64275PathwayHistamine H1 Receptor ActivationHistamine is a ubiquitous messenger molecule released from mast cells, basophils, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3, and H4. Histamine receptor H1 belongs to the family of G-protein-coupled receptors (GPCRs), and it is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. It is linked to an intracellular G-protein (Gαq) that activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway which promotes inflammatory processes through calcium ion release and expression of the NF-κB immune response transcription factor. H1-antihistamines inactivate the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Upon binding by histamine, the H1 receptor allosterically activates the G-protein by exchanging GDP for GTP at the G-protein's alpha subunit (Gαq). This results in the dissociation of a Gαq-GTP monomer and a Gβγ dimer from the receptor . Gαq-GTP activates phospholipase C-beta which cleaves the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into the secondary messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses through the cytoplasm to the ER and binds to the inositol 1,4,5-trisphosphate (Ins3P) receptor, releasing calcium from the endoplasmic reticulum into the cytoplasm. An increase in the calcium concentration results in increased mediator release and decreased mast cell stability. Both calcium and DAG activate the kinase activity of protein kinase C beta (PKC). Among many other functions, PKC activates NF-κB. This leads to increased antigen presentation and increased expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors.SignalingPW064412CenterPathwayVisualizationContext6468912002350#000099PathwayVisualization6415964275Histamine H1 Receptor ActivationHistamine is a ubiquitous messenger molecule released from mast cells, basophils, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3, and H4. Histamine receptor H1 belongs to the family of G-protein-coupled receptors (GPCRs), and it is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. It is linked to an intracellular G-protein (Gαq) that activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway which promotes inflammatory processes through calcium ion release and expression of the NF-κB immune response transcription factor. H1-antihistamines inactivate the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Upon binding by histamine, the H1 receptor allosterically activates the G-protein by exchanging GDP for GTP at the G-protein's alpha subunit (Gαq). This results in the dissociation of a Gαq-GTP monomer and a Gβγ dimer from the receptor . Gαq-GTP activates phospholipase C-beta which cleaves the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into the secondary messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses through the cytoplasm to the ER and binds to the inositol 1,4,5-trisphosphate (Ins3P) receptor, releasing calcium from the endoplasmic reticulum into the cytoplasm. An increase in the calcium concentration results in increased mediator release and decreased mast cell stability. Both calcium and DAG activate the kinase activity of protein kinase C beta (PKC). Among many other functions, PKC activates NF-κB. This leads to increased antigen presentation and increased expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors.Signaling157019Mast Cells Release HistamineSubPathway54877693Compound122952622035879Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27.64275Pathway2295272174351Mignery GA, Sudhof TC: The ligand binding site and transduction mechanism in the inositol-1,4,5-triphosphate receptor. EMBO J. 1990 Dec;9(12):3893-8.64275Pathway1CellCL:00000005HepatocyteCL:00001824Cardiomyocyte CL:00007463NeuronCL:00005407Epithelial CellCL:00000662Platelet CL:00002338Beta cellCL:00006391Homo sapiens9606EukaryoteHuman2Bacteria2ProkaryoteBacteria3Escherichia coli562Prokaryote12Mus musculus10090EukaryoteMouse5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat19Schizosaccharomyces pombe4896Eukaryote24Solanum lycopersicum4081EukaryoteTomato4Arabidopsis thaliana3702EukaryoteThale cress18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog6Caenorhabditis elegans6239EukaryoteRoundworm25Escherichia coli (strain K12)83333Prokaryote49Bathymodiolus platifrons220390EukaryoteDeep sea mussel10Drosophila melanogaster7227EukaryoteFruit fly23Pseudomonas aeruginosa287Prokaryote60Nitzschia sp.0001EukaryoteNitzschia462Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)62977Prokaryote56Andro6666Eukaryote10Cell MembraneGO:00058865CytoplasmGO:00057376LysosomeGO:00057644PeroxisomeGO:00057773Mitochondrial MatrixGO:00057592MitochondrionGO:000573911Extracellular SpaceGO:000561516Lysosomal LumenGO:00432027Endoplasmic Reticulum MembraneGO:00057891CytosolGO:000582918Melanosome MembraneGO:003316213Endoplasmic ReticulumGO:000578325Golgi apparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574320Endoplasmic Reticulum LumenGO:000578821SynapseGO:004520215NucleusGO:000563431Periplasmic SpaceGO:000562035ChloroplastGO:000950736MembraneGO:001602053Endoplasmic Reticulum BodyGO:001016834Plant-Type VacuoleGO:000032540PeriplasmGO:004259719sarcoplasmic reticulumGO:001652924Mitochondrial Intermembrane SpaceGO:00057581LiverBTO:00007597294Adrenal MedullaBTO:000004971825IntestineBTO:000064828StomachBTO:0001307155267Nervous SystemBTO:00014848Blood VesselBTO:0001102741111HeartBTO:000056273102Endothelium BTO:00003935cardiocyteBTO:000153918PancreasBTO:000098824BrainBTO:0000142891632Adrenal CortexBTO:00000453081011PW_BS0000248511PW_BS0000089611PW_BS0000095411PW_BS0000054311PW_BS0000043211PW_BS00000314101PW_BS00001413121PW_BS00001315111PW_BS0000152811611PW_BS000028101711PW_BS000010204111PW_BS000020331811PW_BS000033181311PW_BS0000182111PW_BS000002311511PW_BS00003149711PW_BS000049541315PW_BS000054432511PW_BS0000432441011PW_BS000024221411PW_BS00002260251PW_BS00006046114PW_BS000046171211PW_BS00001729111PW_BS0000297028511PW_BS00007072513PW_BS000072612517PW_BS0000613612011PW_BS0000363772113PW_BS00003793252011PW_BS00009327151PW_BS000027711PW_BS000007971521PW_BS000097100521PW_BS000100943PW_BS000094103331PW_BS000103105113PW_BS0001051115121PW_BS0001111136121PW_BS0001131122121PW_BS000112110231PW_BS0001101231751PW_BS0001231251351PW_BS000125126651PW_BS00012612711651PW_BS00012713013121PW_BS0001301141112PW_BS00011412915121PW_BS0001291355171PW_BS0001351181171PW_BS00011810813PW_BS0001086131PW_BS000006140103PW_BS000140101531PW_BS00010114315191PW_BS0001431465191PW_BS000146107313PW_BS000107951721PW_BS0000951471241PW_BS000147151141PW_BS0001511553241PW_BS0001551572241PW_BS0001571613181PW_BS0001611632181PW_BS00016315924PW_BS00015911PW_BS00000116611PW_BS0001661783211PW_BS0001781802211PW_BS00018015284PW_BS000152117131PW_BS000117188118PW_BS0000241601181PW_BS000160205561PW_BS000024207661PW_BS000024206261PW_BS0000242111018PW_BS0000242137181PW_BS00002421425181PW_BS0000242156181PW_BS0000241985181PW_BS0000242164181PW_BS00002421013181PW_BS00002421217181PW_BS000024222341PW_BS000024224241PW_BS0000241901118PW_BS00002417018PW_BS0001702253541PW_BS000024226441PW_BS00002416212181PW_BS000162261115PW_BS0000262771218PW_BS0000241644PW_BS0001642811251PW_BS0000242851041PW_BS0000242863641PW_BS0000242875341PW_BS0000242491341PW_BS0000242273441PW_BS00002465111PW_BS0000652905491PW_BS0000242916491PW_BS0000242924491PW_BS00002429817101PW_BS00002430013101PW_BS0000243016101PW_BS000024302116101PW_BS0000242231241PW_BS0000242941141PW_BS000024315123PW_BS0000243183123PW_BS0000243221231PW_BS00002429341PW_BS000024253541PW_BS0000241321121PW_BS0001321333121PW_BS00013313412121PW_BS0001343317121PW_BS00002833217121PW_BS0000283331212PW_BS0000281151012PW_BS0001153344121PW_BS0000283361121PW_BS000028337116121PW_BS00002834141121PW_BS00002834318121PW_BS00002834713125PW_BS00002832914121PW_BS0000283522512PW_BS00002835325127PW_BS00002835625121PW_BS000028360410121PW_BS0000283683601PW_BS0000283702601PW_BS000028228361PW_BS0000241192171PW_BS000119383751PW_BS0001003841251PW_BS000100390761PW_BS0001123911261PW_BS0001123987171PW_BS000113232403PW_BS000024122551PW_BS000122406351PW_BS000115407251PW_BS000115408451PW_BS000115124151PW_BS000124412125PW_BS000115405105PW_BS000115409115PW_BS0001154151851PW_BS0001154141551PW_BS0001154251355PW_BS000115429151PW_BS00011512112171PW_BS0001214192551PW_BS00011543441051PW_BS0001153821451PW_BS000100436255PW_BS0001151203171PW_BS0001203744171PW_BS0000534436171PW_BS0001154461217PW_BS0001153761017PW_BS0000531371117PW_BS00013744717171PW_BS00011513613171PW_BS000136448116171PW_BS00011545118171PW_BS00011545015171PW_BS00011546013175PW_BS0001154641171PW_BS00011545525171PW_BS000115469410171PW_BS00011539914171PW_BS0001134712517PW_BS00011547225177PW_BS0001152975101PW_BS0000244793101PW_BS0001154812101PW_BS0001154824101PW_BS0001152991101PW_BS0000244831110PW_BS0001154781010PW_BS00011548718101PW_BS00011549025101PW_BS0001154957101PW_BS00011548414101PW_BS00011548012101PW_BS000115501361PW_BS000115502461PW_BS000115388161PW_BS000112208116PW_BS000024209106PW_BS0000245041861PW_BS0001155072561PW_BS00011551541061PW_BS0001153891461PW_BS0001123951361PW_BS0001135131761PW_BS00011516212PW_BS000016231511PW_BS00002321815181PW_BS00002412815121PW_BS0001284101551PW_BS00011544415171PW_BS00011548515101PW_BS0001155161561PW_BS000115215114PW_BS0000213551914PW_BS000035471914PW_BS000047422411PW_BS0000425811411PW_BS000058711113PW_BS0000716618518PW_BS00006634524121PW_BS0000287413PW_BS0000745181PW_BS0000514182451PW_BS00011545424171PW_BS00011548924101PW_BS0001155062461PW_BS000115731013PW_BS00007385241011PW_BS000085892PW_BS0000896531624PW_BS0005086651818PW_BS000508599856PW_BS000501608321PW_BS00050165413621PW_BS00050824PW_B000024566635ProteinComplex1576636ProteinComplex158936Compound1596637ProteinComplex16931230826PW_B00002663986Compound1646636ProteinComplex169318827PW_B00002765693Compound1666635ProteinComplex170003308936Guanosine diphosphateHMDB0001201Guanosine 5'-(trihydrogen diphosphate). A guanine nucleotide containing two phosphate groups esterified to the sugar moiety. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine. GDP is the product of GTP dephosphorylation by GTPases, e.g. the G-proteins that are involved in signal transduction.146-91-8C00035897717552GDP-4-DEHYDRO-6-DEOXY-D-MANNOSE8630NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]2O)C(=O)N1C10H15N5O11P2InChI=1S/C10H15N5O11P2/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(25-9)1-24-28(22,23)26-27(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1QGWNDRXFNXRZMB-UUOKFMHZSA-N[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]phosphonic acid443.2005443.024329371-2.007{[(2R,3S,4R,5R)-5-(2-amino-6-oxo-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy(hydroxy)phosphoryl}oxyphosphonic acid0-3FDB0224875'-gdp;Gdp;Guanosine 5'-(trihydrogen pyrophosphate);Guanosine 5'-diphosphate;Guanosine 5'-pyrophosphate;Guanosine mono(trihydrogen diphosphate);Guanosine pyrophosphate;Guanosine-5'-diphosphate;Guanosine-diphosphate;Ppg;Guanosine diphosphate;Guanosine 5'-diphosphoric acidPW_C000936GDP83823841762142391241547350078553821036041155610116164881787476222117541151177121111823198127272901339515169322177142133775461117795213280023368800803088012216489115253119983406120068122121205124121847405122766120122820135123775118124400376125363479125445297126905501126984205986Guanosine triphosphateHMDB0001273Guanosine triphosphate (GTP) is a guanine nucleotide containing three phosphate groups esterified to the sugar moiety. GTP functions as a carrier of phosphates and pyrophosphates involved in channeling chemical energy into specific biosynthetic pathways. GTP activates the signal transducing G proteins which are involved in various cellular processes including proliferation, differentiation, and activation of several intracellular kinase cascades. Proliferation and apoptosis are regulated in part by the hydrolysis of GTP by small GTPases Ras and Rho. Another type of small GTPase, Rab, plays a role in the docking and fusion of vesicles and may also be involved in vesicle formation. In addition to its role in signal transduction, GTP also serves as an energy-rich precursor of mononucleotide units in the enzymatic biosynthesis of DNA and RNA.86-01-1C00044683015996GTP6569NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]2O)C(=O)N1C10H16N5O14P3InChI=1S/C10H16N5O14P3/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1XKMLYUALXHKNFT-UUOKFMHZSA-N({[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid523.1804522.990659781-1.708triphosphate, guanosine0-3FDB0225275'-gtp;Gtg;Gtp;Guanosine 5'-(tetrahydrogen triphosphate);Guanosine 5'-triphosphate;Guanosine 5'-triphosphorate;Guanosine 5'-triphosphoric acid;Guanosine triphosphate;Guanosine mono(tetrahydrogen triphosphate) (ester);H4gtp;Guanosine-5'-triphosphatePW_C000986GTP81824041939240911441537350068553841036043155610316164901787478222117531151176919811981151127252906932717696222577144133775441117795113280025368800883088012116489113253119985406120066122121204124122768120122818135123774118125365479125443297126480299126907501126982205128051388693HistamineHMDB0000870Histamine, also known as eramin or ceplene, belongs to the class of organic compounds known as 2-arylethylamines. These are primary amines that have the general formula RCCNH2, where R is an organic group. Histamine exists as a solid, soluble (in water), and a very weakly acidic compound (based on its pKa). Histamine has been found throughout most human tissues, and has also been detected in most biofluids, including feces, saliva, urine, and blood. Within the cell, histamine is primarily located in the myelin sheath. In humans, histamine is involved in the phenbenzamine H1-antihistamine action pathway, the omeprazole action pathway, the levocetirizine H1-antihistamine action pathway, and the propiomazine H1-antihistamine action pathway. Histamine is also involved in several metabolic disorders, some of which include the thiazinamium H1-antihistamine action pathway, the metiamide action pathway, the quetiapine H1-antihistamine action pathway, and the histidinemia pathway. Outside of the human body, histamine can be found in a number of food items such as daikon radish, jicama, caraway, and japanese walnut. This makes histamine a potential biomarker for the consumption of these food products. Histamine is an amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.51-45-6C0038877418295HISTAMINE753NCCC1=CNC=N1C5H9N3InChI=1S/C5H9N3/c6-2-1-5-3-7-4-8-5/h3-4H,1-2,6H2,(H,7,8)NTYJJOPFIAHURM-UHFFFAOYSA-N2-(1H-imidazol-4-yl)ethan-1-amine111.1451111.0796473030.182histamine01FDB0125961h-imidazole-4-ethanamine;2-(1h-imidazol-4-yl)ethanamine;2-(1h-imidazol-4-yl)ethylamine;2-(1h-imidazol-5-yl)ethanamine;2-(1h-imidazol-5-yl)ethylamine;2-(4-imidazolyl)ethanamine;2-(4-imidazolyl)ethylamine;2-imidazol-4-yl-ethylamine;2-imidazol-4-ylethylamine;4-(2-aminoethyl)-1h-imidazole;4-(2-aminoethyl)imidazole;4-imidazoleethylamine;5-imidazoleethylamine;Eramin;Ergamine;Ergotidine;Free histamine;Hsm;Histamine;L-histamin base;L-histamine;Theramine;B-imidazolyl-4-ethylamine;Beta-aminoethylglyoxaline;Beta-aminoethylimidazole;Beta-aminothethylglyoxaline;Beta-imidazolyl-4-ethylaminePW_C000693Hsm131083153144151154159267311170008308781321111210261221235911351420WaterHMDB0002111Water is a chemical substance that is essential to all known forms of life. It appears colorless to the naked eye in small quantities, though it is actually slightly blue in color. It covers 71% of Earth's surface. Current estimates suggest that there are 1.4 billion cubic kilometers (330 million m3) of it available on Earth, and it exists in many forms. It appears mostly in the oceans (saltwater) and polar ice caps, but it is also present as clouds, rain water, rivers, freshwater aquifers, lakes, and sea ice. Water in these bodies perpetually moves through a cycle of evaporation, precipitation, and runoff to the sea. Clean water is essential to human life. In many parts of the world, it is in short supply. From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration). Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH-) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4. (Wikipedia).7732-18-5C0000196215377937OH2OInChI=1S/H2O/h1H2XLYOFNOQVPJJNP-UHFFFAOYSA-Nwater18.015318.0105646861water00FDB013390Dihydrogen oxide;Steam;[oh2];Acqua;Agua;Aqua;Bound water;Dihydridooxygen;Eau;H2o;Hoh;Hydrogen hydroxide;WasserPW_C001420H2O55894910951394151316214481135261562428652106912077033823188382109431137749146554159043201824253222267860272746277817280529314370316472363461459836472737494193503027515675195975214100522794523610352971055319111534311353551125402110547012354831255492126550712755341305537114554112955911355608118562210856916575914057781015841143585314658771075890955910147594015160321556059157608716161231636133159621516218166647717865071806600152671311768401886888160716220571812077193206721121172282137238214724321572951987350216738821074012127467222749222475001907588170820122582372268414162926526118502771192216412011281122132851225028612264287123272491252022712632651269329012705291127152921300729813019300130253011303730213261223133272941534030842327315426953184369132276914293770192537710213277131133772151347737833177397332774713337751611577536334776283367772233777759341778163437798234778071329782353527824235378270356791133608001436880039370805912288065611993830383947943841105573901106393911158443981198792321199151221199634061200084071200464081201131241203654121204304051204384091206064151207944141211584251212404291213511211213814191216074341221183821223844361227531201227973741228044431230124461230643761230721371231314471231421361231624481232314511233844501237304601238104641239404551241654691246703991249384711249454721253052971253534791253864811254244821254802991256824831257074781257454871260544901262384951262734841267644801268965011269635021270173881271772081271992091272275041275065071275765151278363891280823951281765131155Inositol 1,4,5-trisphosphateHMDB0001498Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. (PubChem). Inositol 1,4,5-trisphosphate (InsP3) is traditionally considered to be the messenger that initiates the increase and spreading of the activating Ca2+ wave. In line with this hypothesis, recent evidence suggests that the penetrating sperm delivers into mammalian eggs a novel isoform of phospholipase C (PLC), which promotes the formation of InsP3. The mechanism by which the interacting sperm triggers the production of NAADP and subsequently that of InsP3 remains obscure. (PMID: 15362223).85166-31-0C0124543945616595inositol_1,4,5-trisphosphate388562O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=OC6H15O15P3InChI=1S/C6H15O15P3/c7-1-2(8)5(20-23(13,14)15)6(21-24(16,17)18)3(9)4(1)19-22(10,11)12/h1-9H,(H2,10,11,12)(H2,13,14,15)(H2,16,17,18)/t1-,2+,3+,4-,5-,6-/m1/s1MMWCIQZXVOZEGG-XJTPDSDZSA-N{[(1R,2S,3R,4R,5S,6R)-2,3,5-trihydroxy-4,6-bis(phosphonooxy)cyclohexyl]oxy}phosphonic acid420.0956419.962379346-1.459InsP30-6FDB0226571d-myo-inositol 1,4,5-trisphosphate;D-myo-inositol 1,4,5-trisphosphate;Inositol 1,4,5-trisphosphate;1,4,5-insp3;D-myo-inositol-1,4,5-triphosphate;Ins(1,4,5)p3;Insp3;Ip3;1d-myo-inositol 1,4,5-trisphosphoric acid;D-myo-inositol 1,4,5-trisphosphoric acid;D-myo-inositol-1,4,5-triphosphoric acid;Inositol 1,4,5-trisphosphoric acidPW_C001155Inotp2741665822037232575142792467387160740921812214285693441781691287821113278516115799991880089308802378121975410122442124122511405124528444125009118125081376126124485126593299126664478127732516128165388128241209353CalciumHMDB0000464Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.14127-61-8C0007627129108CA%2b2266DB01373[Ca++]CaInChI=1S/Ca/q+2BHPQYMZQTOCNFJ-UHFFFAOYSA-Ncalcium(2+) ion40.07839.9625911550calcium(2+) ion22FDB003513Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ionPW_C000353Ca2+276163038553146012941159932199735104631163461164471478491491421552432116582138172796182937931597131607239422941866647821048222853401115780101717920572322117258160728119011774213118371981184221012198164122152851528815115350308693361773893317760011578154132782663567852634578724130789081148041374805892288182651120220122120465405121049124121300418121377419121850383121923125122370409122895135123099376123613118123870454123936455124403398124476136124924137125571297125711478125981489126009299126050490126533495127203209127434506127460388127502507128105390344phosphatidylinositol 4,5-bisphosphateCompound6073CompoundPW_EC000344C04637KEGG CompoundP45B2951,2-diacyl-sn-glycerolCompound3149CompoundPW_EC000293C00641KEGG Compound12DSG2161-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1Q9NQ66The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
HMDBP00222PLCB120p12AL05031513.1.4.11257614279046116468969337180090308802308136124653136191665136199663618GβP62873Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a guanine nucleotide-binding protein (G protein) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interactionHMDBP08398GNB11p36.33BC0058881381224138144157735010855161869324170006308135590599136006608136181661361876651591GγP59768Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 is a guanine nucleotide-binding proteins (G protein) involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interactionHMDBP01767GNG214q21BC0207741693251700073088008214136007608136182661361886652116Histamine H1 receptorP35367In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous systemHMDBP02823HRH13p25X767861673121700093081740Guanine nucleotide-binding protein G(q) subunit alphaP50148Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systemsHMDBP02022GNAQ9q21U43083151631469323182715882836308136005608136185665136201662126Inositol 1,4,5-trisphosphate receptor type 1Q14643Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphateHMDBP02849ITPR13p26.1D260701967162794188502108009181361386541279Protein kinase C beta typeP05771Calcium-activated and phospholipid-dependent serine/threonine-protein kinase involved in various processes such as regulation of the B-cell receptor (BCR) signalosome, apoptosis and transcription regulation. Plays a key role in B-cell activation and function by regulating BCR-induced NF-kappa-B activation and B-cell suvival. Required for recruitment and activation of the IKK kinase to lipid rafts and mediates phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser- 652', leading to activate the NF-kappa-B signaling. Involved in apoptosis following oxidative damage:in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. Also involved in triglyceride homeostasis. Serves as the receptor for phorbol esters, a class of tumor promotersHMDBP01372PRKCB16p11.2FJ90724612.7.11.136938888005216480414741808Nuclear factor NF-kappa-B p105 subunitP19838NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post- translationally. p50 binds to the kappa-B consensus sequence 5'- GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105HMDBP02145NFKB14q24BC051765141452414723803568115939276635Histamine H1 receptor1PW_P0066351437621166636Gαq1PW_P0066361437717406930416637Gβγ1PW_P0066371437836181437915916931111140Phospholipase C, beta 11PW_P001140130221614713531270Inositol 1,4,5-trisphosphate receptor type 11PW_P000270289212646638protein kinase C beta1PW_P0066381438012797443533693878988Nuclear factor NF-kappa-B p105 subunit1PW_P000988111718081100922PW_R100922Right3633683441ElementCollectionfalse36336914201Compoundtrue3633702951ElementCollectionfalse36337111551Compoundfalse910351140101579PW_R101579Right365996241Boundfalse365997261Boundfalse365998271Boundfalse36599966371ProteinComplexfalse1035PW_T00103512593531Compound188Right9222702017-09-13T12:02:00-06:002017-09-13T12:02:00-06:0049240ActivationPW_I000240479693Compound148024Bound1241ActivationPW_I00024148126Bound14821140ProteinComplex1242ActivationPW_I0002424831155Compound1484270ProteinComplex1243ActivationPW_I000243485295ElementCollection14866638ProteinComplex1244ActivationPW_I000244487353Compound14886638ProteinComplex1245ActivationPW_I0002454896638ProteinComplex1490988ProteinComplex137024164159370157458821441626104783942144163611478395214416461247839621441653712616415937115745892144167613478397214416837227308641593721574590214417061447839821441711574588936153false34050210regular50301574589986154false90762210regular503015745906933083false75229710regular10010015745851420149false137325310regular78781574586115513false180237410regular100120157458735319false152738410regular1002515745913531851false200080410regular78781574592353851false162880410regular78781574593693181false1858710regular200190157459435389false107780110regular100259027344371false130237612regular100909028295371false170256912regular100905893222116180false1803678subunitregular200130589323174012false3054478proteinregular150705893243618198false4104577subunitregular150705893251591197false4104076subunitregular15070589326174012false9025678proteinregular15070589327211630880false7023678subunitregular200130589319216199false15023998proteinregular15070589320361830898false9474579subunitregular15070589321159130897false9474078subunitregular15070589328212678false17887838subunitregular135120589329127982false10528118proteinregular150705893301808232false3078138subunitregular1507047839466356415915882145893224783956636641591588215589323478396663764159158821658932458821758932547839766366415915882185893264783986635641593085882195893274783921140641591588211589319611415745872144161Cofactor478393663764159308588212589320588213589321478399270641595882205893284784006638641598588221589329611515745942144183Cofactor47840198864159235882225893302144157M1451 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L747 277 z10true182144172M752 347 C722 347 678.5 437 648.5 437 5true18trueM 25.946855044164835 117.26155629629604 L 11 116 L 17.380887721185843 129.57513432307834false2144173M697 437 C667 437 633 438 603 438 218false18trueM 25.946855044164835 117.26155629629604 L 11 116 L 17.380887721185843 129.57513432307834false2144174M2000 843 C1964 843 1958 844 1923 843 83false18trueM 1670.0096189432334 1054.5 L 1683 1047 L 1670.0096189432334 1039.5false2144175M1706 843 C1740 843 1747 843 1788 843 83false18trueM 1723.9903810567666 824 L 1711 831.5 L 1723.9903810567666 839false2144176M385 367.5 C385 337.5 385 372.5 385 342.5 149true18trueM 25.946855044164835 309.261556296296 L 11 308 L 17.380887721185843 321.5751343230783false2144177M285 277 C285 307 285 362 285 392 149false18trueM 277.5 453.0096189432334 L 285 466 L 292.5 453.0096189432334falsefalsefalse2144178M1077 612.5 C1107 612.5 942 577.5 972 577.5 149true182144179M1577 469 C1578 531 1578 506.5 1577 538.5 C1577 570.5 1562 601.5 1525 601.5 C1490 601.5 1086 602 1052 602 149false18trueM 274.94685504416486 320.261556296296 L 260 319 L 266.38088772118584 332.5751343230783false2144180M1852 494 C1853 535 1851 740 1853 783 149false18trueM 1245.7596189432334 960.5 L 1258.75 953 L 1245.7596189432334 945.5false2144181M1888 818.5 C1858 818.5 1388.75 829.5 1358.75 829.5 149true18trueM 831.9468550441649 854.261556296296 L 817 853 L 823.3808877211858 866.5751343230784false2144182M1752 679 C1752 754 1441 797 1202 846 149false18trueM 1521.5096189432334 825.5 L 1534.5 818 L 1521.5096189432334 810.5false2144183M1717 646.5 L1717 696.5 L1767 646.5 z10true182144184M1152 826.5 C1122 826.5 1664.5 694.5 1634.5 694.5 149true18trueM 920.9468550441649 713.261556296296 L 906 712 L 912.3808877211858 725.5751343230784false2144185M1628 843 C1600 843 1260 845 1202 846 149false18trueM 1586.5096189432334 1229.5 L 1599.5 1222 L 1586.5096189432334 1214.5false2144186M1152 826.5 C1122 826.5 1729.5 1098.5 1699.5 1098.5 149true18trueM 1056.9468550441647 783.261556296296 L 1042 782 L 1048.380887721186 795.5751343230784false2144187M1052 846 C985 845 516 847 457 848 149false18trueM 1809.0096189432334 825 L 1822 817.5 L 1809.0096189432334 810false2144188M407 828.5 C377 828.5 1952 694 1922 694 149true18trueM 1044.9468550441647 614.261556296296 L 1030 613 L 1036.380887721186 626.5751343230784false2144191M385 182 C469 180 505 181 532 181 5false18trueM 397.79386831313315 293.1694870164077 L 385 301 L 398.1783573250214 308.1645584800499false48462664159100922308194307115745852144157Left194307215745862144158Right950190272144159Left950290282144160Right44325291035478392484627641591015793083683702144166Left3693712144169Right3703722144172Right104554783932144173Right226891035641594606515745912144174Left4606615745922144175Right222824783999221353240641593084453702144176Right63315745932144177Left1354241641593084463712144178Left14004783922144179Right1355242641591863415745862144180Left14014783992144181Right135624364159822590282144182Left14024784002144184Right135724464159863515745922144185Left14034784002144186Right1358245641592314044784002144187Left14054784012144188Right564005701964159217false53214616regular5335615745932144191Right10315219396810.60.6-90232803601031532207171.01.00214327267219755M125 538.5 C125 488.5 175 438.5 225 438.5 C801 438.5 1549 438.5 2125 438.5 C2175 438.5 2225 488.5 2225 538.5 C2225 670.5 2225 843.5 2225 975.5 C2225 1025.5 2175 1075.5 2125 1075.5 C1549 1075.5 801 1075.5 225 1075.5 C175 1075.5 125 1025.5 125 975.5 C125 843.5 125 670.5 125 538.5 1true60.00.0219756M1855 988.5 C1855 948.5 1855 751.5 1855 701.5 91false60.00.024406215Endoplasmic Reticulum1894684201.01.01601524406315Nucleus295714201.01.01601524406415Calcium Ion Channel1771911201.01.01601524406515Cell Membrane11701036201.01.01601524406615Cytoplasm1170981201.01.016015244067235↑ Antigen Presentation485726201.31.320015244068235↑ Pro-inflammatory Cytokines, Cell Adhesion Molecules, Chemotactic Factors486868141.31.320015244069235↑ Mediator Release1488883201.31.320015244070235↓ Mast Cell Stabilization1486948201.31.3200151020212001592182970021289894#FFEEDE4299289