VEGFA-VEGFR2 signaling (Homo sapiens)

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27STAT3PROCK2PRKD2535327, 102MAPK3Y204T202MAPK1T185Y18758126, 129MAPK1T185Y187155214, 2712301236, 22, 2452544758, 234MAP2K3MAP2K6P24939MAPK9MAPK8T183Y185STAT3PMAPK3T183228MAPK3T202Y20418645, 123, 146, 173MAPK1Y185127PRKCZ128, 238PIK3R2ACACBNCF2MAPK12RAP1B33VEGFR2Y1059MeK1041Y1214Y996Y1175Y1054Y95189201188, 214149AP1complexPKC delta/ZetadependentSoluble andcleaved FLT1may sequesterVEGFA fromVEGFR2Epoxyeicosatrienoicacid regioisomersEC proliferation,migration,tube formationand angiogenesisCYCell motilityand tube formationEC Migration andTube FormationABCF233, 11418FADDTCEB3FAF1FASBIN1BMXHDAC1TNFRSF10CHSPA1ASMARCA257DOK1PGAB1PReceptorPROTEINLigandProtein translocation LEGENDMultiple colored edges are introduced to distinguish the connecting nodesPhosphorylated form with/without site & residueEndosomeNucleusMitochondrionCytoplasmPlasma membraneMTEndoplasmic reticulumCYPMNUERENVEGFR2Y951Y1214Y1054Y1175Y1059Y80130VEGFA259MAPK14P117, 190117F-actinreorganization117, 162117Stress fibreformationFocal adhesionassembly andcell migration117NCK1PFYNPPAK2P33STAT1PSTAT6P105, 137STAT1PSTAT6P137NUFRS2PCRKPPRKCI1515151533SRCY419Y5302087RAPGEF1186186RAP1AGTP186ITGAVITGB3Y773186BCAR1P17630, 187PLCG1Y783Ub16SHC1187, 213SHC218733, 127PTK2Y576Y397Y407Y861S732168IQGAP1PRAC1133, 207GTP149149Directed Cell migration135, 149, 215ITGB5ITGB1ITGAV1717, 811717222SH2D2A175175223VascularpermeabilityNAADP65TPCN2Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+6565H+H+H+ATPADP656565Endolysosomalcalcium storeMAPKAPK2T33469, 190190190190PLAUPIP2IP3DAG274274274CAPN2138Ca2+Ca2+Ca2+166MYL2S20T19168Endothelial cellcontraction athigh VEGFA levels16851ROCK1P51, 75RHOAGTP35, 50, 51, 75, 119...207RHOCGTP3, 228Endothelial cellProliferationand migration228228MAP2K1S218S222188, 22822820, 163CBL163163163ITPR1274228PRKCBPRKCAS65790RAF1P6, 90, 254SPHK1PHRAS19GTP27410PRKD1S738S910S7421551018, 155HDAC5S259S498155HDAC5S498S259PRKCDPRKCEPLA2G4AP66, 22PGI2HSPB1S15S78S8292150NRP1130, 201CAV1Y14878787CDH5106PTPN11106CSK10610610674PTK2BY402132128, 185HSP90AA1464646, 185267MLLT4210210FHL214014038PLCB3S1105S5372626CDC42GTP26WASF1NCF1PPAK1P140152152PTPN988PTPRZ160606060NCLMYH9NCL122122122122109AKT1T308S473109FOXO1S256AKT1T308S47323, 109, 202109FOXO1S256109, 249109106, 109, 250RELANFKBIAP268919163, 91, 165, 26191PLA2G5RPS6KA5P767676136, 154PIK3R1P73154, 202NOS3S114S11791692, 138, 154NO154LIMK1S323CFL1S392162162150, 162VAV2Y1725050, 100FLNB9898, 20498PFN1Y12944G-actin bindingand actinpolymerization4At cellleadingedge1142, 234ATF2T69T71Promotes endothelial-leukocyte interactions23423458Endothelialcell survival58, 134GRB2P2020, 10046, 238PXNpY9, 128, 20336GJA1S282S255S262S368S279184ClathrinmediatedGap junctioninternalization123GJA1S368S282S279S262S255Stress fibreformation11PTPRJ250, 251250, 251250SHBP129129129129114, 235114, 235114185185ROCK1P185RPS6KB1T41256TXNIPACP1S-glutathionylation56, 131TXN5656, 131ONOO-5656109, 273Cysteineoxidationof VEGFR2and SRCPTPN6216216GRB10P5531, 152PRKAA1T183ROSMitochondrial21531CytosolicROS79Angiogenesis7979, 8549, 121, 246cGMP121, 164Angiogenesis49, 121, 246CREB1P68CAMKK285, 217ACACAP85, 20085, 217PRKAA2215ARHGEF156464RHOJ257GTP6464126SHC1S36126, 213PDPK1S241214PIP2PIP3R1CTORMLST8MAPKAP1MTORS2448S2481199199MTORRAPTORMLST8214214214NRDG1T345mTORC2mTORC1142134, 227GSK3BS9202169, 214214AKT1S1T266271271271RPS6S235S236169, 271136RAPTORMTORMLST8mTORC1169ER stress-independentVEGF-UPR machinerymediated pathwayEIF2AK3ERN1PATF6EIF2AS51169169169GeneexpressionATF4169169DNAJB9HERPUD1169AKT1S4731693311CAPN2166EZR138138138TRPC1ITPR1171KL161161Ca2+Ca2+Ca2+Ca2+Ca2+161171Calciumreleasefrom ERPIK3CA210TXNIPVEGFR256PLCG1Y783RAB5ACDH5S665CTNND1S252S268CTNNB1CTNNA1S453MAP2K1S222S218MAP2K2243243VEGFR2UbY1214Y1175192Lysosomemediatedpartialproteosomaldegradation230 kDa160 kDaFBXW11192EEA12525SLC8A1Ca2+Ca2+Ca2+Ca2+232Na+Na+232232232232Mostlyclathrindependentinternalization25HGSY334VEGFR2Y1214Y1175UbSTAM8484GIPC1MYO6236PTPN1151, 236132272NRP1272272ClathrindependentinternalizationNRP1RAB11VEGFR2NRP1174VEGFR2recycling174239SRCY527Y416VAV2Y172RAC1GTP133, 207PAK2PARRB250, 23923950, 207, 239239239239239239CDH5S655CTNND1CTNNB1ARRB2239239239VE CadherinrecyclingEarly endosomes115115115115Regulation ofcell survivalRegulation ofchromatinremodellingRNA elongationby RNA Pol II115115115VCLS346464646, 18546, 185465Regulation ofendothelial cellsproutingCLTC192Involvedin the activationof VEGFR224MAPKAPK5T1822424NRP2MAP3K5S83MAP2K7PMAP2K4T261JUNS63393939AKT1T308S473CAV1Y1487ARF6275ARF6275ANXA1P265265208NFATC2dePNFATC2deP8, 16, 167, 225167NFATC1NFATC144, 86PTGS216EC Migration83RND1838, 237, 253EGR144, 77, 19844, 77, 198SRF44, 77, 198NR4A2NR4A344PPP3CACREB1P686, 228, 16, 167, 225, 237...Ca2+Ca2+Ca2+JAG1DKK1CCL2CXCL8AMOTBMP10237TEAD493, 1242, 82, 23712422554PKC delta/betadependentTEAD412454269EndosomeRegulation of receptor endocytosis and recyclingCYNUCYNUCYNUCYNUCYNUCYNUCYNUCYNUNUCYNFKB1RELANFKB1ICAM1SELE63Promotes endothelial-leukocyte interactions63165Endothelialcell survival105105FOXO4S197FOXO3249FOXO4FOXO3249249CYNUCYNU249Decreasedexpressionby nuclearexport ofFOXO1/3/4Endothelialcell survival249VEGFR2EndosomeRAB4A113RAB4A113ENPMHGSEPS15EPN1OCLNS490UbITCHGap junctiondisruptionNa+Na+264156, 180, 264264264Tight junctiondisruption264Occludininternalizationand proteosomaldegradationHDAC7S479S194S397FLNBK1147204204YWHAE256HDAC7S479S194S397HDAC9S254S245HDAC4S 246S467CY196, 204, 256NUMEF2CCCND1228196, 204, 25654, 196, 204, 256RCAN2MMP10MMP14Activationof MEF2 by nuclearexport ofHDACsEC proliferation,migration,tube formationand angiogenesis196, 204, 25654MKNK1PMKNK1P254NUCYEIF4EP254ELK1160OCLNUbS49045, 264PMENITGAVStimulationof tip cellfilopodiaPLAURPLAU141PLAUProActiveMMP224024012, 141, 252ITGAVITGB1PLAURPLAUCell migrationand invasion141PMENClathrinmediatedF3172NR4A1VCAM1BCL2L1CYP2C8SOD2ADAMTS1ACKR3EGR3172HBEGFRCAN1CDKN1BNUR4A1MEF2C172VCAM1172CCL2BCL2CTNNB1VEGFA SIGNALING PATHWAY IN ENDOTHELIAL CELLSCTNNB1Y142230230112, 230Adherensjunctiondisassembly230ATF2T71T69BCL2L158ERGS21510227NOTCH487ETS1T38S41Ac177AA6, 22, 245245PTGS2S-nitrosylPTGS2242NOS3242T172PRKG1164121, 164ProteinComplexSmallmoleculesTranscriptional regulation of gene expression (multiple colours)Unique solid edges between receptor and other proteinsDirect protein-protein interactions associated with VEGFR2 phospho-Y1175Direct protein-protein interactions associated with VEGFR2 phospho-Y801Direct protein-protein interactions associated with VEGFR2 phospho-Y1214Direct protein-protein interactions associated with VEGFR2 phospho-Y951Direct protein interactions of VEGFR2 for which a specific VEGFR2 phosphosite involvement isnot reported AND also represents direct protein-protein interactions between other proteinsDirect phosphorylations by VEGFR2 AND also represents otherdirect kinase-substrate phosphorylation eventsGeneric edges between proteinsSolid edges Dashed edgesDirect protein-protein interactions or enzyme-substrate reactionsLeads to, through unknown or not reported intermediatesDirect dephosphorylation of substrates by phosphatasesDirect ubiquitination of substrates by E3 ubiquitin ligasesDirect protein cleavage of substrates by proteasesDirect inhibition of protein activityDissociation of direct protein-protein interactionsLeads to, through unknown ornot reported/studied intermediatesUbiquitinated form with/without site & residueMethylated form with/without site & residueGlutathionilated form with/without site & residuePTMsProtein transport across multiple cell compartmentsPIP2 PtdIns(4,5)P2PIP3 PtdIns(3,4,5)P3DAG DiacylglycerolIP3 Inositol triphosphateROS Reactive oxygen speciesONOO- PeroxynitriteNAADP Nicotinic acid adenine dinucleotide phosphateATP Adenosine triphosphateGTP Guanosine triphosphateADP Adenosine diphosphateNO Nitric OxidecGMP Cyclic GMPAA Arachidonic AcidPGI2 Prostaglandin I2S-nitrosilated formPROTEINmRNASmallmoleculesmRNAPROTEINModifiedformIncreasedexpressionDecreasedexpressionPI3K-AKT-MTOR ModuleP38 MAPKModuleJNKModulePLC-PKCModuleERKModuleNFKBModuleFAKModuleRACModuleSTATModuleRHOAModuleADAMTS121VEGFA-165aFGAMMRN2TNXBIGFBP7GPC1CTGF671111104144183PGF34FGBFGGVEGFA-145aVEGFA-145bVEGFA-111VEGFA-148VEGFA-165aVEGFA-165bVEGFA-121aVEGFA-121bVEGFA-183aVEGFA-183bVEGFA-162VEGFA-206VEGFA-189aVEGFA-189bMultiple VEGFA isoforms178FLT1178Y1333Y1169Y1213Y79472, 9718218218218240, 95RACK12206161Direct protein-protein interactions associated with FLT1 phospho -Y794, -Y1169, -Y1213 & -Y1333VEGFAVEGFA-165a25914852BIRC5MDM2P52ADAM952ADAM10201S1PR1201210AFDN46, 21046, 21035, 50, 51, 75, 229SCUBE2195195ENGCDH5241PFGD5118147, 181181LMO2TAL1GATA2LDB2DLL4179GPX1GJA1159CYCS270MAP2K3CHAC1C15ORF39RAB37ADRB2TRAF3IP2DUSP5EPHA2FJX1TMEM170ASDF2L1SLC2A14IER5SLC39A14ZNF555HLXNRARPSLC25A25CCRL2PNPAPOLD1PIK3R1NDRG1FUT1DLL4SIAH2CASC10TRPC328SLC7A128212212ArginineIntakeBRD4103acetylated formLARP7CREBBP103MEF2CCXCL8BMP2SEMA6DNR4A2ADAMTS9EGR3NR4A1IGFBP3103CYBBNOX4EPHB2SDCBPPromotesendocytosis12014ABL1PRCAN1TNFRSF25255PTPN6224ACOT97ACTG1AKAP2ALBALDOAANXA1AP2A1AP2S1ARF4ARMCX1ARPC5LASCC3ATP6V0D1CSRP2CYR61DECR1DHX29DHX36DNAJA1DNAJB4DPM1DSC1EIF3DEIF3FEIF3HEIF4G1EIF4G2GRSF1HBDHMGB1HSP90AA1HSP90AB2PHTRA1HYOU1IDH2INPP5KIQGAP1KANK1KATNAL2LDHALMAN1P4HBPABPC1PBXIP1PDE4DIPPDIA6PFN1PGDPGK1PLOD3PPM1GPPP1CAPPP2CAPRDX2PRDX6PRKRARPL7RPLP2RPS11SARSSETSH3BGRL3SHROOM2SLC25A11SND1SPIRE1SRP54SRPK1SSR3SSR4STIP1ATP6V1E1BSGCACNA2D1CALRCALUCAPZBCCDC124CCT7CDC42BPBCGNL1CLIC1CNPCOPG1CRIP2CSRP1EPB41EPRSEWSR1FAM120AFARSBFGD5FHOD1FLIIFMNL3FN1FSCN1FXR2GAPDHGIGYF2GLUD1LRRC59LRRFIP2LUC7LMICAL2MOV10MYH11MYO1CMYO6NAP1L1NAPANCLNEXNNUMBOCRLP4HA2PRRC2CPSMD11PSMD4PTMAPTPN14QKIRBM39RCN1RPL10ARPL13ARPL18ARPL26RPL27RPL39P5RPL5SYNJ1TAOK2TBCATCEB1TFAMTFCP2TKTTMOD1TMOD3TMSB10TMSB4XTPM3TPP1TRIP4TUBA1CTUBB8TXNDC5UBAP2LUSP10VPS39YWHAEZC3H1577BCAR1interactome(10', 30', 60')


Description

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is central to a number of physiological conditions, from embryogenesis to wound healing in adults and is a hallmark of pathological conditions such as tumorigenesis [1-3]. Angiogenesis is mediated by the coordinated action of a variety of growth factors, metabolites and cell adhesion molecules in endothelial cells [4-6]. Vascular endothelial growth factor (VEGF) is the principal angiogenic growth factor modulating neovascularization [7].

The biological effect of VEGF is mediated through specific VEGF receptors on endothelial cell surface. VEGFs (VEGF-A, VEGF-B, VEGF-C and VEGF-D) interact with VEGF receptors such as VEGFR1, VEGFR2 and VEGFR3. Among them, VEGFA/VEGFR2 signaling appears to mediate cellular responses involved in angiogenesis prominently. Further, VEGF/VEGFR1 signaling, though weak, converges to VEGFR2 signaling pathway. VEGFA binding to VEGFR2 at the surface of endothelial cells leads to dimerization and auto-phosphorylation of specific tyrosine residues in the cytoplasmic domain of VEGFR2. It leads to activation of multiple downstream signaling cascades and promotes endothelial cell proliferation, migration, and tube formation relevant to angiogenesis [8]. VEGFR2 dependent activation of PI3K-AKT-mTOR signaling regulates cell survival, cell proliferation, anti-apoptotic and cell permeability functions [9]. Another important pathway of VEGF mediated cell proliferation appears to be through PLCγ-mediated activation of PKC and downstream induction of the ERK and other PKC-dependent pathways [10]. Endothelial cell migration is induced by VEGFA/VEGFR2 signaling through activation of p38MAPK (actin polymerization) and FAK (focal adhesion turnover) which is particularly important in directed migration. Phosphosite specificity towards downstream signalling has also been documented. Phosphosite mapping documented seven phosphosites in VEGFR2 receptor: Y1054, Y1214, Y801, Y1175, Y951, Y1059 and Y996. Phosphorylation of Y1214 and Y1054 regulates signaling events involved in cell migration. Y801 phosphorylation regulates cell survival. Y1175 regulates both cell proliferation and migration. Y951 and Y1059 phosphorylation regulates cell survival, cell migration and cell proliferation.

VEGFA/VEGFR2 signaling network compiles data available in the literature with respect to VEGFA signaling (especially VEGFA-165) through VEGFR2 in endothelial cells. The signaling events involving these proteins were derived from experimentally validated data involving multiple experimental techniques and approaches. Individual signaling events in VEGFR2 signaling networks leading to cell proliferation, migration and survival were identified and categorized into protein-protein interactions, enzyme-catalyzed events, activation/inhibition reactions, transport of protein across subcellular compartments, and gene regulation events. Signaling molecules involved in VEGFA/VEGFR2 signaling were categorized to enzymes, receptors and transcription factors and the contextual activation/deactivation of these molecules downstream to VEGFA/ VEGFR2 signaling, in modulating angiogenesis, is documented.

VEGFA dependent angiogenesis pathway map depicts the integration of signaling pathways regulating cell survival, cell migration, cell proliferation, cellular interactions downstream of VEGFA/VEGFR2 signaling relevant to angiogenesis, regulation of VEGFR2, phosphosite specificity of VEGFR2 towards downstream signaling, post-translational modifications, molecular function-based information, cross-talks among proteins in the canonical signaling modules and the information on the compartmentalization of proteins. The map of VEGFA/VEGFR2 signaling network is interactive to help investigators to add new information as it becomes available in the future for analysis or representation.


VEGFA dependent angiogenesis pathway map may please be cited as:

1. Abhinand, C. S., Raju, R., Soumya, S. J., Arya, P. S., and Sudhakaran, P. R. (2016). VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. Journal of cell communication and signaling, 10(4), 347-354.

2. Sunitha, P., Raju, R., Sajil, C.K., Abhinand, C.S., Nair, A.S., Oommen, O.V., Sugunan, V.S., and Sudhakaran, P.R. (2019). Temporal VEGFA responsive genes in HUVECs: Gene signatures and potential ligands/receptors fine-tuning angiogenesis. Journal of Cell Communication and Signaling, 13, 561 - 571.


References

[1] Folkman J (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med. 285:1182-1186.

[2] Chatterjee S, Heukamp LC, Siobal M et al., 2013. Tumor VEGF: VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer. J Clin Invest. 123:1732-1740.

[3] Shibuya M (2014). VEGF-VEGFR Signals in Health and Disease. BiomolTher (Seoul). 22:1-9.

[4] Kumar VB, Binu S, Soumya SJ et al., 2014. Regulation of vascular endothelial growth factor by metabolic context of the cell. Glycoconj J. 31:427-434.

[5] Kitazume S, Imamaki R, Ogawa K et al., 2014. Sweet role of platelet endothelial cell adhesion molecule in understanding angiogenesis. Glycobiology. 24:1260-1264.

[6] Kunhiraman H, Edatt L, Thekkeveedu S et al., 2016. 2‐Deoxy Glucose Modulates Expression and Biological Activity of VEGF in a SIRT‐1 Dependent Mechanism. J Cell Biochem.

[7] Lohela M, Bry M, Tammela T et al., 2009. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. Curr Opin Cell Biol. 21:154-165.

[8] Koch S, Claesson-Welsh L, 2012. Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harbor perspectives in medicine. 2(7):a006502.

[9] Koch S, Tugues S, Li X et al., 2011. Signal transduction by vascular endothelial growth factor receptors. Biochem J.437:169-183.

[10] Simons M, Gordon E, Claesson-Welsh L. 2016. Mechanisms and regulation of endothelial VEGF receptor signalling. Nat Rev Mol Cell Biol.




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89246view16:01, 25 August 2016KhanspersReverted to version '06:50, 25 August 2016' by Khanspers
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89241view06:38, 25 August 2016PrslabModified title
89240view06:34, 25 August 2016PrslabNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
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ABL1Protein25 (Entrez Gene)
ACACAProtein31 (Entrez Gene)
ACACBProtein32 (Entrez Gene)
ACKR3Protein57007 (Entrez Gene)
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ACP1Protein52 (Entrez Gene)
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ADAM10Protein102 (Entrez Gene)
ADAM9Protein8754 (Entrez Gene)
ADAMTS1Protein9510 (Entrez Gene)
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ADRB2Protein154 (Entrez Gene)
AFDNProtein4301 (Entrez Gene)
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AKT1Protein207 (Entrez Gene)
AKT1S1Protein84335 (Entrez Gene)
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AMOTProtein154796 (Entrez Gene)
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ARMCX1GeneProduct51309 (Entrez Gene)
ARPC5LGeneProduct81873 (Entrez Gene)
ARRB2Protein409 (Entrez Gene)
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ATF2Protein1386 (Entrez Gene)
ATF4Protein468 (Entrez Gene)
ATF6Protein22926 (Entrez Gene)
ATP6V0D1GeneProduct9114 (Entrez Gene)
ATP6V1E1GeneProduct529 (Entrez Gene)
BCAR1Protein9564 (Entrez Gene)
BCL2Protein596 (Entrez Gene)
BCL2L1Protein598 (Entrez Gene)
BIN1Protein274 (Entrez Gene)
BIRC5Protein332 (Entrez Gene)
BMP10Protein27302 (Entrez Gene)
BMP2Protein650 (Entrez Gene)
BMXProtein660 (Entrez Gene)
BRD4Protein23476 (Entrez Gene)
BSGGeneProduct682 (Entrez Gene)
C15ORF39Protein56905 (Entrez Gene)
CACNA2D1GeneProduct781 (Entrez Gene)
CALRGeneProduct811 (Entrez Gene)
CALUGeneProduct813 (Entrez Gene)
CAMKK2Protein10645 (Entrez Gene)
CAPN2Protein824 (Entrez Gene)
CAPZBGeneProduct832 (Entrez Gene)
CASC10Protein399726 (Entrez Gene)
CAV1 Protein857 (Entrez Gene)
CBLProtein867 (Entrez Gene)
CCDC124GeneProduct115098 (Entrez Gene)
CCL2Protein6347 (Entrez Gene)
CCND1Protein595 (Entrez Gene)
CCRL2Protein9034 (Entrez Gene)
CCT7GeneProduct10574 (Entrez Gene)
CDC42Protein998 (Entrez Gene)
CDC42BPBGeneProduct9578 (Entrez Gene)
CDH5Protein1003 (Entrez Gene)
CDKN1BProtein8013 (Entrez Gene)
CFL1Protein1072 (Entrez Gene)
CGNL1GeneProduct84952 (Entrez Gene)
CHAC1Protein79094 (Entrez Gene)
CLIC1GeneProduct1192 (Entrez Gene)
CLTCProtein1213 (Entrez Gene)
CNPGeneProduct1267 (Entrez Gene)
COPG1GeneProduct22820 (Entrez Gene)
CREB1Protein1385 (Entrez Gene)
CREBBPProtein1387 (Entrez Gene)
CRIP2GeneProduct1397 (Entrez Gene)
CRKProtein1398 (Entrez Gene)
CSKProtein1445 (Entrez Gene)
CSRP1GeneProduct1465 (Entrez Gene)
CSRP2GeneProduct1466 (Entrez Gene)
CTGFProtein1490 (Entrez Gene)
CTNNA1Protein1495 (Entrez Gene)
CTNNB1Protein1499 (Entrez Gene)
CTNND1Protein1500 (Entrez Gene)
CXCL8Protein3576 (Entrez Gene)
CYBBProtein1536 (Entrez Gene)
CYCSProtein54205 (Entrez Gene)
CYP2C8 Protein1558 (Entrez Gene)
CYR61GeneProduct3491 (Entrez Gene)
DECR1GeneProduct1666 (Entrez Gene)
DHX29GeneProduct54505 (Entrez Gene)
DHX36GeneProduct170506 (Entrez Gene)
DKK1Protein22943 (Entrez Gene)
DLL4Protein54567 (Entrez Gene)
DNAJA1GeneProduct3301 (Entrez Gene)
DNAJB4GeneProduct11080 (Entrez Gene)
DNAJB9Protein4189 (Entrez Gene)
DOK1 Protein1796 (Entrez Gene)
DPM1GeneProduct8813 (Entrez Gene)
DSC1GeneProduct1823 (Entrez Gene)
DUSP5Protein1847 (Entrez Gene)
EEA1Protein8411 (Entrez Gene)
EGR1Protein1958 (Entrez Gene)
EGR3Protein1960 (Entrez Gene)
EIF2AProtein83939 (Entrez Gene)
EIF2AK3Protein9451 (Entrez Gene)
EIF3DGeneProduct8664 (Entrez Gene)
EIF3FGeneProduct8665 (Entrez Gene)
EIF3HGeneProduct8667 (Entrez Gene)
EIF4EProtein1977 (Entrez Gene)
EIF4G1GeneProduct1981 (Entrez Gene)
EIF4G2GeneProduct1982 (Entrez Gene)
ELK1Protein2002 (Entrez Gene)
ENGProtein2022 (Entrez Gene)
EPB41GeneProduct2035 (Entrez Gene)
EPHA2Protein1969 (Entrez Gene)
EPHB2Protein2048 (Entrez Gene)
EPN1Protein29924 (Entrez Gene)
EPRSGeneProduct2058 (Entrez Gene)
EPS15Protein2060 (Entrez Gene)
ERGProtein2078 (Entrez Gene)
ERN1Protein2081 (Entrez Gene)
ETS1Protein2113 (Entrez Gene)
EWSR1GeneProduct2130 (Entrez Gene)
EZRProtein7430 (Entrez Gene)
F3Protein2152 (Entrez Gene)
FADDProtein8772 (Entrez Gene)
FAF1Protein11124 (Entrez Gene)
FAM120AGeneProduct23196 (Entrez Gene)
FARSBGeneProduct10056 (Entrez Gene)
FASProtein355 (Entrez Gene)
FBXW11Protein23291 (Entrez Gene)
FGAProtein2243 (Entrez Gene)
FGBProtein2244 (Entrez Gene)
FGD5GeneProduct152273 (Entrez Gene)
FGGProtein2266 (Entrez Gene)
FHL2Protein2274 (Entrez Gene)
FHOD1GeneProduct29109 (Entrez Gene)
FJX1Protein24147 (Entrez Gene)
FLIIGeneProduct2314 (Entrez Gene)
FLNBProtein2317 (Entrez Gene)
FLT1Protein2321 (Entrez Gene)
FMNL3GeneProduct91010 (Entrez Gene)
FN1GeneProduct2335 (Entrez Gene)
FOXO1Protein2308 (Entrez Gene)
FOXO3Protein2309 (Entrez Gene)
FOXO4Protein4303 (Entrez Gene)
FRS2Protein10818 (Entrez Gene)
FSCN1GeneProduct6624 (Entrez Gene)
FUT1Protein2523 (Entrez Gene)
FXR2GeneProduct9513 (Entrez Gene)
FYN Protein2534 (Entrez Gene)
GAB1Protein2549 (Entrez Gene)
GAPDHGeneProduct2597 (Entrez Gene)
GATA2Protein2624 (Entrez Gene)
GIGYF2GeneProduct26058 (Entrez Gene)
GIPC1Protein10755 (Entrez Gene)
GJA1Protein2697 (Entrez Gene)
GLUD1GeneProduct2746 (Entrez Gene)
GPC1Protein2817 (Entrez Gene)
GPX1Protein2876 (Entrez Gene)
GRB10Protein2887 (Entrez Gene)
GRB2Protein2885 (Entrez Gene)
GRSF1GeneProduct2926 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
HBDGeneProduct3045 (Entrez Gene)
HBEGFProtein1839 (Entrez Gene)
HDAC1Protein3065 (Entrez Gene)
HDAC4Protein9759 (Entrez Gene)
HDAC5Protein10014 (Entrez Gene)
HDAC7Protein51564 (Entrez Gene)
HDAC9Protein9734 (Entrez Gene)
HERPUD1Protein9709 (Entrez Gene)
HGSProtein9146 (Entrez Gene)
HLXProtein3142 (Entrez Gene)
HMGB1GeneProduct3146 (Entrez Gene)
HRASProtein3265 (Entrez Gene)
HSP90AA1GeneProduct3320 (Entrez Gene)
HSP90AB2PGeneProduct391634 (Entrez Gene)
HSPA1AProtein3303 (Entrez Gene)
HSPB1Protein3315 (Entrez Gene)
HTRA1GeneProduct5654 (Entrez Gene)
HYOU1GeneProduct10525 (Entrez Gene)
ICAM1Protein3383 (Entrez Gene)
IDH2GeneProduct3418 (Entrez Gene)
IER5Protein51278 (Entrez Gene)
IGFBP3Protein3486 (Entrez Gene)
IGFBP7Protein3490 (Entrez Gene)
INPP5KGeneProduct51763 (Entrez Gene)
IQGAP1GeneProduct8826 (Entrez Gene)
ITCHProtein83737 (Entrez Gene)
ITGAVProtein3685 (Entrez Gene)
ITGB1Protein3688 (Entrez Gene)
ITGB3Protein3690 (Entrez Gene)
ITGB5Protein3693 (Entrez Gene)
ITPR1Protein3748 (Entrez Gene)
JAG1Protein182 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
KANK1GeneProduct23189 (Entrez Gene)
KATNAL2GeneProduct83473 (Entrez Gene)
KLProtein9365 (Entrez Gene)
LARP7Protein51574 (Entrez Gene)
LDB2Protein9079 (Entrez Gene)
LDHAGeneProduct3939 (Entrez Gene)
LIMK1Protein3984 (Entrez Gene)
LMAN1GeneProduct3998 (Entrez Gene)
LMO2Protein405 (Entrez Gene)
LRRC59GeneProduct55379 (Entrez Gene)
LRRFIP2GeneProduct9209 (Entrez Gene)
LUC7LGeneProduct55692 (Entrez Gene)
MAP2K1Protein5604 (Entrez Gene)
MAP2K2Protein5605 (Entrez Gene)
MAP2K3Protein5606 (Entrez Gene)
MAP2K4Protein6416 (Entrez Gene)
MAP2K6Protein5608 (Entrez Gene)
MAP2K7Protein5609 (Entrez Gene)
MAP3K5Protein4217 (Entrez Gene)
MAPK12Protein6300 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5595 (Entrez Gene)
MAPK8Protein5599 (Entrez Gene)
MAPK9Protein5601 (Entrez Gene)
MAPKAP1Protein79109 (Entrez Gene)
MAPKAPK2Protein9261 (Entrez Gene)
MAPKAPK5Protein8550 (Entrez Gene)
MDM2Protein4193 (Entrez Gene)
MEF2CProtein4208 (Entrez Gene)
MICAL2GeneProduct9645 (Entrez Gene)
MKNK1Protein8569 (Entrez Gene)
MLLT4Protein4301 (Entrez Gene)
MLST8Protein64223 (Entrez Gene)
MMP10Protein4319 (Entrez Gene)
MMP14Protein4323 (Entrez Gene)
MMP2Protein4313 (Entrez Gene)
MMRN2Protein79812 (Entrez Gene)
MOV10GeneProduct4343 (Entrez Gene)
MTORProtein2475 (Entrez Gene)
MYH11GeneProduct4629 (Entrez Gene)
MYH9Protein4627 (Entrez Gene)
MYL2Protein4633 (Entrez Gene)
MYO1CGeneProduct4641 (Entrez Gene)
MYO6GeneProduct4646 (Entrez Gene)
NAP1L1GeneProduct4673 (Entrez Gene)
NAPAGeneProduct8775 (Entrez Gene)
NCF1Protein653361 (Entrez Gene)
NCF2Protein4688 (Entrez Gene)
NCK1Protein4690 (Entrez Gene)
NCLGeneProduct4691 (Entrez Gene)
NDRG1Protein10397 (Entrez Gene)
NEXNGeneProduct91624 (Entrez Gene)
NFATC1Protein4772 (Entrez Gene)
NFATC2Protein4773 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NFKBIAProtein4792 (Entrez Gene)
NOS3Protein4846 (Entrez Gene)
NOTCH4Protein4855 (Entrez Gene)
NOX4Protein50507 (Entrez Gene)
NR4A1Protein3164 (Entrez Gene)
NR4A2Protein4929 (Entrez Gene)
NR4A3Protein8013 (Entrez Gene)
NRARPProtein441478 (Entrez Gene)
NRDG1Protein10397 (Entrez Gene)
NRP1Protein8821 (Entrez Gene)
NRP2Protein8828 (Entrez Gene)
NUMBGeneProduct8650 (Entrez Gene)
NUR4A1Protein3164 (Entrez Gene)
OCLNProtein100506658 (Entrez Gene)
OCRLGeneProduct4952 (Entrez Gene)
P4HA2GeneProduct8974 (Entrez Gene)
P4HBGeneProduct5034 (Entrez Gene)
PABPC1GeneProduct26986 (Entrez Gene)
PAK1Protein5058 (Entrez Gene)
PAK2Protein5062 (Entrez Gene)
PBXIP1GeneProduct57326 (Entrez Gene)
PDE4DIPGeneProduct9659 (Entrez Gene)
PDIA6GeneProduct10130 (Entrez Gene)
PDPK1Protein5170 (Entrez Gene)
PFN1GeneProduct5216 (Entrez Gene)
PGDGeneProduct5226 (Entrez Gene)
PGFProtein5228 (Entrez Gene)
PGK1GeneProduct5230 (Entrez Gene)
PIK3CAProtein5290 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PLA2G4AProtein5321 (Entrez Gene)
PLA2G5Protein5322 (Entrez Gene)
PLAUProtein5328 (Entrez Gene)
PLAURProtein5329 (Entrez Gene)
PLCB3Protein5331 (Entrez Gene)
PLCG1Protein5335 (Entrez Gene)
PLOD3GeneProduct8985 (Entrez Gene)
PNPProtein4860 (Entrez Gene)
PPM1GGeneProduct5496 (Entrez Gene)
PPP1CAGeneProduct5499 (Entrez Gene)
PPP2CAGeneProduct5515 (Entrez Gene)
PPP3CAProtein5530 (Entrez Gene)
PRDX2GeneProduct7001 (Entrez Gene)
PRDX6GeneProduct9588 (Entrez Gene)
PRKAA1Protein5562 (Entrez Gene)
PRKAA2Protein5563 (Entrez Gene)
PRKCAProtein5578 (Entrez Gene)
PRKCBProtein5579 (Entrez Gene)
PRKCDProtein5580 (Entrez Gene)
PRKCEProtein5581 (Entrez Gene)
PRKCIProtein5584 (Entrez Gene)
PRKCZProtein5590 (Entrez Gene)
PRKD1Protein5587 (Entrez Gene)
PRKD2Protein25865 (Entrez Gene)
PRKG1Protein5592 (Entrez Gene)
PRKRAGeneProduct8575 (Entrez Gene)
PRRC2CGeneProduct23215 (Entrez Gene)
PSMD11GeneProduct5717 (Entrez Gene)
PSMD4GeneProduct5710 (Entrez Gene)
PTGS2Protein5743 (Entrez Gene)
PTK2Protein5747 (Entrez Gene)
PTK2BProtein2185 (Entrez Gene)
PTMAGeneProduct5757 (Entrez Gene)
PTPN11Protein5781 (Entrez Gene)
PTPN14GeneProduct5784 (Entrez Gene)
PTPN1Protein5770 (Entrez Gene)
PTPN6Protein5777 (Entrez Gene)
PTPN9Protein5780 (Entrez Gene)
PTPRJProtein5795 (Entrez Gene)
PTPRZ1Protein5803 (Entrez Gene)
PXNProtein5829 (Entrez Gene)
QKIGeneProduct9444 (Entrez Gene)
R1CTOR Protein253260 (Entrez Gene)
RAB11Protein8766 (Entrez Gene)
RAB37Protein326624 (Entrez Gene)
RAB4AProtein5867 (Entrez Gene)
RAB5AProtein5868 (Entrez Gene)
RAC1Protein5879 (Entrez Gene)
RACK1Protein10399 (Entrez Gene)
RAF1Protein5894 (Entrez Gene)
RAP1AProtein5906 (Entrez Gene)
RAP1BProtein5908 (Entrez Gene)
RAPGEF1Protein2889 (Entrez Gene)
RAPTORProtein253260 (Entrez Gene)
RBM39GeneProduct9584 (Entrez Gene)
RCAN1Protein1827 (Entrez Gene)
RCAN2Protein10231 (Entrez Gene)
RCN1GeneProduct5954 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RHOAProtein387 (Entrez Gene)
RHOCProtein389 (Entrez Gene)
RHOJProtein57381 (Entrez Gene)
RND1Protein27289 (Entrez Gene)
ROCK1Protein6093 (Entrez Gene)
ROCK2Protein9475 (Entrez Gene)
RPL10AGeneProduct4736 (Entrez Gene)
RPL13AGeneProduct23521 (Entrez Gene)
RPL18AGeneProduct6142 (Entrez Gene)
RPL26GeneProduct6154 (Entrez Gene)
RPL27GeneProduct6155 (Entrez Gene)
RPL39P5GeneProduct553117 (Entrez Gene)
RPL5GeneProduct6125 (Entrez Gene)
RPL7GeneProduct6129 (Entrez Gene)
RPLP2GeneProduct6181 (Entrez Gene)
RPS11GeneProduct6205 (Entrez Gene)
RPS6Protein6194 (Entrez Gene)
RPS6KA5Protein9252 (Entrez Gene)
RPS6KB1Protein6198 (Entrez Gene)
S1PR1Protein1901 (Entrez Gene)
SARSGeneProduct6301 (Entrez Gene)
SCUBE2Protein57758 (Entrez Gene)
SDCBPProtein6386 (Entrez Gene)
SDF2L1Protein23753 (Entrez Gene)
SELEProtein6401 (Entrez Gene)
SEMA6DProtein80031 (Entrez Gene)
SETGeneProduct6418 (Entrez Gene)
SH2D2AProtein9047 (Entrez Gene)
SH3BGRL3GeneProduct83442 (Entrez Gene)
SHBProtein6461 (Entrez Gene)
SHC1Protein6464 (Entrez Gene)
SHC2Protein25759 (Entrez Gene)
SHROOM2GeneProduct357 (Entrez Gene)
SIAH2Protein6478 (Entrez Gene)
SLC25A11GeneProduct8402 (Entrez Gene)
SLC25A25Protein114789 (Entrez Gene)
SLC2A14Protein144195 (Entrez Gene)
SLC39A14Protein21356 (Entrez Gene)
SLC7A1Protein6541 (Entrez Gene)
SLC8A1Protein6546 (Entrez Gene)
SMARCA2Protein6595 (Entrez Gene)
SND1GeneProduct27044 (Entrez Gene)
SOD2Protein6648 (Entrez Gene)
SPHK1Protein55872 (Entrez Gene)
SPIRE1GeneProduct56907 (Entrez Gene)
SRCProtein6714 (Entrez Gene)
SRFProtein6722 (Entrez Gene)
SRP54GeneProduct6729 (Entrez Gene)
SRPK1GeneProduct6732 (Entrez Gene)
SSR3GeneProduct6747 (Entrez Gene)
SSR4GeneProduct6748 (Entrez Gene)
STAMProtein8027 (Entrez Gene)
STAT1Protein6772 (Entrez Gene)
STAT3Protein6774 (Entrez Gene)
STAT6Protein6778 (Entrez Gene)
STIP1GeneProduct10963 (Entrez Gene)
SYNJ1GeneProduct8867 (Entrez Gene)
TAL1Protein6886 (Entrez Gene)
TAOK2GeneProduct9344 (Entrez Gene)
TBCAGeneProduct6902 (Entrez Gene)
TCEB1GeneProduct6921 (Entrez Gene)
TCEB3Protein6924 (Entrez Gene)
TEAD4Protein7004 (Entrez Gene)
TFAMGeneProduct7019 (Entrez Gene)
TFCP2GeneProduct7024 (Entrez Gene)
TKTGeneProduct7086 (Entrez Gene)
TMEM170AProtein124491 (Entrez Gene)
TMOD1GeneProduct7111 (Entrez Gene)
TMOD3GeneProduct29766 (Entrez Gene)
TMSB10GeneProduct9168 (Entrez Gene)
TMSB4XGeneProduct7114 (Entrez Gene)
TNFRSF10CProtein8794 (Entrez Gene)
TNFRSF25Protein8718 (Entrez Gene)
TNXBProtein7148 (Entrez Gene)
TPCN2Protein219931 (Entrez Gene)
TPM3GeneProduct7170 (Entrez Gene)
TPP1GeneProduct1200 (Entrez Gene)
TRAF3IP2Protein10758 (Entrez Gene)
TRIP4GeneProduct9325 (Entrez Gene)
TRPC1Protein7220 (Entrez Gene)
TRPC3Protein7222 (Entrez Gene)
TUBA1CGeneProduct84790 (Entrez Gene)
TUBB8GeneProduct347688 (Entrez Gene)
TXNProtein7295 (Entrez Gene)
TXNDC5GeneProduct81567 (Entrez Gene)
TXNIPProtein10628 (Entrez Gene)
UBAP2LGeneProduct9898 (Entrez Gene)
USP10GeneProduct9100 (Entrez Gene)
VAV2Protein7410 (Entrez Gene)
VCAM1Protein5328 (Entrez Gene)
VCLProtein7414 (Entrez Gene)
VEGFAProtein7422 (Entrez Gene)
VEGFR2Protein3791 (Entrez Gene)
VPS39GeneProduct23339 (Entrez Gene)
WASF1Protein8936 (Entrez Gene)
YWHAEGeneProduct7531 (Entrez Gene)
ZC3H15GeneProduct55854 (Entrez Gene)
ZNF555Protein148254 (Entrez Gene)

Annotated Interactions

No annotated interactions

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