Progesterone
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Basic Info
| Common Name | Progesterone(F05298) |
| 2D Structure | |
| Description | The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation, pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Progesterone is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. Progesterone belongs to a class of hormones called progestagens, and is the major naturally occurring human progestagen. During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy. Progesterone decreases contractility of the uterine smooth muscle. The fetus metabolizes placental progesterone in the production of adrenal mineralo- and glucosteroids. A drop in progesterone levels is possibly one step that facilitates the onset of labor. In addition progesterone inhibits lactation during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production. |
| FRCD ID | F05298 |
| CAS Number | 57-83-0 |
| PubChem CID | 5994 |
| Formula | C21H30O2 |
| IUPAC Name | (8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one |
| InChI Key | RJKFOVLPORLFTN-LEKSSAKUSA-N |
| InChI | InChI=1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1 |
| Canonical SMILES | CC(=O)C1CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C |
| Isomeric SMILES | CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C |
| Wikipedia | Progesterone |
| Synonyms |
Pregn-4-ene-3,20-dione
progesterone
57-83-0
Agolutin
Luteohormone
Crinone
4-Pregnene-3,20-dione
Corpus luteum hormone
Progestin
Syngesterone
|
| Classifies |
Veterinary Drug
Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Lipids and lipid-like molecules |
| Class | Steroids and steroid derivatives |
| Subclass | Pregnane steroids |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Gluco/mineralocorticoids, progestogins and derivatives |
| Alternative Parents | |
| Molecular Framework | Aliphatic homopolycyclic compounds |
| Substituents | Progestogin-skeleton - 20-oxosteroid - Oxosteroid - 3-oxosteroid - 3-oxo-delta-4-steroid - Delta-4-steroid - Cyclohexenone - Cyclic ketone - Ketone - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Carbonyl group - Aliphatic homopolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 314.469 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 1 |
| Complexity | 589 |
| Monoisotopic Mass | 314.225 |
| Exact Mass | 314.225 |
| XLogP | 3.9 |
| Formal Charge | 0 |
| Heavy Atom Count | 23 |
| Defined Atom Stereocenter Count | 6 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9820 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.7724 |
| P-glycoprotein Substrate | Substrate | 0.5449 |
| P-glycoprotein Inhibitor | Inhibitor | 0.8841 |
| Inhibitor | 0.6043 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.6931 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6698 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8470 |
| CYP450 2D6 Substrate | Non-substrate | 0.8795 |
| CYP450 3A4 Substrate | Substrate | 0.7408 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9045 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9533 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.6514 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8203 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.7451 |
| Non-inhibitor | 0.7454 | |
| AMES Toxicity | Non AMES toxic | 0.9626 |
| Carcinogens | Non-carcinogens | 0.9151 |
| Fish Toxicity | High FHMT | 0.9772 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9576 |
| Honey Bee Toxicity | High HBT | 0.8388 |
| Biodegradation | Not ready biodegradable | 0.9575 |
| Acute Oral Toxicity | III | 0.8127 |
| Carcinogenicity (Three-class) | Warning | 0.4528 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.3674 | LogS |
| Caco-2 Permeability | 1.7921 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.8041 | LD50, mol/kg |
| Fish Toxicity | 0.1402 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.7068 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Chlorinated insecticides (toxaphene and endrin) affect oxytocin, testosterone,oestradiol and prostaglandin secretion from ovarian and uterine cells as well as myometrial contractions in cow in vitro. | Chemosphere | 2018 May | 29425943 |
| A mutation in the progesterone receptor predisposes to HEV infection inHIV-positive patients. | Liver Int | 2018 May | 29285885 |
| Maternal N-Carbamylglutamate Supply during Early Pregnancy Enhanced PregnancyOutcomes in Sows through Modulations of Targeted Genes and Metabolism Pathways. | J Agric Food Chem | 2018 Jun 13 | 29804448 |
| Efficacy of using previously used controlled internal drug release (CIDR) insert on the reproductive performance, hormone profiles and economic measures of sheep. | Reprod Domest Anim | 2018 Jun 12 | 29892981 |
| Mechanism of bisphenol AF-induced progesterone inhibition in human chorionic gonadotrophin-stimulated mouse Leydig tumor cell line (mLTC-1) cells. | Environ Toxicol | 2018 Jun | 29575470 |
| Ameliorative effect of ginseng extract on phthalate and bisphenol A reprotoxicity during pregnancy in rats. | Environ Sci Pollut Res Int | 2018 Jul | 29777495 |
| River otters (Lontra canadensis) "trapped" in a coastal environment contaminated with persistent organic pollutants: Demographic and physiological consequences. | Environ Pollut | 2018 Jul | 29573713 |
| Modulation of HIV replication in monocyte derived macrophages (MDM) by steroidhormones. | PLoS One | 2018 Jan 26 | 29373606 |
| Prenatal exposure to di(2-ethylhexyl) phthalate disrupts ovarian function in atransgenerational manner in female mice. | Biol Reprod | 2018 Jan 1 | 29165555 |
| Sex differences in ochratoxin a toxicity in F344 rats after 7 and 21 days of daily oral administration. | Food Chem Toxicol | 2018 Jan | 29126803 |
| Corpora lutea in superovulated ewes fed different planes of nutrition. | Domest Anim Endocrinol | 2018 Jan | 28886590 |
| Impacts of estrus expression and intensity during a timed-AI protocol onvariables associated with fertility and pregnancy success in Bosindicus-influenced beef cows. | J Anim Sci | 2018 Feb 15 | 29408965 |
| Cyanidin-3-O-glucoside promotes the biosynthesis of progesterone through theprotection of mitochondrial function in Pb-exposed rat leydig cells. | Food Chem Toxicol | 2018 Feb | 29030260 |
| Nanosized titanium dioxide-induced premature ovarian failure is associated withabnormalities in serum parameters in female mice. | Int J Nanomedicine | 2018 Apr 27 | 29731629 |
| Evaluation of three hormonal protocols for anovulatory lactating cows underregulations restricting the use of estrogenic compounds. | Anim Sci J | 2018 Apr | 29318710 |
| Neospora caninum Infection during the First Gestation of Holstein Heifers ThatConsume Food Contaminated Naturally with Zearalenone under Field Conditions. | Iran J Parasitol | 2017 Oct-Dec | 29317881 |
| Effects of chronic exposure to octamethylcyclotetrasiloxane anddecamethylcyclopentasiloxane in the aging female Fischer 344 rat. | Toxicol Lett | 2017 Oct 20 | 28842205 |
| Glycidamide inhibits progesterone production through reactive oxygen species-induced apoptosis in R2C Rat Leydig Cells. | Food Chem Toxicol | 2017 Oct | 27984162 |
| Effects of different fat sources (saturated and unsaturated) on reproductiveperformance and biological indices of ewes during flushing period. | Trop Anim Health Prod | 2017 Oct | 28687939 |
| Lack of immunotoxic effects of repeated exposure to atrazine associated with the adaptation of adrenal gland activation. | Regul Toxicol Pharmacol | 2017 Oct | 28736286 |
Targets
- General Function:
- Zinc ion binding
- Specific Function:
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
- Gene Name:
- PGR
- Uniprot ID:
- P06401
- Molecular Weight:
- 98979.96 Da
References
- Madauss KP, Stewart EL, Williams SP: The evolution of progesterone receptor ligands. Med Res Rev. 2007 May;27(3):374-400. [17013809 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
- Gene Name:
- AR
- Uniprot ID:
- P10275
- Molecular Weight:
- 98987.9 Da
References
- Hamann LG, Farmer LJ, Johnson MG, Bender SL, Mais DE, Wang MW, Crombie D, Goldman ME, Jones TK: Synthesis and biological activity of novel nonsteroidal progesterone receptor antagonists based on cyclocymopol monomethyl ether. J Med Chem. 1996 Apr 26;39(9):1778-89. [8627601 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
References
- Kumar AS, Cureton E, Shim V, Sakata T, Moore DH, Benz CC, Esserman LJ, Hwang ES: Type and duration of exogenous hormone use affects breast cancer histology. Ann Surg Oncol. 2007 Feb;14(2):695-703. Epub 2006 Nov 14. [17103262 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
- Gene Name:
- NR1I2
- Uniprot ID:
- O75469
- Molecular Weight:
- 49761.245 Da
References
- Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.
- Gene Name:
- NR3C2
- Uniprot ID:
- P08235
- Molecular Weight:
- 107066.575 Da
References
- Rupprecht R, Reul JM, van Steensel B, Spengler D, Soder M, Berning B, Holsboer F, Damm K: Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol. 1993 Oct 15;247(2):145-54. [8282004 ]
- General Function:
- Xenobiotic-transporting atpase activity
- Specific Function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular Weight:
- 141477.255 Da
References
- Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [11716514 ]
- General Function:
- Transmembrane signaling receptor activity
- Specific Function:
- Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.
- Gene Name:
- EBP
- Uniprot ID:
- Q15125
- Molecular Weight:
- 26352.615 Da
References
- Laggner C, Schieferer C, Fiechtner B, Poles G, Hoffmann RD, Glossmann H, Langer T, Moebius FF: Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. J Med Chem. 2005 Jul 28;48(15):4754-64. [16033255 ]
- General Function:
- Xenobiotic-transporting atpase activity
- Specific Function:
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. Implicated in the efflux of numerous drugs and xenobiotics: mitoxantrone, the photosensitizer pheophorbide, camptothecin, methotrexate, azidothymidine (AZT), and the anthracyclines daunorubicin and doxorubicin.
- Gene Name:
- ABCG2
- Uniprot ID:
- Q9UNQ0
- Molecular Weight:
- 72313.47 Da
References
- Pick A, Muller H, Wiese M: Structure-activity relationships of new inhibitors of breast cancer resistance protein (ABCG2). Bioorg Med Chem. 2008 Sep 1;16(17):8224-36. doi: 10.1016/j.bmc.2008.07.034. Epub 2008 Jul 20. [18678495 ]
- Specific Function:
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
- Gene Name:
- ORM1
- Uniprot ID:
- P02763
- Molecular Weight:
- 23511.38 Da
References
- Albani JR: Progesterone binding to the tryptophan residues of human alpha1-acid glycoprotein. Carbohydr Res. 2006 Nov 6;341(15):2557-64. Epub 2006 Aug 8. [16901474 ]
- General Function:
- Transcription regulatory region dna binding
- Specific Function:
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
- Gene Name:
- AHR
- Uniprot ID:
- P35869
- Molecular Weight:
- 96146.705 Da
References
- Ricci MS, Toscano DG, Toscano WA Jr: ECC-1 human endometrial cells as a model system to study dioxin disruption of steroid hormone function. In Vitro Cell Dev Biol Anim. 1999 Apr;35(4):183-9. [10478797 ]
- General Function:
- Transporter activity
- Specific Function:
- Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
- Gene Name:
- ABCB11
- Uniprot ID:
- O95342
- Molecular Weight:
- 146405.83 Da
References
- Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [12739759 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
- Gene Name:
- CYP2C9
- Uniprot ID:
- P11712
- Molecular Weight:
- 55627.365 Da
References
- Afzelius L, Zamora I, Masimirembwa CM, Karlen A, Andersson TB, Mecucci S, Baroni M, Cruciani G: Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors. J Med Chem. 2004 Feb 12;47(4):907-14. [14761192 ]
- General Function:
- Transporter activity
- Specific Function:
- FABP are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds saturated long-chain fatty acids with a high affinity, but binds with a lower affinity to unsaturated long-chain fatty acids. FABP2 may also help maintain energy homeostasis by functioning as a lipid sensor.
- Gene Name:
- FABP2
- Uniprot ID:
- P12104
- Molecular Weight:
- 15207.165 Da
References
- Chuang S, Velkov T, Horne J, Porter CJ, Scanlon MJ: Characterization of the drug binding specificity of rat liver fatty acid binding protein. J Med Chem. 2008 Jul 10;51(13):3755-64. doi: 10.1021/jm701192w. Epub 2008 Jun 6. [18533710 ]
- General Function:
- Sterol 14-demethylase activity
- Specific Function:
- Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
- Gene Name:
- CYP51A1
- Uniprot ID:
- Q16850
- Molecular Weight:
- 56805.26 Da
References
- Ekins S, Mankowski DC, Hoover DJ, Lawton MP, Treadway JL, Harwood HJ Jr: Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors. Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28. [17194716 ]
- General Function:
- Androgen binding
- Specific Function:
- Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.
- Gene Name:
- SHBG
- Uniprot ID:
- P04278
- Molecular Weight:
- 43778.755 Da
References
- Cherkasov A, Ban F, Santos-Filho O, Thorsteinson N, Fallahi M, Hammond GL: An updated steroid benchmark set and its application in the discovery of novel nanomolar ligands of sex hormone-binding globulin. J Med Chem. 2008 Apr 10;51(7):2047-56. doi: 10.1021/jm7011485. Epub 2008 Mar 11. [18330978 ]
- General Function:
- Secondary active organic cation transmembrane transporter activity
- Specific Function:
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
- Gene Name:
- SLC22A1
- Uniprot ID:
- O15245
- Molecular Weight:
- 61153.345 Da
References
- Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [12110607 ]
- General Function:
- Toxin transporter activity
- Specific Function:
- Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
- Gene Name:
- SLC22A3
- Uniprot ID:
- O75751
- Molecular Weight:
- 61279.485 Da
References
- Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [12110607 ]
- General Function:
- Steroid 17-alpha-monooxygenase activity
- Specific Function:
- Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.
- Gene Name:
- CYP17A1
- Uniprot ID:
- P05093
- Molecular Weight:
- 57369.995 Da
References
- Haidar S, Hartmann RW: C16 and C17 substituted derivatives of pregnenolone and progesterone as inhibitors of 17alpha-hydroxylase-C17, 20-lyase: synthesis and biological evaluation. Arch Pharm (Weinheim). 2002;335(11-12):526-34. [12596217 ]
- General Function:
- Sterol o-acyltransferase activity
- Specific Function:
- Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase.
- Gene Name:
- SOAT1
- Uniprot ID:
- P35610
- Molecular Weight:
- 64733.975 Da
References
- DeVries VG, Schaffer SA, Largis EE, Dutia MD, Wang CH, Bloom JD, Katocs AS Jr: Potential antiatherosclerotic agents. 5. An acyl-CoA:cholesterol O-acyltransferase inhibitor with hypocholesterolemic activity. J Med Chem. 1986 Jul;29(7):1131-3. [3100794 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
- Gene Name:
- CYP2C19
- Uniprot ID:
- P33261
- Molecular Weight:
- 55930.545 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
- Gene Name:
- NR1H4
- Uniprot ID:
- Q96RI1
- Molecular Weight:
- 55913.915 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Cholesterol binding
- Specific Function:
- Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
- Gene Name:
- TSPO
- Uniprot ID:
- P30536
- Molecular Weight:
- 18827.81 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP2C18
- Uniprot ID:
- P33260
- Molecular Weight:
- 55710.075 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Nucleoside transmembrane transporter activity
- Specific Function:
- Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs).
- Gene Name:
- SLC29A1
- Uniprot ID:
- Q99808
- Molecular Weight:
- 50218.805 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
- Gene Name:
- NR3C1
- Uniprot ID:
- P04150
- Molecular Weight:
- 85658.57 Da
References
- Hamann LG, Farmer LJ, Johnson MG, Bender SL, Mais DE, Wang MW, Crombie D, Goldman ME, Jones TK: Synthesis and biological activity of novel nonsteroidal progesterone receptor antagonists based on cyclocymopol monomethyl ether. J Med Chem. 1996 Apr 26;39(9):1778-89. [8627601 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
References
- Dang Z: Comparison of relative binding affinities to fish and mammalian estrogen receptors: the regulatory implications. Toxicol Lett. 2010 Feb 15;192(3):298-315. doi: 10.1016/j.toxlet.2009.11.004. Epub 2009 Nov 12. [19913605 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
- Gene Name:
- OPRK1
- Uniprot ID:
- P41145
- Molecular Weight:
- 42644.665 Da
References
- Dawson-Basoa ME, Gintzler AR: Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms. Pain. 1996 Jan;64(1):169-77. [8867260 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
- Gene Name:
- SIGMAR1
- Uniprot ID:
- Q99720
- Molecular Weight:
- 25127.52 Da
References
- Laggner C, Schieferer C, Fiechtner B, Poles G, Hoffmann RD, Glossmann H, Langer T, Moebius FF: Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. J Med Chem. 2005 Jul 28;48(15):4754-64. [16033255 ]
- General Function:
- Quaternary ammonium group transmembrane transporter activity
- Specific Function:
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
- Gene Name:
- SLC22A2
- Uniprot ID:
- O15244
- Molecular Weight:
- 62579.99 Da
References
- Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [12110607 ]