CYP19A1

Protein identityUniProt · HPA

UniProt accession

P11511

Gene

CYP19A1

Ensembl

ENSG00000137869

Chromosome

15

Canonical length

503 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and catalyzes the last steps of estrogen biosynthesis. Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

Canonical amino-acid sequenceUniProt

503 residues, UniProt reviewed canonical sequence.

>P11511|CYP19A1
     1  MVLEMLNPIH YNITSIVPEA MPAATMPVLL LTGLFLLVWN YEGTSSIPGP GYCMGIGPLI
    61  SHGRFLWMGI GSACNYYNRV YGEFMRVWIS GEETLIISKS SSMFHIMKHN HYSSRFGSKL
   121  GLQCIGMHEK GIIFNNNPEL WKTTRPFFMK ALSGPGLVRM VTVCAESLKT HLDRLEEVTN
   181  ESGYVDVLTL LRRVMLDTSN TLFLRIPLDE SAIVVKIQGY FDAWQALLIK PDIFFKISWL
   241  YKKYEKSVKD LKDAIEVLIA EKRRRISTEE KLEECMDFAT ELILAEKRGD LTRENVNQCI
   301  LEMLIAAPDT MSVSLFFMLF LIAKHPNVEE AIIKEIQTVI GERDIKIDDI QKLKVMENFI
   361  YESMRYQPVV DLVMRKALED DVIDGYPVKK GTNIILNIGR MHRLEFFPKP NEFTLENFAK
   421  NVPYRYFQPF GFGPRGCAGK YIAMVMMKAI LVTLLRRFHV KTLQGQCVES IQKIHDLSLH
   481  PDETKNMLEM IFTPRNSDRC LEH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYP19A1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

2

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

117 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYP19A1.

Disease | AllUniProt

Conditions CYP19A1 is implicated in, by any mechanism.

• Aromatase excess syndrome (AEXS) MIM:139300
• Aromatase deficiency (AROD) MIM:613546

Disease | GeneticClinVar

85 pathogenic / likely-pathogenic of 572 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aromatase deficiency
• Aromatase excess syndrome

Disease | ImmuneIEDB

Conditions an epitope on CYP19A1 was assayed in.

• breast cancer T cell

ReferencesPubMed · IEDB

Publications for CYP19A1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.88

gnomAD pLI

0

gnomAD missense Z

0.54

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• androgen catabolic process
• estrogen biosynthetic process
• female genitalia development
• female gonad development
• mammary gland development
• negative regulation of chronic inflammatory response
• negative regulation of macrophage chemotaxis
• positive regulation of estradiol secretion
• prostate gland growth
• response to estradiol
• steroid biosynthetic process
• sterol metabolic process
• syncytium formation
• testosterone biosynthetic process
• uterus development

Molecular functions

• aromatase activity
• electron transfer activity
• estrogen 2-hydroxylase activity
• heme binding
• iron ion binding
• 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
• oxygen binding
• steroid hydroxylase activity

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum membrane
• membrane

Protein domainsUniProt · Pfam · InterPro

• Cytochrome P450
• Cytochrome P450, E-class, group I
• Cytochrome P450, conserved site
• Cytochrome P450 superfamily
• Cytochrome P450 Monooxygenases
• Cytochrome P450

KeywordsUniProt

• Endoplasmic reticulum
• Heme
• Iron
• Lipid metabolism
• Membrane
• Metal-binding
• Microsome
• Monooxygenase
• Oxidoreductase
• Pseudohermaphroditism
• Transmembrane
• Transmembrane helix