64689PathwayEGF Signalling PathwayEpidermal growth factor (EGF) is a potent polypeptide mitogen that initiates its biological activity by interacting with the cell surface. The E G F receptors are both transmembrane proteins with cytosolically exposed tyrosine specific protein kinases which are stimulated by ligand binding. Current data strongly suggests that these kinases are causally linked to many if not all of the biological activities of the EGF receptors. Transmembrane signalling is the result of a composite of ligand-receptor interactions in the endosome (stimulation) and modifications of the primary or quaternary structure of the receptor (activation).ProteinPW064815CenterPathwayVisualizationContext6509116552095#000099PathwayVisualization6457164689EGF Signalling PathwayEpidermal growth factor (EGF) is a potent polypeptide mitogen that initiates its biological activity by interacting with the cell surface. The E G F receptors are both transmembrane proteins with cytosolically exposed tyrosine specific protein kinases which are stimulated by ligand binding. Current data strongly suggests that these kinases are causally linked to many if not all of the biological activities of the EGF receptors. Transmembrane signalling is the result of a composite of ligand-receptor interactions in the endosome (stimulation) and modifications of the primary or quaternary structure of the receptor (activation).Protein122999816729045Oda K, Matsuoka Y, Funahashi A, Kitano H: A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 2005;1:2005.0010. doi: 10.1038/msb4100014. Epub 2005 May 25.64689Pathway230006https://www.wikipathways.org/index.php/Pathway:WP43764689Pathway230007https://www.sigmaaldrich.com/technical-documents/articles/biology/egf-egfr-signaling.html64689Pathway2Platelet CL:00002331CellCL:00000004Cardiomyocyte CL:00007463NeuronCL:00005408Beta cellCL:00006391Homo sapiens9606EukaryoteHuman18Saccharomyces cerevisiae4932EukaryoteYeast4Arabidopsis thaliana3702EukaryoteThale cress12Mus musculus10090EukaryoteMouse5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly6Caenorhabditis elegans6239EukaryoteRoundworm3Escherichia coli562Prokaryote24Solanum lycopersicum4081EukaryoteTomato21Xenopus laevis8355EukaryoteAfrican clawed frog49Bathymodiolus platifrons220390EukaryoteDeep sea mussel60Nitzschia sp.0001EukaryoteNitzschia41CytosolGO:000582915NucleusGO:000563410Cell MembraneGO:000588613Endoplasmic ReticulumGO:00057835CytoplasmGO:000573711Extracellular SpaceGO:000561519sarcoplasmic reticulumGO:00165292MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578924Mitochondrial Intermembrane SpaceGO:000575825Golgi apparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:00057436LysosomeGO:000576416Lysosomal LumenGO:004320236MembraneGO:001602026Golgi apparatus membraneGO:00001393Mitochondrial MatrixGO:000575935ChloroplastGO:000950739Mitochondrial membraneGO:00319662Endothelium BTO:00003935cardiocyteBTO:00015391LiverBTO:000075972918PancreasBTO:00009888Blood VesselBTO:0001102741124BrainBTO:0000142891616212PW_BS0000162111PW_BS000002231511PW_BS00002314101PW_BS00001446114PW_BS0000461601181PW_BS00016021815181PW_BS0000242851041PW_BS00002411PW_BS00000112815121PW_BS0001281321121PW_BS0001321151012PW_BS000115181311PW_BS0000183081011PW_BS0000248511PW_BS0000084101551PW_BS000115124151PW_BS000124405105PW_BS00011544415171PW_BS0001151181171PW_BS0001183761017PW_BS00005348515101PW_BS0001152991101PW_BS0000244781010PW_BS0001155161561PW_BS000115388161PW_BS000112209106PW_BS00002415111PW_BS000015215114PW_BS0000213551914PW_BS0000353211PW_BS000003471914PW_BS00004749711PW_BS000049422411PW_BS000042432511PW_BS0000435811411PW_BS000058171211PW_BS0000179611PW_BS000009711113PW_BS00007172513PW_BS00007229111PW_BS0000296618518PW_BS000066101711PW_BS0000102811611PW_BS0000281115121PW_BS000111101531PW_BS000101205561PW_BS0000242111018PW_BS0000241901118PW_BS0000242137181PW_BS0000241985181PW_BS00002421013181PW_BS0000241644PW_BS000164151141PW_BS0001513317121PW_BS00002835625121PW_BS00002834524121PW_BS00002813013121PW_BS0001301141112PW_BS0001147413PW_BS000074228361PW_BS0000245181PW_BS000051122551PW_BS0001224182451PW_BS0001154192551PW_BS000115383751PW_BS0001001251351PW_BS000125409115PW_BS0001151355171PW_BS00013545424171PW_BS00011545525171PW_BS0001153987171PW_BS00011313613171PW_BS0001361371117PW_BS0001372975101PW_BS00002448924101PW_BS00011549025101PW_BS0001154957101PW_BS0001155062461PW_BS0001155072561PW_BS000115390761PW_BS000112562611PW_BS0000564311PW_BS000004731013PW_BS00007385241011PW_BS000085103331PW_BS0001031553241PW_BS0001551613181PW_BS0001611783211PW_BS000178222341PW_BS0000242905491PW_BS0000242253541PW_BS0000241333121PW_BS0001333683601PW_BS000028253541PW_BS000024406351PW_BS0001151203171PW_BS0001204793101PW_BS000115501361PW_BS00011527151PW_BS000027231391PW_BS00002416611PW_BS000166711PW_BS0000071155Inositol 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+27616303855314601294115993219973510463116346116447147849149142155243211658213817279618293793159713160723942294186664782104822285340111578010171792057232211725816072811901177421311837198118422101219816412215285152881511535030869336177389331776001157815413278266356785263457872413078908114804137480589228818265112022012212046540512104912412130041812137741912185038312192312512237040912289513512309937612361311812387045412393645512440339812447613612492413712557129712571147812598148912600929912605049012653349512720320912743450612746038812750250712810539097074phosphatidylinositol 4,5-diphosphatePhosphatidylinositol 4,5-bisphosphate is considered to be a practically insoluble (in water) and relatively neutral molecule. Phosphatidylinositol 4,5-diphosphate has the chemical formula C47H80O19P3, and an average molecular weight of 1042.048. Phosphatidylinositol 4,5-diphosphate is involved in few pathways, which are EGF Signalling Pathway, EGF Signalling Pathway, EGF Signalling Pathway, and EGF Signalling Pathway.24742074CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)O[C@@H]1[C@H](O)[C@H](O)[C@@H](OP([O-])([O-])=O)[C@H](OP([O-])([O-])=O)[C@H]1O)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCCC47H80O19P3InChI=1S/C47H85O19P3/c1-3-5-7-9-11-13-15-17-19-20-22-24-26-28-30-32-34-36-41(49)63-39(37-61-40(48)35-33-31-29-27-25-23-21-18-16-14-12-10-8-6-4-2)38-62-69(59,60)66-45-42(50)43(51)46(64-67(53,54)55)47(44(45)52)65-68(56,57)58/h11,13,17,19,22,24,28,30,39,42-47,50-52H,3-10,12,14-16,18,20-21,23,25-27,29,31-38H2,1-2H3,(H,59,60)(H2,53,54,55)(H2,56,57,58)/p-5/b13-11-,19-17-,24-22-,30-28-/t39?,42-,43+,44+,45-,46-,47-/m1/s1CNWINRVXAYPOMW-WJUYXORRSA-I1042.0481041.450664914-4.593-5-5PW_C097074P45D808528406821,2-diacylglycerolHMDB0061362(±)-glycerol 1,2-diacetate, also known as 1,2-diacylglycerol or 1,2-diacetin, belongs to the class of organic compounds known as 1,2-diacylglycerols. These are diacylglycerols containing a glycerol acylated at positions 1 and 2 (±)-glycerol 1,2-diacetate is soluble (in water) and a very weakly acidic compound (based on its pKa). Within the cell, (±)-glycerol 1,2-diacetate is primarily located in the cytoplasm. In humans, (±)-glycerol 1,2-diacetate is involved in the lamivudine metabolism pathway and the inositol metabolism pathway.CC(=O)OCC(CO)OC(C)=OC7H12O5InChI=1S/C7H12O5/c1-5(9)11-4-7(3-8)12-6(2)10/h7-8H,3-4H2,1-2H3UXDDRFCJKNROTO-UHFFFAOYSA-N(2R)-1-(formyloxy)-3-hydroxypropan-2-yl acetate176.1672176.068473494-0.381(2R)-1-(formyloxy)-3-hydroxypropan-2-yl acetate002,3-diacetin;Glycerol diacetate;1,2-diacetin;(hydroxymethyl)ethylene acetate;Glycerin diacetate;Glycerine diacetate;1,2,3-propanetriol, diacetate;Acetin, di-;1,2-diacylglycerol;1,2-diacetylglycerol;Acetin, 1,2-di-;Diacetylglycerol;Acetic acid, diglyceride;Glycerol 1,2-diacetate;Glyceryl diacetate;2,3-diacetoxypropan-1-ol;3-hydroxypropane-1,2-diyl diacetate;2,3-diacetoxypropanol;Estol 1582;Estol 1583PW_C04068212DIAC44222497756497943742016078187132808538122000124124553118126149299127756388986Guanosine 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_C000986GTP81824041939240911441537350068553841036043155610316164901787478222117531151176919811981151127252906932717696222577144133775441117795113280025368800883088012116489113253119985406120066122121204124122768120122818135123774118125365479125443297126480299126907501126982205128051388936Guanosine 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_C000936GDP8382384176214239124154735007855382103604115561011616488178747622211754115117712111182319812727290133951516932217714213377546111779521328002336880080308801221648911525311998340612006812212120512412184740512276612012282013512377511812440037612536347912544529712690550112698420597004Phosphate ionPhosphate ion, also known as orthophosphate or [PO4](3-), belongs to the class of inorganic compounds known as non-metal phosphates. These are inorganic non-metallic compounds containing a phosphate as its largest oxoanion. Inorganic salts of phosphoric acid.\n1061[O-]P([O-])([O-])=OO4PInChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)/p-3NBIIXXVUZAFLBC-UHFFFAOYSA-Kphosphate94.971494.953420phosphate-3-2PW_C097003PhosIon80534840075Guanosine 3',5'-bis(diphosphate)HMDB0059638Guanosine 3,5-bis(diphosphate), also known as guanosine-5',3'-tetraphosphate or tetraphosphate, guanosine, belongs to the class of organic compounds known as purine ribonucleoside diphosphates. These are purine ribobucleotides with diphosphate group linked to the ribose moiety. Guanosine 3,5-bis(diphosphate) is soluble (in water) and a moderately acidic compound (based on its pKa). Guanosine 3,5-bis(diphosphate) exists in all living organisms, ranging from bacteria to humans. Guanosine 3,5-bis(diphosphate) is part of the Purine metabolism pathway. It is a substrate for: Guanosine-3,5-bis(diphosphate) 3-pyrophosphohydrolase MESH1.C0122843945017633388557[H][C@]1(COP(O)(=O)OP(O)(O)=O)O[C@@]([H])(N2C=NC3=C2NC(=N)N=C3O)[C@]([H])(O)[C@]1([H])OP(O)(=O)OP(O)(O)=OC10H17N5O17P4InChI=1S/C10H17N5O17P4/c11-10-13-7-4(8(17)14-10)12-2-15(7)9-5(16)6(30-36(26,27)32-34(21,22)23)3(29-9)1-28-35(24,25)31-33(18,19)20/h2-3,5-6,9,16H,1H2,(H,24,25)(H,26,27)(H2,18,19,20)(H2,21,22,23)(H3,11,13,14,17)/t3-,5-,6-,9-/m1/s1BUFLLCUFNHESEH-UUOKFMHZSA-N{[hydroxy({[(2R,3S,4R,5R)-4-hydroxy-2-({[hydroxy(phosphonooxy)phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}phosphonic acid603.1603602.956990191-1.7710{hydroxy[(2R,3S,4R,5R)-4-hydroxy-2-({[hydroxy(phosphonooxy)phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3H-purin-9-yl)oxolan-3-yl]oxyphosphoryl}oxyphosphonic acid0-5Guanosine 3'-diphosphate 5'-diphosphate;Guanosine 5'-diphosphate,3'-diphosphate;Guanosine-5',3'-tetraphosphate;Guanosine 3'-diphosphoric acid 5'-diphosphoric acid;Guanosine 3',5'-bis(diphosphoric acid);Guanosine 5'-diphosphoric acid,3'-diphosphoric acid;Guanosine-5',3'-tetraphosphoric acidPW_C040075G53T8096681944Pro-epidermal growth factorP01133EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6HMDBP02438EGF4q25X04571111649228116518808493081351Epidermal growth factor receptorP00533Isoform 2 may act as an antagonist of EGF actionHMDBP01456EGFR7p12AY58824612.7.10.13399234071411650228808503082381-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1P19174Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration.
HMDBP00244PLCG120q12-q13.1CH47107713.1.4.11421728022988059022882835308889961414389Protein kinase C alpha typeP17252
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
PRKCA12.7.11.138026188026227802632311279Protein 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 promotersHMDBP01372PRKCB16p11.2FJ90724612.7.11.136938888005216480414745770ETS domain-containing protein Elk-1P19419ELK114089234166280327894260271184Mitogen-activated protein kinase 3P27361Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1. Phosphorylates heat shock factor protein 4 (HSF4)HMDBP01263MAPK316p11.2AC01264512.7.11.2411659880758231227Tyrosine-protein kinase JAK1P23458Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptorHMDBP01309JAK11p32.3-p31.3BC13272912.7.10.28085888953Signal transducer and activator of transcription 1-alpha/betaP42224
Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4.
STAT1111661880953238930Signal transducer and activator of transcription 3P40763
Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G (By similarity).
STAT3111660880952231703GTPase HRasP01112Ras proteins bind GDP/GTP and possess intrinsic GTPase activityHMDBP01958HRAS11p15.5BC00649914092144235243718805351827233088911425314459GTPase HRasP0111218088581084RAF proto-oncogene serine/threonine-protein kinaseP04049Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3HMDBP01153RAF13p25M1137612.7.11.1423624544141165781067Mitogen-activated protein kinase kinase kinase 1Q13233Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathwayHMDBP01134MAP3K15q11.2AC00893712.7.11.254097280348228803578134682145788Dual specificity mitogen-activated protein kinase kinase 1Q02750Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.MAP2K112.7.12.2423724545148032681274Dual specificity mitogen-activated protein kinase kinase 4P45985Dual specificity kinase that activates the JUN kinases MAPK8 (JNK1) and MAPK9 (JNK2) as well as MAPK14 (p38) but not MAPK1 (ERK2) or MAPK3 (ERK1)HMDBP01366MAP2K417p11.2CH47110812.7.12.2422828035881424Mitogen-activated protein kinase 8P45983JNK1 isoforms display different binding patterns:beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta- 2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoformsHMDBP01536MAPK810q11.22CH47118712.7.11.24410328036088076423949012713467716613470071783Transcription factor AP-1P05412Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'HMDBP02090JUN1p32-p31BC00617514109234170280286894902278784Proto-oncogene c-FosP01100
Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.
FOS1809512385949894903278954Signal transducer and activator of transcription 2P52630
Signal transducer and activator of transcription that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state.
STAT2111662880954239533Signal transducer and activator of transcription 6P42226
Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling.
STAT6111663880955231331Casein kinase II subunit alphaP68400Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. The alpha and alpha' chains contain the catalytic site. Participates in Wnt signaling. CK2 phosphorylates 'Ser-392' of p53/TP53 following UV irradiationHMDBP01433CSNK2A120p13X7025112.7.11.1809572394934278746Serum response factorP11831
SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as FOS). Required for cardiac differentiation and maturation.
SRF18008688095823131574279226Ras GTPase-activating protein 1P20936
Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1.
RASA118096085154Growth factor receptor-bound protein 2P62993Isoform GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell deathHMDBP11487GRB217q24-q25AF0636141423126553351165485797SHC-transforming protein 1P293531438021165283798Son of sevenless homolog 1Q07889Promotes the exchange of Ras-bound GDP by GTPHMDBP08580SOS12p21L138571423221165585205pro-epidermal growth factor1PW_P005205125181944822Epidermal growth factor receptor1PW_P0008229461351278251-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma_11PW_P007825158682388085587714Protein kinase C complex1PW_P00771115669143891567012798053087826ETS domain-containing protein Elk_11PW_P00782615869577080856235207Mitogen-activated protein kinase 31PW_P0052071252411847827Tyrosine-protein kinase JAK11PW_P0078271587012278085787828Signal transducer and activator of transcription 1-alpha/beta1PW_P0078281587189538085987829Signal transducer and activator of transcription 31PW_P007829158728930808608954GTPase HRas with GTP1PW_P00095410801703139798617831GTPase HRas with GDP, Phosphate1PW_P0078311587414459804936805970048088487832RAF proto-oncogene serine/threonine-protein kinase without zinc1PW_P0078321587510848088687833Mitogen-activated protein kinase kinase kinase 1 without Magnesium1PW_P0078331587610678088787724Dual specificity mitogen-activated protein kinase kinase 11PW_P0077241569757888054781014Dual specificity mitogen-activated protein kinase kinase 41PW_P0010141158127417834Mitogen-activated protein kinase 8 without Magnesium1PW_P0078341587714248088887847FOS,JUN Complex1PW_P00784715896178315897878480950235208STATs1PW_P0052081252589301252689531252789541252895337848Casein kinase II subunit alpha1PW_P0078481589813318095687532Serum response factor1PW_P00753215408874680076237849Ras GTPase-activating protein 11PW_P0078491589992268095981025Growth factor receptor-bound protein 21PW_P0010251169515411074SHC-transforming protein 11PW_P0010741234579711026Son of sevenless homolog 11PW_P00102611703798110121-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-11PW_P001012115623814193531110956PW_R110956Right403706970741Compoundfalse403707406821Compoundfalse1011891012110957PW_R110957Right403708970741Compoundfalse40370911551Compoundfalse1011901012110971PW_R110971Right4037419861Compoundfalse403742400751Compoundfalse198ActivationPW_I0001983955205ProteinComplex1396822ProteinComplex1637ActivationPW_I00063712731155Compound11274353Compound1640ActivationPW_I00064012797825ProteinComplex1128097074Compound1641ActivationPW_I000641128140682Compound112827714ProteinComplex1642ActivationPW_I00064212837714ProteinComplex112847826ProteinComplex1643ActivationPW_I00064312855207ProteinComplex112867826ProteinComplex1644ActivationPW_I0006441287822ProteinComplex112887827ProteinComplex1645ActivationPW_I00064512897827ProteinComplex112907828ProteinComplex1646ActivationPW_I00064612917827ProteinComplex112927829ProteinComplex1669ActivationPW_I0006691337954ProteinComplex113387831ProteinComplex1671ActivationPW_I0006711341954ProteinComplex113427832ProteinComplex1672ActivationPW_I0006721343954ProteinComplex113447833ProteinComplex1673ActivationPW_I00067313457832ProteinComplex113467724ProteinComplex1674ActivationPW_I00067413477833ProteinComplex113487724ProteinComplex1676ActivationPW_I00067613517724ProteinComplex113525207ProteinComplex1677ActivationPW_I00067713537833ProteinComplex113541014ProteinComplex1678ActivationPW_I00067813551014ProteinComplex113567834ProteinComplex1706ActivationPW_I00070614117834ProteinComplex114127847ProteinComplex1708ActivationPW_I00070814157829ProteinComplex114165208ProteinComplex1710ActivationPW_I00071014197826ProteinComplex114207847ProteinComplex1711ActivationPW_I00071114217848ProteinComplex114227532ProteinComplex1717ActivationPW_I00071714337849ProteinComplex114347831ProteinComplex1566ActivationPW_I0005661131822ProteinComplex111321025ProteinComplex1722ActivationPW_I0007221443822ProteinComplex114441074ProteinComplex1723ActivationPW_I0007231445822ProteinComplex114461026ProteinComplex1724ActivationPW_I0007241447822ProteinComplex114487849ProteinComplex1725ActivationPW_I00072514491026ProteinComplex11450986Compound11590153115583false57352810regular1001201590154353851false58383410regular787815901559707483false47632310regular10011015901564068283false30143310regular100110159018098689false168066910regular10035159018193689false160041910regular1003515901829700489false160039910regular100251590245986854false148854010regular503015902524007583false146365010regular10012059626519443082false8681158subunitregular15070596266135130880false8382158subunitregular20013059627423882false7463038subunitregular150705962751438982false2766938subunitregular15070596276127982false2767538subunitregular15070596277577082false4819688subunitregular150705962781184232false2269688subunitregular15070596279122782false8884308subunitregular15070596280895382false8136258subunitregular15070596281893082false9636258subunitregular15070596363170382false16506848subunitregular150705963641445982false15754448subunitregular15070596366108482false14558218subunitregular15070596367106782false17608568subunitregular15070596368578882false14559818subunitregular15070596371118482false145511318subunitregular15070596372127482false17609818subunitregular15070596373142482false176012568subunitregular150705966211783232false8709718subunitregular150705966228784232false87010318subunitregular150705966318930232false67311158subunitregular150705966328953232false67311758subunitregular150705966338954232false56811508subunitregular150705966349533232false56812108subunitregular150705966351331232false24611618subunitregular150705966368746232false53610468subunitregular15070596642922682false17754468subunitregular15070596647515482false11534158subunitregular15070596651579782false12183408subunitregular15070596652379882false11885208subunitregular15070596653922682false14482958subunitregular150704838055205645713085947845962654838068226457130859478559626648381378256457185947935962744838147714645718594794596275594795596276483815782664571859479659627748381652076457123594797596278483817782764571859479859627948381878286457185947995962804838197829645718594800596281483889954645718594870596363838815901802169448Cofactor4838907831645718594871596364838915901812169450Cofactor839015901822169451Cofactor48389278326457185948735963664838937833645718594874596367483894772464571859487559636848389752076457185948785963714838981014645718594879596372483899783464571859488059637348402478476457123595126596621595127596622484030520864571235951365966315951375966325951385966335951395966344840317848645712359514059663548403275326457123595141596636484038784964571859514759664248404310256457185951525966474840471074645718595156596651484048102664571859515759665248404978496457185951585966532169230M1023 100 C1053 100 618 175 648 175 149true182169231M943 240 C944 208 943 234 943 185 149false18trueM 900.9468550441649 321.261556296296 L 886 320 L 892.3808877211858 333.5751343230783false2169241M673 588 C703 588 712.5 588 742.5 588 149true182169242M622 834 C623 793 622 710 623 648 149false18trueM 498.94685504416486 334.261556296296 L 484 333 L 490.38088772118584 346.5751343230783false2169243M621 268 C651 268 161 203 191 203 5true182169244M401 488 C449 488 475 488 527 488 C527 444 527 469 526 433 5false18trueM 498.94685504416486 334.261556296296 L 484 333 L 490.38088772118584 346.5751343230783false2169247M621 268 C651 268 587 273 617 273 5true182169248M623 528 C624 495 624 411 624 378 C605 378 589 378 576 378 5false18trueM 498.94685504416486 272.261556296296 L 484 271 L 490.38088772118584 284.5751343230783false2169252M476 378 C446 378 468.5 273 438.5 273 149true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false2169253M821 373 C821 405 821 411 822 433 C759 433 602 431 526 433 149false18trueM 882.5096189432334 453.5 L 895.5 446 L 882.5096189432334 438.5false2169254M401 488 C431 488 433.5 463 463.5 463 149true182169255M351 693 C351 640 352 600 351 543 149false18trueM 588.9468550441649 433.261556296296 L 574 432 L 580.3808877211858 445.5751343230783false2169256M426 788 C456 788 471 758 501 758 149true182169257M481 1003 C482 906 482 860 484 788 C444 788 467 788 426 788 149false18trueM 600.9468550441649 768.261556296296 L 586 767 L 592.3808877211858 780.5751343230784false2169258M376 1003 C406 1003 296 1023 326 1023 149true182169259M481 1003 C445 1003 411 1003 376 1003 149false18trueM 600.9468550441649 768.261556296296 L 586 767 L 592.3808877211858 780.5751343230784false2169264M1038 285 C1068 285 1075.5 280 1105.5 280 149true182169265M963 430 C964 398 964 368 963 330 149false18trueM 600.9468550441649 407.261556296296 L 586 406 L 592.3808877211858 419.5751343230783false2169268M1038 465 C1068 465 1083 480 1113 480 149true182169269M888 625 C888 583 888 525 888 465 149false18trueM 600.9468550441649 417.261556296296 L 586 416 L 592.3808877211858 429.5751343230783false2169270M1038 465 C1068 465 1083 480 1113 480 149true182169271M1038 625 C1039 561 1037 523 1038 465 149false18trueM 1457.0096189432334 830.5 L 1470 823 L 1457.0096189432334 815.5false2169448M1635 664 L1635 714 L1685 664 z10true182169449M1800 719 C1830 719 1065 151.5 1095 151.5 149true182169450M1620 419 L1620 469 L1670 419 z10true182169451M1620 399 L1620 449 L1670 399 z10true182169452M1650 514 C1651 583 1650 649 1650 719 149false18trueM 1352.9468550441647 325.261556296296 L 1338 324 L 1344.380887721186 337.5751343230783false2169455M1800 719 C1830 719 1810 716.5 1840 716.5 149true182169456M1530 821 C1600 821 1672 822 1725 821 C1725 806 1726 766 1725 754 149false18trueM 920.9468550441649 469.261556296296 L 906 468 L 912.3808877211858 481.5751343230783false2169457M1800 719 C1830 719 1810 716.5 1840 716.5 149true182169458M1835 856 C1835 813 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