Protein:CYP19A1 |
Protein Summary |
 Gene summary |
| Gene name: CYP19A1 | ASpdb.0 ID: 1588 | Gene | Gene symbol | CYP19A1 | Gene ID | 1588 |
| Gene name | cytochrome P450 family 19 subfamily A member 1 |
| Synonyms | ARO|ARO1|CPV1|CYAR|CYP19|CYPXIX|P-450AROM |
| Cytomap | 15q21.2 |
| Type of gene | protein-coding |
| Description | aromatasecytochrome P-450AROMcytochrome P450 19A1cytochrome P450, family 19, subfamily A, polypeptide 1cytochrome P450, subfamily XIX (aromatization of androgens)estrogen synthaseestrogen synthetaseflavoprotein-linked monooxygenasemicrosomal monoo |
| Modification date | 20240411 |
| UniProtAcc | P11511 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CYP19A1 | GO:0005783 | endoplasmic reticulum | - |
| Gene | CYP19A1 | GO:0006710 | androgen catabolic process | 26482249 |
| Gene | CYP19A1 | GO:0020037 | heme binding | 19129847 |
| Gene | CYP19A1 | GO:0070330 | aromatase activity | 19129847|26482249 |
| Gene | CYP19A1 | GO:2000866 | positive regulation of estradiol secretion | 26482249 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P11511-1 | P11511-1_3s79_A.pdb | 3S79 | X-ray | 2.75 | A | 45 | 496 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P11511 | CYP19A1 | P11511-1 | P11511-2 | 503 | 218 | 210 | 218 | Substitution | ESAIVVKIQ | GTEIFTLTS | 210 | 218 |
| P11511 | CYP19A1 | P11511-1 | P11511-2 | 503 | 218 | 219 | 503 | Deletion | none | none | 218 | 218 |
| Multiple sequence alignment of our canonical and alternatively spliced CYP19A1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CYP19A1 |
| UniProt-id | ENSG | ENST | ENSP |
| P11511-1 | ENSG00000137869.16 | ENST00000396402.6 | ENSP00000379683.1 |
| P11511-1 | ENSG00000137869.16 | ENST00000396404.8 | ENSP00000379685.4 |
| P11511-1 | ENSG00000137869.16 | ENST00000559878.5 | ENSP00000453149.1 |
| P11511-2 | ENSG00000137869.16 | ENST00000405913.7 | ENSP00000383930.3 |
| P11511-2 | ENSG00000137869.16 | ENST00000557858.5 | ENSP00000452627.1 |
| UniProt-id | NM ID | NP ID |
| P11511-1 | NM_000103.3 | NP_000094.2 |
| P11511-1 | NM_001347248.1 | NP_001334177.1 |
| P11511-1 | NM_001347249.1 | NP_001334178.1 |
| P11511-1 | NM_001347250.1 | NP_001334179.1 |
| P11511-1 | NM_001347251.1 | NP_001334180.1 |
| P11511-1 | NM_001347252.1 | NP_001334181.1 |
| P11511-1 | NM_001347253.1 | NP_001334182.1 |
| P11511-1 | NM_001347254.1 | NP_001334183.1 |
| P11511-1 | NM_001347255.1 | NP_001334184.1 |
| P11511-1 | NM_001347256.1 | NP_001334185.1 |
| P11511-1 | NM_031226.2 | NP_112503.1 |
| Amino acid sequences of our canonical and alternatively spliced CYP19A1 |
| accession_id | Protein sequence |
| P11511-1 | MVLEMLNPIHYNITSIVPEAMPAATMPVLLLTGLFLLVWNYEGTSSIPGPGYCMGIGPLISHGRFLWMGIGSACNYYNRVYGEFMRVWIS GEETLIISKSSSMFHIMKHNHYSSRFGSKLGLQCIGMHEKGIIFNNNPELWKTTRPFFMKALSGPGLVRMVTVCAESLKTHLDRLEEVTN ESGYVDVLTLLRRVMLDTSNTLFLRIPLDESAIVVKIQGYFDAWQALLIKPDIFFKISWLYKKYEKSVKDLKDAIEVLIAEKRRRISTEE KLEECMDFATELILAEKRGDLTRENVNQCILEMLIAAPDTMSVSLFFMLFLIAKHPNVEEAIIKEIQTVIGERDIKIDDIQKLKVMENFI YESMRYQPVVDLVMRKALEDDVIDGYPVKKGTNIILNIGRMHRLEFFPKPNEFTLENFAKNVPYRYFQPFGFGPRGCAGKYIAMVMMKAI |
| P11511-2 | MVLEMLNPIHYNITSIVPEAMPAATMPVLLLTGLFLLVWNYEGTSSIPGPGYCMGIGPLISHGRFLWMGIGSACNYYNRVYGEFMRVWIS GEETLIISKSSSMFHIMKHNHYSSRFGSKLGLQCIGMHEKGIIFNNNPELWKTTRPFFMKALSGPGLVRMVTVCAESLKTHLDRLEEVTN |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CYP19A1 (go to UniProt):P11511 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P11511 | Transmembrane | 303 | 323 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=219;End=503 |
Gene Isoform Structures and Expression Levels for CYP19A1 |
| Gene structures of our canonical and alternative spliced genes of CYP19A1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P11511-1 |
| 3D view using mol* of P11511-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P11511-1 |
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| pLDDT distribution across the protein length of P11511-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P11511-1 |
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| Ramachandran plot of P11511-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P11511-1 | 1.161 | 263 | 1.169 | 494.263 | 0.285 | 0.928 | 1.218 | 1.966 | 1.005 | 1.956 | 0.446 | 115,132,133,134,141,145,148,152,160,199,203,221,22 4,302,303,305,306,307,309,310,311,313,314,364,368, 369,370,371,372,373,374,375,429,430,431,435,436,43 7,438,439,442,443,446,447,477,478,480 |
| P11511-2 | 0.816 | 52 | 0.714 | 139.258 | 0.574 | 0.729 | 0.973 | 0.448 | 1.232 | 0.363 | 0.739 | 171,174,175,177,178,190,193,196,197,200,207,208,20 9,210,211 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P11511-1_P11511-1_3s79_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P11511-1_3s79_A_P11511-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P11511-1_P11511-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P11511-1_vs_P11511-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P11511-1_vs_P11511-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CYP19A1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P11511 | CYP19A1 | DB16236 | Mitapivat | approved, investigational | inhibitor |
| P11511 | CYP19A1 | DB00357 | Aminoglutethimide | approved, investigational | inhibitor |
| P11511 | CYP19A1 | DB01006 | Letrozole | approved, investigational | antagonist |
| P11511 | CYP19A1 | DB01217 | Anastrozole | approved, investigational | inhibitor |
| P11511 | CYP19A1 | DB03467 | Naringenin | experimental | inhibitor |
| P11511 | CYP19A1 | DB04539 | Glyphosate | experimental | |
| P11511 | CYP19A1 | DB00990 | Exemestane | approved, investigational | inhibitor |
| P11511 | CYP19A1 | DB02342 | 2-Methoxyestradiol | investigational | |
| P11511 | CYP19A1 | DB05749 | MPI-674 | investigational | |
| P11511 | CYP19A1 | DB00894 | Testolactone | approved, investigational | inhibitor |
| P11511 | CYP19A1 | DB00184 | Nicotine | approved | inhibitor |
| P11511 | CYP19A1 | DB00655 | Estrone | approved |
Related Diseases to CYP19A1 |
| Previous studies relating to the alternative splicing of CYP19A1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CYP19A1 | 11850209 | Aromatase in atherosclerotic lesions of human aorta. | It is well documented that estrogens have atheroprotective effects in humans. Peripheral aromatization of circulating androgens has been demonstrated to exert estrogenic actions in many human tissues, especially in men and post-menopausal women. Recently, production of estrogens mediated by aromatase was detected in cultured smooth muscle cells and aortic endothelial cells and it has been proposed that this in situ produced estrogen may influence the development of atherosclerosis. In this study, we first examined aromatase expression by immunohistochemistry in human aortic tissues obtained from 85 autopsy cases (50 males, 35 females, 49.6 +/- 2.9-year-old) and by mRNA in situ hybridization in 10 cases. We then semi-quantified the level of aromatase mRNA in aortic tissues of 12 men and 12 post-menopausal women by reverse transcriptase-polymerase chain reaction (RT-PCR) to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon 1 of its gene and immunolocalization of 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen. Aromatase immunoreactivity and mRNA hybridization signals and 17beta-HSD I immunoreactivity were all detected in smooth muscle cell (SMC) of the media and thickened intima, especially in SMC adjacent to an atheromatous plaque. The levels of aromatase mRNA were significantly higher in female cases than in male cases (P<0.05). The amount of aromatase mRNA was significantly higher in the specimens with fibroatheroma (P<0.05) than other lesions, and was also significantly higher in the cases utilizing 1c (I.3) or 1d (PII) of exon 1, i.e. gonadal types than those utilizing 1b (I.4), i.e. fibroblasts type as the promoter (P<0.01). These results suggest that estrone and estradiol are produced in SMC of the human aortic wall and that their production is mediated by aromatase and 17beta-HSD I, respectively. Moreover, it was suggested that aromatase overexpression, possibly as a result of alternative splicing, may play some roles in the development of atherosclerosis. | D001161 | Arteriosclerosis |
Clinically important variants in CYP19A1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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