70568PathwayEPO Signaling PathwayThe hormone erythropoietin, is a 166 amino acid protein with an apparent molecular weight in its native form of 39,000 Da. The molecule is heavily glycosylated since its mass derived from its amino acid content is 18,398. The selective interaction of a hormone with its target cells is usually mediated by cell membrane receptors specific for the particular hormone. Erythropoietin-responsive cells have a trypsin-sensitive receptor for the hormone which requires protein synthesis for its maintenance. Erythropoietin-responsive cells can interact with other hematopoietic growth factors, and such interactions may lead to competition for pathway-specific differentiation, particularly under conditions of high cell density. The amino-terminal region of the hormone is not involved in receptor binding.ProteinPW070692CenterPathwayVisualizationContext7096816301730#000099PathwayVisualization7044870568EPO Signaling PathwayThe hormone erythropoietin, is a 166 amino acid protein with an apparent molecular weight in its native form of 39,000 Da. The molecule is heavily glycosylated since its mass derived from its amino acid content is 18,398. The selective interaction of a hormone with its target cells is usually mediated by cell membrane receptors specific for the particular hormone. Erythropoietin-responsive cells have a trypsin-sensitive receptor for the hormone which requires protein synthesis for its maintenance. Erythropoietin-responsive cells can interact with other hematopoietic growth factors, and such interactions may lead to competition for pathway-specific differentiation, particularly under conditions of high cell density. The amino-terminal region of the hormone is not involved in receptor binding.Protein124111525887776Kuhrt D, Wojchowski DM: Emerging EPO and EPO receptor regulators and signal transducers. Blood. 2015 Jun 4;125(23):3536-41. doi: 10.1182/blood-2014-11-575357. Epub 2015 Apr 17.70568Pathway24111627164096Ma C, Cheng F, Wang X, Zhai C, Yue W, Lian Y, Wang Q: Erythropoietin Pathway: A Potential Target for the Treatment of Depression. Int J Mol Sci. 2016 May 6;17(5). pii: ijms17050677. doi: 10.3390/ijms17050677.70568Pathway24111723028796Wu P, Zhang N, Wang X, Zhang C, Li T, Ning X, Gong K: The erythropoietin/erythropoietin receptor signaling pathway promotes growth and invasion abilities in human renal carcinoma cells. PLoS One. 2012;7(9):e45122. doi: 10.1371/journal.pone.0045122. Epub 2012 Sep 18.70568Pathway2Platelet CL:00002331CellCL:00000004Cardiomyocyte CL:00007463NeuronCL:00005408Beta cellCL:00006397Epithelial CellCL:00000665HepatocyteCL:00001821Homo 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 aeruginosa287Prokaryote10Cell MembraneGO:00058865CytoplasmGO:00057371CytosolGO: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:000577715NucleusGO:000563431Periplasmic SpaceGO:000562035ChloroplastGO:000950734Plant-Type VacuoleGO:000032532Inner MembraneGO:007025827Peroxisome MembraneGO:000577826Golgi apparatus membraneGO:00001392Endothelium BTO:00003935cardiocyteBTO:00015391LiverBTO:000075972918PancreasBTO:00009888Blood VesselBTO:0001102741124BrainBTO:0000142891625IntestineBTO:000064811HeartBTO:000056273107Nervous SystemBTO:000148414101PW_BS00001416212PW_BS0000168511PW_BS0000082111PW_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_BS000004731013PW_BS00007385241011PW_BS000085103331PW_BS0001031553241PW_BS0001551613181PW_BS0001611783211PW_BS000178222341PW_BS0000242905491PW_BS0000241333121PW_BS0001333683601PW_BS000028253541PW_BS000024406351PW_BS0001151203171PW_BS0001204793101PW_BS000115501361PW_BS0001155411PW_BS000005612517PW_BS000061231511PW_BS000023221411PW_BS000022311511PW_BS00003127151PW_BS000027711PW_BS000007971521PW_BS000097100521PW_BS0001001122121PW_BS00011212915121PW_BS00012910813PW_BS0001086131PW_BS00000614315191PW_BS0001431465191PW_BS0001461471241PW_BS000147107313PW_BS000107117131PW_BS000117188118PW_BS000024206261PW_BS00002421217181PW_BS0000241632181PW_BS0001632253541PW_BS0000242273441PW_BS000024241529PW_BS00002425715291PW_BS00002417018PW_BS0001702811251PW_BS0000242231241PW_BS00002430412PW_BS000024315123PW_BS0000243183123PW_BS0000243221231PW_BS00002429341PW_BS00002413412121PW_BS0001343361121PW_BS00002833217121PW_BS00002832914121PW_BS00002835325127PW_BS0000283841251PW_BS0001003911261PW_BS000112943PW_BS000094109323PW_BS000109407251PW_BS000115429151PW_BS00011512112171PW_BS0001211231751PW_BS0001233821451PW_BS0001001192171PW_BS0001194641171PW_BS00011544717171PW_BS00011539914171PW_BS00011347225177PW_BS0001154812101PW_BS00011530013101PW_BS00002429817101PW_BS00002448414101PW_BS0001153951361PW_BS0001135131761PW_BS0001153891461PW_BS00011265111PW_BS000065261115PW_BS000026397113PW_BS000039592711PW_BS000059918511PW_BS000091541315PW_BS000054562611PW_BS0000561041431PW_BS00010416611PW_BS00016619914181PW_BS00002421425181PW_BS0000242164181PW_BS0000242491341PW_BS0000242881441PW_BS000024226441PW_BS0000243344121PW_BS00002833527121PW_BS000028184121PW_BS000024372102PW_BS000028408451PW_BS0001154222751PW_BS0001153744171PW_BS00005337527171PW_BS0000534824101PW_BS00011549127101PW_BS000115502461PW_BS0001155082761PW_BS00011596PW_B0000962387956ProteinComplex12397957ProteinComplex12401012ProteinComplex12416629ProteinComplex12427880ProteinComplex1889901497PW_B0000972431025ProteinComplex12441074ProteinComplex12451026ProteinComplex1100PW_B000100251972ProteinComplex12527927ProteinComplex1353CalciumHMDB0000464Calcium 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+276163038553146012941159932199735104631163461164471478491491421552432116582138172796182937931597131607239422941866647821048222853401115780101717920572322117258160728119011774213118371981184221012198164122152851528815115350308693361773893317760011578154132782663567852634578724130789081148041374805892288182651120220122120465405121049124121300418121377419121850383121923125122370409122895135123099376123613118123870454123936455124403398124476136124924137125571297125711478125981489126009299126050490126533495127203209127434506127460388127502507128105390936Guanosine 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_C000936GDP838238417621423912415473500785538210360411556101161648817874762221175411511771211118231981272729013395151693221771421337754611177952132800233688008030880122164891152531199834061200681221212051241218474051227661201228201351237751181244003761253634791254452971269055011269842051104PhosphateHMDB0001429Phosphate 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_C001104Pi2448488145818188312980317631417674925001027294727374631292931667236366138512342492244753150312751587520797521610053171115351112538110354471205543129557313356051355625108569365848143585514659111475941151604015561001616294107648717866911016714117684218868891607161205718920672122117306198738921074022127436163747522281962258258227101182411013425711748132117611151177321311904170119271641201428112728290132632233481917422553044235031542435318436923227701825377194293772171347794033677966130780483327805732978245353786693318002236889279308938313839479638411055839011064039111323594115845398116206109119982406120069122120699407121057124121216125121268429121352121121409123121423382121852405123304119123621118123786136123838464123968447123981399124405376124948472125362479125446297125774481125954299126221478126594300126604298126723484126904501127413388127783209128166395128177513128315389986Guanosine 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_C000986GTP818240419392409114415373500685538410360431556103161649017874782221175311511769198119811511272529069327176962225771441337754411177951132800253688008830880121164891132531199854061200661221212041241227681201228181351237741181253654791254432971264802991269075011269822051280513889795ZincHMDB0015532Zinc 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_C009795Zinc578171121904321371721544936102940837446918454314499931668910766901016699108702016011758115122291511263365423973154239931877030253780231327832811278811111120119124120898122122308407122852118123469135124860119125486299126474481127023388127317205128043206423MagnesiumHMDB0000547Magnesium 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+868227426816476272726811581918883229363998339922111674614834915294317641421241024115929422331262933737454031477491486954497456525310453291115356112537610359061475934151603815560941616250166648417865941646881160697919971702057194206722721372332117250214731021673131987473222117631321184321012312225123242491251328812581226127292901527528515337308771371337723632977937336783933347841733578489115785223317853635678574130800203688004518480048372806231188065413580865158096525381841519383238394900271085962231105593901156873981199744061200701221202473821207024071209814081211811241212654291213194191219241251220864051224084221227591201229213991233071191235463741238354641238894551244771361246373761249783751254472971255984841256694791257774811259214821259472991259734951260004901262434781265534911267533001271253891271645011273805021274073881274515071278042091281255081283473959530Signal transducer and activator of transcription 5AP42229
Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation.
STAT5A14381388059223889941489156279422978775ErythropoietinP01588
Erythropoietin is the principal hormone involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.
EPO1889951414716Erythropoietin receptorP19235
Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase.
EPOR188984142381-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-q13.1CH47107713.1.4.1142172802298805902288283530888996141121Tyrosine-protein kinase JAK2O60674Non-receptor tyrosine kinase involved in various processes such as cell cycle progression, apoptosis, mitotic recombination, genetic instability and histone modifications. In the cytoplasm, plays a pivotal role in signal transduction via its association with cytokine receptors, which constitutes an initiating step in signaling for many members of the cytokine receptor superfamily including the receptors for growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), granulocyte-macrophage colony-stimulating factor (CSF2), thrombopoietin (THPO) and multiple interleukins. Following stimulation with erythropoietin (EPO) during erythropoiesis, it is autophosphorylated and activated, leading to its association with erythropoietin receptor (EPOR) and tyrosine phosphorylation of residues in the EPOR cytoplasmic domain. Also involved in promoting the localization of EPOR to the plasma membrane. Also acts downstream of some G-protein coupled receptors. Plays a role in the control of body weight. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatinHMDBP01194JAK29p24AF05892512.7.10.243814888997141961Tyrosine-protein phosphatase non-receptor type 6P29350Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.
HMDBP02499PTPN612p13U1552913.1.3.4880606888998145797SHC-transforming protein 1P293531438021165285154Growth 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 activityHMDBP01958HRAS11p15.5BC0064991409214423524371880535182723308891142531084RAF 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.MAP2K112.7.12.2423724545148032681184Mitogen-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)HMDBP01263MAPK316p11.2AC01264512.7.11.2411659880758235770ETS domain-containing protein Elk-1P19419ELK114089234166280327894260271424Mitogen-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.
FOS18095123859498949032714752Transcription factor AP-1P05412
Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the USP28 promoter in colorectal cancer (CRC) cells (PubMed:24623306).
JUN1949282714753Casein kinase II subunit alphaP68400
Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073).
CSNK2A112.7.11.194951277956Erythropoietin1PW_P00795616094877588980147957Erythropoietin receptor1PW_P007957160951471610121-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-11PW_P0010121156238141935316629Tyrosine-protein kinase JAK21PW_P0066291436711214380687880Tyrosine-protein phosphatase non-receptor type 61PW_P0078801595219611025Growth factor receptor-bound protein 21PW_P0010251169515411074SHC-transforming protein 11PW_P0010741234579711026Son of sevenless homolog 11PW_P001026117037981972Transcription factor AP-11PW_P0009721098178317927Proto-oncogene c-Fos1PW_P0079271603987848594883177STAT5A homodimer complex1PW_P003177910395301954GTPase HRas with GTP1PW_P0009541080170313979861953GTPase HRas with GDP1PW_P00095310791703139693611030RAF proto-oncogene serine/threonine-protein kinase1PW_P001030117410841422979527724Dual specificity mitogen-activated protein kinase kinase 11PW_P0077241569757888054785207Mitogen-activated protein kinase 31PW_P005207125241184950ETS domain-containing protein Elk-11PW_P000950107657701971Mitogen-activated protein kinase 81PW_P00097110971424140642313837PW_T003837408031771ProteinComplex723Unknown875ActivationPW_I000875174996Bound117503177ProteinComplex1879ActivationPW_I00087917571012ProteinComplex1175896Bound1882ActivationPW_I00088217633177ProteinComplex1176496Bound1883ActivationPW_I000883176596Bound117661074ProteinComplex1884ActivationPW_I00088417671074ProteinComplex1176897Bound1885ActivationPW_I000885176997Bound11770936Compound1886ActivationPW_I0008861771986Compound11772936Compound1888ActivationPW_I0008881775954ProteinComplex11776953ProteinComplex1201ActivationPW_I000201401954ProteinComplex14021030ProteinComplex1779ActivationPW_I00077915571030ProteinComplex115587724ProteinComplex1676ActivationPW_I00067613517724ProteinComplex113525207ProteinComplex1423ActivationPW_I0004238455207ProteinComplex1846950ProteinComplex1939ActivationPW_I0009391877971ProteinComplex11878100Bound150396147044880751805223300138085180532330014809518054233001681051805523300178115180562330018504978704488125185922332435813518593233243681451859423324375081002770448819535601241164982053560224116501709424353149false53610610regular10025170966535389false26630818regular100251711349936853false361117510regular50301711363110446false403115910regular44431711405986854false251108510regular5030171159298625354false500134610regular5030171159393625353false230134610regular50301711643110446false260134010regular44431711783979589false760135310regular100251769634423279false1354102810regular100256308958775142false6261438subunitregular1507063089614716142false5061788subunitregular15070630897238142false5111208subunitregular150706308981121142false7361788subunitregular150706308991961142false7361188subunitregular15070631452515482false1719408subunitregular15070631453579782false3119408subunitregular15070631454379882false4519408subunitregular150706484881783272false9699818subunitregular150706484898784272false96910418subunitregular150706308949530142false7363888subunitregular1507063097923882false2413238subunitregular15070631043953082false5114758subunitregular1507063107095308186false7363901subunitregular1507063135111212false9703168subunitregular1507063136319612false11952468subunitregular15070631402579782false3117208subunitregular1507063157317032532false45013668subunitregular1507063157417032532false20513668subunitregular15070631634108482false73513688subunitregular15070631661578882false102513658subunitregular15070631723118482false132513658subunitregular1507064554495307186false7373821subunitregular150706455459530232false9077628subunitregular150706456825770272false132511608subunitregular150706484871424272false132910438subunitregular15070648618147522false13298938subunitregular15070648683147532false13297068subunitregular15070518052795670448146293896308955180537957704481462939063089651805410127044814629391630897846517094242330015Cofactor5180556629704481462939263089851805678807044814629393630899518592102570448862994463145251859310747044886299456314535185941026704488629946631454535601972704482764697964848853560279277044827646980648489518051317770448146293886308945181311012704488629473630979846617096652330345Cofactor51819431777044886295376310435182213177704488629564631070518542107470448862989463140251871095470448253630065631573846717115922332963Cofactor51871195370448253630066631574846817115932332965Cofactor5187701030704488630126631634847317117832333225Cofactor5187977724704488630153631661518859520770448863021563172353265731777044876440356455445326583177704482364403664554553279595070448276441736456825356009717044827646978648487850017696342411647Cofactor2330012M811 388 C811 358 811 278 811 248 149false18trueM 428.28019855002424 13.26155629629604 L 413.3333435058594 12 L 419.7142312270452 25.575134323078345false2330013M646 278 L646 328 L696 278 z10true182330014M786 278 L786 328 L836 278 z10true182330015M951 270.5 L951 320.5 L1001 270.5 z10true182330016M926 270.5 L926 320.5 L976 270.5 z10true182330017M1066 278 L1066 328 L1116 278 z10true182330018M1206 278 L1206 328 L1256 278 z10true182330019M577 482 C577 512 576 480 576 510 149false12330345M606 553 L606 603 L656 553 z10true182330346M565 501 C595 501 571 500.5 601 500.5 149false12330347M511 155 C486 155 328 156 315 155 C315 173 317 281 316 323 149false17trueM 296.28019855002424 106.26155629629604 L 281.3333435058594 105 L 287.7142312270452 118.57513432307834false2330624M581 510 C581 480 581 511.75 581 481.75 149false12330625M631 293 C631 323 586 445 586 475 149false18trueM 472.28019855002424 106.26155629629604 L 457.3333435058594 105 L 463.7142312270452 118.57513432307834false2330743M579 512 C579 482 580 511.75 579 481.75 149false1falsefalse2330744M706 248 C706 278 657 408 657 423 C686 424 719 424 736 423 149false18trueM 969.472450657888 515.2498792403859 L 982 507 L 968.5916203286159 500.2757636427609false2332006M886 213 C886 237 887 305 889 351 C924 352 952 350 970 351 83false18trueM 1206.9468550441647 303.261556296296 L 1192 302 L 1198.380887721186 315.5751343230783false2332045M886 153 C934 152 1066 154 1102 153 C1101 171 1101 260 1101 281 C1127 282 1180 284 1195 281 83false18trueM 1336.9468550441647 303.261556296296 L 1322 302 L 1328.380887721186 315.5751343230783false2332088M811 188 C854 187 1002 185 1046 187 C1046 287 1046 271 1045 316 148false18falsetrueM 1252.477154137976 428.5090339862284 L 1266 435 L 1279.522845862024 441.49096601377162332206M386 720 C388 442 388 454 387 438 C401 439 509 437 508 436 C508 436 546 247 546 248 149false18trueM 472.28019855002424 158.26155629629605 L 457.3333435058594 157 L 463.7142312270452 170.57513432307834false2332207M584 481 C584 511 586 481.75 586 511.75 149false12332434M386 790 C386 820 386 910 386 940 149false18trueM 619.5 751.0096189432334 L 627 764 L 634.5 751.0096189432334false2332435M361 885 L361 935 L411 885 z10true182332436M501 885 L501 935 L551 885 z10true182332437M641 885 L641 935 L691 885 z10true182332438M573 512 C573 482 574 511 574 481 149false1falsefalse2332630M386 1175 C386 1145 386 1040 386 1010 149false18trueM 285.6135115383055 536.9282433080148 L 270.6666564941406 535.6666870117188 L 277.04754421532647 549.2418213347971false2332631M593 480 C593 510 592 479 592 509 149false12332707M301 1100 C301 1102 384 1099 386 1100 149false182332708M386 1175 C386 1145 386 1130 386 1100 149false18trueM 285.6135115383055 536.9282433080148 L 270.6666564941406 535.6666870117188 L 277.04754421532647 549.2418213347971false2332963M690 1231 L690 1281 L740 1231 z10true182332964M590 492 C560 492 574 502.5 591 487.5 149false12332965M285 126 L285 176 L335 126 z10true182332966M355 1401 C385 1401 420 1401 450 1401 149false18trueM 336.94685504416486 118.26155629629604 L 322 117 L 328.38088772118584 130.57513432307834false2333224M600 1401 C601 1403 727 1403 735 1403 149false18trueM 879.0096189432334 1246.5 L 892 1239 L 879.0096189432334 1231.5false2333225M950 1238 L950 1288 L1000 1238 z10true182333226M596 490.5 C566 490.5 595 491 565 491 149false1falsefalse2333349M567 494 C597 494 565 490.5 595 490.5 149false12333350M1025 1400 C995 1400 915 1403 885 1403 149false18trueM 272.28019855002424 640.9282433080148 L 257.3333435058594 639.6666870117188 L 263.7142312270452 653.2418213347971false2333623M565 497 C595 497 570 495 600 495 149false12333624M1325 1400 C1295 1400 1205 1400 1175 1400 149false18trueM 384.28019855002424 588.9282433080148 L 369.3333435058594 587.6666870117188 L 375.7142312270452 601.2418213347971false2398180M812 452 C815 467 815 629 816 663 C833 664 963 662 980 661 C981 679 983 738 982 762 83false18trueM 1140.5 798.0096189432334 L 1148 811 L 1155.5 798.0096189432334false2398181M580 511 C580 481 579 512 579 482 83false12398803M1400 1365 C1400 1335 1400 1320 1400 1290 149false182398804M1400 1230 C1400 1260 1400 1260 1400 1290 149false18trueM 891.4468550441649 728.761556296296 L 876.5 727.5 L 882.8808877211858 741.0751343230784false2411647M274 68.5 L274 118.5 L324 68.5 z10true182411648M598 497 C568 497 598 500 568 500 149false12411649M-51 46 L-51 96 L-1 46 z10true182411650M-51 106 L-51 156 L-1 106 z10true182411651M1119 1076 C1149 1076 1299 1078 1329 1078 149false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false2411780M1044 1111 C1045 1125 1047 1177 1045 1192 C1067 1192 1298 1199 1325 1195 149false18trueM 1659.9468550441647 1088.261556296296 L 1645 1087 L 1651.380887721186 1100.5751343230784false2412317M1044 981 C1045 969 1045 943 1044 932 C1065 932 1291 931 1329 928 83false18trueM 1340.178104160403 980.9221011047807 L 1335 995 L 1349.7808701553704 992.4454202987414false2412651M1404 893 C1404 879 1406 777 1404 776 148false18falsetrueM 1520 822 L 1535 822 L 1550 822325913837704481655326572398180Left1665326582398181Right233687570448146275032330019Left28535180512330012Right23398797044886285032330347Right28585181312330346Left23428827044886295032330625Right28635181942330624Left23438757044886305032330744Left28645182212330743Right23448837044886315032332207Left28655185422332206Right23458847044886325042332438Right28665185422332434Left23468857044886335042332631Left72217113492332630Right234788670448872317114052332707Left72417113492332708Right23498887044825328695187102332964Left28705187112332966Right235120170448828735187102333224Left28745187702333226Right235277970448828755187702333349Left28765187972333350Right235567670448828815187972333623Left28825188592333624Right2414423704482729915188592398803Left29925327952398804Right241593970448276395082411651Right29935356002411648Left101317113631014171164363905233200663906233204563907233208863921241178063922241231763923241265115266313511527631363152964861815306486831615939097512.82.802667815416159411853731.01.00114327267238358M130 293 C130 243 180 193 230 193 C616 193 1119 193 1505 193 C1555 193 1605 243 1605 293 C1605 630 1605 1068 1605 1405 C1605 1455 1555 1505 1505 1505 C1119 1505 616 1505 230 1505 C180 1505 130 1455 130 1405 C130 1068 130 630 130 293 1true61475.01312.0345251235Nucleus1034681201.31.320015345257235Cytoplasm537666201.31.320015345258235Extracellular125276201.31.3200151575631372560888675152912504#FFF9C91641575