64690PathwayGnRH Signaling PathwayGonadotropin-releasing hormone (GnRH), a hypothalamic neuropeptide, is a main regulator of male and female reproductive function in mammals. GnRH is required for reproduction. GnRH is secreted from the hypothalamus and acts on G-protein coupled receptors in the anterior pituitary. GnRH regulates the production and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) gonadotropins, controlling gametogenesis and steroidogenesis. Activated phospholipase C activates IP3 to release intracellular calcium from the endoplasmic reticulum thereby increasing cytoplasmic calcium. Diacylglycerol is also activated by phospholipase C to stimulate the PKC pathway. The PKC pathway leads to the activation of epidermal growth factor (EGF) receptor and mitogen-activated protein kinases (MAPKs), extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. MAPKs are activated and translocate to the nucleus causing the transcription of gonadotropin genes. GnRH also activates G proteins causing the activation of adenylyl cyclase to generate cAMP. cAMP stimulates PKA to phosphorylate and activate transcription factors that translocate to the nucleus for gene transcription. GnRH also promotes secretion of metalloproteinases (MMPs) which regulate the transcription of gonadotropin subunit genes and the GnRHR gene via autocrine/paracrine mechanisms. PKC induces the release of activated MMPs that mediate transactivation of epidermal growth factor receptor (EGFR) which may result in the modulation of gonadotropin subunit genes.ProteinPW064816CenterPathwayVisualizationContext6509228692527#000099PathwayVisualization6457264690GnRH Signaling PathwayGonadotropin-releasing hormone (GnRH), a hypothalamic neuropeptide, is a main regulator of male and female reproductive function in mammals. GnRH is required for reproduction. GnRH is secreted from the hypothalamus and acts on G-protein coupled receptors in the anterior pituitary. GnRH regulates the production and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) gonadotropins, controlling gametogenesis and steroidogenesis. Activated phospholipase C activates IP3 to release intracellular calcium from the endoplasmic reticulum thereby increasing cytoplasmic calcium. Diacylglycerol is also activated by phospholipase C to stimulate the PKC pathway. The PKC pathway leads to the activation of epidermal growth factor (EGF) receptor and mitogen-activated protein kinases (MAPKs), extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. MAPKs are activated and translocate to the nucleus causing the transcription of gonadotropin genes. GnRH also activates G proteins causing the activation of adenylyl cyclase to generate cAMP. cAMP stimulates PKA to phosphorylate and activate transcription factors that translocate to the nucleus for gene transcription. GnRH also promotes secretion of metalloproteinases (MMPs) which regulate the transcription of gonadotropin subunit genes and the GnRHR gene via autocrine/paracrine mechanisms. PKC induces the release of activated MMPs that mediate transactivation of epidermal growth factor receptor (EGFR) which may result in the modulation of gonadotropin subunit genes.Protein123000324312080Perrett RM, McArdle CA: Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network. Front Endocrinol (Lausanne). 2013 Nov 20;4:180. doi: 10.3389/fendo.2013.00180.64690Pathway23000423994024Pincas H, Choi SG, Wang Q, Jia J, Turgeon JL, Sealfon SC: Outside the box signaling: secreted factors modulate GnRH receptor-mediated gonadotropin regulation. Mol Cell Endocrinol. 2014 Mar 25;385(1-2):56-61. doi: 10.1016/j.mce.2013.08.015. Epub 2013 Aug 28.64690Pathway230005https://www.genome.jp/kegg-bin/show_pathway?hsa0491264690Pathway2Platelet CL:00002331CellCL:00000004Cardiomyocyte CL:00007463NeuronCL:00005408Beta cellCL:00006395HepatocyteCL:00001827Epithelial CellCL:00000666MyocyteCL:00001871Homo sapiens9606EukaryoteHuman12Mus musculus10090EukaryoteMouse3Escherichia coli562Prokaryote6Caenorhabditis elegans6239EukaryoteRoundworm18Saccharomyces cerevisiae4932EukaryoteYeast4Arabidopsis thaliana3702EukaryoteThale cress5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly24Solanum lycopersicum4081EukaryoteTomato21Xenopus laevis8355EukaryoteAfrican clawed frog49Bathymodiolus platifrons220390EukaryoteDeep sea mussel60Nitzschia sp.0001EukaryoteNitzschia42Bacteria2ProkaryoteBacteria19Schizosaccharomyces pombe4896Eukaryote29Saccharomyces cerevisiae (strain ATCC 204508 / S288c)559292EukaryoteBaker's yeast25Escherichia coli (strain K12)83333Prokaryote23Pseudomonas aeruginosa287Prokaryote56Andro6666Eukaryote62Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)62977Prokaryote5CytoplasmGO:000573710Cell MembraneGO:00058861CytosolGO:000582911Extracellular SpaceGO:000561519sarcoplasmic reticulumGO:00165292MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578924Mitochondrial Intermembrane SpaceGO:000575825Golgi apparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574313Endoplasmic ReticulumGO:00057836LysosomeGO:000576416Lysosomal LumenGO:004320236MembraneGO:00160203Mitochondrial MatrixGO:00057594PeroxisomeGO:000577727Peroxisome MembraneGO:000577815NucleusGO:000563426Golgi apparatus membraneGO:000013935ChloroplastGO:000950731Periplasmic SpaceGO:000562034Plant-Type VacuoleGO:000032532Inner MembraneGO:007025839Mitochondrial membraneGO:00319662Endothelium BTO:00003935cardiocyteBTO:00015391LiverBTO:000075972918PancreasBTO:00009888Blood VesselBTO:000110274117Nervous SystemBTO:000148425IntestineBTO:000064811HeartBTO:0000562731024BrainBTO:000014289169MuscleBTO:0000887141184Adrenal MedullaBTO:000004971816212PW_BS0000168511PW_BS00000814101PW_BS0000142111PW_BS00000215111PW_BS000015215114PW_BS0000213551914PW_BS0000353211PW_BS00000346114PW_BS000046471914PW_BS00004749711PW_BS000049422411PW_BS000042432511PW_BS0000435811411PW_BS000058171211PW_BS000017181311PW_BS0000189611PW_BS000009711113PW_BS00007172513PW_BS00007229111PW_BS0000296618518PW_BS000066101711PW_BS0000102811611PW_BS0000281115121PW_BS000111101531PW_BS000101205561PW_BS0000242111018PW_BS0000241601181PW_BS0001601901118PW_BS0000242137181PW_BS0000241985181PW_BS00002421013181PW_BS0000241644PW_BS0001642851041PW_BS000024151141PW_BS0001513081011PW_BS00002411PW_BS0000013317121PW_BS0000281151012PW_BS0001151321121PW_BS00013235625121PW_BS00002834524121PW_BS00002813013121PW_BS0001301141112PW_BS0001147413PW_BS000074228361PW_BS0000245181PW_BS000051122551PW_BS000122405105PW_BS000115124151PW_BS0001244182451PW_BS0001154192551PW_BS000115383751PW_BS0001001251351PW_BS000125409115PW_BS0001151355171PW_BS0001353761017PW_BS0000531181171PW_BS00011845424171PW_BS00011545525171PW_BS0001153987171PW_BS00011313613171PW_BS0001361371117PW_BS0001372975101PW_BS0000244781010PW_BS00011548924101PW_BS0001152991101PW_BS00002449025101PW_BS0001154957101PW_BS000115209106PW_BS0000245062461PW_BS000115388161PW_BS0001125072561PW_BS000115390761PW_BS0001124311PW_BS000004261115PW_BS0000265411PW_BS000005221411PW_BS000022397113PW_BS000039592711PW_BS000059231511PW_BS000023711PW_BS000007311511PW_BS000031918511PW_BS000091541315PW_BS000054562611PW_BS0000561041431PW_BS0001041122121PW_BS000112103331PW_BS0001031471241PW_BS0001471553241PW_BS0001551613181PW_BS00016116611PW_BS0001661783211PW_BS00017819914181PW_BS000024206261PW_BS00002421425181PW_BS0000242164181PW_BS000024222341PW_BS0000242253541PW_BS0000242491341PW_BS0000242881441PW_BS000024226441PW_BS0000242905491PW_BS0000241333121PW_BS00013332914121PW_BS0000283361121PW_BS0000283344121PW_BS00002833527121PW_BS0000283683601PW_BS000028184121PW_BS000024372102PW_BS000028253541PW_BS00002427151PW_BS0000272231241PW_BS000024406351PW_BS0001153821451PW_BS000100407251PW_BS000115408451PW_BS000115429151PW_BS0001154222751PW_BS0001151203171PW_BS00012039914171PW_BS0001131192171PW_BS0001193744171PW_BS0000534641171PW_BS00011537527171PW_BS00005348414101PW_BS0001154793101PW_BS0001154812101PW_BS0001154824101PW_BS00011549127101PW_BS00011530013101PW_BS0000243891461PW_BS000112501361PW_BS000115502461PW_BS0001155082761PW_BS0001153951361PW_BS000113612517PW_BS000061971521PW_BS000097100521PW_BS00010012915121PW_BS00012910813PW_BS0001086131PW_BS00000614315191PW_BS0001431465191PW_BS000146107313PW_BS000107117131PW_BS000117188118PW_BS00002421217181PW_BS0000241632181PW_BS0001632273441PW_BS000024241529PW_BS00002425715291PW_BS00002417018PW_BS0001702811251PW_BS00002430412PW_BS000024315123PW_BS0000243183123PW_BS0000243221231PW_BS00002429341PW_BS00002413412121PW_BS00013433217121PW_BS00002835325127PW_BS0000283841251PW_BS0001003911261PW_BS000112943PW_BS000094109323PW_BS00010912112171PW_BS0001211231751PW_BS00012344717171PW_BS00011547225177PW_BS00011529817101PW_BS0000245131761PW_BS00011565111PW_BS000065731013PW_BS00007385241011PW_BS000085599856PW_BS0005016531624PW_BS000508892PW_BS0000896651818PW_BS00050865413621PW_BS0005088424111PW_BS0000848724511PW_BS000087231391PW_BS0000243451014PW_BS000034451014PW_BS0000455291016PW_BS00005265110624PW_BS0005082171518PW_BS000024204111PW_BS00002073PW_B0000731907786ProteinComplex11911104Compound174PW_B0000741921015ProteinComplex11931104Compound175PW_B0000751941017ProteinComplex11951104Compound176PW_B0000761961030ProteinComplex11971104Compound178PW_B0000782007724ProteinComplex12011104Compound179PW_B0000792021104Compound1203948ProteinComplex180PW_B0000802041104Compound12057791ProteinComplex12067633ProteinComplex181PW_B0000812071104Compound1208965ProteinComplex182PW_B0000822091104Compound1210971ProteinComplex183PW_B0000832111104Compound1212972ProteinComplex11104PhosphateHMDB0001429Phosphate is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry, biogeochemistry and ecology. Phosphate (Pi) is an essential component of life. In biological systems, phosphorus is found as a free phosphate ion in solution and is called inorganic phosphate, to distinguish it from phosphates bound in various phosphate esters. Inorganic phosphate is generally denoted Pi and at physiological (neutral) pH primarily consists of a mixture of HPO<sup>2-</sup><sub>4</sub> and H<sub>2</sub>PO<sup>-</sup><sub>4</sub> ions. phosphates are most commonly found in the form of adenosine phosphates, (AMP, ADP and ATP) and in DNA and RNA and can be released by the hydrolysis of ATP or ADP. Similar reactions exist for the other nucleoside diphosphates and triphosphates. Phosphoanhydride bonds in ADP and ATP, or other nucleoside diphosphates and triphosphates, contain high amounts of energy which give them their vital role in all living organisms. Phosphate must be actively transported into cells against its electrochemical gradient. In vertebrates, two unrelated families of Na+-dependent Pi transporters carry out this task. Remarkably, the two families transport different Pi species: whereas type II Na+/Pi cotransporters (SCL34) prefer divalent HPO4(2), type III Na+/Pi cotransporters (SLC20) transport monovalent H2PO4. The SCL34 family comprises both electrogenic and electroneutral members that are expressed in various epithelia and other polarized cells. Through regulated activity in apical membranes of the gut and kidney, they maintain body Pi homeostasis, and in salivary and mammary glands, liver, and testes they play a role in modulating the Pi content of luminal fluids. Phosphate levels in the blood play an important role in hormone signaling and in bone homeostasis. In classical endocrine regulation, low serum phosphate induces the renal production of the seco-steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3).This active metabolite of vitamin D acts to restore circulating mineral (i.e. phosphate and calcium) levels by increasing absorption in the intestine, reabsorption in the kidney, and mobilization of calcium and phosphate from bone. Thus, chronic renal failure is associated with hyperparathyroidism, which in turn contributes to osteomalacia (softening of the bones). Another complication of chronic renal failure is hyperphosphatemia (low levels of phosphate in the blood). Hyperphosphatemia (excess levels of phosphate in the blood) is a prevalent condition in kidney dialysis patients and is associated with increased risk of mortality. Hypophosphatemia (hungry bone syndrome) has been associated to postoperative electrolyte aberrations and after parathyroidectomy. (PMID: 17581921, 11169009, 11039261, 9159312, 17625581)Fibroblast growth factor 23 (FGF-23) has recently been recognized as a key mediator of phosphate homeostasis, its most notable effect being promotion of phosphate excretion. FGF-23 was discovered to be involved in diseases such as autosomal dominant hypophosphatemic rickets, X-linked hypophosphatemia, and tumor-induced osteomalacia in which phosphate wasting was coupled to inappropriately low levels of 1,25(OH)2D3. FGF-23 is regulated by dietary phosphate in humans. In particular it was found that phosphate restriction decreased FGF-23, and phosphate loading increased FGF-23.14265-44-2C00009106118367CPD-85871032[O-]P([O-])([O-])=OO4PInChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)/p-3NBIIXXVUZAFLBC-UHFFFAOYSA-Kphosphoric acid94.971494.953423phosphoric acid0-2DBMET00532FDB022617Nfb orthophosphate;O-phosphoric acid;Ortho-phosphate;Orthophosphate (po43-);Orthophosphate(3-);Phosphate;Phosphate (po43-);Phosphate anion(3-);Phosphate ion (po43-);Phosphate ion(3-);Phosphate trianion;Phosphate(3-);Phosphoric acid ion(3-);Pi;[po4](3-);Orthophosphate;Phosphate ion;Po4(3-);Phosphoric acid;Orthophosphoric acid;Phosphoric acid ionPW_C001104Pi2448488145818188312980317631417674925001027294727374631292931667236366138512342492244753150312751587520797521610053171115351112538110354471205543129557313356051355625108569365848143585514659111475941151604015561001616294107648717866911016714117684218868891607161205718920672122117306198738921074022127436163747522281962258258227101182411013425711748132117611151177321311904170119271641201428112728290132632233481917422553044235031542435318436923227701825377194293772171347794033677966130780483327805732978245353786693318002236889279308938313839479638411055839011064039111323594115845398116206109119982406120069122120699407121057124121216125121268429121352121121409123121423382121852405123304119123621118123786136123838464123968447123981399124405376124948472125362479125446297125774481125954299126221478126594300126604298126723484126904501127413388127783209128166395128177513128315389353CalciumHMDB0000464Calcium 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+276163038553146012941159932199735104631163461164471478491491421552432116582138172796182937931597131607239422941866647821048222853401115780101717920572322117258160728119011774213118371981184221012198164122152851528815115350308693361773893317760011578154132782663567852634578724130789081148041374805892288182651120220122120465405121049124121300418121377419121850383121923125122370409122895135123099376123613118123870454123936455124403398124476136124924137125571297125711478125981489126009299126050490126533495127203209127434506127460388127502507128105390423MagnesiumHMDB0000547Magnesium salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Physiologically, it exists as an ion in the body. It is a component of both intra- and extracellular fluids and is excreted in the urine and feces. Deficiency causes irritability of the nervous system with tetany, vasodilatation, convulsions, tremors, depression, and psychotic behavior. Magnesium ion in large amounts is an ionic laxative, and magnesium sulfate (Epsom salts) is sometimes used for this purpose. So-called "milk of magnesia" is a water suspension of one of the few insoluble magnesium compounds, magnesium hydroxide; the undissolved particles give rise to its appearance and name. Milk of magnesia is a mild base, and is commonly used as an antacid.22537-22-0C003058881842013-HYDROXY-MAGNESIUM-PROTOPORP865DB01378[Mg++]MgInChI=1S/Mg/q+2JLVVSXFLKOJNIY-UHFFFAOYSA-Nmagnesium(2+) ion24.30523.9850418980magnesium(2+) ion22FDB003518Magnesium;Magnesium ions;Magnesium ion;Magnesium, doubly charged positive ion;Magnesium, ion (mg(2+));Mg(2+);Mg2+PW_C000423Mg2+8682274268164762727268115819188832293639983399221116746148349152943176414212410241159294223312629337374540314774914869544974565253104532911153561125376103590614759341516038155609416162501666484178659416468811606979199717020571942067227213723321172502147310216731319874732221176313211843210123122251232424912513288125812261272929015275285153373087713713377236329779373367839333478417335784891157852233178536356785741308002036880045184800483728062311880654135808651580965253818415193832383949002710859622311055939011568739811997440612007012212024738212070240712098140812118112412126542912131941912192412512208640512240842212275912012292139912330711912354637412383546412388945512447713612463737612497837512544729712559848412566947912577748112592148212594729912597349512600049012624347812655349112675330012712538912716450112738050212740738812745150712780420912812550812834739541cAMPHMDB0000058cAMP or cyclic AMP is an adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. cAMP is synthesized from ATP by adenylate cyclase. Adenylate cyclase is located at the cell membranes. Adenylate cyclase is activated by the hormones glucagon and adrenaline and by G protein. Liver adenylate cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline. cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase.60-92-4C00575607617489CAMP5851DB02527NC1=NC=NC2=C1N=CN2[C@@H]1O[C@@H]2COP(O)(=O)O[C@H]2[C@H]1OC10H12N5O6PInChI=1S/C10H12N5O6P/c11-8-5-9(13-2-12-8)15(3-14-5)10-6(16)7-4(20-10)1-19-22(17,18)21-7/h2-4,6-7,10,16H,1H2,(H,17,18)(H2,11,12,13)/t4-,6-,7-,10-/m1/s1IVOMOUWHDPKRLL-KQYNXXCUSA-N(4aR,6R,7R,7aS)-6-(6-amino-9H-purin-9-yl)-2,7-dihydroxy-hexahydro-2lambda5-furo[3,2-d][1,3,2]dioxaphosphinin-2-one329.2059329.052519653-1.963(4aR,6R,7R,7aS)-6-(6-aminopurin-9-yl)-2,7-dihydroxy-tetrahydro-4H-2lambda5-furo[3,2-d][1,3,2]dioxaphosphinin-2-one0-1FDB001497Cyclic AMP;3'5'-cyclic amp;6-(6-amino-9h-purin-9-yl)tetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinine-2,7-diol 2-oxide;Acrasin;Adenosine 3',5'-cyclic monophosphate;Adenosine 3',5'-cyclic phosphate;Adenosine 3',5'-cyclophosphate;Adenosine 3',5'-monophosphate;Adenosine 3,5'-cyclic monophosphorate;Adenosine 3,5'-cyclic monophosphoric acid;Adenosine cyclic monophosphate;Adenosine cyclic-monophosphate;Adenosine-cyclic-phosphate;Adenosine-cyclic-phosphoric-acid;Cyclic 3',5'-amp;Cyclic 3',5'-adenylate;Cyclic 3',5'-adenylic acid;Cyclic amp;Cyclic adenosine 3',5'-phosphate;Camp;Adenosine 3',5'-phosphate;Adenosine-3',5'-cyclic-monophosphate;Cyclic adenylic acid;Adenosine 3',5'-cyclic monophosphoric acid;Adenosine 3',5'-cyclic phosphoric acid;Adenosine 3',5'-phosphoric acid;Adenosine-3',5'-cyclic-monophosphoric acid;Cyclic adenylatePW_C000041cAMP2671647529353910002119168417414118301987870911180044184121904122124457135821Arachidonic acidHMDB0001043Arachidonic acid is a polyunsaturated, essential fatty acid that has a 20-carbon chain as a backbone and four cis-double bonds at the C5, C8, C11, and C14 positions. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is synthesized from dietary linoleic acid. Arachidonic acid mediates inflammation and the functioning of several organs and systems either directly or upon its conversion into eicosanoids. Arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. Arachidonic acid can be metabolized by cytochrome p450 (CYP450) enzymes into 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs), their corresponding dihydroxyeicosatrienoic acids (DHETs), and 20-hydroxyeicosatetraenoic acid (20-HETE). The production of kidney CYP450 arachidonic acid metabolites is altered in diabetes, pregnancy, hepatorenal syndrome, and in various models of hypertension, and it is likely that changes in this system contribute to the abnormalities in renal function that are associated with many of these conditions. Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (PMID: 12736897, 12736897, 12700820, 12570747, 12432908).506-32-1C0021944489915843ARACHIDONIC_ACID392692DB04557CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=OC20H32O2InChI=1S/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h6-7,9-10,12-13,15-16H,2-5,8,11,14,17-19H2,1H3,(H,21,22)/b7-6-,10-9-,13-12-,16-15-YZXBAPSDXZZRGB-DOFZRALJSA-N(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid304.4669304.240230268-6.301arachidonic acid0-1FDB011872(all-z)-5,8,11,14-eicosatetraenoate;(all-z)-5,8,11,14-eicosatetraenoic acid;5,8,11,14-all-cis-eicosatetraenoate;5,8,11,14-all-cis-eicosatetraenoic acid;5,8,11,14-eicosatetraenoate;5,8,11,14-eicosatetraenoic acid;5-cis,8-cis,11-cis,14-cis-eicosatetraenoate;5-cis,8-cis,11-cis,14-cis-eicosatetraenoic acid;5z,8z,11z,14z-eicosatetraenoate;5z,8z,11z,14z-eicosatetraenoic acid;All-cis-5,8,11,14-eicosatetraenoate;All-cis-5,8,11,14-eicosatetraenoic acid;Arachidonic acid;Immunocytophyte;Cis-d5,8,11,14-eicosatetraenoate;Cis-d5,8,11,14-eicosatetraenoic acid;(5z,8z,11z,14z)-5,8,11,14-icosatetraenoic acid;(5z,8z,11z,14z)-icosatetraenoic acid;Aa;Ara;Arachidonate;Arachidonsaeure;Cis-5,8,11,14-eicosatetraenoic acid;Cis-delta(5,8,11,14)-eicosatetraenoic acid;(5z,8z,11z,14z)-5,8,11,14-icosatetraenoate;(5z,8z,11z,14z)-icosatetraenoate;Cis-5,8,11,14-eicosatetraenoate;Cis-delta(5,8,11,14)-eicosatetraenoate;Cis-δ(5,8,11,14)-eicosatetraenoate;Cis-δ(5,8,11,14)-eicosatetraenoic acid;FA(20:4(5Z,8Z,11Z,14Z))PW_C00082120:42441629618600213728772721301202131251228901361255663001270973959795ZincHMDB0015532Zinc is an essential element, necessary for sustaining all life. It is a trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Physiologically, it exists as an ion in the body. It is estimated that 3000 of the hundreds of thousands of proteins in the human body contain zinc prosthetic groups. In addition, there are over a dozen cell types in the human body that secrete zinc ions, and the roles of these secreted zinc signals in medicine and health are now being actively studied. Intriguingly, brain cells in the mammalian forebrain are one type of cell that secretes zinc, along with its other neuronal messenger substances. Cells in the salivary gland, prostate, immune system, and intestine are other types that secrete zinc. Obtaining a sufficient zinc intake during pregnancy and in young children is a problem, especially among those who cannot afford a good and varied diet. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. Brain development is stunted by zinc deficiency in utero and in youth. Zinc is an activator of certain enzymes, such as carbonic anhydrase. Carbonic anhydrase is important in the transport of carbon dioxide in vertebrate blood. Even though zinc is an essential requirement for a healthy body, too much zinc can be harmful. Excessive absorption of zinc can also suppress copper and iron absorption. The free zinc ion in solution is highly toxic to plants, invertebrates, and even vertebrate fish. The Free Ion Activity Model (FIAM) is well-established in the literature and shows that just micromolar amounts of the free ion kill some organisms.7440-66-6239942736322430DB01593[Zn]ZnInChI=1S/ZnHCHKCACWOHOZIP-UHFFFAOYSA-Nzinc(2+) ion65.40963.9291465780zinc(2+) ion2230zn;Cinc;Zincum;Zink;Zn;Zn(ii);Zn2+PW_C009795Zinc578171121904321371721544936102940837446918454314499931668910766901016699108702016011758115122291511263365423973154239931877030253780231327832811278811111120119124120898122122308407122852118123469135124860119125486299126474481127023388127317205128043206375IP3CompoundCompoundPW_EC000375IP3290DGCompound3149CompoundPW_EC000290DG377Phosphatidic AcidCompoundCompoundPW_EC000377PA1601Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortP63092Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase:it activates the cyclase in response to beta-adrenergic stimuliHMDBP01781GNAS20q13.3M1463113810241391441587350118551628135588599675Adenylate cyclase type 1Q08828This is a calmodulin-sensitive adenylyl cyclase. May be involved in regulatory processes in the central nervous system. It may play a role in memory acquisition and learning.
HMDBP00711ADCY17p13-p12AC06900814.6.1.1800848136380741262cAMP-dependent protein kinase catalytic subunit alphaP17612Phosphorylates a large number of substrates in the cytoplasm and the nucleusHMDBP01352PRKACA19p13.1X0776712.7.11.11990212762468052081361296531742Guanine nucleotide-binding protein subunit alpha-11P29992Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Acts as an activator of phospholipase CHMDBP02024GNA1119p13.3AF49390018074182161-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.
HMDBP00222PLCB120p12AL05031513.1.4.11257614279046116468969337180090308802308136124653136191665136199662126Inositol 1,4,5-trisphosphate receptor type 1Q14643Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphateHMDBP02849ITPR13p26.1D2607019671627941885021080091813613865414645Calmodulin-like protein 6Q8TD86CALML618074389229Alpha-actinin-4O43707
F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778).
ACTN416557846569878074489550Calcium/calmodulin-dependent protein kinase type II subunit alphaQ9UQM7
CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity (By similarity).
CAMK2A12.7.11.178074589551Leucine-rich repeat-containing protein 7Q96NW7
Required for normal synaptic spine architecture and function. Necessary for DISC1 and GRM5 localization to postsynaptic density complexes and for both N-methyl D-aspartate receptor-dependent and metabotropic glutamate receptor-dependent long term depression.
LRRC7180746814389Protein 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 promotersHMDBP01372PRKCB16p11.2FJ90724612.7.11.136938888005216480414741719Voltage-dependent L-type calcium channel subunit alpha-1DQ01668Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)HMDBP01990CACNA1D3p14.3AC1328101805528807482282719Voltage-dependent L-type calcium channel subunit alpha-1SQ13698Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscleHMDBP07498CACNA1S1q32U306871805538807492282715Voltage-dependent L-type calcium channel subunit alpha-1FO60840Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)HMDBP07494CACNA1FAF1967791805548807502281845Voltage-dependent L-type calcium channel subunit alpha-1CQ13936Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel functionHMDBP02220CACNA1C12p13.3L29537199134276745351314353852509465805558807512281361316512706Voltage-dependent calcium channel subunit alpha-2/delta-2Q9NY47The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosisHMDBP07485CACNA2D23p21.3AJ25136819403927684535141435395250956584992281361326512720Voltage-dependent L-type calcium channel subunit beta-1Q02641The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targetingHMDBP07499CACNB117q21-q22CH471152193839276945351514354052509665807532281361336512152Matrix metalloproteinase-14P50281Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surfaceHMDBP02912MMP1414q11-q12AL13599813.4.24.808075415210672 kDa type IV collagenaseP08253PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vesselsHMDBP02804MMP216q13-q21M5558413.4.24.2480755152061Proheparin-binding EGF-like growth factorQ99075May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts and smooth muscle but not endothelial cells. It is able to bind EGF receptors with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptorHMDBP02701HBEGF5q23M60278180756151351Epidermal growth factor receptorP00533Isoform 2 may act as an antagonist of EGF actionHMDBP01456EGFR7p12AY58824612.7.10.13399234071411650228808503085154Growth 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-q25AF0636141423126553351165483798Son of sevenless homolog 1Q07889Promotes the exchange of Ras-bound GDP by GTPHMDBP08580SOS12p21L138571423221165581703GTPase HRasP01112Ras proteins bind GDP/GTP and possess intrinsic GTPase activityHMDBP01958HRAS11p15.5BC0064991409214423524371880535182723308891142533966Mitogen-activated protein kinase kinase kinase 2Q9Y2U5Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7. Plays a role in caveolae kiss-and-run dynamicsHMDBP08750MAP3K22q14.3AF11110512.7.11.25807611807628134645234323Cytosolic phospholipase A2 betaP0C869Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position with a preference for arachidonoyl phospholipids. Has a much weaker activity than PLA2G4A. Isoform 3 has calcium-dependent activity against palmitoyl-arachidonyl-phosphatidylethanolamine and low level lysophospholipase activity but no activity against phosphatidylcholine. Isoform 5 does have activity against phosphatidylcholine.
HMDBP09120PLA2G4B15q11.2-q21.3AC02065913.1.1.430281509141559214449Phospholipase D1Q13393
Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity).
PLD113.1.4.48029081078Proto-oncogene tyrosine-protein kinase SrcP12931ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphateHMDBP01147SRC20q12-q13X0264712.7.10.28056481346131661604Cell division control protein 42 homologP60953Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Causes the formation of thin, actin-rich surface projections called filopodiaHMDBP01784CDC421p36.1AF4989631409528029481346791661067Mitogen-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 pathwayHMDBP01134MAP3K15q11.2AC00893712.7.11.2540972803482288035781346821414643Progonadoliberin-1P01148
Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones.
GNRH11807382281130Mitogen-activated protein kinase 7Q13164Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras- independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathwaysHMDBP01203MAPK717p11.2U2527812.7.11.241324Protein-tyrosine kinase 2-betaQ14289Involved in calcium induced regulation of ion channel and activation of the map kinase signaling pathway. May represent an important signaling intermediate between neuropeptide activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. Interacts with the SH2 domain of Grb2. May phosphorylate the voltage-gated potassium channel protein Kv1.2. Its activation is highly correlated with the stimulation of c-Jun N-terminal kinase activity. Involved in osmotic stress-dependent SNCA 'Tyr-125' phosphorylationHMDBP01425PTK2B8p21.1CH47108012.7.10.282785813592129314644Gonadotropin-releasing hormone receptorP30968
Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.
GNRHR180739228809203083334Cyclic AMP-dependent transcription factor ATF-4P18848Transcriptional activator. Binds the cAMP response element (CRE) (consensus:5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. It binds to a Tax- responsive enhancer element in the long terminal repeat of HTLV-IHMDBP08114ATF422q13.1M86842180740238094685777Follitropin subunit betaP0122514191154193280767235778Lutropin subunit betaP01229LHB1419415419528076523809472175776Glycoprotein hormones alpha chainP0121514190154192280766232078Dual specificity mitogen-activated protein kinase kinase 3P46734Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38HMDBP02743MAP2K317q11.2D8711612.7.12.2422928036181405Mitogen-activated protein kinase 14Q16539Responds to activation by environmental stress, pro- inflammatory cytokines and lipopolysaccharide (LPS) by phosphorylating a number of transcription factors, such as ELK1 and ATF2 and several downstream kinases, such as MAPKAPK2 and MAPKAPK5. Plays a critical role in the production of some cytokines, for example IL-6. May play a role in stabilization of EPO mRNA during hypoxic stress. Isoform Mxi2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform Exip may play a role in the early onset of apoptosisHMDBP01516MAPK146p21.3-p21.2AB07415012.7.11.244230280354882153231084RAF 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 STK3HMDBP01153RAF13p25M1137612.7.11.1423624544141165785788Dual 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.MAP2K112.7.12.2423724545148032681117Mitogen-activated protein kinase 1P28482Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activityHMDBP01190MAPK122q11.2|22q11.21Z1169412.7.11.244038211658880757238730Early growth response protein 1P18146
Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'(EGR-site). Activates the transcription of target genes whose products are required for mitogenesis and differentiation.
EGR11807602314458ETS domain-containing protein Elk-1P19419
Transcription factor that binds to purine-rich DNA sequences. Forms a ternary complex with SRF and the ETS and SRF motifs of the serum response element (SRE) on the promoter region of immediate early genes such as FOS and IER2. Induces target gene transcription upon JNK-signaling pathway stimulation (By similarity).
ELK1180320880759233977Dual specificity mitogen-activated protein kinase kinase 7O14733Stress activated, dual specificity kinase that activates the JUN kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3HMDBP08761MAP2K719p13.3-p13.2AF01358912.7.12.24098280359880763231424Mitogen-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-p31BC00617514109234170280286894902277786Cyclic AMP-dependent transcription factor ATF-41PW_P0077861580833341015Dual specificity mitogen-activated protein kinase kinase 31PW_P0010151159207811017Mitogen-activated protein kinase 141PW_P00101711611405142142311030RAF proto-oncogene serine/threonine-protein kinase1PW_P001030117410841422979527724Dual specificity mitogen-activated protein kinase kinase 11PW_P007724156975788805478948Mitogen-activated protein kinase 11PW_P00094810731117139442317791Early growth response protein 11PW_P0077911581487307633ELK11PW_P0076331551914458965Dual specificity mitogen-activated protein kinase kinase 71PW_P0009651091397714054231971Mitogen-activated protein kinase 81PW_P0009711097142414064231972Transcription factor AP-11PW_P000972109817831121Guanine nucleotide-binding protein alpha1PW_P00012113916011464207529Adenylate cyclase type 11PW_P00752915405675789423280066308217cAMP-dependent protein kinase catalytic subunit alpha1PW_P00021723512627787Guanine nucleotide-binding protein subunit alpha-111PW_P00778715809174277271-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta11PW_P00772715704216805578708Inositol 1,4,5-trisphosphate receptor type 1 1PW_P00070880121262795187788Calmodulin-like protein 61PW_P00778815810146453210Ternary complex (LRRC7, CAMK2a, ACTN4)1PW_P0032109198922919199955019200955117714Protein kinase C complex1PW_P00771115669143891567012798053087726Voltage-dependent L-type calcium channel1PW_P0077261570017191570127191570227151570318458055014321Voltage-depenent L-type calcium channel1PW_P0003213401845134127061342272011162457789MMP2-MMP141PW_P0077891581121521581221067790Proheparin-binding EGF-like growth factor1PW_P007790158132061822Epidermal growth factor receptor1PW_P000822946135121025Growth factor receptor-bound protein 21PW_P0010251169515411026Son of sevenless homolog 11PW_P001026117037981955GTPase HRas1PW_P0009551081170317792Mitogen-activated protein kinase kinase kinase 21PW_P00779215815396677Cytosolic phospholipase A2 beta1PW_P000077914323143353130087625Phospholipase D11PW_P00762515511144497728Proto-oncogene tyrosine-protein kinase Src1PW_P0077281570510781805638959Cell division control protein 42 homolog1PW_P000959108516041963Mitogen-activated protein kinase kinase kinase 11PW_P00096310891067140242317784Progonadoliberin-11PW_P00778415806146437785Gonadotropin-releasing hormone receptor1PW_P00778515807146447793Follitropin subunit beta1PW_P0077931581657771001Lutropin subunit beta1PW_P0010011142577811000Glycoprotein hormones alpha chain1PW_P0010001140577611187PW_T00118714303531Compound188Unknown549ActivationPW_I0005491097121ProteinComplex110987529ProteinComplex1550ActivationPW_I00055010997529ProteinComplex1110041Compound1551ActivationPW_I000551110141Compound11102217ProteinComplex1554ActivationPW_I00055411077787ProteinComplex111087727ProteinComplex1555ActivationPW_I00055511097727ProteinComplex11110375ElementCollection1556ActivationPW_I0005561111375ElementCollection11112708ProteinComplex1557ActivationPW_I0005571113353Compound111147788ProteinComplex1558ActivationPW_I00055811157788ProteinComplex111163210ProteinComplex1559ActivationPW_I00055911177727ProteinComplex11118290ElementCollection1560ActivationPW_I0005601119290ElementCollection111207714ProteinComplex1561ActivationPW_I0005611121353Compound111227726ProteinComplex1562ActivationPW_I00056211237726ProteinComplex111247714ProteinComplex1563ActivationPW_I00056311257714ProteinComplex11126321ProteinComplex1564ActivationPW_I00056411277789ProteinComplex111287790ProteinComplex1565ActivationPW_I00056511297790ProteinComplex11130822ProteinComplex1566ActivationPW_I0005661131822ProteinComplex111321025ProteinComplex1533ActivationPW_I00053310651025ProteinComplex110661026ProteinComplex1567ActivationPW_I00056711331026ProteinComplex11134955ProteinComplex1576ActivationPW_I000576115177ProteinComplex11152821Compound1577ActivationPW_I00057711537625ProteinComplex11154377ElementCollection1578ActivationPW_I00057811557728ProteinComplex11156959ProteinComplex1579ActivationPW_I0005791157959ProteinComplex11158963ProteinComplex1547ActivationPW_I00054710937784ProteinComplex110947785ProteinComplex1553ActivationPW_I00055311057785ProteinComplex111067787ProteinComplex1548ActivationPW_I00054810957785ProteinComplex11096121ProteinComplex1696ActivationPW_I0006961391217ProteinComplex1139273Bound1697ActivationPW_I000697139373Bound113947793ProteinComplex1698ActivationPW_I000698139573Bound113961001ProteinComplex1699ActivationPW_I000699139773Bound113981000ProteinComplex1700ActivationPW_I00070013997792ProteinComplex1140074Bound1701ActivationPW_I000701140174Bound1140275Bound1702ActivationPW_I00070214037714ProteinComplex1140476Bound1703ActivationPW_I0007031405955ProteinComplex1140676Bound1705ActivationPW_I000705140976Bound1141078Bound1707ActivationPW_I000707141378Bound1141479Bound1709ActivationPW_I000709141779Bound1141880Bound1712ActivationPW_I000712142380Bound114241001ProteinComplex1713ActivationPW_I000713142580Bound114261000ProteinComplex1714ActivationPW_I000714142780Bound114287793ProteinComplex1715ActivationPW_I0007151429963ProteinComplex1143081Bound1716ActivationPW_I000716143181Bound1143282Bound1718ActivationPW_I000718143582Bound1143683Bound1719ActivationPW_I000719143783Bound114381001ProteinComplex1720ActivationPW_I000720143983Bound114401000ProteinComplex1721ActivationPW_I000721144183Bound114427793ProteinComplex1476738645724191590222216969677248401321696974777486457242015902232169710773484017216971147875864572421159022421697177744840192169719480768645724231590230216973177648402121697334827886457242515902342169743778484023216974448379236457242615902352169749779484025216975148480236457242715902372169756780484028216975778148402921697584858186457242815902382169773782484036216977548682236457242915902402169778783484037216978048783236457243015902422169785784484039216978615902221104846false2025194010regular444315902231104846false1485145010regular444315902241104846false1485165310regular4443159022542389true1530169810regular1002515902301104846false516125110regular44431590231979589true501119110regular1002515902341104846false526156510regular444315902351104846false526185510regular4443159023642389true501173510regular10025159023711042346false531220410regular444315902381104846false875166010regular4443159023942389true920164510regular10025159024011042346false870190310regular44431590241423239true920191310regular10025159024211042346false870214610regular444315901183531851false1792114010regular78781590119353851false1792134810regular7878159012042389true161066010regular1002515901214183false2065107510regular100100159012235322851false140232510regular7878159012582183false1225140210regular100110159012635389true920101510regular10025159012742389true965155510regular1002597843751448false1680107012regular150709785290378false153593512regular100909786377378false1060141012regular10090596608333482false204019308subunitregular15070596612207882false150514408subunitregular15070596616140582false150516388subunitregular15070596618108482false55112468subunitregular15070596620578882false55115508subunitregular15070596623111782false55118458subunitregular150705966298730232false55121648subunitregular1507059663014458232false55122248subunitregular15070596640397782false89016508subunitregular150705966411424232false89018938subunitregular150705966431783232false89021368subunitregular15070596035160182false20407558subunitregular1507059603667582false20409108subunitregular15070596037126282false204012808subunitregular15070596039174282false16807508subunitregular1507059604021682false16809158sub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452.94685504416486 13.26155629629604 L 438 12 L 444.38088772118584 25.575134323078345false2168923M1755 1070 C1755 1040 1755 1097.5 1755 1067.5 149false18trueM 452.94685504416486 13.26155629629604 L 438 12 L 444.38088772118584 25.575134323078345false2168924M1755 985 C1755 1015 1755 1037.5 1755 1067.5 149false182168925M1755 1140 C1755 1170 1755 1210 1755 1240 149false12168926M1755 1235 C1755 1205 1755 1265 1755 1235 149false1trueM 452.94685504416486 13.26155629629604 L 438 12 L 444.38088772118584 25.575134323078345false2168927M1831 1426 C1831 1456 1831 1469 1831 1499 149false182168928M1831 1511 C1831 1481 1831 1456 1831 1426 149false18trueM 310.94685504416486 248.26155629629605 L 296 247 L 302.38088772118584 260.5751343230783false2168929M1831 1581 C1831 1611 1831 1626 1831 1656 149false22168930M1831 1656 C1831 1626 1831 1611 1831 1581 149false18trueM 310.94685504416486 248.26155629629605 L 296 247 L 302.38088772118584 260.5751343230783false2168931M1635 985 C1681 991 1755 1015 1755 985 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219false18true286.94685504416486,816.261556296296 272,815 278.38088772118584,828.5751343230784false2169019M815 1260 C838 1160 1356 1068 1380 1085 219false18true444.86064878524815,919.4003586637191 453,932 459.8419338684158,918.6512944095607false2169020M1544 2049 C1571 2025 1807 1709 1831 1726 219false18trueM 1193.7264030638546 1729.7640906831357 L 1189 1744 L 1203.6918606463034 1740.9752304633905false2169021M1580 1708 C1603 1724 1530 1983 1514 2040 219false18trueM 1155.2898205670533 1720.4660890130929 L 1159 1735 L 1169.7316464145301 1724.5199348650162false2169022M1275 1512 C1298 1528 1448 2004 1458 2035 219false18trueM 1091.8741022701126 1719.9394632497026 L 1103 1730 L 1106.149731536521 1715.3344215508612false2169023M1110 1520 C1133 1536 1414 2025 1424 2040 219false18trueM 1046.0644009829866 1721.611518094107 L 1061 1723 L 1054.7346610946918 1709.371150877582false2169024M1197 645 C1216 667 1356 928 1380 945 219false18true1188.9468550441647,627.261556296296 1174,626 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681 C126 631 176 581 226 581 C855 581 1673 581 2302 581 C2352 581 2402 631 2402 681 C2402 1188 2402 1846 2402 2353 C2402 2403 2352 2453 2302 2453 C1673 2453 855 2453 226 2453 C176 2453 126 2403 126 2353 C126 1846 126 1188 126 681 1true62276.01872.024561615Neuroactive ligand-receptor interaction2004285201.01.01601524561715Gonadotropins gene expression & secretion14082036201.01.01601524561815Indirect link or Unknown reaction12091100201.31.31601524561915cytokine-cytokine receptor interactions660250201.31.31601524562015Indirect link or Unknown reaction14001864201.01.016015245621235Extracellular Space110175201.61.620015245622235Cytoplasm of Pituitary gonadotrope cell165620201.61.620015245623235Nucleus19182250201.61.62001524562415Indirect link or Unknown reaction1125695201.31.31601524565515cAMP Signaling Pathway21301153201.31.31601524565615Calcium Signaling Pathway14591039201.31.31601524565715Erk1/Erk2 Mapk Signaling Pathway7011421201.31.316015102309297218850618092278236539#FFF9C941772556