108936PathwayActivation of PKC Through G Protein-Coupled ReceptorG protein-coupled receptors sense stimuli outside the cell and transmit signals across the plasma membrane. Activation of protein kinase C (PKC) is one of the common signaling pathways. When a class of GPCRs are activated by a ligand, they activate Gq protein to bind GTP instead of GDP. After the Gq becomes active, it activates phospholipase C (PLC) to cleave the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacyl glycerol (DAG). IP3 can bind Ins3P receptor to open calcium channel by diffusion from cytoplasm to ER. Activated calcium channel will release the calcium from ER into cytoplasm. Calcium can activate the kinase activity of PKC.SignalingPW109042CenterPathwayVisualizationContext10931817001700#000099PathwayVisualization108799108936Activation of PKC Through G Protein-Coupled ReceptorG protein-coupled receptors sense stimuli outside the cell and transmit signals across the plasma membrane. Activation of protein kinase C (PKC) is one of the common signaling pathways. When a class of GPCRs are activated by a ligand, they activate Gq protein to bind GTP instead of GDP. After the Gq becomes active, it activates phospholipase C (PLC) to cleave the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacyl glycerol (DAG). IP3 can bind Ins3P receptor to open calcium channel by diffusion from cytoplasm to ER. Activated calcium channel will release the calcium from ER into cytoplasm. Calcium can activate the kinase activity of PKC.Signaling52Platelet 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:00057377Endoplasmic Reticulum MembraneGO:000578911Extracellular SpaceGO:000561519sarcoplasmic reticulumGO:00165292MitochondrionGO:000573924Mitochondrial Intermembrane SpaceGO:000575825Golgi apparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:00057436LysosomeGO:000576416Lysosomal LumenGO:004320236MembraneGO:00160203Mitochondrial MatrixGO:000575935ChloroplastGO:00095072Endothelium 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_BS00002449711PW_BS0000493317121PW_BS000028383751PW_BS000100390761PW_BS0001123987171PW_BS00011315111PW_BS000015215114PW_BS0000213551914PW_BS0000353211PW_BS000003471914PW_BS000047422411PW_BS000042432511PW_BS0000435811411PW_BS000058171211PW_BS0000179611PW_BS000009711113PW_BS00007172513PW_BS00007229111PW_BS0000296618518PW_BS000066101711PW_BS0000102811611PW_BS0000281115121PW_BS000111101531PW_BS000101205561PW_BS0000242111018PW_BS0000241901118PW_BS0000242137181PW_BS0000241985181PW_BS00002421013181PW_BS0000241644PW_BS000164151141PW_BS00015135625121PW_BS00002834524121PW_BS00002813013121PW_BS0001301141112PW_BS0001147413PW_BS000074228361PW_BS0000245181PW_BS000051122551PW_BS0001224182451PW_BS0001154192551PW_BS0001151251351PW_BS000125409115PW_BS0001151355171PW_BS00013545424171PW_BS00011545525171PW_BS00011513613171PW_BS0001361371117PW_BS0001372975101PW_BS00002448924101PW_BS00011549025101PW_BS0001154957101PW_BS0001155062461PW_BS0001155072561PW_BS0001154311PW_BS000004731013PW_BS00007385241011PW_BS000085103331PW_BS0001031553241PW_BS0001551613181PW_BS0001611783211PW_BS000178222341PW_BS0000242905491PW_BS0000241333121PW_BS0001333683601PW_BS000028253541PW_BS000024406351PW_BS0001151203171PW_BS0001204793101PW_BS000115501361PW_BS0001152253541PW_BS0000241825PW_BS0000243851051PW_BS000100569154PW_BS000314140PW_B00014036310518ProteinComplex1364936Compound1141PW_B00014136510518ProteinComplex1366986Compound1936Guanosine 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_C000986GTP818240419392409114415373500685538410360431556103161649017874782221175311511769198119811511272529069327176962225771441337754411177951132800253688008830880121164891132531199854061200661221212041241227681201228181351237741181253654791254432971264802991269075011269822051280513886174PIP2(20:4(5Z,8Z,11Z,14Z)/18:0)HMDB0010133PIP2(20:4(5Z,8Z,11Z,14Z)/18:0) is a phosphatidylinositol bisphosphate. Phosphatidylinositol bisphosphates are acidic (anionic) phospholipids that consist of a phosphatidic acid backbone, linked via the phosphate group to a bisphosphorylated inositol (hexahydroxycyclohexane). Phosphatidylinositol bisphosphates are generated from phosphatidylinositols which are phosphorylated by a number of different kinases that place the phosphate moiety on positions 4 and 5 of the inositol ring, although position 3 can also be phosphorylated. Phosphatidylinositols bisphosphates can have many different combinations of fatty acids of varying lengths and saturation attached at the C-1 and C-2 positions. Fatty acids containing 18 and 20 carbons are the most common. PIP2(20:4(5Z,8Z,11Z,14Z)/18:0), in particular, consists of one chain of arachidonic acid at the C-1 position and one chain of stearic acid at the C-2 position. The arachidonic acid moiety is derived from animal fats and eggs, while the stearic acid moiety is derived from animal fats, coco butter and sesame oil. The most important phosphatidylinositol bisphosphate in both quantitative and biological terms is phosphatidylinositol 4,5-bisphosphate. Phosphatidylinositol and the phosphatidylinositol phosphates are the main source of diacylglycerols that serve as signaling molecules, via the action of phospholipase C enzymes. Phosphatidylinositols phosphates are usually present at low levels only in tissues, typically at about 1 to 3% of the concentration of phosphatidylinositol.C0062653480324Phosphatidylinositols24768010CCCCCCCCCCCCCCCCCC(=O)O[C@]([H])(COC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC)COP(O)(=O)O[C@H]1C(O)C(O)C(OP(=O)(O)O)[C@@H](OP(=O)(O)O)C1OC47H85O19P3InChI=1S/C47H85O19P3/c1-3-5-7-9-11-13-15-17-19-20-22-23-25-27-29-31-33-35-40(48)61-37-39(63-41(49)36-34-32-30-28-26-24-21-18-16-14-12-10-8-6-4-2)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/h11,13,17,19,22-23,27,29,39,42-47,50-52H,3-10,12,14-16,18,20-21,24-26,28,30-38H2,1-2H3,(H,59,60)(H2,53,54,55)(H2,56,57,58)/b13-11-,19-17-,23-22-,29-27-/t39-,42?,43?,44?,45+,46?,47+/m1/s1WSOUXFSBLZNSFX-POGCKTLGSA-N{[(4S,6S)-2,3,5-trihydroxy-4-({hydroxy[(2R)-3-[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyloxy]-2-(octadecanoyloxy)propoxy]phosphoryl}oxy)-6-(phosphonooxy)cyclohexyl]oxy}phosphonic acid1047.08771046.489790074-4.638[(4S,6S)-2,3,5-trihydroxy-4-{[hydroxy(2R)-3-[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyloxy]-2-(octadecanoyloxy)propoxyphosphoryl]oxy}-6-(phosphonooxy)cyclohexyl]oxyphosphonic acid0-5C006261-(5z,8z,11z,14z-eicosatetraenoyl)-2-octadecanoyl-sn-glycero-3-phospho-(1'-myo-inositol-3',4'-bisphosphate);1-arachidonoyl-2-stearoyl-sn-glycero-3-phosphoinositol-bisphosphate;1-phosphatidyl-d-myo-inositol 4,5-bisphosphate;Pip2(20:4/18:0);Pip2(20:4n6/18:0);Pip2(20:4w6/18:0);Pip2(38:4);Pip2[3',4'](20:4(5z,8z,11z,14z)/18:0);Phosphatidylinositol diphosphate(20:4/18:0);Phosphatidylinositol diphosphate(20:4n6/18:0);Phosphatidylinositol diphosphate(20:4w6/18:0);Phosphatidylinositol diphosphate(38:4)PW_C006174PIP22041155Inositol 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_C001155Inotp27416658220372325751427924673871607409218122142856934417816912878211132785161157999918800893088023781219754101224421241225114051245284441250091181250813761261244851265932991266644781277325161281653881282412093221DG(18:0/20:4(5Z,8Z,11Z,14Z)/0:0)HMDB0007170DG(18:0/20:4(5Z,8Z,11Z,14Z)/0:0) is a diglyceride, or a diacylglycerol (DAG). It is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Diacylglycerols can have many different combinations of fatty acids attached at both the C-1 and C-2 positions. DG(18:0/20:4(5Z,8Z,11Z,14Z)/0:0), in particular, consists of one chain of stearic acid at the C-1 position and one chain of arachidonic acid at the C-2 position. The stearic acid moiety is derived from animal fats, coco butter and sesame oil, while the arachidonic acid moiety is derived from animal fats and eggs. Mono- and diacylglycerols are common food additives used to blend together certain ingredients, such as oil and water, which would not otherwise blend well. Dacylglycerols are often found in bakery products, beverages, ice cream, chewing gum, shortening, whipped toppings, margarine, and confections. Synthesis of diacylglycerol begins with glycerol-3-phosphate, which is derived primarily from dihydroxyacetone phosphate, a product of glycolysis (usually in the cytoplasm of liver or adipose tissue cells). Glycerol-3-phosphate is first acylated with acyl-coenzyme A (acyl-CoA) to form lysophosphatidic acid, which is then acylated with another molecule of acyl-CoA to yield phosphatidic acid. Phosphatidic acid is then de-phosphorylated to form diacylglycerol.Diacylglycerols are precursors to triacylglycerols (triglyceride), which are formed by the addition of a third fatty acid to the diacylglycerol under the catalysis of diglyceride acyltransferase. Since diacylglycerols are synthesized via phosphatidic acid, they will usually contain a saturated fatty acid at the C-1 position on the glycerol moiety and an unsaturated fatty acid at the C-2 position.65914-84-3C00165643858775728DIACYLGLYCEROL4943054[H][C@](CO)(COC(=O)CCCCCCCCCCCCCCCCC)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCCC41H72O5InChI=1S/C41H72O5/c1-3-5-7-9-11-13-15-17-19-20-22-24-26-28-30-32-34-36-41(44)46-39(37-42)38-45-40(43)35-33-31-29-27-25-23-21-18-16-14-12-10-8-6-4-2/h11,13,17,19,22,24,28,30,39,42H,3-10,12,14-16,18,20-21,23,25-27,29,31-38H2,1-2H3/b13-11-,19-17-,24-22-,30-28-/t39-/m0/s1NSXLMTYRMFVYNT-IUJDHQGTSA-N(2S)-1-hydroxy-3-(octadecanoyloxy)propan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate645.0074644.537975414-7.681diacylglycerol00FDB0243641-stearoyl-2-arachidonoyl-sn-glycerol;Dag(18:0/20:4);Dag(18:0/20:4n6);Dag(18:0/20:4w6);Dag(38:4);Dg(18:0/20:4);Dg(18:0/20:4n6);Dg(18:0/20:4w6);Dg(38:4);Diacylglycerol;Diacylglycerol(18:0/20:4);Diacylglycerol(18:0/20:4n6);Diacylglycerol(18:0/20:4w6);Diacylglycerol(38:4);Diglyceride;(2s)-1-hydroxy-3-(stearoyloxy)propan-2-yl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate;1-octadecanoyl-2-(5z,8z,11z,14z-eicosatetraenoyl)-sn-glycerol;1-stearoyl-2-arachidonoylglycerol;Dag(18:0/20:4omega6);Dg(18:0/20:4(5z,8z,11z,14z)/0:0);Dg(18:0/20:4(5z,8z,11z,14z)/0:0)[iso2];Dg(18:0/20:4(omega-6)/0:0);Dg(18:0/20:4/0:0)[iso2];Dg(18:0/20:4omega6);Diacylglycerol(18:0/20:4omega6);(2s)-1-hydroxy-3-(stearoyloxy)propan-2-yl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoic acidPW_C003221DG38:416681498434933198149383115067390117380398353CalciumHMDB0000464Calcium 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+27616303855314601294115993219973510463116346116447147849149142155243211658213817279618293793159713160723942294186664782104822285340111578010171792057232211725816072811901177421311837198118422101219816412215285152881511535030869336177389331776001157815413278266356785263457872413078908114804137480589228818265112022012212046540512104912412130041812137741912185038312192312512237040912289513512309937612361311812387045412393645512440339812447613612492413712557129712571147812598148912600929912605049012653349512720320912743450612746038812750250712810539079G protein-coupled receptorCompoundProteinComplexPW_EC000079GPCR19709Inositol 1,4,5-trisphosphate receptor type 1Q7M2U0
Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways.
ITPR1513304212213413112519705Guanine nucleotide-binding protein subunit alpha-11Q2TA47
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
GNA115131852405131857182135019122135141385174061-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1P10894
The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
PLCB153.1.4.1112251240513185318213186712213300238513411756919608Protein kinase C alpha typeP04409
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, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP. Depending on the cell type, is 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 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. Depending on the cell type, exhibits anti-apoptotic function and protects cells from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or 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. 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.
PRKCA52.7.11.1313192612213298112410518Guanine nucleotide-binding protein G(q)5PW_P0105181895219705110520Inositol 1,4,5-trisphosphate receptor5PW_P0105201895419709110519Phospholipase C, beta 15PW_P0105191895317406110521Protein kinase C5PW_P01052118955196081173900falsePW_R173900Right65537961741Compoundfalse65538011551Compoundfalse65538132211Compoundtrue164186105193.1.4.119386PW_T00938696573531Compound125122Right1156105202018-08-21T17:21:19-06:002018-08-21T17:21:19-06:003831106ActivationPW_I001106221179ElementCollection12212140Bound11303ActivationPW_I0013032605141Bound1260610519ProteinComplex11108ActivationPW_I00110822151155Compound1221610520ProteinComplex11109ActivationPW_I00110922173221Compound1221810521ProteinComplex11110ActivationPW_I0011102219353Compound1222010521ProteinComplex11335140405108799880266991336378581955796949363785913361411087998812669915363786119567969513637862266991393640553false56527210regular5030266991598654false103526710regular50302669908617481false133016010regular2001902669909115581false87070010regular2001902669910322181false133075010regular200190266991135312551false490113010regular7878266991235312251false1063113010regular787826699143539false132046410regular100251392179200405false20012512regular200130933205197054052false5151628proteinregular15070933207197052false9851628subunitregular150709332041970976false74811348subunitregular15070933206174062false13554148proteinregular15070933208196082false135611318subunitregular15070796949105181087994059295539332057969511051810879992955593320779694810520108799929552933204796950105191087999295549332063418026699143637874Cofactor796952105211087999295569332083463599M665 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5false183598629M910 272 C910 243 886 197 844 197 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637858M590 232 C590 258 590 248 590 272 10false183637859M11 1319.5 C34 1335.5 74 1362.5 98 1379.5 5true183637860M665 197 C695 197 769 197 816 197 5false183637861M1060 232 C1060 268 1060 232 1060 267 10false183637862M11 1239 C34 1255 74 1282 98 1299 5true183637863M985 197 C955 197 868 197 815 197 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637864M745 272 C745 241 776 197 808 197 5false183637865M910 272 C910 243 886 197 844 197 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637866M1430 350 C1430 393 1430 373 1430 414 5false18falsefalse3637867M1070 795 C1139 789 1430 553 1430 484 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637868M1430 750 C1430 696 1430 558 1430 484 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637869M568 1169 C598 1169 718 1169 748 1169 83false183637870M1063 1169 C1033 1169 928 1169 898 1169 83false18trueM 965.0096189432334 976.5 L 978 969 L 965.0096189432334 961.5false3637871M515 197 C464 197 469 195 400 195 149false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637872M350 335 C380 335 517.25 303 541.25 320 149true183637873M1135 197 C1165 197 1256 392.5 1280 409.5 149true183637874M1505 474.5 L1505 524.5 L1555 474.5 z10true183637875M1355 449 C1230 449 1223 197 1135 197 149false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637876M1070 795 C1100 795 963.5 663 987.5 680 149true183637877M823 1134 C823 970 970 1012 970 890 149false18trueM 742.9903810567666 642.5 L 730 650 L 742.9903810567666 657.5falsefalsefalse3637878M1430 940 C1430 982 1431 1087 1431 1131 149false18trueM 1647.5 777.0096189432334 L 1655 790 L 1662.5 777.0096189432334false3637879M1356 1166 C1326 1166 1506 828 1530 845 149true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3637880M1141 1169 C1171 1169 1285 1166 1356 1166 149false18trueM 1081.0096189432334 1315.5 L 1094 1308 L 1081.0096189432334 1300.5false3637881M1356 1166 C1326 1166 1155 1152 1179 1169 149true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false794750108799173900321604426699083637866Left321604526699093637867Right321604626699103637868Right77251938610879915520126699113637869Left15520226699123637870Right24183796948115655741106108799405129613353637871Right2025139213637872Left55751303108799129713363637873Left63267969503637875Right55761108108799148426699093637876Left63277969483637877Right55771109108799148526699103637878Left63287969523637879Right55781110108799148626699123637880Left63297969523637881Right185385663004151.31.3023280360368881M254 1051 C254 1001 304 951 354 951 C466 951 612 951 724 951 C774 951 824 1001 824 1051 C824 1126 824 1225 824 1300 C824 1350 774 1400 724 1400 C612 1400 466 1400 354 1400 C304 1400 254 1350 254 1300 C254 1225 254 1126 254 1051 91true6570.0449.0368882M80 295 C80 245 130 195 180 195 C529 195 983 195 1332 195 C1382 195 1432 245 1432 295 C1432 655 1432 1122 1432 1482 C1432 1532 1382 1582 1332 1582 C983 1582 529 1582 180 1582 C130 1582 80 1532 80 1482 C80 1122 80 655 80 295 1true61352.01387.044809915Endoplasmic Reticulum320630201.01.01601544810015Extracellular Space64530201.01.01601544810115Intracellular Space850435201.01.01601518002946074522492189814294#FFEEDE4674508