Caffeine
Relevant Data
Food Additives Approved in the United States:
General Information
| Chemical name | Caffeine |
| CAS number | 58-08-2 |
| COE number | 11741 |
| Flavouring type | substances |
| FL No. | 16.016 |
| Mixture | No |
| Purity of the named substance at least 95% unless otherwise specified | |
| Reference body | EFSA |
From webgate.ec.europa.eu
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 2519 |
| IUPAC Name | 1,3,7-trimethylpurine-2,6-dione |
| InChI | InChI=1S/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3 |
| InChI Key | RYYVLZVUVIJVGH-UHFFFAOYSA-N |
| Canonical SMILES | CN1C=NC2=C1C(=O)N(C(=O)N2C)C |
| Molecular Formula | C8H10N4O2 |
| Wikipedia | caffeine |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 194.194 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 0 |
| Complexity | 293.0 |
| CACTVS Substructure Key Fingerprint | A A A D c c B z s A A A A A A A A A A A A A A A A A A A A W A A A A A s A A A A A A A A A F g B g A A A H g A A A A A A C A g B l g Q H s B c M E A C o A Q d x d A C A g C 0 X E K A B U A G o V E C A S A h A S C A U A I g I B y J A A G A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = = |
| Topological Polar Surface Area | 58.4 |
| Monoisotopic Mass | 194.08 |
| Exact Mass | 194.08 |
| Compound Is Canonicalized | True |
| Formal Charge | 0 |
| Heavy Atom Count | 14 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
From Pubchem
Food Additives Biosynthesis/Degradation
ADMET Predicted Profile --- Classification
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9935 |
| Human Intestinal Absorption | HIA+ | 0.9974 |
| Caco-2 Permeability | Caco2+ | 0.6330 |
| P-glycoprotein Substrate | Non-substrate | 0.7572 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8086 |
| Non-inhibitor | 0.8471 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8872 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7450 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7484 |
| CYP450 2D6 Substrate | Non-substrate | 0.5869 |
| CYP450 3A4 Substrate | Non-substrate | 0.5305 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9046 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9906 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9836 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9927 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9618 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9924 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8925 |
| Non-inhibitor | 0.8702 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9359 |
| Fish Toxicity | Low FHMT | 0.8127 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.7541 |
| Honey Bee Toxicity | Low HBT | 0.7460 |
| Biodegradation | Ready biodegradable | 0.6696 |
| Acute Oral Toxicity | II | 0.7405 |
| Carcinogenicity (Three-class) | Non-required | 0.6936 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.0324 | LogS |
| Caco-2 Permeability | 1.5801 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.9741 | LD50, mol/kg |
| Fish Toxicity | 2.0541 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.3005 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
| Route of Exposure | Readily absorbed after oral or parenteral administration. The peak plasma level for caffeine range from 6-10mg/L and the mean time to reach peak concentration ranged from 30 minutes to 2 hours. |
|---|---|
| Mechanism of Toxicity | Caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3′,5′-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as caffeine act as antagonists at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of caffeine. Blockade of the adenosine A1 receptor in the heart leads to the accelerated, pronounced "pounding" of the heart upon caffeine intake. |
| Metabolism | Hepatic cytochrome P450 1A2 (CYP 1A2) is involved in caffeine biotransformation. About 80% of a dose of caffeine is metabolized to paraxanthine (1,7-dimethylxanthine), 10% to theobromine (3,7-dimethylxanthine), and 4% to theophylline (1,3-dimethylxanthine). Route of Elimination: In young infants, the elimination of caffeine is much slower than that in adults due to immature hepatic and/or renal function. Half Life: 3 to 7 hours in adults, 65 to 130 hours in neonates |
| Toxicity Values | LD50: 127 mg/kg (Oral, Mouse) |
| Lethal Dose | |
| Carcinogenicity (IARC Classification) | 3, not classifiable as to its carcinogenicity to humans. |
| Minimum Risk Level | |
| Health Effects | Caffeine may increase rates of miscarriage and low birth weight. Caffeine withdrawal symptoms include fatigue, headache, nausea and irritability. Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion. |
| Treatment | Convulsions may be treated with IV administration of diazepam or a barbiturate such as pentobarbital sodium. |
| Reference |
|
From T3DB
Taxonomic Classification
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organoheterocyclic compounds |
| Class | Imidazopyrimidines |
| Subclass | Purines and purine derivatives |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Xanthines |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Xanthine - 6-oxopurine - Purinone - Alkaloid or derivatives - Pyrimidone - N-substituted imidazole - Pyrimidine - Azole - Imidazole - Heteroaromatic compound - Vinylogous amide - Lactam - Urea - Azacycle - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Organooxygen compound - Organonitrogen compound - Organic oxygen compound - Organic nitrogen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety. |
From ClassyFire
Targets
- General Function:
- G-protein coupled adenosine receptor activity
- Specific Function:
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
- Gene Name:
- ADORA2B
- Uniprot ID:
- P29275
- Molecular Weight:
- 36332.655 Da
References
- Scheiff AB, Yerande SG, El-Tayeb A, Li W, Inamdar GS, Vasu KK, Sudarsanam V, Muller CE: 2-Amino-5-benzoyl-4-phenylthiazoles: Development of potent and selective adenosine A1 receptor antagonists. Bioorg Med Chem. 2010 Mar 15;18(6):2195-203. doi: 10.1016/j.bmc.2010.01.072. Epub 2010 Feb 4. [20188574 ]
- General Function:
- Protein serine/threonine kinase activity
- Specific Function:
- Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response.
- Gene Name:
- ATM
- Uniprot ID:
- Q13315
- Molecular Weight:
- 350684.105 Da
References
- Charrier JD, Durrant SJ, Golec JM, Kay DP, Knegtel RM, MacCormick S, Mortimore M, O'Donnell ME, Pinder JL, Reaper PM, Rutherford AP, Wang PS, Young SC, Pollard JR: Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J Med Chem. 2011 Apr 14;54(7):2320-30. doi: 10.1021/jm101488z. Epub 2011 Mar 17. [21413798 ]
- General Function:
- Metal ion binding
- Specific Function:
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
- Gene Name:
- PDE4B
- Uniprot ID:
- Q07343
- Molecular Weight:
- 83342.695 Da
References
- 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. [17016423 ]
- General Function:
- Primary amine oxidase activity
- Specific Function:
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
- Gene Name:
- MAOB
- Uniprot ID:
- P27338
- Molecular Weight:
- 58762.475 Da
References
- Van der Walt EM, Milczek EM, Malan SF, Edmondson DE, Castagnoli N Jr, Bergh JJ, Petzer JP: Inhibition of monoamine oxidase by (E)-styrylisatin analogues. Bioorg Med Chem Lett. 2009 May 1;19(9):2509-13. doi: 10.1016/j.bmcl.2009.03.030. Epub 2009 Mar 14. [19342233 ]
- General Function:
- Transcription factor binding
- Specific Function:
- Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect machanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation.
- Gene Name:
- PRKDC
- Uniprot ID:
- P78527
- Molecular Weight:
- 469084.155 Da
References
- Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [12145276 ]
- General Function:
- Pyridoxal phosphate binding
- Specific Function:
- Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
- Gene Name:
- PYGM
- Uniprot ID:
- P11217
- Molecular Weight:
- 97091.265 Da
References
- Wen X, Sun H, Liu J, Wu G, Zhang L, Wu X, Ni P: Pentacyclic triterpenes. Part 1: the first examples of naturally occurring pentacyclic triterpenes as a new class of inhibitors of glycogen phosphorylases. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4944-8. [16169219 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.
- Gene Name:
- GDA
- Uniprot ID:
- Q9Y2T3
- Molecular Weight:
- 51002.565 Da
References
- Fernandez JR, Sweet ES, Welsh WJ, Firestein BL: Identification of small molecule compounds with higher binding affinity to guanine deaminase (cypin) than guanine. Bioorg Med Chem. 2010 Sep 15;18(18):6748-55. doi: 10.1016/j.bmc.2010.07.054. Epub 2010 Jul 27. [20716488 ]
- General Function:
- Protein serine/threonine kinase activity
- Specific Function:
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and 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. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.
- Gene Name:
- PIK3CA
- Uniprot ID:
- P42336
- Molecular Weight:
- 124283.025 Da
References
- Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [12145276 ]
- General Function:
- Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
- Specific Function:
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and 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. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors.
- Gene Name:
- PIK3CB
- Uniprot ID:
- P42338
- Molecular Weight:
- 122761.225 Da
References
- Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [12145276 ]
- General Function:
- Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
- Specific Function:
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.
- Gene Name:
- PIK3CD
- Uniprot ID:
- O00329
- Molecular Weight:
- 119478.065 Da
References
- Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [12145276 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).
- Gene Name:
- RYR1
- Uniprot ID:
- P21817
- Molecular Weight:
- 565170.715 Da
References
- Daly JW: Caffeine analogs: biomedical impact. Cell Mol Life Sci. 2007 Aug;64(16):2153-69. [17514358 ]
- General Function:
- Protein serine/threonine kinase activity
- Specific Function:
- Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication.
- Gene Name:
- ATR
- Uniprot ID:
- Q13535
- Molecular Weight:
- 301363.675 Da
References
- Charrier JD, Durrant SJ, Golec JM, Kay DP, Knegtel RM, MacCormick S, Mortimore M, O'Donnell ME, Pinder JL, Reaper PM, Rutherford AP, Wang PS, Young SC, Pollard JR: Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J Med Chem. 2011 Apr 14;54(7):2320-30. doi: 10.1021/jm101488z. Epub 2011 Mar 17. [21413798 ]
- General Function:
- Tfiiic-class transcription factor binding
- Specific Function:
- Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. Regulates osteoclastogensis by adjusting the expression of CEBPB isoforms (By similarity).
- Gene Name:
- MTOR
- Uniprot ID:
- P42345
- Molecular Weight:
- 288889.05 Da
References
- Charrier JD, Durrant SJ, Golec JM, Kay DP, Knegtel RM, MacCormick S, Mortimore M, O'Donnell ME, Pinder JL, Reaper PM, Rutherford AP, Wang PS, Young SC, Pollard JR: Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J Med Chem. 2011 Apr 14;54(7):2320-30. doi: 10.1021/jm101488z. Epub 2011 Mar 17. [21413798 ]
- General Function:
- Identical protein binding
- Specific Function:
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
- Gene Name:
- ADORA2A
- Uniprot ID:
- P29274
- Molecular Weight:
- 44706.925 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Purine nucleoside binding
- Specific Function:
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name:
- ADORA1
- Uniprot ID:
- P30542
- Molecular Weight:
- 36511.325 Da
References
- Shimada J, Suzuki F, Nonaka H, Karasawa A, Mizumoto H, Ohno T, Kubo K, Ishii A: 8-(Dicyclopropylmethyl)-1,3-dipropylxanthine: a potent and selective adenosine A1 antagonist with renal protective and diuretic activities. J Med Chem. 1991 Jan;34(1):466-9. [1992150 ]
- General Function:
- G-protein coupled adenosine receptor activity
- Specific Function:
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
- Gene Name:
- ADORA3
- Uniprot ID:
- P0DMS8
- Molecular Weight:
- 36184.175 Da
References
- Muller CE, Thorand M, Qurishi R, Diekmann M, Jacobson KA, Padgett WL, Daly JW: Imidazo[2,1-i]purin-5-ones and related tricyclic water-soluble purine derivatives: potent A(2A)- and A(3)-adenosine receptor antagonists. J Med Chem. 2002 Aug 1;45(16):3440-50. [12139454 ]
- General Function:
- Endochitinase activity
- Specific Function:
- Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.
- Gene Name:
- CHIT1
- Uniprot ID:
- Q13231
- Molecular Weight:
- 51680.985 Da
References
- Rao FV, Andersen OA, Vora KA, Demartino JA, van Aalten DM: Methylxanthine drugs are chitinase inhibitors: investigation of inhibition and binding modes. Chem Biol. 2005 Sep;12(9):973-80. [16183021 ]
From T3DB