Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol CYP19A1 contributors: mct/npt - updated : 22-05-2010
HGNC name cytochrome P450, family 19, subfamily A, polypeptide 1
HGNC id 2594
DNA
TYPE functioning gene
SPECIAL FEATURE opposite orientation
text opposite orientation with TMOD3 and KIAA1749
STRUCTURE 130.54 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • tissue-specific promoter : an endothelial promoter, GATA-2-regulated , immediately upstream of exon I.7 and mapped to about 36 kb upstream of ATG translation start site, increasing estrogen biosynthesis in vascular endothelial cells of breast cancer and modulating intracrine and paracrine effects of estrogen on blood vessels
  • partially tissue-specific promoters used in the gonads, bone, brain, vascular tissue, adipose tissue, skin, fetal liver and placenta for physiologic estrogen biosynthesis
  • 30 kb 3' end of this gene contains nine exons (II-X), which encode the aromatase protein
  • ATG translation initiation site is located 38 bp downstream of a common splice acceptor site in coding exon II
  • base pair changes in physiological promoters gene may increase the enhancer activity of the regulatory sequences
  • promoter I.3 is one of the major promoters that control the expression of aromatase in breast cancer tissue, interacting with SNAI1 (Okubo 2001)
  • important role of the alternative exons 1 in posttranscriptional regulation of aromatase gene expression (Wang 2009)
    • MAPPING cloned Y linked N status confirmed
    Map Cen - CYP19 - DMXL2 - TMOD3 - MAPK6 - CGNL1 - TLN2 - qter
    Authors Demura (2007)
    RNA
    TRANSCRIPTS type messenger
    text multiple tissue-specific promoters, which result in the production of various mRNA transcripts that contain an alternative noncoding exon 1 followed by a common protein-coding region (Wang 2009)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 4422 - 503 ovarian specific Simpson, Harada (1992)
    lack exon 2a
    11 - 4531 57.8 503 ovarian specific Simpson, Harada (1992)
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainlimbic systemhippocampus highly
    Reproductivefemale systemovary   
     female systemplacenta   
     male systemtestis   
    Skin/Tegumentskin    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    Nervouspyramidal cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • juxtaposition of the hydrophobic N-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site (Ghosh 2009)
    • conjugated HemoP
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to murine Cyp19
    Homologene
    FAMILY
  • cytochrome P450 subfamily XIX
  • multigenic cytochrome P450 superfamily of mixed-function monooxygenases
    • CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    basic FUNCTION
  • catalyzes the conversion of androgens to estrogens through a sequential three-step reaction, generating 19-hydroxy and 19-aldehyde intermediates en route to the product estrogen (Sohl 2010)
  • catalyzing the last steps of estrogen biosynthesis, three successive hydroxylations of the A ring of androgens
  • plays a crucial role in the endocrine and paracrine biosynthesis of estrogens from androgens in many diverse estrogen-responsive tissues
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism hormone
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
  • NADPH, heme
    • protein
  • flavoprotein P450 oxidoreductase (POR)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AROD , AROE
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    four promoters (II, I.3, I.7 and I.4) markedly increasing total expression in breast cancer
    Susceptibility
  • endometrial cancer development (A6 and A7 allele over represented)
  • to bone mineral density variability in men
  • to breast cancer
    • Variant & Polymorphism SNP , insertion/deletion
  • associations for five SNPs with age at menarche in Caucasian females
  • common haplotype of aromatase associated with gene expression is also associated with the risk of osteoporotic vertebral fractures in postmenopausal women
  • polymorphism associated with femoral neck bone mineral density in men
  • 3-bp I/D polymorphisms of the CYP19A1 gene may be associated with breast cancer in Korean women (Kim 2009)
    • Candidate gene
    Marker
    Therapy target important target in endocrine therapy for estrogen receptor (ER)-positive postmenopausal breast cancer (Wang 2009)
    ANIMAL & CELL MODELS