
M28420 mRNA. Translation: AAA52141.1.
PIRO4HU19. A34451.
RefSeqNP_000094.2. NM_000103.3.
NP_112503.1. NM_031226.2.
XP_005254247.1. XM_005254190.1.
XP_005254248.1. XM_005254191.1.
UniGeneHs.260074.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP11511.
SMRP11511. Positions 45-496.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP11511. 1 interaction.
MINTMINT-4054553.
STRING9606.ENSP00000260433.

Chemistry

BindingDBP11511.
ChEMBLCHEMBL1978.
DrugBankDB00357. Aminoglutethimide.
DB01217. Anastrozole.
DB00286. Conjugated Estrogens.
DB01406. Danazol.
DB00255. Diethylstilbestrol.
DB00990. Exemestane.
DB01006. Letrozole.
DB00894. Testolactone.
DB00624. Testosterone.

PTM databases

PhosphoSiteP11511.

Polymorphism databases

DMDM117293.

Proteomic databases

PaxDbP11511.
PRIDEP11511.

Protocols and materials databases

DNASU1588.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260433; ENSP00000260433; ENSG00000137869.
ENST00000396402; ENSP00000379683; ENSG00000137869.
ENST00000396404; ENSP00000379685; ENSG00000137869.
ENST00000559878; ENSP00000453149; ENSG00000137869.
GeneID1588.
KEGGhsa:1588.
UCSCuc001zyz.4. human.

Organism-specific databases

CTD1588.
GeneCardsGC15M051500.
HGNCHGNC:2594. CYP19A1.
HPACAB000355.
HPA051194.
MIM107910. gene.
139300. phenotype.
613546. phenotype.
neXtProtNX_P11511.
Orphanet91. Aromatase deficiency.
178345. Aromatase excess syndrome.
PharmGKBPA27091.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000111912.
HOVERGENHBG050750.
InParanoidP11511.
KOK07434.
OMAMRRIMLD.
OrthoDBEOG7D85W5.
PhylomeDBP11511.
TreeFamTF352039.

Enzyme and pathway databases

BioCycMetaCyc:HS06413-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
SABIO-RKP11511.

Gene expression databases

ArrayExpressP11511.
BgeeP11511.
CleanExHS_CYP19A1.
GenevestigatorP11511.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYP19A1. human.
EvolutionaryTraceP11511.
GeneWikiAromatase.
GenomeRNAi1588.
NextBio6526.
PROP11511.
SOURCESearch...

Entry information

Entry nameCP19A_HUMAN
AccessionPrimary (citable) accession number: P11511
Secondary accession number(s): Q16731, Q3B764, Q58FA0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 160 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM