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Identification
- Summary
Quercetin is a natural flavonoid found in foods and natural supplement products.
- Generic Name
- Quercetin
- DrugBank Accession Number
- DB04216
- Background
Quercetin is a flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin.
- Type
- Small Molecule
- Groups
- Experimental, Investigational
- Structure
Structure for Quercetin (DB04216)
- Weight
- Average: 302.2357
Monoisotopic: 302.042652674 - Chemical Formula
- C15H10O7
- Synonyms
- 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one
- 3,3',4',5,7-pentahydroxyflavone
- 3,5,7,3',4'-Pentahydroxyflavone
- 3'-HYDROXYKAEMPFEROL
- FLAVONE, 3,3',4',5,7-PENTAHYDROXY-
- poly (lactide-co-glycolide)-polyethylene glycol nanoparticles encapsulating quercetin
- Sophoretin
- Xanthaurine
- External IDs
- LDN-0052529
- NSC-57655
- NSC-9219
Pharmacology
- Indication
Not Available
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Quercetin is a specific quinone reductase 2 (QR2) inhibitor, an enzyme (along with the human QR1 homolog) which catalyzes metabolism of toxic quinolines. Inhibition of QR2 in plasmodium may potentially cause lethal oxidative stress. The inhibition of antioxidant activity in plasmodium may contribute to killing the malaria causing parasites.
- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib Quercetin may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Quercetin. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Quercetin. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Quercetin. Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Quercetin. - Food Interactions
- Not Available
Products
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Categories
- Drug Categories
- Antioxidants
- BCRP/ABCG2 Inhibitors
- Benzopyrans
- Biological Factors
- Chromones
- Compounds used in a research, industrial, or household setting
- COMT Inhibitors
- COMT Substrates
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (weak)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Flavonoids
- Flavonols
- Heterocyclic Compounds, Fused-Ring
- OATP1B1/SLCO1B1 Inhibitors
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- P-glycoprotein inhibitors
- Protective Agents
- Pyrans
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as flavonols. These are compounds that contain a flavone (2-phenyl-1-benzopyran-4-one) backbone carrying a hydroxyl group at the 3-position.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Flavonoids
- Sub Class
- Flavones
- Direct Parent
- Flavonols
- Alternative Parents
- 3'-hydroxyflavonoids / 3-hydroxyflavonoids / 4'-hydroxyflavonoids / 5-hydroxyflavonoids / 7-hydroxyflavonoids / Chromones / Catechols / 1-hydroxy-2-unsubstituted benzenoids / Pyranones and derivatives / 1-hydroxy-4-unsubstituted benzenoids show 7 more
- Substituents
- 1-benzopyran / 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 3'-hydroxyflavonoid / 3-hydroxyflavone / 3-hydroxyflavonoid / 4'-hydroxyflavonoid / 5-hydroxyflavonoid / 7-hydroxyflavonoid / Aromatic heteropolycyclic compound show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- pentahydroxyflavone, 7-hydroxyflavonol (CHEBI:16243) / flavonols, Flavones and Flavonols (C00389) / Flavones and Flavonols (LMPK12110004)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 9IKM0I5T1E
- CAS number
- 117-39-5
- InChI Key
- REFJWTPEDVJJIY-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H10O7/c16-7-4-10(19)12-11(5-7)22-15(14(21)13(12)20)6-1-2-8(17)9(18)3-6/h1-5,16-19,21H
- IUPAC Name
- 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one
- SMILES
- OC1=CC2=C(C(O)=C1)C(=O)C(O)=C(O2)C1=CC=C(O)C(O)=C1
References
- Synthesis Reference
Miguel M. Taya, Dionisio M. Aedo, Rene Ricard, "Quercetin pentamethyl carbamate and a process for its preparation." U.S. Patent US4202825, issued October, 1975.
US4202825- General References
- Not Available
- External Links
- PDB Entries
- 1e8w / 1gp6 / 1h1i / 2c9z / 2hck / 2jj2 / 2ms6 / 2n6c / 2o3p / 2uxh … show 24 more
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Recruiting Supportive Care Hematopoietic Stem Cell Transplantation (SCT) 1 somestatus stop reason just information to hide Not Available Terminated Prevention Colorectal Cancer 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Coronavirus Disease 2019 (COVID‑19) / COVID-19 Acute Bronchitis / COVID-19 Pneumonia / COVID-19 Respiratory Infection 1 somestatus stop reason just information to hide 4 Unknown Status Treatment Coronavirus Disease 2019 (COVID‑19) 1 somestatus stop reason just information to hide 4 Withdrawn Prevention Menopause related conditions 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- V Sab Medical Labs Inc.
- Dosage Forms
Form Route Strength Tablet Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 316.5 °C PhysProp water solubility 60 mg/L (at 16 °C) SEIDELL,A (1941) - Predicted Properties
Property Value Source Water Solubility 0.261 mg/mL ALOGPS logP 1.81 ALOGPS logP 2.16 Chemaxon logS -3.1 ALOGPS pKa (Strongest Acidic) 6.38 Chemaxon pKa (Strongest Basic) -4 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 127.45 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 76.86 m3·mol-1 Chemaxon Polarizability 28.54 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.965 Blood Brain Barrier - 0.5711 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.5629 P-glycoprotein inhibitor I Non-inhibitor 0.9297 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.931 CYP450 2C9 substrate Non-substrate 0.7898 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.653 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Non-inhibitor 0.5823 CYP450 2D6 inhibitor Non-inhibitor 0.9287 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Inhibitor 0.6951 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5822 Ames test Non AMES toxic 0.722 Carcinogenicity Non-carcinogens 0.945 Biodegradation Not ready biodegradable 0.8672 Rat acute toxicity 3.0200 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9781 hERG inhibition (predictor II) Non-inhibitor 0.8161
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 180.9728845 predictedDarkChem Lite v0.1.0 [M-H]- 162.8392822 predictedDarkChem Standard v0.1.0 [M-H]- 167.7951469 predictedDarkChem Lite v0.1.0 [M-H]- 181.5542845 predictedDarkChem Lite v0.1.0 [M-H]- 181.3557845 predictedDarkChem Lite v0.1.0 [M-H]- 169.74606 predictedDeepCCS 1.0 (2019) [M+H]+ 179.2740845 predictedDarkChem Lite v0.1.0 [M+H]+ 164.904221 predictedDarkChem Standard v0.1.0 [M+H]+ 170.223561 predictedDarkChem Lite v0.1.0 [M+H]+ 182.5602845 predictedDarkChem Lite v0.1.0 [M+H]+ 177.2410845 predictedDarkChem Lite v0.1.0 [M+H]+ 172.10406 predictedDeepCCS 1.0 (2019) [M+Na]+ 176.4729845 predictedDarkChem Lite v0.1.0 [M+Na]+ 176.7530845 predictedDarkChem Lite v0.1.0 [M+Na]+ 173.9441599 predictedDarkChem Lite v0.1.0 [M+Na]+ 182.1622845 predictedDarkChem Lite v0.1.0 [M+Na]+ 176.6825845 predictedDarkChem Lite v0.1.0 [M+Na]+ 178.69855 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18242580, PubMed:18782771, PubMed:22306293, PubMed:23084476, PubMed:28262505, PubMed:32929201). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18782771, PubMed:28262505, PubMed:32929201). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acetylation promotes its transcription activity and cell differentiation while deacetylation and oxidation of lysine residues by LOXL3 inhibits differentiation (PubMed:28065600, PubMed:28262505). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC3 and NFATC4, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity)
- Specific Function
- chromatin DNA binding
- Gene Name
- STAT3
- Uniprot ID
- P40763
- Uniprot Name
- Signal transducer and activator of transcription 3
- Molecular Weight
- 88067.215 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Exhibits both acyltransferase and acetyltransferase activities (PubMed:17182612, PubMed:20363836, PubMed:21498505). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:21498505). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:20363836). Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) (PubMed:17182612). Also converts lyso-PAF to 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (PC), a major component of cell membranes and a PAF precursor (By similarity). Under resting conditions, acyltransferase activity is preferred (By similarity). Upon acute inflammatory stimulus, acetyltransferase activity is enhanced and PAF synthesis increases (By similarity). Involved in the regulation of lipid droplet number and size (PubMed:25491198)
- Specific Function
- 1-acylglycerol-3-phosphate O-acyltransferase activity
- Gene Name
- LPCAT2
- Uniprot ID
- Q7L5N7
- Uniprot Name
- Lysophosphatidylcholine acyltransferase 2
- Molecular Weight
- 60207.295 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Exhibits acyltransferase activity (PubMed:18156367, PubMed:21498505). Exhibits acetyltransferase activity (By similarity). Activity is calcium-independent (By similarity). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:18156367, PubMed:21498505). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Displays a clear preference for saturated fatty acyl-CoAs, and 1-myristoyl or 1-palmitoyl LPC as acyl donors and acceptors, respectively (By similarity). Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) (By similarity). May synthesize phosphatidylcholine in pulmonary surfactant, thereby playing a pivotal role in respiratory physiology (By similarity). Involved in the regulation of lipid droplet number and size (PubMed:25491198)
- Specific Function
- 1-acylglycerol-3-phosphate O-acyltransferase activity
- Gene Name
- LPCAT1
- Uniprot ID
- Q8NF37
- Uniprot Name
- Lysophosphatidylcholine acyltransferase 1
- Molecular Weight
- 59150.675 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity)
- Specific Function
- 1-phosphatidylinositol-3-kinase activity
- Gene Name
- PIK3CG
- Uniprot ID
- P48736
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
- Molecular Weight
- 126452.625 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT3A1
- Uniprot ID
- Q6NUS8
- Uniprot Name
- UDP-glucuronosyltransferase 3A1
- Molecular Weight
- 59150.34 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159)
- Specific Function
- ADP binding
- Gene Name
- ATP5F1A
- Uniprot ID
- P25705
- Uniprot Name
- ATP synthase subunit alpha, mitochondrial
- Molecular Weight
- 59750.06 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits
- Specific Function
- angiostatin binding
- Gene Name
- ATP5F1B
- Uniprot ID
- P06576
- Uniprot Name
- ATP synthase subunit beta, mitochondrial
- Molecular Weight
- 56559.42 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and the central stalk which is part of the complex rotary element. The gamma subunit protrudes into the catalytic domain formed of alpha(3)beta(3). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits
- Specific Function
- proton-transporting ATP synthase activity, rotational mechanism
- Gene Name
- ATP5F1C
- Uniprot ID
- P36542
- Uniprot Name
- ATP synthase subunit gamma, mitochondrial
- Molecular Weight
- 32995.665 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis (PubMed:15528381, PubMed:1825810, PubMed:31548394). Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3) (PubMed:18593906). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (By similarity). The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (By similarity). Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (By similarity). Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis (PubMed:19749799). Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (PubMed:16356754). Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability (PubMed:12431783). Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (PubMed:18593906). Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (PubMed:18593906). May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (PubMed:10664448). Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (By similarity). Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394). Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol (PubMed:37797010). Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (PubMed:18056989). Promotes brown adipocyte differentiation (By similarity)
- Specific Function
- ATP binding
- Gene Name
- PIM1
- Uniprot ID
- P11309
- Uniprot Name
- Serine/threonine-protein kinase pim-1
- Molecular Weight
- 35685.44 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Pseudomonas putida (strain DOT-T1E)
- Pharmacological action
- Unknown
- General Function
- Represses expression from the ttgABC operon promoter and its own expression. Binds to a promoter region between the divergently transcribed ttgR and ttgABC genes/operons; in the presence of chloramphenicol or tetracycline this binding no longer occurs and ttgR and ttgABC are derepressed. This suggests that TtgR binds these antibiotics.
- Specific Function
- DNA-binding transcription repressor activity
- Gene Name
- ttgR
- Uniprot ID
- Q9AIU0
- Uniprot Name
- HTH-type transcriptional regulator TtgR
- Molecular Weight
- 23854.075 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA
- Specific Function
- 3-hydroxyisobutyryl-CoA hydrolase activity
- Gene Name
- HIBCH
- Uniprot ID
- Q6NVY1
- Uniprot Name
- 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial
- Molecular Weight
- 43481.935 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Helicobacter pylori
- Pharmacological action
- Unknown
- General Function
- Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.
- Specific Function
- (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity
- Gene Name
- fabZ
- Uniprot ID
- Q5G940
- Uniprot Name
- 3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ
- Molecular Weight
- 18184.08 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Phosphorylates myosin light chains (By similarity). Acts as a positive regulator of apoptosis
- Specific Function
- ATP binding
- Gene Name
- STK17B
- Uniprot ID
- O94768
- Uniprot Name
- Serine/threonine-protein kinase 17B
- Molecular Weight
- 42343.595 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General 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. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity)
- Specific Function
- 14-3-3 protein binding
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Maggiolini M, Bonofiglio D, Marsico S, Panno ML, Cenni B, Picard D, Ando S: Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol. 2001 Sep;60(3):595-602. [Article]
- Leung LK, Po LS, Lau TY, Yuen YM: Effect of dietary flavonols on oestrogen receptor transactivation and cell death induction. Br J Nutr. 2004 Jun;91(6):831-9. [Article]
- van der Woude H, Ter Veld MG, Jacobs N, van der Saag PT, Murk AJ, Rietjens IM: The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol Nutr Food Res. 2005 Aug;49(8):763-71. [Article]
- Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998 Oct;139(10):4252-63. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560)
- Specific Function
- DNA binding
- Gene Name
- ESR2
- Uniprot ID
- Q92731
- Uniprot Name
- Estrogen receptor beta
- Molecular Weight
- 59215.765 Da
References
- Maggiolini M, Bonofiglio D, Marsico S, Panno ML, Cenni B, Picard D, Ando S: Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol. 2001 Sep;60(3):595-602. [Article]
- Leung LK, Po LS, Lau TY, Yuen YM: Effect of dietary flavonols on oestrogen receptor transactivation and cell death induction. Br J Nutr. 2004 Jun;91(6):831-9. [Article]
- van der Woude H, Ter Veld MG, Jacobs N, van der Saag PT, Murk AJ, Rietjens IM: The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol Nutr Food Res. 2005 Aug;49(8):763-71. [Article]
- Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998 Oct;139(10):4252-63. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis
- Specific Function
- chloride ion binding
- Gene Name
- NQO2
- Uniprot ID
- P16083
- Uniprot Name
- Ribosyldihydronicotinamide dehydrogenase [quinone]
- Molecular Weight
- 25918.4 Da
References
- Buryanovskyy L, Fu Y, Boyd M, Ma Y, Hsieh TC, Wu JM, Zhang Z: Crystal structure of quinone reductase 2 in complex with resveratrol. Biochemistry. 2004 Sep 14;43(36):11417-26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820)
- Specific Function
- cis-regulatory region sequence-specific DNA binding
- Gene Name
- AHR
- Uniprot ID
- P35869
- Uniprot Name
- Aryl hydrocarbon receptor
- Molecular Weight
- 96146.705 Da
References
- Flaveny CA, Murray IA, Chiaro CR, Perdew GH: Ligand selectivity and gene regulation by the human aryl hydrocarbon receptor in transgenic mice. Mol Pharmacol. 2009 Jun;75(6):1412-20. doi: 10.1124/mol.109.054825. Epub 2009 Mar 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (PubMed:10426814). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376, PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (PubMed:21068195). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (PubMed:10426814). Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity)
- Specific Function
- aromatase activity
- Gene Name
- CYP1B1
- Uniprot ID
- Q16678
- Uniprot Name
- Cytochrome P450 1B1
- Molecular Weight
- 60845.33 Da
References
- Shimada T, Tanaka K, Takenaka S, Murayama N, Martin MV, Foroozesh MK, Yamazaki H, Guengerich FP, Komori M: Structure-function relationships of inhibition of human cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives. Chem Res Toxicol. 2010 Dec 20;23(12):1921-35. doi: 10.1021/tx100286d. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity)
- Specific Function
- ATP binding
- Gene Name
- ACTB
- Uniprot ID
- P60709
- Uniprot Name
- Actin, cytoplasmic 1
- Molecular Weight
- 41736.37 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:19188443, PubMed:20545769, PubMed:20625391, PubMed:22017874, PubMed:22406621, PubMed:24962073, PubMed:30898438, PubMed:31439799). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (PubMed:12631575, PubMed:19387551, PubMed:19387552). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (PubMed:12631575, PubMed:19387551, PubMed:19387552). During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage (PubMed:11704824, PubMed:19188443). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation (PubMed:11239457). Phosphorylates a number of DNA repair proteins in response to DNA damage, such as MDC1, MRE11, RAD9A, RAD51 and HTATSF1, promoting their recruitment to DNA damage sites (PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:20545769, PubMed:21482717, PubMed:22325354, PubMed:26811421, PubMed:28512243, PubMed:30898438, PubMed:35597237). Can also negatively regulate apoptosis (PubMed:16193064, PubMed:22184066). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:16193064). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:16193064). Phosphorylates YY1, protecting YY1 from cleavage by CASP7 during apoptosis (PubMed:22184066). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552, PubMed:23123191). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552, PubMed:23123191). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (PubMed:19387550). Mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, leading to activate both kinase and non-kinase client proteins of Hsp90 (PubMed:30699359). Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 (PubMed:19387549). Acts as an ectokinase that phosphorylates several extracellular proteins (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552). Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation (PubMed:20625391, PubMed:22406621). Plays an important role in the circadian clock function by phosphorylating BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (By similarity). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073). Phosphorylates FMR1, promoting FMR1-dependent formation of a membraneless compartment (PubMed:30765518, PubMed:31439799). May phosphorylate histone H2A on 'Ser-1' (PubMed:38334665)
- Specific Function
- ATP binding
- Gene Name
- CSNK2A1
- Uniprot ID
- P68400
- Uniprot Name
- Casein kinase II subunit alpha
- Molecular Weight
- 45143.25 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Regulatory subunit of casein kinase II/CK2. As part of the kinase complex regulates the basal catalytic activity of the alpha subunit a constitutively active serine/threonine-protein kinase that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (PubMed:11239457, PubMed:16818610). Participates in Wnt signaling (By similarity)
- Specific Function
- chromatin binding
- Gene Name
- CSNK2B
- Uniprot ID
- P67870
- Uniprot Name
- Casein kinase II subunit beta
- Molecular Weight
- 24942.25 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773)
- Specific Function
- cysteine-type deubiquitinase activity
- Gene Name
- EIF3F
- Uniprot ID
- O00303
- Uniprot Name
- Eukaryotic translation initiation factor 3 subunit F
- Molecular Weight
- 37563.48 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812)
- Specific Function
- ATP binding
- Gene Name
- HSP90AA1
- Uniprot ID
- P07900
- Uniprot Name
- Heat shock protein HSP 90-alpha
- Molecular Weight
- 84659.015 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity)
- Specific Function
- ATP binding
- Gene Name
- HSPA2
- Uniprot ID
- P54652
- Uniprot Name
- Heat shock-related 70 kDa protein 2
- Molecular Weight
- 70020.43 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:10428817, PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026)
- Specific Function
- ADP binding
- Gene Name
- RUVBL2
- Uniprot ID
- Q9Y230
- Uniprot Name
- RuvB-like 2
- Molecular Weight
- 51156.08 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10490618, PubMed:10882114, PubMed:12234937, PubMed:27720643, PubMed:28781166, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:12234937, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B3 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937, PubMed:27720643). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932)
- Specific Function
- protein-containing complex binding
- Gene Name
- SF3B3
- Uniprot ID
- Q15393
- Uniprot Name
- Splicing factor 3B subunit 3
- Molecular Weight
- 135576.25 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334)
- Specific Function
- ATP binding
- Gene Name
- UBA1
- Uniprot ID
- P22314
- Uniprot Name
- Ubiquitin-like modifier-activating enzyme 1
- Molecular Weight
- 117848.075 Da
References
- Wang RE, Hunt CR, Chen J, Taylor JS: Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General 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
- Specific Function
- androgen binding
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Curator comments
- Non-competitive inhibitor
- General Function
- NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol (PubMed:15799708, PubMed:17344335, PubMed:17912391, PubMed:18449627, PubMed:18826943, PubMed:1921984, PubMed:7005231). Can convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione (PubMed:17344335, PubMed:18826943). In addition, participates in the glucocorticoid metabolism by catalyzing the NADPH-dependent cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF) or 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1 and NR3C2 in adipose tissue (PubMed:28878267)
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NADP+) activity
- Gene Name
- CBR1
- Uniprot ID
- P16152
- Uniprot Name
- Carbonyl reductase [NADPH] 1
- Molecular Weight
- 30374.73 Da
References
- Hintzpeter J, Hornung J, Ebert B, Martin HJ, Maser E: Curcumin is a tight-binding inhibitor of the most efficient human daunorubicin reductase--Carbonyl reductase 1. Chem Biol Interact. 2015 Jun 5;234:162-8. doi: 10.1016/j.cbi.2014.12.019. Epub 2014 Dec 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:12048245, PubMed:1741402, PubMed:18647749, PubMed:9374525). Also plays a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant roles with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipocytes but has an antiproliferative effect on T-cells by repressing MYC expression, facilitating differentiation along the T-helper 2 lineage. Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Also plays a role in intracellular bacteria killing (By similarity). During adipogenesis, is rapidly expressed and, after activation by phosphorylation, induces CEBPA and PPARG, which turn on the series of adipocyte genes that give rise to the adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG genes by CEBPB appears necessary to allow mitotic clonal expansion and thereby progression of terminal differentiation (PubMed:20829347). Essential for female reproduction because of a critical role in ovarian follicle development (By similarity). Restricts osteoclastogenesis: together with NFE2L1; represses expression of DSPP during odontoblast differentiation (By similarity)
- Specific Function
- chromatin DNA binding
- Gene Name
- CEBPB
- Uniprot ID
- P17676
- Uniprot Name
- CCAAT/enhancer-binding protein beta
- Molecular Weight
- 36105.36 Da
References
- Shimizu M, Li J, Inoue J, Sato R: Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPbeta. PLoS One. 2015 Apr 15;10(4):e0121784. doi: 10.1371/journal.pone.0121784. eCollection 2015. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Activator
- General 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
- Specific Function
- DNA-binding transcription activator activity, RNA polymerase II-specific
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Lau AJ, Chang TK: 3-Hydroxyflavone and structural analogues differentially activate pregnane X receptor: Implication for inflammatory bowel disease. Pharmacol Res. 2015 Oct;100:64-72. doi: 10.1016/j.phrs.2015.07.031. Epub 2015 Jul 31. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS
- Specific Function
- ATP binding
- Gene Name
- HCK
- Uniprot ID
- P08631
- Uniprot Name
- Tyrosine-protein kinase HCK
- Molecular Weight
- 59599.355 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Elbarbry F, Ung A, Abdelkawy K: Studying the Inhibitory Effect of Quercetin and Thymoquinone on Human Cytochrome P450 Enzyme Activities. Pharmacogn Mag. 2018 Jan;13(Suppl 4):S895-S899. doi: 10.4103/0973-1296.224342. Epub 2018 Jan 31. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
Components:
| Name | UniProt ID |
|---|---|
| Cytochrome P450 3A4 | P08684 |
| Cytochrome P450 3A43 | Q9HB55 |
| Cytochrome P450 3A5 | P20815 |
| Cytochrome P450 3A7 | P24462 |
References
- Flockhart Table of Drug Interactions [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Kaldas MI, Walle UK, van der Woude H, McMillan JM, Walle T: Covalent binding of the flavonoid quercetin to human serum albumin. J Agric Food Chem. 2005 May 18;53(10):4194-7. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- Kauffmann HM, Pfannschmidt S, Zoller H, Benz A, Vorderstemann B, Webster JI, Schrenk D: Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression. Toxicology. 2002 Feb 28;171(2-3):137-46. [Article]
- Leslie EM, Mao Q, Oleschuk CJ, Deeley RG, Cole SP: Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and atpase activities by interaction with dietary flavonoids. Mol Pharmacol. 2001 May;59(5):1171-80. [Article]
- Nguyen H, Zhang S, Morris ME: Effect of flavonoids on MRP1-mediated transport in Panc-1 cells. J Pharm Sci. 2003 Feb;92(2):250-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Bock KW, Eckle T, Ouzzine M, Fournel-Gigleux S: Coordinate induction by antioxidants of UDP-glucuronosyltransferase UGT1A6 and the apical conjugate export pump MRP2 (multidrug resistance protein 2) in Caco-2 cells. Biochem Pharmacol. 2000 Mar 1;59(5):467-70. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Proton-coupled monocarboxylate symporter. Catalyzes the rapid transport across the plasma membrane of monocarboxylates such as L-lactate, pyruvate and ketone bodies, acetoacetate, beta-hydroxybutyrate and acetate (PubMed:32415067, PubMed:9786900). Dimerization is functionally required and both subunits work cooperatively in transporting substrate (PubMed:32415067)
- Specific Function
- identical protein binding
- Gene Name
- SLC16A7
- Uniprot ID
- O60669
- Uniprot Name
- Monocarboxylate transporter 2
- Molecular Weight
- 52199.745 Da
References
- Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76697.93 Da
References
- Satoh H, Yamashita F, Tsujimoto M, Murakami H, Koyabu N, Ohtani H, Sawada Y: Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos. 2005 Apr;33(4):518-23. Epub 2005 Jan 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Shapiro AB, Ling V: Effect of quercetin on Hoechst 33342 transport by purified and reconstituted P-glycoprotein. Biochem Pharmacol. 1997 Feb 21;53(4):587-96. [Article]
- Eagling VA, Profit L, Back DJ: Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999 Oct;48(4):543-52. [Article]
- Choi CH, Kim JH, Kim SH: Reversal of P-glycoprotein-mediated MDR by 5,7,3',4',5'-pentamethoxyflavone and SAR. Biochem Biophys Res Commun. 2004 Jul 30;320(3):672-9. [Article]
- Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]
- Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ: Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004 Mar 1;36(5):592-604. [Article]
- Borska S, Sopel M, Chmielewska M, Zabel M, Dziegiel P: Quercetin as a potential modulator of P-glycoprotein expression and function in cells of human pancreatic carcinoma line resistant to daunorubicin. Molecules. 2010 Feb 9;15(2):857-70. doi: 10.3390/molecules15020857. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Bidirectional proton-coupled monocarboxylate transporter (PubMed:12946269, PubMed:32946811, PubMed:33333023). Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH (PubMed:12946269, PubMed:33333023). The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (By similarity). Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart (PubMed:32946811). Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition (PubMed:33333023)
- Specific Function
- carboxylic acid transmembrane transporter activity
- Gene Name
- SLC16A1
- Uniprot ID
- P53985
- Uniprot Name
- Monocarboxylate transporter 1
- Molecular Weight
- 53943.685 Da
References
- Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Zhang S, Yang X, Morris ME: Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol. 2004 May;65(5):1208-16. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 03, 2024 04:26