Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.14.14.1

Official Name

unspecific monooxygenase

Name from literature

Aromatase

Pathway from literature

estrogen biosynthesis

Pathway from KEGG

Lipid Metabolism; Androgen and estrogen metabolism; map00150

Xenobiotics Biodegradation and Metabolism; gamma-Hexachlorocyclohexane degradation; map00361

Xenobiotics Biodegradation and Metabolism; Metabolism of xenobiotics by cytochrome P450; map00980

Metabolism of Cofactors and Vitamins; Retinol metabolism; map00830

Lipid Metabolism; Fatty acid metabolism; map00071

Lipid Metabolism; Linoleic acid metabolism; map00591

Lipid Metabolism; Arachidonic acid metabolism; map00590

Amino Acid Metabolism; Tryptophan metabolism; map00380

Xenobiotics Biodegradation and Metabolism; Drug metabolism - cytochrome P450; map00982

Xenobiotics Biodegradation and Metabolism; Drug metabolism - other enzymes; map00983

Biosynthesis of Secondary Metabolites; Caffeine metabolism; map00232

Organisms

Human (9606)

Genome localization

15q21.1[1588 ], 7q21.1[64816 ], 7q21.1[1577 ], 7q21.1[1576 ], 10q24[1559 ], 10q24.3-qter[1571 ], 10q24[1562 ], 15q24.1[1544 ], 2p21[1545 ], 1p33[260293 ], 22q13.1[1565 ], 15q24.1[1543 ], 1p31.3-p31.2[1573 ], 19q13.2[1548 ], 19q13.1[29785 ], 19q13.2[1555 ], 19q13.2[1572 ], 19q13.2[1549 ], 10q23.33[1558 ], 19q13.2[1553 ], 10q24.1-q24.3[1557 ], 1p33[199974 ], 1p34-p12[1580 ], 7q21-q22.1[1551 ],

Comments

A group of heme-thiolate proteins (P-450), acting on a wide range of substrates including many xenobiotics, steroids, fatty acids, vitamins and prostaglandins; reactions catalysed include hydroxylation, epoxidation, N-oxidation, sulfooxidation, N-, S- and O-dealkylations, desulfation, deamination, and reduction of azo, nitro and N-oxide groups. Together with EC 1.6.2.4, NADPH---hemoprotein reductase, it forms a system in which two reducing equivalents are supplied by NADPH. Some of the reactions attributed to EC 1.14.15.3, alkane 1-monooxygenase, belong here.

Rate-limiting Description

"Aromatase is the rate-limiting enzyme playing a role at the final step of estrogen biosynthesis, which is attracting attention as the target enzyme of hormone therapy of postmenopausal breast cancer." (14501171)

"Aromatase, the cytochrome P450 Cyp19 enzyme, catalyzes the rate-limiting step in estrogen biosynthesis." (10690899)

"We studied in vitro the effects of Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH) on: 1) mature human granulosa cell proliferation and steroidogenesis; 2) intra-cellular second messenger (cAMP) generation, and the effects of cAMP analogues on cell function; and 3) mRNA expression of the rate limiting enzymes for progesterone and oestradiol synthesis namely: Cholesterol side chain cleavage (P450 SCC), Aromatase (P450 Arom); and 4) LH receptor mRNA expression." (1339246)

"Aromatase is the rate limiting enzyme that catalyzes the conversion of androgens to estrogens." (12957661)

Regulatory Information

Upstream transcription factor

6667;3725;1385;3727;10891;3172;2624;8648

Regulatory type

Detail

phosphorylation;

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." (17081983#16964243#15302935)

transcriptional factor;"PGC1alpha(10891),SRC1(8648),HNF4alpha(3172)"

"These results establish the importance of coactivators PGC1alpha and SRC1 for the hepatic expression of human P450s and uncover a new HNF4alpha-dependent regulatory mechanism to constitutively control the CYP1A1/2 cluster." (16882880)

transcriptional factor;HNF4alpha(3172)

"These results establish the importance of coactivators PGC1alpha and SRC1 for the hepatic expression of human P450s and uncover a new HNF4alpha-dependent regulatory mechanism to constitutively control the CYP1A1/2 cluster." (16882880)

transcriptional factor;Sp1(6667)

"Transcription factors with an affinity for Sp1 sites mediate transcriptional activation of the CYP1B1 gene in biotin-supplemented T cells, increasing the occurrence of single-stranded DNA breaks." (15333708)

transcriptional factor;HNF4alpha(3172)

"Constitutive hepatic expression of CYP2A6 is governed by an interplay between the transcription factors HNF-4alpha, C/EBPalpha, C/EBPbeta, and Oct-1." (15671201)

transcriptional factor;HNF4alpha(3172)

"These results establish the importance of coactivators PGC1alpha and SRC1 for the hepatic expression of human P450s and uncover a new HNF4alpha-dependent regulatory mechanism to constitutively control the CYP1A1/2 cluster." (16882880)

transcriptional factor;HNF4alpha(3172)

"The coactivator NCOA6 mediates the mechanism of the synergistic activation of the CYP2C9 gene by CAR and HNF4alpha." (18552123)

transcriptional factor;AP-1(3725)

"The c-Jun-responsive module between -122 and -50 in the CYP2J2 proximal promoter contains an atypical AP-1 element at -105/-95 that has a major role in c-Jun transactivation and acts in conjunction with the -56/-63 element to regulate expression." (16008525)

inhibitor;

"inhibited by Sophora flavescens" (17622974)

transcriptional factor;GATA-2(2624)

"Promoter I.7 is a GATA-2-regulated endothelial promoter of the human CYP19 gene and may increase estrogen biosynthesis in vascular endothelial cells of breast cancer." (12351690)

transcriptional factor;AP-1(3725)

"activating transcription factor 1(AP-1) motif is important in determining the up-regulatory effects induced by leptin on aromatase expression in MCF-7 breast cancer cells" (12734209)

phosphorylation;

P04798

phosphorylation;

P05181

phosphorylation;

P10632

phosphorylation;

P11511

phosphorylation;

P20813

phosphorylation;

P20815

phosphorylation;

P33260

phosphorylation;

P04798:from_uniprot:360_Phosphoserine

phosphorylation;

P05181:from_uniprot:129_Phosphoserine

phosphorylation;

P11511:from_uniprot:162_Phosphothreonine

phosphorylation;

P20813:from_uniprot:128_Phosphoserine; by PKA

phosphorylation;

P33260:from_uniprot:99_Phosphoserine

transcriptional factor;CREB1(1385)

"Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a cAMP-responsive element." (15688015)

transcriptional factor;JUN(3725)

"Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a cAMP-responsive element." (15688015)

transcriptional factor;JUND(3727)

"Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a cAMP-responsive element." (15688015)

Gene ontology

Gene ontology

GO:0005624 (C) membrane fraction [P11511 ];
GO:0006954 (P) inflammatory response [Q9HBI6 ];
GO:0006693 (P) prostaglandin metabolic process [P98187 ];
GO:0016020 (C) membrane [P11511 ];
GO:0008389 (F) coumarin 7-hydroxylase activity [P11509 ];
GO:0020037 (F) heme binding [Q16678, B0AZN2, Q9HCS2, P05177, P11511, Q3YA63, P20815, Q38LF9, P33260, P24903, Q9HB55, P51589, P20853, Q86W10, Q45RG7, Q38LG0, Q16750, P98187, P04798, P05181, P10635, Q5JPJ7, Q7Z449, P20813, Q16696, Q38LG2, Q96SQ9, P10632, P24462, Q9HBI6, P11509, P13584, Q8N118 ];
GO:0008393 (F) fatty acid (omega-1)-hydroxylase activity [P98187 ];
GO:0016021 (C) integral to membrane [Q9HCS2, Q9HBI6, Q86W10, Q7Z449, P98187 ];
GO:0009055 (F) electron carrier activity [Q16678, B0AZN2, Q9HCS2, P05177, P11511, Q3YA63, P20815, Q38LF9, P33260, P24903, Q9HB55, P51589, P20853, Q86W10, Q45RG7, Q38LG0, Q16750, P98187, P04798, P05181, P10635, Q5JPJ7, Q7Z449, P20813, Q16696, Q38LG2, Q96SQ9, P10632, P24462, Q9HBI6, P11509, P13584, Q8N118 ];
GO:0008392 (F) arachidonic acid epoxygenase activity [P51589 ];
GO:0006694 (P) steroid biosynthetic process [P11511 ];
GO:0005515 (F) protein binding [Q16678, P98187 ];
GO:0050381 (F) unspecific monooxygenase activity [P05181, P04798, P10635, Q7Z449, Q16678, P20813, Q38LG2, Q16696, B0AZN2, Q96SQ9, Q9HCS2, P05177, P11511, Q3YA63, P20815, Q38LF9, P33260, P24903, Q9HB55, P51589, P20853, P10632, P24462, Q9HBI6, Q86W10, P11509, Q8N118, Q45RG7, Q38LG0, Q16750, P13584, P98187 ];
GO:0005783 (C) endoplasmic reticulum [P11511 ];
GO:0008202 (P) steroid metabolic process [P20815 ];
GO:0007601 (P) visual perception [Q16678 ];
GO:0019825 (F) oxygen binding [P33260, P24903, P05181, P04798, Q16678, P20853, P24462, P05177, P11509, P11511, P13584, P20815 ];
GO:0005506 (F) iron ion binding [Q16678, B0AZN2, Q9HCS2, P05177, P11511, Q3YA63, P20815, Q38LF9, P33260, P24903, Q9HB55, P51589, P20853, Q86W10, Q45RG7, Q38LG0, Q16750, P98187, P04798, P05181, P10635, Q5JPJ7, Q7Z449, P20813, Q16696, Q38LG2, Q96SQ9, P10632, P24462, Q9HBI6, P11509, P13584, Q8N118 ];
GO:0005789 (C) endoplasmic reticulum membrane [P05181, P04798, P10635, Q7Z449, Q16678, P20813, Q16696, Q96SQ9, Q9HCS2, P05177, P20815, P33260, P24903, Q9HB55, P51589, P20853, P10632, P24462, Q9HBI6, Q86W10, P11509, Q8N118, P13584, P98187 ];
GO:0032451 (F) demethylase activity [P05177 ];
GO:0008016 (P) regulation of heart contraction [P51589 ];
GO:0005792 (C) microsome [P05181, P04798, P10635, Q7Z449, Q16678, P20813, Q16696, Q96SQ9, Q9HCS2, P05177, P20815, P33260, P24903, Q9HB55, P51589, P20853, P10632, P24462, Q9HBI6, Q86W10, P11509, Q8N118, P13584, P98187 ];
GO:0006690 (P) icosanoid metabolic process [P51589 ];
GO:0004497 (F) monooxygenase activity [Q5JPJ7 ];
GO:0055114 (P) oxidation reduction [P05181, P04798, P10635, Q7Z449, Q16678, P20813, Q38LG2, Q16696, B0AZN2, Q96SQ9, Q9HCS2, P05177, P11511, Q3YA63, P20815, Q38LF9, P33260, P24903, Q9HB55, P51589, P20853, P10632, P24462, Q9HBI6, Q86W10, P11509, Q8N118, Q45RG7, Q38LG0, Q16750, P13584, P98187 ];

Tissue expression

Tissue From HPRD

Hippocampus [00477, 00488, 07101 ];
Jejunum [03159, 05617 ];
Alpha cell [03159 ];
Aorta [00477 ];
Islets of Langerhans [03159 ];
Urinary bladder [00491 ];
Macrophage [03159, 05617, 00491 ];
Hepatocyte [00148 ];
Spleen [05942, 03464 ];
Vascular system [00488 ];
Endometrium [05630, 00491 ];
Nasal mucosa [00486, 07454 ];
Vascular endothelium [03159 ];
Thymus [05942, 03464 ];
Bronchial epithelial cell [11813, 00484 ];
Syncytiotrophoblast [00488 ];
Occipital lobe [00477 ];
Substantia nigra [00477 ];
Leukocyte [05942, 03464 ];
Intestine [05630, 03464 ];
Caudate nucleus [00477 ];
Putamen [00477 ];
Liver [07453, 07101, 00487, 00486, 07454, 03464, 00477, 00488, 03085, 05617, 08518, 03083, 00490, 07102, 05942, 03159, 11813, 00489, 00484, 03084, 05630 ];
Blood [05617 ];
Muscle [03464 ];
Prostate [08518, 00488, 05942, 05617, 07454, 03464, 00491 ];
Astrocyte [00477 ];
Smooth muscle [03159 ];
Adrenal gland [03083 ];
Delta cell [03159 ];
Gastric mucosa [00489 ];
Lung [00487, 07454, 03464, 00148, 00477, 03085, 05617, 03083, 00490, 05942, 03159, 11813, 00489, 00484, 00491, 05630 ];
Skin [05617 ];
Epidermis [08518, 03085 ];
Ovary [03083, 00488, 03464, 00148 ];
Cervix [05630 ];
Globus pallidus [00477 ];
Hair follicle [08518 ];
Midbrain [03083 ];
Atrium [00477 ];
Renal cortex [08518 ];
Frontal lobe [00477 ];
Colon [03159, 07102, 05942, 05617, 03464, 00491 ];
Spermatozoa [00488 ];
Vermis [00477 ];
Fetus [03159, 08518, 07453, 00488, 05942, 05617, 05630 ];
Beta cell [03159 ];
Testis [03159, 00488, 05942, 07454, 03464 ];
Sertoli cell [00488 ];
Adenohypophysis [05617 ];
Brain [03083, 07101, 05942, 07454, 03464, 00148, 13110, 11813, 00488, 03085 ];
Small intestine [03159, 07102, 05942, 00487, 00486, 05617, 00484 ];
Bronchus [03083, 03085 ];
Adipose tissue [00488 ];
Ventricle [00477 ];
Artery [00477, 00488 ];
Heart [03083, 07102, 07101, 05942, 03464, 03159, 03085, 00491 ];
Amygdala [00488 ];
Mature gut mucosal epithelium [05630 ];
Cerebellum [00477 ];
Lymphocyte [00491, 00148 ];
Purkinje cell [00477 ];
Duodenum [03083, 03085, 05617 ];
Uterus [03083, 03085, 00488, 07454 ];
Seminal vesicle [08518 ];
Oesophagus [07453, 05617, 00484 ];
Temporal lobe [00477 ];
Skeletal muscle [07101, 05942 ];
Dentate gyrus [00477 ];
Blastocyst [00488 ];
Granulosa lutein cell [00488 ];
Bone [00488 ];
Hypothalamus [00488 ];
Kidney [03083, 07102, 07101, 05942, 03464, 03085, 11813, 05617 ];
Corneal epithelial cell [08518 ];
Mammary gland [03083, 07454, 00148, 00488, 03085, 05617, 13111, 00491 ];
Pancreas [05942, 05617, 00489 ];
Trachea [07454 ];
Placenta [00490, 07101, 05942, 03464, 00148, 11813, 00488, 00489, 05617, 00491, 05630 ];
Stomach [05942, 05617 ];

Tissue specificity

Expressed in small intestine, liver, colon and heart [Q9HCS2 ];

Widely expressed with stronger expression in thymus, heart and cerebellum [Q7Z449 ];

Expressed mainly in human liver, followed by kidney, heart, and skeletal muscle [Q9HBI6 ];

Expressed in the epithelium of seminal vesicles, in renal cortex, in adult and fetal liver, in epidermis, in corneal epithelium, in sweat glands, hair follicles, epithelial linings of the ampulla of vas deferens and of the somach and small intestine, as well as in the transitional epithelium of the bladder and ureter (at protein level). In the epidermis, expressed from the basal cell to the granular cell layers. In the corneal epithelium, expressed in all cell layers. Also detected in prostate. Up-regulated in the epidermis of psoriatic lesions [P98187 ];

Highest expression level in prostate. Also expressed in liver, kidney, pancreas, fetal liver and fetal skeletal muscle [Q9HB55 ];

Brain, placenta and gonads [P11511 ];

Liver [P11509, P05177 ];

High level of expression in trachea, lung, stomach, small intestine, and spleen [Q96SQ9 ];

Expressed in liver, lung and heart right ventricle [P20813 ];

Expressed in many tissues [Q16678 ];

Expressed in liver and a number of extrahepatic tissues, including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle [Q16696 ];

Highly expressed in heart, present at lower levels in liver, ileum, jejunum, colon, and kidney [P51589 ];

Preferentially detected in breast carcinoma tissue and mammary gland, whereas only marginal expression is found in all other tested tissues [Q86W10 ];

Lung, lymphocytes and placenta [P04798 ];

Subcellular localization

Localization

cell membrane [P11511 ];

endoplasmic reticulum [P05181, P04798, P10635, Q7Z449, Q16678, P20813, Q16696, Q96SQ9, Q9HCS2, P05177, P20815, P33260, P24903, Q9HB55, P51589, P20853, P10632, P24462, Q9HBI6, Q86W10, P11509, Q8N118, P13584, P98187 ];

microsome [P05181, P04798, P10635, Q7Z449, Q16678, P20813, Q16696, Q96SQ9, Q9HCS2, P05177, P20815, P33260, P24903, Q9HB55, P51589, P20853, P10632, P24462, Q9HBI6, Q86W10, P11509, Q8N118, P13584, P98187 ];

membrane [P05181, P04798, P10635, Q16678, P20813, Q16696, Q96SQ9, P05177, P20815, P33260, P24903, Q9HB55, P51589, P20853, P10632, P24462, Q86W10, P11509, P13584, Q8N118 ];

Disease relevance

Disease

Defects in CYP1B1 are the cause of primary congenital glaucoma type 3A (GLC3A) [MIM:231300]. Primary congenital glaucoma is characterized by large ocular globes resulting from increased intraocular pressure dating from intrauterine life [Q16678 ];

Defects in CYP19A1 are the cause of aromatase deficiency (AROD) [MIM:107910]. AROD is 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 [P11511 ];

Defects in CYP1B1 are a cause of Peters anomaly [MIM:604229]. It is a congenital defect of the anterior chamber of the eye [Q16678 ];

Defects in CYP19A1 are a cause of familial gynecomastia [MIM:139300]. This is characterized by an estrogen excess due to an increased aromatase activity [P11511 ];

Links

SwissProt

B0AZN2; P04798; P05177; P05181; P10632; P10635; P11509; P11511; P13584; P20813; P20815; P20853; P24462; P24903; P33260; P51589; P98187; Q16678; Q16696; Q16750; Q38LF9; Q38LG0; Q38LG2; Q3YA63; Q45RG7; Q5JPJ7; Q7Z449; Q86W10; Q8N118; Q96SQ9; Q9HB55; Q9HBI6; Q9HCS2

Entrez Gene

1543; 1544; 1545; 1548; 1549; 1551; 1553; 1555; 1557; 1558; 1559; 1562; 1565; 1571; 1572; 1573; 1576; 1577; 1580; 1588; 199974; 260293; 29785; 64816

HPRD

13110; 00488; 03084; 07453; 00484; 00491; 03464; 03085; 00487; 00148; 05942; 11813; 08518; 03159; 05617; 13111; 00477; 00486; 07101; 07454; 07481; 03083; 05630; 00420; 00489; 07102; 00490



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min