DEPOD - human DEPhOsphorylation Database

Basic Information
Phosphatases
Pathway
Interacting Proteins
Phosphorylating Kinases

Gene Name	PLCG1 (QuickGO)	Interactive visualization of PLCG1 structures (A quick tutorial to explore the interctive visulaization) Representative structure: 2HSP
Synonyms	PLCG1, PLC1
Protein Name	PLCG1
Alternative Name(s)	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1;3.1.4.11;PLC-148;Phosphoinositide phospholipase C-gamma-1;Phospholipase C-II;PLC-II;Phospholipase C-gamma-1;PLC-gamma-1;
Protein Family	noSimilarity_annotations
EntrezGene ID	5335 (Comparitive Toxicogenomics)
UniProt AC (Human)	P19174 (protein sequence)
Enzyme Class	3.1.4.11 (BRENDA )
Molecular Weight	148532 Dalton
Protein Length	1290 amino acids (AA)
Genome Browsers	NCBI \| ENSG00000124181 (Ensembl) \| UCSC
Crosslinking annotations	Query our ID-mapping table
Orthologues	Quest For Orthologues (QFO) \| GeneTree \| eggNOG - KOG1264 \| eggNOG - ENOG410XPXE
Phosphorylation Network	Visualize

Domain organization, Expression, Diseases

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Localization, Function, Catalytic activity and Sequence

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Localization (UniProt annotation)
Cell projection, lamellipodium Cellprojection, ruffle Note=Rapidly redistributed to ruffles andlamellipodia structures in response to epidermal growth factor(EGF) treatment
Function (UniProt annotation)
Mediates the production of the second messengermolecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate(IP3) Plays an important role in the regulation of intracellularsignaling cascades Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such asPDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4 Plays a role inactin reorganization and cell migration
Catalytic Activity (UniProt annotation)
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate +diacylglycerol
Protein Sequence
MAGAASPCANGCGPGAPSDAEVLHLCRSLEVGTVMTLFYSKKSQRPERKTFQVKLETRQITWSRGADKIEGAIDIREIKE IRPGKTSRDFDRYQEDPAFRPDQSHCFVILYGMEFRLKTLSLQATSEDEVNMWIKGLTWLMEDTLQAPTPLQIERWLRKQ FYSVDRNREDRISAKDLKNMLSQVNYRVPNMRFLRERLTDLEQRSGDITYGQFAQLYRSLMYSAQKTMDLPFLEASTLRA GERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVTFLFSKENSVWNSQLDAVCPD TMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEH AFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKLAEGSAYEEVPTSMM YSENDISNSIKNGILYLEDPVNHEWYPHYFVLTSSKIYYSEETSSDQGNEDEEEPKEVSSSTELHSNEKWFHGKLGAGRD GRHIAERLLTEYCIETGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFLTDNLVFDSLYDLITHYQ QVPLRCNEFEMRLSEPVPQTNAHESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQE GQTVMLGNSEFDSLVDLISYYEKHPLYRKMKLRYPINEEALEKIGTAEPDYGALYEGRNPGFYVEANPMPTFKCAVKALF DYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEMVNPVALEPEREHLDENSPLGDLLRGVLDVPA CQIAIRPEGKNNRLFVFSISMASVAHWSLDVAADSQEELQDWVKKIREVAQTADARLTEGKIMERRKKIALELSELVVYC RPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNF QTPDKPMQMNQALFMTGRHCGYVLQPSTMRDEAFDPFDKSSLRGLEPCAISIEVLGARHLPKNGRGIVCPFVEIEVAGAE YDSTKQKTEFVVDNGLNPVWPAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRAVPLKNNYSEDL ELASLLIKIDIFPAKENGDLSPFSGTSLRERGSDASGQLFHGRAREGSFESRYQQPFEDFRISQEHLADHFDSRERRAPR RTRVNGDNRL

Motif information from Eukaryotic Linear Motif atlas (ELM)

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Gene Ontology (P: Process; F: Function and C: Component terms)

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KEGG Pathway
Reactome Pathway

Pathway ID	Pathway Name	Pathway Description (KEGG)
hsa00562	Inositol phosphate metabolism
hsa01100	Metabolic pathways
hsa01521	EGFR tyrosine kinase inhibitor resistance	EGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. EGFR also serves as a stimulus for cancer growth. EGFR gene mutations and protein overexpression, both of which activate down- stream pathways, are associated with cancers, especially lung cancer. Several tyrosine kinase inhibitor (TKI) therapies against EGFR are currently administered and are initially effective in cancer patients who have EGFR mutations or aberrant activation of EGFR. However, the development of TKI resistance is common and results in the recurrence of tumors. Studies over the last decade have identified mechanisms that drive resistance to EGFR TKI treatment. Most outstanding mechanisms are: the secondary EGFR mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, etc.
hsa04012	ErbB signaling pathway	The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase.
hsa04014	Ras signaling pathway	The Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras proteins transduce signals from extracellular growth factors by cycling between inactive GDP-bound and active GTP-bound states. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated RAS (RAS-GTP) regulates multiple cellular functions through effectors including Raf, phosphatidylinositol 3-kinase (PI3K) and Ral guanine nucleotide-dissociation stimulator (RALGDS).
hsa04015	Rap1 signaling pathway	Rap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an active GTP-bound conformation. A variety of extracellular signals control this cycle through the regulation of several unique guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Rap1 plays a dominant role in the control of cell-cell and cell-matrix interactions by regulating the function of integrins and other adhesion molecules in various cell types. Rap1 also regulates MAP kinase (MAPK) activity in a manner highly dependent on the context of cell types.
hsa04020	Calcium signaling pathway	Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs).The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it.The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM).
hsa04064	NF-kappa B signaling pathway	Nuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are several pathways leading to NF-kappa B-activation. The canonical pathway is induced by tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or byproducts of bacterial and viral infections. This pathway relies on IKK- mediated IkappaB-alpha phosphorylation on Ser32 and 36, leading to its degradation, which allows the p50/p65 NF-kappa B dimer to enter the nucleus and activate gene transcription. Atypical pathways are IKK-independent and rely on phosphorylation of IkappaB-alpha on Tyr42 or on Ser residues in IkappaB-alpha PEST domain. The non-canonical pathway is triggered by particular members of the TNFR superfamily, such as lymphotoxin-beta (LT-beta) or BAFF. It involves NIK and IKK-alpha-mediated p100 phosphorylation and processing to p52, resulting in nuclear translocation of p52/RelB heterodimers.
hsa04066	HIF-1 signaling pathway	Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a constitutively-expressed HIF-1beta subunit. Under normoxia, HIF-1 alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the subunit. In contrast, under hypoxia, HIF-1 alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, or various growth factors.
hsa04070	Phosphatidylinositol signaling system
hsa04072	Phospholipase D signaling pathway	Phospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). The PLD-produced PA activates signaling proteins and acts as a node within the membrane to which signaling proteins translocate. Several signaling proteins, including Raf-1 and mTOR, directly bind PA to mediate translocation or activation, respectively.
hsa04360	Axon guidance	Axon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are read by growth cone receptors, and signal transduction pathways downstream of these receptors converge onto the Rho GTPases to elicit changes in cytoskeletal organization that determine which way the growth cone will turn.
hsa04370	VEGF signaling pathway	There is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic angiogenesis. The binding of VEGF to VEGFR-2 leads to a cascade of different signaling pathways, resulting in the up-regulation of genes involved in mediating the proliferation and migration of endothelial cells and promoting their survival and vascular permeability. For example, the binding of VEGF to VEGFR-2 leads to dimerization of the receptor, followed by intracellular activation of the PLCgamma;PKC-Raf kinase-MEK-mitogen-activated protein kinase (MAPK) pathway and subsequent initiation of DNA synthesis and cell growth, whereas activation of the phosphatidylinositol 3' -kinase (PI3K)-Akt pathway leads to increased endothelial-cell survival. Activation of PI3K, FAK, and p38 MAPK is implicated in cell migration signaling.
hsa04650	Natural killer cell mediated cytotoxicity	Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. This inhibitory signal is lost when the target cells do not express MHC class I and perhaps also in cells infected with virus, which might inhibit MHC class I exprssion or alter its conformation. The mechanism of NK cell killing is the same as that used by the cytotoxic T cells generated in an adaptive immune response; cytotoxic granules are released onto the surface of the bound target cell, and the effector proteins they contain penetrate the cell membrane and induce programmed cell death.
hsa04658	Th1 and Th2 cell differentiation	Immunity to different classes of microorganisms is orchestrated by separate lineages of effector T helper (TH)-cells, which differentiate from naive CD4+ precursor cells in response to cues provided by antigen presenting cells (APC) and include T helper type 1 (Th1) and Th2. Th1 cells are characterized by the transcription factor T-bet and signal transducer and activator of transcription (STAT) 4, and the production of IFN-gamma. These cells stimulate strong cell-mediated immune responses, particularly against intracellular pathogens. On the other hand, transcription factors like GATA-3 and STAT6 drive the generation of Th2 cells that produce IL-4, IL-5 and IL-13 and are necessary for inducing the humoral response to combat parasitic helminths (type 2 immunity) and isotype switching to IgG1 and IgE. The balance between Th1/Th2 subsets determines the susceptibility to disease states, where the improper development of Th2 cells can lead to allergy, while an overactive Th1 response can lead to autoimmunity.
hsa04659	Th17 cell differentiation	Interleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the pathogenesis of autoimmune diseases. In vivo, Th17 differentiation requires antigen presentation and co-stimulation, and activation of antigen presenting-cells (APCs) to produce TGF-beta, IL-6, IL-1, IL-23 and IL-21. This initial activation results in the activation and up-regulation of STAT3, ROR(gamma)t and other transcriptional factors in CD4+ T cells, which bind to the promoter regions of the IL-17, IL-21 and IL-22 genes and induce IL-17, IL-21 and IL-22. In contrast, the differentiation of Th17 cells and their IL-17 expression are negatively regulated by IL-2, Th2 cytokine IL-4, IL-27 and Th1 cytokine IFN-gamma through STAT5, STAT6 and STAT1 activation, respectively. Retinoid acid and the combination of IL-2 and TGF-beta upregulate Foxp3, which also downregulates cytokines like IL-17 and IL-21. The inhibition of Th17 differentiation may serve as a protective strategy to 'fine-tune' the expression IL-17 so it does not cause excessive inflammation. Thus, balanced differentiation of Th cells is crucial for immunity and host protection.
hsa04660	T cell receptor signaling pathway	Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions, leading to T-cell proliferation, cytokine production and differentiation into effector cells.
hsa04664	Fc epsilon RI signaling pathway	Fc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation pathways are regulated both positively and negatively by the interactions of numerous signaling molecules. Mast cells that are thus activated release preformed granules which contain biogenic amines (especially histamines) and proteoglycans (especially heparin). The activation of phospholipase A2 causes the release of membrane lipids followed by development of lipid mediators such as leukotrienes (LTC4, LTD4 and LTE4) and prostaglandins (especially PDG2). There is also secretion of cytokines, the most important of which are TNF-alpha, IL-4 and IL-5. These mediators and cytokines contribute to inflammatory responses.
hsa04666	Fc gamma R-mediated phagocytosis	Phagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes take part in this process in higher organisms. After opsonization with antibodies (IgG), foreign extracellular materials are recognized by Fc gamma receptors. Cross-linking of Fc gamma receptors initiates a variety of signals mediated by tyrosine phosphorylation of multiple proteins, which lead through the actin cytoskeleton rearrangements and membrane remodeling to the formation of phagosomes. Nascent phagosomes undergo a process of maturation that involves fusion with lysosomes. The acquisition of lysosomal proteases and release of reactive oxygen species are crucial for digestion of engulfed materials in phagosomes.
hsa04670	Leukocyte transendothelial migration	Leukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (CAM) and then migrate across the vascular endothelium. A leukocyte adherent to CAMs on the endothelial cells moves forward by leading-edge protrusion and retraction of its tail. In this process, alphaL /beta2 integrin activates through Vav1, RhoA, which subsequently activates the kinase p160ROCK. ROCK activation leads to MLC phosphorylation, resulting in retraction of the actin cytoskeleton. Moreover, Leukocytes activate endothelial cell signals that stimulate endothelial cell retraction during localized dissociation of the endothelial cell junctions. ICAM-1-mediated signals activate an endothelial cell calcium flux and PKC, which are required for ICAM-1 dependent leukocyte migration. VCAM-1 is involved in the opening of the endothelial passagethrough which leukocytes can extravasate. In this regard, VCAM-1 ligation induces NADPH oxidase activation and the production of reactive oxygen species (ROS) in a Rac-mediated manner, with subsequent activation of matrix metallopoteinases and loss of VE-cadherin-mediated adhesion.
hsa04722	Neurotrophin signaling pathway	Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory.
hsa04750	Inflammatory mediator regulation of TRP channels	The TRP channels that exhibit a unique response to temperature have been given the name thermo-TRPs. Among all thermo- TRP channels, TRPV1-4, TRPM8, and TRPA1 are expressed in subsets of nociceptive dorsal root ganglion (DRG) neuron cell bodies including their peripheral and central projections. These channels can be modulated indirectly by inflammatory mediators such as PGE2, bradykinin, ATP, NGF, and proinflammatory cytokines that are generated during tissue injury. While the noxious heat receptor TRPV1 is sensitized (that is, their excitability can be increased) by post-translational modifications upon activation of G-protein coupled receptors (GPCRs) or tyrosine kinase receptors, the receptors for inflammatory mediators, the same action appears to mainly desensitize TRPM8, the main somatic innocuous cold sensor. This aforementioned sensitization could allow the receptor to become active at body temperature, so it not only contributes toward thermal hypersensitivity but also is possibly a substrate for ongoing persistent pain.
hsa04919	Thyroid hormone signaling pathway	The thyroid hormones (THs) are important regulators of growth, development and metabolism. The action of TH is mainly mediated by T3 (3,5,3'-triiodo-L-thyronine). Thyroid hormones, L-thyroxine (T4) and T3 enter the cell through transporter proteins. Although the major form of TH in the blood is T4, it is converted to the more active hormone T3 within cells. T3 binds to nuclear thyroid hormone receptors (TRs), which functions as a ligand-dependent transcription factor and controls the expression of target genes (genomic action). Nongenomic mechanisms of action is initiated at the integrin receptor. The plasma membrane alpha(v)beta(3)-integrin has distinct binding sites for T3 and T4. One binding site binds only T3 and activates the phosphatidylinositol 3-kinase (PI3K) pathway. The other binding site binds both T3 and T4 and activates the ERK1/2 MAP kinase pathway.
hsa04933	AGE-RAGE signaling pathway in diabetic complications	Advanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and under certain pathologic condition such as huperglycemia. Some of the best chemically characterized AGEs include N-epsilon-carboxy-methyl-lysine (CML), N-epsilon-carboxy-ethyl-lysine (CEL), and Imidazolone. The major receptor for AGEs, known as receptor for advanced glycation end products (RAGE or AGER), belongs to the immunoglobulin superfamily and has been described as a pattern recognition receptor. AGE/RAGE signaling elicits activation of multiple intracellular signal pathways involving NADPH oxidase, protein kinase C, and MAPKs, then resulting in NF-kappaB activity. NF-kappa B promotes the expression of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha and a variety of atherosclerosis-related genes, including VCAM-1, tissue factor, VEGF, and RAGE. In addition, JAK-STAT-mediated and PI3K-Akt-dependent pathways are induced via RAGE, which in turn participate in cell proliferation and apoptosis respectively. Hypoxia-mediated induction of Egr-1 was also shown to require the AGE-RAGE interaction. The results of these signal transductions have been reported to be the possible mechanism that initates diabetic complications.
hsa05110	Vibrio cholerae infection	Cholera toxin (CTX) is one of the main virulence factors of Vibrio cholerae. Once secreted, CTX B-chain (CTXB) binds to ganglioside GM1 on the surface of the host's cells. After binding takes place, the entire CTX complex is carried from plasma membrane (PM) to endoplasmic reticulum (ER). In the ER, the A-chain (CTXA) is recognized by protein disulfide isomerase (PDI), unfolded, and delivered to the membrane where the membrane-associated ER-oxidase, Ero1, oxidizes PDI to release the CTXA into the protein-conducting channel, Sec61. CTXA is then retro-translocated to the cytosol and induces water and electrolyte secretion by increasing cAMP levels via adenylate cyclase (AC) to exert toxicity.Other than CTX, Vibrio cholerae generates several toxins that are perilous to eukaryotic cells. Zonula occludens toxin (ZOT) causes tight junction disruption through protein kinase C-dependent actin polymerization. RTX toxin (RtxA) causes actin depolymerization by covalently cross-linking actin monomers into dimers, trimers, and higher multimers. Vibrio cholerae cytolysin (VCC) is an important pore-forming toxin. The assembly of VCC anion channels in cells cause vacuolization and lysis.
hsa05120	Epithelial cell signaling in Helicobacter pylori infection	Two major virulence factors of H. pylori are the vacuolating cytotoxin (VacA) and the cag type-IV secretion system (T4SS) and its translocated effector protein, cytotoxin-associated antigen A (CagA).VacA binds to lipid rafts and glycosylphosphatidylinositol-anchored proteins (GPI-APs) of the target cell membrane. After insertion into the plasma membrane, VacA channels are endocytosed and eventually reach late endosomal compartments, increasing their permeability to anions with enhancement of the electrogenic vacuolar ATPase (v-ATPase) proton pump. In the presence of weak bases, osmotically active acidotropic ions will accumulate in the endosomes. This leads to water influx and vesicle swelling, an essential step in vacuole formation. In addition, it is reported that the VacA cleavage product binds to the tyrosine phosphatase receptor zeta (Ptprz) on epithelial cells and the induced signaling leads to the phosphorylation of the G protein-coupled receptor kinase-interactor 1 (Git1) and induces ulcerogenesis in mice.The other virulence factor cag T4SS mediates the translocation of the effector protein CagA, which is subsequently phosphorylated by a Src kinase. Phosphorylated CagA interacts with the protein tyrosine phosphatase SHP-2, thus stimulating its phosphatase activity. Activated SHP-2 is able to induce MAPK signalling through Ras/Raf-dependent and -independent mechanisms. Deregulation of this pathway by CagA may lead to abnormal proliferation and movement of gastric epithelial cells.
hsa05167	Kaposi sarcoma-associated herpesvirus infection	Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the most recently identified human tumor virus, and is associated with the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and Multicentric Castleman's disease (MCD). Like all other herpesviruses, KSHV displays two modes of life cycle, latency and lytic replication, which are characterized by the patterns of viral gene expression. Genes expressed in latency (LANA, v-cyclin, v-FLIP, Kaposins A, B and C and viral miRNAs) are mainly thought to facilitate the establishment of life long latency in its host and survival against the host innate, and adaptive immune surveillance mechanisms. Among the viral proteins shown to be expressed during lytic replication are potent signaling molecules such as vGPCR, vIL6, vIRFs, vCCLs, K1 and K15, which have been implicated experimentally in the angiogenic and inflammatory phenotype observed in KS lesions. Several of these latent viral and lytic proteins are known to transform host cells, linking KSHV with the development of severe human malignancies.
hsa05170	Human immunodeficiency virus 1 infection	Human immunodeficiency virus type 1 (HIV-1) , the causative agent of AIDS (acquired immunodeficiency syndrome), is a lentivirus belonging to the Retroviridae family. The primary cell surface receptor for HIV-1, the CD4 protein, and the co-receptor for HIV-1, either CCR5 or CXCR4, are found on macrophages and T lymphocytes. At the earliest step, sequential binding of virus envelope (Env) glycoprotein gp120 to CD4 and the co-receptor CCR5 or CXCR4 facilitates HIV-1 entry and has the potential to trigger critical signaling that may favor viral replication. At advanced stages of the disease, HIV-1 infection results in dramatic induction of T-cell (CD4+ T and CD8+ T cell) apoptosis both in infected and uninfected bystander T cells, a hallmark of HIV-1 pathogenesis. On the contrary, macrophages are resistant to the cytopathic effect of HIV-1 and produce virus for longer periods of time.
hsa05200	Pathways in cancer
hsa05205	Proteoglycans in cancer	Many proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis and metastasis, affecting tumor progress. The four main types of proteoglycans include hyaluronan (HA), which does not occur as a PG but in free form, heparan sulfate proteoglycans (HSPGs), chondroitin sulfate proteoglycans (CSPGs), dematan sulfate proteoglycans (DSPG) and keratan sulfate proteoglycans (KSPGs) [BR:00535]. Among these proteoglycans such as HA, acting with CD44, promotes tumor cell growth and migration, whereas other proteoglycans such as syndecans (-1~-4), glypican (-1, -3) and perlecan may interact with growth factors, cytokines, morphogens and enzymes through HS chains [BR: 00536], also leading to tumor growth and invasion. In contrast, some of the small leucine-rich proteolgycans, such as decorin and lumican, can function as tumor repressors, and modulate the signaling pathways by the interaction of their core proteins and multiple receptors.
hsa05206	MicroRNAs in cancer	MicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or the inhibition of protein translation. Using high-throughput profiling, dysregulation of miRNAs has been widely observed in different stages of cancer. The upregulation (overexpression) of specific miRNAs could lead to the repression of tumor suppressor gene expression, and conversely the downregulation of specific miRNAs could result in an increase of oncogene expression; both these situations induce subsequent malignant effects on cell proliferation, differentiation, and apoptosis that lead to tumor growth and progress. The miRNA signatures of cancer observed in various studies differ significantly. These inconsistencies occur due to the differences in the study populations and methodologies used. This pathway map shows the summarized results from various studies in 9 cancers, each of which is presented in a review article.
hsa05214	Glioma	Gliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), mixtures of various glial cells (for example,oligoastrocytomas) and ependymal cells (ependymomas). The most malignant form of infiltrating astrocytoma - glioblastoma multiforme (GBM) - is one of the most aggressive human cancers. GBM may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). Primary glioblastomas develop in older patients and typically show genetic alterations (EGFR amplification, p16/INK4a deletion, and PTEN mutations) at frequencies of 24-34%. Secondary glioblastomas develop in younger patients and frequently show overexpression of PDGF and CDK4 as well as p53 mutations (65%) and loss of Rb playing major roles in such transformations. Loss of PTEN has been implicated in both pathways, although it is much more common in the pathogenesis of primary GBM.
hsa05223	Non-small cell lung cancer	Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heterogeneous group of cancers, consisting mainly of squamous cell (SCC), adeno (AC) and large-cell carcinoma. Molecular mechanisms altered in NSCLC include activation of oncogenes, such as K-RAS, EGFR and EML4-ALK, and inactivation of tumorsuppressor genes, such as p53, p16INK4a, RAR-beta, and RASSF1. Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. Mutations or overexpression of EGFR leads to a proliferative advantage. EML4-ALK fusion leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. Inactivating mutation of p53 can lead to more rapid proliferation and reduced apoptosis. The protein encoded by the p16INK4a inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. Loss of p16INK4a expression is a common feature of NSCLC. RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. RASSF1A is able to form heterodimers with Nore-1, an RAS effector.Therefore loss of RASSF1A might shift the balance of RAS activity towards a growth-promoting effect.
hsa05225	Hepatocellular carcinoma	Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. It has been shown that, after HBV/HCV infection and alcohol or aflatoxin B1 exposure, genetic and epigenetic changes occur. The recurrent mutated genes were found to be highly enriched in multiple key driver signaling processes, including telomere maintenance, TP53, cell cycle regulation, the Wnt/beta-catenin pathway (CTNNB1 and AXIN1), the phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Recent studies using whole-exome sequencing have revealed recurrent mutations in new driver genes involved in the chromatin remodelling (ARID1A and ARID2) and the oxidative stress (NFE2L2) pathways.
hsa05231	Choline metabolism in cancer	Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, oncogenic signalling via pathways such as the RAS and PI3K-AKT pathways, and transcription factors associated with oncogenesis such as hypoxia-inducible factor 1 (HIF1) mediate overexpression and activation of choline cycle enzymes, which causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These products of choline phospholipid metabolism, such as phosphocholine (PCho), diacylglycerol (DAG) and phosphatidic acid, may function as second messengers that are essential for the mitogenic activity of growth factors, particularly in the activation of the ras-raf-1-MAPK cascade and protein kinase C pathway.

Pathway ID	Pathway Name	Pathway Description (KEGG)
R-HSA-1169408	ISG15 antiviral mechanism.	Interferon-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (Ubl) family. It is strongly induced upon exposure to type I Interferons (IFNs), viruses, bacterial LPS, and other stresses. Once released the mature ISG15 conjugates with an array of target proteins, a process termed ISGylation. ISGylation utilizes a mechanism similar to ubiquitination, requiring a three-step enzymatic cascade. UBE1L is the ISG15 E1 activating enzyme which specifically activates ISG15 at the expense of ATP. ISG15 is then transfered from E1 to the E2 conjugating enzyme UBCH8 and then to the target protein with the aid of an ISG15 E3 ligase, such as HERC5 and EFP. Hundreds of target proteins for ISGylation have been identified. Several proteins that are part of antiviral signaling pathways, such as RIG-I, MDA5, Mx1, PKR, filamin B, STAT1, IRF3 and JAK1, have been identified as targets for ISGylation. ISG15 also conjugates some viral proteins, inhibiting viral budding and release. ISGylation appears to act either by disrupting the activity of a target protein and/or by altering its localization within the cell
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.	Signaling by EGFR is frequently activated in cancer through activating mutations in the coding sequence of the EGFR gene, resulting in expression of a constitutively active mutant protein. Epidermal growth factor receptor kinase domain mutants are present in ~16% of non-small-cell lung cancers (NSCLCs), but are also found in other cancer types, such as breast cancer, colorectal cancer, ovarian cancer and thyroid cancer. EGFR kinase domain mutants harbor activating mutations in exons 18-21 which code for the kinase domain (amino acids 712-979) . Small deletions, insertions or substitutions of amino acids within the kinase domain lock EGFR in its active conformation in which the enzyme can dimerize and undergo autophosphorylation spontaneously, without ligand binding (although ligand binding ability is preserved), and activate downstream signaling pathways that promote cell survival (Greulich et al. 2005, Zhang et al. 2006, Yun et al. 2007, Red Brewer et al. 2009). Point mutations in the extracellular domain of EGFR are frequently found in glioblastoma. Similar to kinase domain mutations, point mutations in the extracellular domain result in constitutively active EGFR proteins that signal in the absence of ligands, but ligand binding ability and responsiveness are preserved (Lee et al. 2006). EGFR kinase domain mutants need to maintain association with the chaperone heat shock protein 90 (HSP90) for proper functioning (Shimamura et al. 2005, Lavictoire et al. 2003). CDC37 is a co-chaperone of HSP90 that acts as a scaffold and regulator of interaction between HSP90 and its protein kinase clients. CDC37 is frequently over-expressed in cancers involving mutant kinases and acts as an oncogene (Roe et al. 2004, reviewed by Gray Jr. et al. 2008). Over-expression of the wild-type EGFR or EGFR cancer mutants results in aberrant activation of downstream signaling cascades, namely RAS/RAF/MAP kinase signaling and PI3K/AKT signaling, and possibly signaling by PLCG1, which leads to increased cell proliferation and survival, providing selective advantage to cancer cells that harbor activating mutations in the EGFR gene (Sordella et al. 2004, Huang et al. 2007). While growth factor activated wild-type EGFR is promptly down-regulated by internalization and degradation, cancer mutants of EGFR demonstrate prolonged activation (Lynch et al. 2004). Association of HSP90 with EGFR kinase domain mutants negatively affects CBL-mediated ubiquitination, possibly through decreasing the affinity of EGFR kinase domain mutants for phosphorylated CBL, so that CBL dissociates from the complex upon phosphorylation and cannot perform ubiquitination (Yang et al. 2006, Padron et al. 2007). Various molecular therapeutics are being developed to target aberrantly activated EGFR in cancer. Non-covalent (reversible) small tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, selectively bind kinase domain of EGFR, competitively inhibiting ATP binding and subsequent autophosphorylation of EGFR dimers. EGFR kinase domain mutants sensitive to non-covalent TKIs exhibit greater affinity for TKIs than ATP compared with the wild-type EGFR protein, and are therefore preferential targets of non-covalent TKI therapeutics (Yun et al. 2007). EGFR proteins that harbor point mutations in the extracellular domain also show sensitivity to non-covalent tyrosine kinase inhibitors (Lee et al. 2006). EGFR kinase domain mutants harboring small insertions in exon 20 or a secondary T790M mutation are resistant to reversible TKIs (Balak et al. 2006) due to increased affinity for ATP (Yun et al. 2008), and are targets of covalent (irreversible) TKIs that form a covalent bond with EGFR cysteine residue C397. However, effective concentrations of covalent TKIs also inhibit wild-type EGFR, causing severe side effects (Zhou et al. 2009). Hence, covalent TKIs have not shown much promise in clinical trials (Reviewed by Pao and Chmielecki in 2010)
R-HSA-1251932	PLCG1 events in ERBB2 signaling.	Activation of PLCG1 signaling is observed only in the presence of ERBB2:EGFR heterodimers, with PLCG1 binding to phosphorylated tyrosine Y992 and Y1173 in the C-tail of EGFR (Chattopadhyay et al. 1999), and potentially Y1023 in the C-tail of ERBB2 (Fazioli et al. 1991, Cohen et al. 1996)
R-HSA-1489509	DAG and IP3 signaling.	This pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events
R-HSA-167021	PLC-gamma1 signalling.	The activation of phosphlipase C-gamma (PLC-gamma) and subsequent mobilization of calcium from intracellular stores are essential for neurotrophin secretion. PLC-gamma is activated through the phosphorylation by TrkA receptor kinase and this form hydrolyses PIP2 to generate inositol tris-phosphate (IP3) and diacylglycerol (DAG). IP3 promotes the release of Ca2+ from internal stores and this results in activation of enzymes such as protein kinase C and Ca2+ calmodulin-regulated protein kinases
R-HSA-170968	Frs2-mediated activation.	The adaptor protein Frs2 (Fibroblast growth factor receptor substrate 2) can mediate the prolonged activation of the MAPK (ERK) cascade
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol.	An array of inositol trisphosphate (IP3) and tetrakisphosphate (IP4) molecules are synthesised by the action of various kinases and phosphatases in the cytosol (Irvine & Schell 2001, Bunney & Katan 2010)
R-HSA-186763	Downstream signal transduction.	The role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of around 100 amino acids that can bind a phosphorylated tyrosine residue. These downstream molecules are activated upon binding to, or phosphorylated by, the receptor kinases intrinsic to PDGF receptors.Some of the dowstream molecules are themselves enzymes, such as phosphatidylinositol 3'-kinase (PI3K), phospholipase C (PLC-gamma), the Src family of tyrosine kinases, the tyrosine phosphatase SHP2, and a GTPase activating protein (GAP) for Ras. Others such as Grb2 are adaptor molecules which link the receptor with downstream catalytic molecules
R-HSA-202433	Generation of second messenger molecules.	In addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have been recognized to play pivotal role in TCR signaling by releasing second messengers. When phosphorylated, LAT and SLP-76 act as adaptor proteins which serve as nucleation points for the construction of a higher order signalosome: GADS, PLC-gamma1 and GRB2 bind to the LAT on the phosphorylated tyrosine residues (steps 8 and 13). SLP-76 and SOS are then moved to the signalosome by interacting with the SH3 domains of GRB2 and GADS via their proline rich sequences (step 9). Three SLP-76 acidic domain N-term tyrosine residues are phosphorylated by ZAP-70, once SLP-76 binds to GADS (step 10). These phospho-tyrosine residues act as binding sites to the SH2 domains of PLC-gamma1, Vav and Itk (steps 11 and 12). PLC-gamma1 is activated by dual phosphorylation on the tyrosine residues at positions 771, 783 and 1254 by Itk and ZAP-70 (step 14). Phosphorylated PLC-gamma1 subsequently detaches from LAT and SLP-76 and translocates to the plasma membrane by binding to phosphatidylinositol-4,5-bisphosphate (PIP2) via its PH domain (step 15). PLC-gamma1 goes on to hydrolyse PIP2 to second messengers DAG and IP3. These second messengers are involved in PKC and NF-kB activation and calcium mobilization (step 16)
R-HSA-2029485	Role of phospholipids in phagocytosis.	Phospholipases play an integral role in phagocytosis by generating essential second messengers. An early step in phagocytic signaling is the association of PIP2 and IP3 with the phagocytic cup. These are formed by the activity of phosphoinositol kinases and phospholipases. PI3K is has been shown to accumulate at phagocytic cups and converts PI (4,5)P2 to PI (3,4,5)P3. These phosphoinositides are capable of binding and increasing the activity of proteins that regulate the actin cytoskeleton. Phospholipases are lipid modifying enzymes that produce lipid mediators such as diacylglycerol (DAG), arachidonic acid (AA) and IP3. Phopsholipases PLA, PLC and PLD have been shown to be involved in antibody (IgG) mediated phagocytosis. The PLC product IP3 stimulates release of calcium from the endoplasmic reticulum. This Ca+2 concentration increase is greatest in the cytoplasm surrounding the phagocytic cup. Calcium is involved in the various stages of phagosome formation, including phagocytic ingestion and phagosome maturation
R-HSA-210990	PECAM1 interactions.	PECAM-1/CD31 is a member of the immunoglobulin superfamily (IgSF) and has been implicated to mediate the adhesion and trans-endothelial migration of T-lymphocytes into the vascular wall, T cell activation and angiogenesis. It has six Ig homology domains within its extracellularly and an ITIM motif within its cytoplasmic region. PECAM-1 mediates cellular interactions by both homophilic and heterophilic interactions. The cytoplasmic domain of PECAM-1 contains tyrosine residues which serves as docking sites for recruitment of cytosolic signaling molecules. Under conditions of platelet activation, PECAM-1 is phosphorylated by Src kinase members. The tyrosine residues 663 and 686 are required for recruitment of the SH2 domain containing PTPs
R-HSA-212718	EGFR interacts with phospholipase C-gamma.	Activated epidermal growth factor receptors (EGFR) can stimulate phosphatidylinositol (PI) turnover. Activated EGFR can activate phospholipase C-gamma1 (PLC-gamma1, i.e. PLCG1) which hydrolyses phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 is instrumental in the release of calcium from intracellular stores and DAG is involved in protein kinase C activation
R-HSA-2424491	DAP12 signaling.	In response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the docking site for the protein tyrosine kinase SYK in myeloid cells and SYK and ZAP70 in NK cells. DAP12-bound SYK autophosphorylates and phosphorylates the scaffolding molecule LAT, recruiting the proximal signaling molecules phosphatidylinositol-3-OH kinase (PI3K), phospholipase-C gamma (PLC-gamma), GADS (GRB2-related adapter downstream of SHC), SLP76 (SH2 domain-containing leukocyte protein of 76 kDa), GRB2:SOS (Growth factor receptor-bound protein 2:Son of sevenless homolog 1) and VAV. All of these intermediate signalling molecules result in the recruitment and activation of kinases AKT, CBL (Casitas B-lineage lymphoma) and ERK (extracellular signal-regulated kinase), and rearrangement of the actin cytoskeleton (actin polymerization) finally leading to cellular activation. PLC-gamma generates the secondary messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (InsP3), leading to activation of protein kinase C (PKC) and calcium mobilization, respectively (Turnbull & Colonna 2007, Klesney-Tait et al. 2006)
R-HSA-2871796	FCERI mediated MAPK activation.	Formation of the LAT signaling complex leads to activation of MAPK and production of cytokines. The sequence of events that leads from LAT to cytokine production has not been as clearly defined as the sequence that leads to degranulation. However, the pathways that lead to cytokine production require the guanine-nucleotide-exchange factors SOS and VAV that regulate GDP-GTP exchange of RAS. After its activation, RAS positively regulates the RAF-dependent pathway that leads to phosphorylation and, in part, activation of the mitogen-activated protein kinases (MAPKs) extracellular-signal-regulated kinase 1 (ERK1) and ERK2 (Gilfillan & Tkaczyk 2006)
R-HSA-2871809	FCERI mediated Ca+2 mobilization.	Increase of intracellular calcium in mast cells is most crucial for mast cell degranulation. Elevation of intracellular calcium is achieved by activation of PLC-gamma. Mast cells express both PLC-gamma1 and PLC-gamma2 isoforms and activation of these enzymes leads to conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). The production of IP3 leads to mobilization of intracellular Ca+2, which later results in a sustained Ca+2 flux response that is maintained by an influx of extracellular Ca+2. In addition to degranulation, an increase in intracellular calcium concentration also activates the Ca2+/calmodulin-dependent serine phosphatase calcineurin. Calcineurin dephosphorylates the nuclear factor for T cell activation (NFAT) which exposes nuclear-localization signal sequence triggering translocation of the dephosphorylated NFAT-CaN complex to the nucleus. Once in the nucleus, NFAT regulates the transcription of several cytokine genes (Kambayashi et al. 2007, Hoth & Penner 1992, Ebinu et al. 2000, Siraganian et al)
R-HSA-418890	Role of second messengers in netrin-1 signaling.	The levels of second messengers such as Ca+2, cAMP and cGMP may regulate the response of the growth cone to a particular cue. Netrin-1 as a guidance molecule depends on intracellular Ca+2 concentration, coactivation of PI3K and PLCgamma, and the type of response depends on the levels of cAMP. \nNetrin first stimulates its receptor DCC, resulting in the activation of the enzyme phospholipase C. This then produces the messenger molecules, inositol-1,4,5-trisphosphate (IP3) and DAG, which in turn causes the release of Ca+2 from intracellular stores. Ca+2 release from the stores then activates TRPC channels on the cell surface. DAG activates TRPC3 and TRPC6 in a direct, membrane delimited manner, and IP3 may activate TRPC channels by depleting the ER Ca+2 levels
R-HSA-5218921	VEGFR2 mediated cell proliferation.	VEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf/MEK/ERK pathway. PKC alpha can intersect the Ras/Raf/MEK/ERK cascade at the level of Ras (Clark et al. 2004) or downstream of Ras through direct phosphorylation of Raf (Kolch et al. 1993). VEGF stimulation leads to Ras activation in a Ras-guanine nucleotide exchange factor (GEF) independent mechanism. It rather relies on modulating the regulation of Ras-GTPase activating protein (GAP) than regulation of Ras-GEFS (Wu et al. 2003)
R-HSA-5637810	Constitutive Signaling by EGFRvIII.	In glioblastoma, the most prevalent EGFR mutation, present in ~25% of tumors, is the deletion of the ligand binding domain of EGFR, accompanied with amplification of the mutated allele, which results in over-expression of the mutant protein known as EGFRvIII. EGFRvIII mutant is not able to bind a ligand, but dimerizes and autophosphorylates spontaneously and is therefore constitutively active (Fernandes et al. 2001). Point mutations in the extracellular domain of EGFR are also frequently found in glioblastoma, but ligand binding ability and responsiveness are preserved (Lee et al. 2006). Similar to EGFR kinase domain mutants, EGFRvIII mutant needs to maintain association with the chaperone heat shock protein 90 (HSP90) for proper functioning (Shimamura et al. 2005, Lavictoire et al. 2003). CDC37 is a co-chaperone of HSP90 that acts as a scaffold and regulator of interaction between HSP90 and its protein kinase clients. CDC37 is frequently over-expressed in cancers involving mutant kinases and acts as an oncogene (Roe et al. 2004, reviewed by Gray Jr. et al. 2008). Expression of EGFRvIII mutant results in aberrant activation of downstream signaling cascades, namely RAS/RAF/MAP kinase signaling and PI3K/AKT signaling, and possibly signaling by PLCG1, which leads to increased cell proliferation and survival, providing selective advantage to cancer cells that harbor EGFRvIII (Huang et al. 2007). EGFRvIII mutant does not autophosorylate on the tyrosine residue Y1045, a docking site for CBL, and is therefore unable to recruit CBL ubiquitin ligase, which enables it to escape degradation (Han et al
R-HSA-5654219	Phospholipase C-mediated cascade: FGFR1.	Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 domain) of PLC-gamma and of other signaling molecules (such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85) direct their binding toward autophosphorylated tyrosine residues of the FGFR. Recruitment of PLC-gamma results in its phosphorylation and activation by the receptor. Activated PLC-gamma hydrolyzes phosphatidyl inositol[4,5] P2 to form the second messengers diacylglycerol (DAG) and Ins [1,4,5]P3, which stimulate calcium release and activation of calcium/calmodulin dependent kinases
R-HSA-5654221	Phospholipase C-mediated cascade, FGFR2.	Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 domain) of PLC-gamma and of other signaling molecules (such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85) direct their binding toward autophosphorylated tyrosine residues of the FGFR. Recruitment of PLC-gamma results in its phosphorylation and activation by the receptor. Activated PLC-gamma hydrolyzes phosphatidyl inositol[4,5] P2 to form the second messengers diacylglycerol (DAG) and Ins [1,4,5]P3, which stimulate calcium release and activation of calcium/calmodulin dependent kinases
R-HSA-5654227	Phospholipase C-mediated cascade, FGFR3.	Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 domain) of PLC-gamma and of other signaling molecules (such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85) direct their binding toward autophosphorylated tyrosine residues of the FGFR. Recruitment of PLC-gamma results in its phosphorylation and activation by the receptor. Activated PLC-gamma hydrolyzes phosphatidyl inositol[4,5] P2 to form the second messengers diacylglycerol (DAG) and Ins [1,4,5]P3, which stimulate calcium release and activation of calcium/calmodulin dependent kinases
R-HSA-5654228	Phospholipase C-mediated cascade, FGFR4.	Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 domain) of PLC-gamma and of other signaling molecules (such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85) direct their binding toward autophosphorylated tyrosine residues of the FGFR. Recruitment of PLC-gamma results in its phosphorylation and activation by the receptor. Activated PLC-gamma hydrolyzes phosphatidyl inositol[4,5] P2 to form the second messengers diacylglycerol (DAG) and Ins [1,4,5]P3, which stimulate calcium release and activation of calcium/calmodulin dependent kinases
R-HSA-5655253	Signaling by FGFR2 in disease.	The FGFR2 gene has been shown to be subject to activating mutations and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in the germline or arise somatically. Activating FGFR2 mutations in the germline give rise to a range of craniosynostotic conditions including Pfeiffer, Apert, Jackson-Weiss, Crouzon and Beare-Stevensen Cutis Gyrata syndromes. These autosomal dominant skeletal disorders are characterized by premature fusion of several sutures in the skull, and in some cases also involve syndactyly (abnormal bone fusions in the hands and feet) (reviewed in Webster and Donoghue, 1997; Burke, 1998; Cunningham, 2007). Activating FGFR2 mutations arising somatically have been linked to the development of gastric and endometrial cancers (reviewed in Greulich and Pollock, 2011; Wesche, 2011). Many of these mutations are similar or identical to those that contribute to the autosomal disorders described above. Notably, loss-of-function mutations in FGFR2 have also been recently described in melanoma (Gartside, 2009). FGFR2 may also contribute to tumorigenesis through overexpression, as FGFR2 has been identified as a target of gene amplification in gastric and breast cancers (Kunii, 2008; Takeda, 2007)
R-HSA-5655291	Signaling by FGFR4 in disease.	FGFR4 is perhaps the least well studied of the FGF receptors, and unlike the case for the other FGFR genes, mutations in FGFR4 are not known to be associated with any developmental disorders. Recently, however, somatically arising mutations in the FGFR4 coding sequence have begun to be identified in some cancers. 8% of rhabdomyosarcomas have activating mutations in the kinase domain of FGFR4. Two of these mutations - N535K (paralogous to the FGFR2 N550K allele found in endometrial cancers) and V550E - have been shown to support the oncogenic transformation of NIH 3T3 cells (Taylor, 2009). An FGFR4 Y367C mutation has also been identified in breast cancers (Ruhe, 2007; Roidl, 2010); mutations of paralogous residues in FGFR2 and FGFR3 are associated with both skeletal dysplasias and the development of diverse cancers (Pollock, 2007; Ruhe, 2007; Rousseau, 1996; Chesi, 1997, 2001).Finally, a SNP at position 388 of FGFR4 is associated with aggressive disease development. Expression of the G388R allele in breast, colorectal and prostate cancers is correlated with rapid progression times and increased rates of recurrence and metastasis (Bange, 2002; Spinola, 2005; Wang, 2004)
R-HSA-5655302	Signaling by FGFR1 in disease.	The FGFR1 gene has been shown to be subject to activating mutations, chromosomal rearrangements and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in the germline or arise somatically (reviewed in Webster and Donoghue, 1997; Burke, 1998; Cunningham, 2007; Wesche, 2011; Greulich and Pollock, 2011). Activating mutation P252R in FGFR1 is associated with the development of Pfeiffer syndrome, characterized by craniosynostosis (premature fusion of several sutures in the skull) and broadened thumbs and toes (Muenke, 1994; reviewed in Cunningham, 2007). This residue falls in a highly conserved Pro-Ser dipeptide between the second and third Ig domains of the extracellular region of the receptor. The mutation is thought to increase the number of hydrogen bonds formed with the ligand and to thereby increase ligand-binding affinity (Ibrahimi, 2004a). Unlike other FGF receptors, few activating point mutations in the FGFR1 coding sequence have been identified in cancer. Point mutations in the Ig II-III linker analagous to the P252R Pfeiffer syndrome mutation have been identified in lung cancer and melanoma (Ruhe, 2007; Davies, 2005), and two kinase-domain mutations in FGFR1 have been identified in glioblastoma (Rand, 2005, Network TCGA, 2008).In contrast, FGFR1 is a target of chromosomal rearrangements in a number of cancers. FGFR1 has been shown to be recurrently translocated in the 8p11 myeloproliferative syndrome (EMS), a pre-leukemic condition also known as stem cell leukemia/lymphoma (SCLL) that rapidly progresses to leukemia. This translocation fuses the kinase domain of FGFR1 with the dimerization domain of one of 10 identified fusion partners, resulting in the constitutive dimerization and activation of the kinase (reviewed in Jackson, 2010). Amplification of the FGFR1 gene has been implicated as a oncogenic factor in a range of cancers, including breast, ovarian, bladder, lung, oral squamous carcinomas, and rhabdomyosarcoma (reviewed in Turner and Grose, 2010; Wesche, 2011; Greulich and Pollock, 2011), although there are other candidate genes in the amplified region and the definitive role of FGFR1 has not been fully established.More recently, FGFR1 fusion proteins have been identified in a number of cancers; these are thought to undergo constitutive ligand-independent dimerization and activation based on dimerization motifs found in the fusion partners (reviewed in Parker, 2014)
R-HSA-8853338	Signaling by FGFR3 point mutants in cancer.	The FGFR3 gene has been shown to be subject to activating mutations and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in the germline or arise somatically. Activating mutations in FGFR3 are associated with the development of a range of skeletal dysplasias that result in dwarfism (reviewed in Webster and Donoghue, 1997; Burke et al, 1998; Harada et al, 2009). The most common form of human dwarfism is achondroplasia (ACH), which is caused by mutations G380R and G375C in the transmembrane domain of FGFR3 that are thought to promote ligand-independent dimerization (Rousseau et al, 1994; Shiang et al, 1994; Bellus et al, 1995a) Hypochondroplasia (HCH) is a milder form dwarfism that is the result of mutations in the tyrosine kinase domain of FGFR3 (Bellus et al, 1995b). Two neonatal lethal conditions, thanatophoric dysplasia type I and II (TDI and TDII) are also the result of mutations in FGFR3; TDI arises from a range of mutations that either result in the formation of unpaired cysteine residues in the extracellular region that promote aberrant ligand-independent dimerization or by mutations that introduce stop codons (Rousseau et al, 1995; Rousseau et al, 1996, D'Avis et al,1998). A single mutation, K650E in the second tyrosine kinase domain of FGFR3 is responsible for all identified cases of TDII (Tavormina et al, 1995a, b). Other missense mutations at the same K650 residue give rise to Severe Achondroplasia with Developmental Disorders and Acanthosis Nigricans (SADDAN) syndrome (Tavormina et al, 1999; Bellus et al, 1999). The severity of the phenotype arising from many of the activating FGFR3 mutations has recently been shown to correlate with the extent to which the mutations activate the receptor (Naski et al, 1996; Bellus et al, 2000) In addition to mutations that cause dwarfism syndromes, a Pro250Arg mutation in the conserved dipeptide between the IgII and IgIII domains has been identified in an atypical craniosynostosis condition (Bellus et al, 1996; Reardon et al, 1997). This mutation, which is paralogous to mutations seen in FGFR1 and 2 in Pfeiffer and Apert Syndrome, respectively, results in an increase in ligand-binding affinity for the receptor (Ibrahimi et al, 2004b).Of all the FGF receptors, FGFR3 has perhaps the best established link to the development in cancer. 50% of bladder cancers have somatic mutations in the coding sequence of FGFR3; of these, more than half occur in the extracellular region at a single position (S249C) (Cappellen et al, 1999; Naski et al, 1996; di Martino et al, 2009, Sibley et al, 2001). Activating mutations are also seen in the juxta- and trans-membrane domains, as well as in the kinase domain (reviewed in Weshe et al, 2011). As is the case for the other receptors, many of the activating mutations that are seen in FGFR3-related cancers mimic the germline FGFR3 mutations that give rise to autosomal skeletal disorders and include both ligand-dependent and independent mechanisms (reviewed in Webster and Donoghue, 1997; Burke et al, 1998). In addition to activating mutations, the FGFR3 gene is subject to a translocation event in 15% of multiple myelomas (Avet-Loiseau et al, 1998; Chesi et al, 1997). This chromosomal rearrangement puts the FGFR3 gene under the control of the highly active IGH promoter and promotes overexpression and constitutive activation of FGFR3. In a small proportion of multiple myelomas, the translocation event is accompanied by activating mutations in the FGFR3 coding sequence (Chesi et al, 1997).More recently, a number of fusion proteins of FGFR3 have been identified in various cancers (Singh et al, 2012; Williams et al, 2013; Parker et al, 2013; Wu et al, 2013; Wang et al, 2014; Yuan et al, 2014; reviewed in Parker et al, 2014). The most common fusion protein is TACC3, a coiled coil protein involved in mitotic spindle assembly. FGFR3 fusion proteins are constitutively active and appear to contribute to proliferation and tumorigenesis through activation of the ERK and AKT signaling pathways (reviewed in Parker et al, 2014)
R-HSA-8853659	RET signaling.	The RET proto-oncogene encodes a receptor tyrosine kinase expressed primarily in urogenital precursor cells, spermatogonocytes, dopaminergic neurons, motor neurons and neural crest progenitors and derived cells. It is essential for kidney genesis, spermatogonial self-renewal and survivial, specification, migration, axonal growth and axon guidance of developing enteric neurons, motor neurons, parasympathetic neurons and somatosensory neurons (Schuchardt et al. 1994, Enomoto et al. 2001, Naughton et al. 2006, Kramer et al. 2006, Luo et al. 2006, 2009). RET was identified as the causative gene for human papillary thyroid carcinoma (Grieco et al. 1990), multiple endocrine neoplasia (MEN) type 2A (Mulligan et al. 1993), type 2B (Hofstra et al. 1994, Carlson et al. 1994), and Hirschsprung's disease (Romeo et al. 1994, Edery et al. 1994). RET contains a cadherin-related motif and a cysteine-rich domain in the extracellular domain (Takahashi et al. 1988). It is the receptor for members of the glial cell-derived neurotrophic factor (GDNF) family of ligands, GDNF (Lin et al. 1993), neurturin (NRTN) (Kotzbauer et al. 1996), artemin (ARTN) (Baloh et al. 1998), and persephin (PSPN) (Milbrandt et al. 1998), which form a family of neurotrophic factors. To stimulate RET, these ligands need a glycosylphosphatidylinositol (GPI)-anchored co-receptor, collectively termed GDNF family receptor-alpha (GFRA) (Treanor et al. 1996, Jing et al. 1996). The four members of this family have different, overlapping ligand preferences. GFRA1, GFRA2, GFRA3, and GFRA4 preferentially bind GDNF, NRTN, ARTN and PSPN, respectively (Jing et al. 1996, 1997, Creedon et al. 1997, Baloh et al. 1997, 1998, Masure et al. 2000). The GFRA co-receptor can come from the same cell as RET, or from a different cell. When the co-receptor is produced by the same cell as RET, it is termed cis signaling. When the co-receptor is produced by another cell, it is termed trans signaling. Cis and trans activation has been proposed to diversify RET signaling, either by recruiting different downstream effectors or by changing the kinetics or efficacy of kinase activation (Tansey et al. 2000, Paratcha et al. 2001). Whether cis and trans signaling has significant differences in vivo is unresolved (Fleming et al. 2015). Different GDNF family members could activate similar downstream signaling pathways since all GFRAs bind to and activate the same tyrosine kinase and induce coordinated phosphorylation of the same four RET tyrosines (Tyr905, Tyr1015, Tyr1062, and Tyr1096) with similar kinetics (Coulpier et al. 2002). However the exact RET signaling pathways in different types of cells and neurons remain to be determined
R-HSA-9026527	Activated NTRK2 signals through PLCG1.	Activation of the neurotrophin receptor NTRK2 (TRKB) by BDNF or NTF4 triggers downstream PLCgamma (PLCG1) signaling, resulting in formation of secondary messengers DAG and IP3 (Eide et al. 1996, Minichiello et al. 1998, McCarthy and Feinstein 1999, Yuen and Mobley 1999, Minichiello et al. 2002, Yamada et al. 2002)
R-HSA-9034793	Activated NTRK3 signals through PLCG1.	The receptor tyrosine kinase NTRK3 (TRKC), when activated by its ligand NTF3 (NT-3), induces PLCG1 phosphorylation, triggering PLCG1 signaling (Marsh and Palfrey 1996, Yuen and Mobley 1999)
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.	Mature B cells express IgM and IgD immunoglobulins which are complexed with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, Fu et al. 1975, Kunkel et al. 1975, Van Noesal et al. 1992, Sanchez et al. 1993, reviewed in Brezski and Monroe 2008). Binding of antigen to the immunoglobulin activates phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of Ig-alpha and Ig-beta by Src family tyrosine kinases, including LYN, FYN, and BLK (Nel et al. 1984, Yamanashi et al. 1991, Flaswinkel and Reth 1994, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Gauld and Cambier 2004, reviewed in Harwood and Batista 2010). The protein kinase SYK may also be involved in phosphorylating the ITAMs.The protein kinase SYK binds the phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on the cytoplasmic tails of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Wienands et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding causes the activation and autophosphorylation of SYK (Law et al. 1994, Irish et al. 2006, Baldock et al. 2008, Tsang et al. 2008, reviewed in Bradshaw 2010).Activated SYK and other kinases phosphorylate BLNK (SLP-65, BASH) and BCAP. LYN and FYN phosphorylate CD19. Phosphorylated BLNK, BCAP, and CD19 serve as scaffolds which recruit effectors to the plasma membrane and assemble large complexes, the signalosomes. BCAP and CD19 recruit phosphoinositol 3-kinase (PI3K). BLNK recruits phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.Phosphorylated BCAP recruits PI3K, which is phosphorylated by a SYK-dependent mechanism (Kuwahara et al. 1996) and produces phosphatidylinositol-3,4,5-trisphosphate (PIP3). Phosphorylated CD19 likewise recruits PIP3K. PIP3 recruits BAM32 (Marshall et al. 2000) and BTK (de Weers et al. 1994, Baba et al. 2001) to the plasma membrane via their PH domains. PIP3 also recruits and activates PLC-gamma1 and PLC-gamma2 (Bae et al. 1998). BTK binds phosphorylated BLNK via its SH2 domain (Baba et al. 2001). BTK phosphorylates PLC-gamma2 (Rodriguez et al. 2001), which activates phospholipase activity (Carter et al. 1991, Roifman and Wang 1992, Kim et al. 2004, Sekiya et al. 2004). Phosphorylated BLNK recruits PLC-gamma, VAV, GRB2, and NCK (Fu and Chan 1997, Fu et al. 1998, Chiu et al. 2002).PLC-gamma hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (Carter et al. 1991, Kim et al. 2004). IP3 binds receptors on the endoplasmic reticulum and causes release of Ca2+ ions from the ER into the cytosol. The depletion of calcium from the ER in turn activates STIM1 to interact with ORAI and TRPC1 channels (and possibly other TRP channels) in the plasma membrane, resulting in an influx of extracellular calcium ions (Mori et al. 2002, Muik et al. 2008, Luik et al. 2008, Park et al. 2009)

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Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
ABL1	Reconstituted Complex, peptide array	physical, physical association	10708759, 17474147, (Europe PMC)	0.40	BioGRID, IntAct
AKT1	Affinity Capture-Western, Biochemical Activity, Reconstituted Complex, anti bait coimmunoprecipitation, pull down	direct interaction, physical, physical association	16525023, (Europe PMC)	0.60	BioGRID, IntAct, MINT
ALK	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex	physical	11888936, 14968112, 9819383, (Europe PMC)	NA	BioGRID
ARHGAP32	Affinity Capture-Western	physical	12454018, (Europe PMC)	NA	BioGRID
ARHGEF2	Affinity Capture-Western	physical	19805522, (Europe PMC)	NA	BioGRID
BAG3	Affinity Capture-Western, Reconstituted Complex	physical	10980614, 21233200, (Europe PMC)	NA	BioGRID
BLNK	Affinity Capture-Western	physical	10684856, (Europe PMC)	NA	BioGRID
CACNB3	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CAMK2A	Affinity Capture-Western	physical	18292392, (Europe PMC)	NA	BioGRID
CAV1	Affinity Capture-Western, protein array, pull down	association, direct interaction, physical	20808760, (Europe PMC)	0.52	BioGRID, IntAct
CBL	Affinity Capture-MS, Affinity Capture-Western, Co-localization, FRET, Far Western, Reconstituted Complex, proximity ligation assay	physical, physical association	12061819, 12803489, 12941616, 16467851, 16503409, 17372230, 25241761, 9712732, (Europe PMC)	0.40	BioGRID, IntAct
CCDC120	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CD22	Affinity Capture-Western, coimmunoprecipitation	association, physical, physical association	8627166, (Europe PMC)	0.50	BioGRID, IntAct
CTPS1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
DGKZ	Affinity Capture-Western	physical	12890670, (Europe PMC)	NA	BioGRID
DOK1	Reconstituted Complex	physical	11071635, (Europe PMC)	NA	BioGRID
DOK2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
DPP7	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
EEF1A1	Affinity Capture-Western, Far Western, Protein-peptide, Reconstituted Complex, Two-hybrid	physical	11886851, 12898421, (Europe PMC)	NA	BioGRID
EGFR	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, cross-linking study, far western blotting, protein array, pull down	association, direct interaction, physical, physical association	11983899, 12061819, 12803489, 14568990, 16273093, 19605547, 24797263, 7693694, 7993895, 9020117, 9207933, 9756944, (Europe PMC)	0.85	BioGRID, IntAct, MINT
EHD4	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
EPHB2	Two-hybrid	physical	9632142, (Europe PMC)	NA	BioGRID
EPOR	PCA	physical	15644415, (Europe PMC)	NA	BioGRID
ERBB2	Affinity Capture-Western, Co-fractionation, Protein-peptide, protein array	direct interaction, physical	16273093, 1676673, 1683701, (Europe PMC)	0.44	BioGRID, IntAct, MINT
ERBB3	Protein-peptide, protein array	direct interaction, physical	16273093, (Europe PMC)	0.44	BioGRID, IntAct, MINT
FGFR1	Biochemical Activity, Co-localization, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, bioluminescence resonance energy transfer, isothermal titration calorimetry, protein kinase assay, proximity ligation assay, pull down	association, direct interaction, phosphorylation reaction, physical, physical association	15117958, 1656221, 20932831, 23063561, 25241761, 8321198, 9660748, (Europe PMC)	0.87	BioGRID, IntAct, MINT
FGFR2	Affinity Capture-Western, Co-localization, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, fluorescent resonance energy transfer, microscale thermophoresis, proximity ligation assay, pull down	association, direct interaction, physical, physical association	15629145, 24440983, 25241761, (Europe PMC)	0.40, 0.70	BioGRID, IntAct
FLT1	Reconstituted Complex, Two-hybrid, proximity ligation assay	physical, physical association	23397142, 9398617, (Europe PMC)	0.40	BioGRID, IntAct
GAB1	Affinity Capture-Western, Far Western, fluorescence polarization spectroscopy	direct interaction, physical	11507676, 24728074, 8596638, (Europe PMC)	0.44	BioGRID, IntAct
GAB2	Reconstituted Complex	physical	10391903, (Europe PMC)	NA	BioGRID
GAS2L1	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
GHR	Reconstituted Complex, peptide array	physical, physical association	17474147, 9632636, (Europe PMC)	0.40	BioGRID, IntAct
GIT1	Affinity Capture-Western, Reconstituted Complex	physical	14523024, (Europe PMC)	NA	BioGRID
GRB2	Affinity Capture-Western, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	10940929, 16038803, 21706016, 7629168, 9020117, 9281317, (Europe PMC)	0.56	BioGRID, IntAct, MINT
GSN	Reconstituted Complex	physical	9164868, (Europe PMC)	NA	BioGRID
GTF3C4	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
HNRNPK	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
HNRNPL	Affinity Capture-RNA	physical	28611215, (Europe PMC)	NA	BioGRID
IBTK	Affinity Capture-Western	physical	18596081, (Europe PMC)	NA	BioGRID
INSR	Protein-peptide, coimmunoprecipitation, cross-linking study, fluorescence microscopy, pull down	colocalization, direct interaction, physical, physical association	11796522, 14568990, 22974441, 9593725, (Europe PMC)	0.80	BioGRID, IntAct, MINT
IRS2	Affinity Capture-Western, Protein-peptide	physical	22974441, 9535722, (Europe PMC)	NA	BioGRID
ITK	Affinity Capture-Western, Biochemical Activity, Reconstituted Complex	physical	10586033, 12163161, (Europe PMC)	NA	BioGRID
JAK1	Affinity Capture-Western	physical	14978237, (Europe PMC)	NA	BioGRID
JAK2	Affinity Capture-Western, peptide array	physical, physical association	14978237, 17474147, (Europe PMC)	0.40	BioGRID, IntAct
KCNJ5	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
KDR	Reconstituted Complex, pull down	association, physical	12598525, 9398617, (Europe PMC)	0.35	BioGRID, IntAct, MINT
KHDRBS1	Affinity Capture-Western, Reconstituted Complex	physical	10467411, 11960376, 8977179, 9743338, (Europe PMC)	NA	BioGRID
KHDRBS2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
KIT	Co-localization, Reconstituted Complex, coimmunoprecipitation, fluorescence polarization spectroscopy, proximity ligation assay	association, direct interaction, physical, physical association	11071635, 24728074, 25241761, 7536744, 7537096, (Europe PMC)	0.70	BioGRID, IntAct, MINT
LAT	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, FRET, Reconstituted Complex, anti bait coimmunoprecipitation, coimmunoprecipitation, pull down, surface plasmon resonance	association, direct interaction, physical, physical association	10811803, 11368773, 16467851, 16938345, 24642916, 27221712, 9489702, 9729044, (Europe PMC)	0.81	BioGRID, IntAct, MINT
LAT2	Affinity Capture-Western	physical	12514734, (Europe PMC)	NA	BioGRID
LCP2	Affinity Capture-MS, Affinity Capture-Western, FRET, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	11390650, 15929943, 16467851, 21725281, (Europe PMC)	0.56	BioGRID, IntAct, MINT
LDLRAD4	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
LIMD1	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
LTK	Affinity Capture-Western	physical	8084603, (Europe PMC)	NA	BioGRID
LZTS2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
MCMBP	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
MST1R	Affinity Capture-Western	physical	8918464, (Europe PMC)	NA	BioGRID
MVB12B	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
NCAM1	Reconstituted Complex	physical	23061666, (Europe PMC)	NA	BioGRID
NCKIPSD	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
NPEPL1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
NPM1	Affinity Capture-Western, Reconstituted Complex	physical	9819383, (Europe PMC)	NA	BioGRID
NTMT1	Co-fractionation	physical	22939629, (Europe PMC)	NA	BioGRID
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 1715690, 25921289, 8384556, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
NTRK2	Reconstituted Complex, Two-hybrid	physical	10092678, 12074588, (Europe PMC)	NA	BioGRID
NTRK3	Reconstituted Complex	physical	10092678, (Europe PMC)	NA	BioGRID
NXF1	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
PAK1	Reconstituted Complex	physical	12085993, (Europe PMC)	NA	BioGRID
PDGFA	Affinity Capture-Western	physical	8443409, (Europe PMC)	NA	BioGRID
PDGFRA	Affinity Capture-Western, Biochemical Activity, Co-localization, Reconstituted Complex, experimental interaction detection, proximity ligation assay	association, physical, physical association	25241761, 7535778, 7682895, (Europe PMC)	0.51	BioGRID, IntAct, MINT
PDGFRB	Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, nuclear magnetic resonance, proximity ligation assay	association, direct interaction, physical, physical association	11896612, 1396585, 15641795, 22974441, 23063561, 23397142, 8443409, (Europe PMC)	0.82	BioGRID, IntAct, MINT
PECAM1	Far Western, Reconstituted Complex	physical	10350061, (Europe PMC)	NA	BioGRID
PFKP	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PICALM	Reconstituted Complex	physical	10926122, (Europe PMC)	NA	BioGRID
PKN2	Reconstituted Complex	physical	8910519, (Europe PMC)	NA	BioGRID
PLCG2	Co-localization, proximity ligation assay	physical, physical association	25241761, (Europe PMC)	0.40	BioGRID, IntAct
PLD2	Affinity Capture-Western, Reconstituted Complex	physical	12646582, (Europe PMC)	NA	BioGRID
PLXNB1	Affinity Capture-Western	physical	19805522, (Europe PMC)	NA	BioGRID
PLXNB2	Affinity Capture-Western	physical	19805522, (Europe PMC)	NA	BioGRID
PML	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation	physical	17419608, (Europe PMC)	NA	BioGRID
PRKD1	Affinity Capture-Western	physical	8885868, (Europe PMC)	NA	BioGRID
PRKN	Affinity Capture-Western	physical	18671761, (Europe PMC)	NA	BioGRID
PTK2	Affinity Capture-Western, proximity ligation assay	physical, physical association	10430888, 23397142, (Europe PMC)	0.40	BioGRID, IntAct
PTPN6	Affinity Capture-Western	physical	27221712, (Europe PMC)	NA	BioGRID
PTPRJ	Biochemical Activity	physical	11259588, (Europe PMC)	NA	BioGRID
PYGB	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
RAB11A	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
RACK1	Far Western	physical	8290562, (Europe PMC)	NA	BioGRID
RASA1	Affinity Capture-Western, pull down	physical, physical association	8977179, 9020117, 9743338, (Europe PMC)	0.40	BioGRID, IntAct, MINT
RET	Co-localization, Reconstituted Complex, competition binding, proximity ligation assay	association, physical, physical association	25241761, 8628282, (Europe PMC)	0.56	BioGRID, IntAct, MINT
RHOA	Affinity Capture-Western, Reconstituted Complex	physical	12071848, (Europe PMC)	NA	BioGRID
RIC8A	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
RNF40	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
RPL38	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
SARNP	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
SELE	Affinity Capture-Western	physical	12960351, (Europe PMC)	NA	BioGRID
SH2B3	Affinity Capture-Western	physical	8649391, (Europe PMC)	NA	BioGRID
SH3BP2	Far Western, Reconstituted Complex, pull down	association, physical	11390470, 15345594, 9846481, (Europe PMC)	0.53	BioGRID, IntAct, MINT
SHB	Affinity Capture-Western	physical	10488157, (Europe PMC)	NA	BioGRID
SHC1	Affinity Capture-Western	physical	8662733, (Europe PMC)	NA	BioGRID
SKIV2L	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
SNX11	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
SOS1	Affinity Capture-Western, Reconstituted Complex, fluorescence technology, peptide array, pull down	direct interaction, physical, physical association	10913276, 10940929, 17474147, 9020117, (Europe PMC)	0.67	BioGRID, IntAct, MINT
SOS2	Affinity Capture-Western, Two-hybrid, anti bait coimmunoprecipitation, fluorescence technology, peptide array	direct interaction, physical, physical association	10940929, 17474147, (Europe PMC)	0.60	BioGRID, IntAct
SPRY1	Affinity Capture-Western	physical	19915061, (Europe PMC)	NA	BioGRID
SRC	Affinity Capture-Western	physical	7510703, (Europe PMC)	NA	BioGRID
STRAP	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
SYK	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	7831290, 8657103, (Europe PMC)	0.46	BioGRID, IntAct, MINT
SYNCRIP	Reconstituted Complex	physical	9341187, (Europe PMC)	NA	BioGRID
TEKT2	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
TIPRL	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
TNK1	Reconstituted Complex	physical	10873601, (Europe PMC)	NA	BioGRID
TRPM7	Reconstituted Complex	physical	11941371, (Europe PMC)	NA	BioGRID
TTC9B	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TUB	Affinity Capture-Western, Reconstituted Complex	physical	10455176, (Europe PMC)	NA	BioGRID
UBR7	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
UCHL5	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
UNC45A	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
VAV1	Affinity Capture-MS, Affinity Capture-Western, FRET	physical	16467851, 9891995, (Europe PMC)	NA	BioGRID
WAS	Reconstituted Complex, pull down	physical, physical association	8805332, 8824280, 8892607, (Europe PMC)	0.40	BioGRID, IntAct
WDR61	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
ZAP70	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex	physical	16467851, 7629168, 8906806, (Europe PMC)	NA	BioGRID
ZNF785	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID

Visualize Download

Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
ABL1	Reconstituted Complex, peptide array	physical, physical association	10708759, 17474147, (Europe PMC)	0.40	BioGRID, IntAct
ABL2	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
ADNP	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AFF2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AGTR1	pull down	association	9516477, (Europe PMC)	0.35	IntAct, MINT
AIRE	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AKAP2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AKT1	Affinity Capture-Western, Biochemical Activity, Reconstituted Complex, anti bait coimmunoprecipitation, pull down	direct interaction, physical, physical association	16525023, (Europe PMC)	0.60	BioGRID, IntAct, MINT
AR	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
ARHGEF11	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
ASAP1	anti bait coimmunoprecipitation, fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
ASAP2	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
AXL	coimmunoprecipitation, far western blotting	association	9178760, (Europe PMC)	0.46	IntAct, MINT
BICRA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CAST	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CAV1	Affinity Capture-Western, protein array, pull down	association, direct interaction, physical	20808760, (Europe PMC)	0.52	BioGRID, IntAct
CBL	Affinity Capture-MS, Affinity Capture-Western, Co-localization, FRET, Far Western, Reconstituted Complex, proximity ligation assay	physical, physical association	12061819, 12803489, 12941616, 16467851, 16503409, 17372230, 25241761, 9712732, (Europe PMC)	0.40	BioGRID, IntAct
CD22	Affinity Capture-Western, coimmunoprecipitation	association, physical, physical association	8627166, (Europe PMC)	0.50	BioGRID, IntAct
CD244	pull down, surface plasmon resonance	association, direct interaction	24642916, (Europe PMC)	0.52	IntAct
CHAF1A	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CKAP5	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CSMD2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DDIT4	anti tag coimmunoprecipitation	association	19557001, (Europe PMC)	0.35	IntAct, MINT
DLGAP1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DLGAP3	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DLX4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DTNBP1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DUSP15	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
EBI-1108795	anti bait coimmunoprecipitation	association	14968112, (Europe PMC)	0.35	IntAct
EFS	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
EGFR	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, cross-linking study, far western blotting, protein array, pull down	association, direct interaction, physical, physical association	11983899, 12061819, 12803489, 14568990, 16273093, 19605547, 24797263, 7693694, 7993895, 9020117, 9207933, 9756944, (Europe PMC)	0.85	BioGRID, IntAct, MINT
EPX	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
ERBB2	Affinity Capture-Western, Co-fractionation, Protein-peptide, protein array	direct interaction, physical	16273093, 1676673, 1683701, (Europe PMC)	0.44	BioGRID, IntAct, MINT
ERBB3	Protein-peptide, protein array	direct interaction, physical	16273093, (Europe PMC)	0.44	BioGRID, IntAct, MINT
EXTL3	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
F2RL2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FANCA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FAS	anti bait coimmunoprecipitation	association	20696918, (Europe PMC)	0.35	IntAct
FCGR2B	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
FCGR2C	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FGFR1	Biochemical Activity, Co-localization, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, bioluminescence resonance energy transfer, isothermal titration calorimetry, protein kinase assay, proximity ligation assay, pull down	association, direct interaction, phosphorylation reaction, physical, physical association	15117958, 1656221, 20932831, 23063561, 25241761, 8321198, 9660748, (Europe PMC)	0.87	BioGRID, IntAct, MINT
FGFR2	Affinity Capture-Western, Co-localization, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, fluorescent resonance energy transfer, microscale thermophoresis, proximity ligation assay, pull down	association, direct interaction, physical, physical association	15629145, 24440983, 25241761, (Europe PMC)	0.40, 0.70	BioGRID, IntAct
FLNA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FLNB	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FLNC	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FLT1	Reconstituted Complex, Two-hybrid, proximity ligation assay	physical, physical association	23397142, 9398617, (Europe PMC)	0.40	BioGRID, IntAct
FYB1	pull down	association	22074159, (Europe PMC)	0.35	IntAct
GAB1	Affinity Capture-Western, Far Western, fluorescence polarization spectroscopy	direct interaction, physical	11507676, 24728074, 8596638, (Europe PMC)	0.44	BioGRID, IntAct
GHR	Reconstituted Complex, peptide array	physical, physical association	17474147, 9632636, (Europe PMC)	0.40	BioGRID, IntAct
GRB2	Affinity Capture-Western, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	10940929, 16038803, 21706016, 7629168, 9020117, 9281317, (Europe PMC)	0.56	BioGRID, IntAct, MINT
HAVCR2	anti bait coimmunoprecipitation, pull down	association	26492563, (Europe PMC)	0.46	IntAct
HCK	proximity ligation assay	physical association	23397142, (Europe PMC)	0.40	IntAct
HSCB	anti bait coimmunoprecipitation	association	28380382, (Europe PMC)	0.35	IntAct
ID4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
IL3RA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
INSR	Protein-peptide, coimmunoprecipitation, cross-linking study, fluorescence microscopy, pull down	colocalization, direct interaction, physical, physical association	11796522, 14568990, 22974441, 9593725, (Europe PMC)	0.80	BioGRID, IntAct, MINT
ISG20L2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
JAK2	Affinity Capture-Western, peptide array	physical, physical association	14978237, 17474147, (Europe PMC)	0.40	BioGRID, IntAct
KDR	Reconstituted Complex, pull down	association, physical	12598525, 9398617, (Europe PMC)	0.35	BioGRID, IntAct, MINT
KHDRBS1	coimmunoprecipitation, pull down	physical association	7537265, 9045636, (Europe PMC)	0.59	IntAct
KIT	Co-localization, Reconstituted Complex, coimmunoprecipitation, fluorescence polarization spectroscopy, proximity ligation assay	association, direct interaction, physical, physical association	11071635, 24728074, 25241761, 7536744, 7537096, (Europe PMC)	0.70	BioGRID, IntAct, MINT
LAT	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, FRET, Reconstituted Complex, anti bait coimmunoprecipitation, coimmunoprecipitation, pull down, surface plasmon resonance	association, direct interaction, physical, physical association	10811803, 11368773, 16467851, 16938345, 24642916, 27221712, 9489702, 9729044, (Europe PMC)	0.81	BioGRID, IntAct, MINT
LCP2	Affinity Capture-MS, Affinity Capture-Western, FRET, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	11390650, 15929943, 16467851, 21725281, (Europe PMC)	0.56	BioGRID, IntAct, MINT
LIG3	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
MAP4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
MAP4K1	anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.66	IntAct
MEPE	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
MET	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
NELFB	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
NELL1	phage display	physical association	21723284, (Europe PMC)	0.40	IntAct, MINT
NFAT5	anti tag coimmunoprecipitation	physical association	20080774, (Europe PMC)	0.40	IntAct
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 1715690, 25921289, 8384556, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
PDGFRA	Affinity Capture-Western, Biochemical Activity, Co-localization, Reconstituted Complex, experimental interaction detection, proximity ligation assay	association, physical, physical association	25241761, 7535778, 7682895, (Europe PMC)	0.51	BioGRID, IntAct, MINT
PDGFRB	Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, nuclear magnetic resonance, proximity ligation assay	association, direct interaction, physical, physical association	11896612, 1396585, 15641795, 22974441, 23063561, 23397142, 8443409, (Europe PMC)	0.82	BioGRID, IntAct, MINT
PDIA2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
PHACTR2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
PIK3R1	pull down	physical association	9020117, (Europe PMC)	0.40	IntAct, MINT
PLCG1	biochemical	dephosphorylation reaction	11434923, (Europe PMC)	0.44	IntAct, MINT
PLCG2	Co-localization, proximity ligation assay	physical, physical association	25241761, (Europe PMC)	0.40	BioGRID, IntAct
PLD1	atomic force microscopy	direct interaction	19323535, (Europe PMC)	0.36	IntAct, MINT
PPFIA4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
PTK2	Affinity Capture-Western, proximity ligation assay	physical, physical association	10430888, 23397142, (Europe PMC)	0.40	BioGRID, IntAct
PTPN11	pull down	physical association	9020117, (Europe PMC)	0.40	IntAct, MINT
RAC1	anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down	direct interaction, physical association	19264842, (Europe PMC)	0.64	IntAct, MINT
RAG1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RASA1	Affinity Capture-Western, pull down	physical, physical association	8977179, 9020117, 9743338, (Europe PMC)	0.40	BioGRID, IntAct, MINT
RET	Co-localization, Reconstituted Complex, competition binding, proximity ligation assay	association, physical, physical association	25241761, 8628282, (Europe PMC)	0.56	BioGRID, IntAct, MINT
RGS7	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RHOU	pull down	physical association	15556869, (Europe PMC)	0.40	IntAct, MINT
RIN3	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
RPL13	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RRAS	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RYR1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SCARB2	pull down	direct interaction	14570588, (Europe PMC)	0.44	IntAct, MINT
SEC24B	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SERPINC1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SH2D1B	pull down, surface plasmon resonance	association, direct interaction	24642916, (Europe PMC)	0.52	IntAct
SH3BP2	Far Western, Reconstituted Complex, pull down	association, physical	11390470, 15345594, 9846481, (Europe PMC)	0.53	BioGRID, IntAct, MINT
SHANK2	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
SHANK3	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
SLC23A1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SNX17	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
SNX7	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SOS1	Affinity Capture-Western, Reconstituted Complex, fluorescence technology, peptide array, pull down	direct interaction, physical, physical association	10913276, 10940929, 17474147, 9020117, (Europe PMC)	0.67	BioGRID, IntAct, MINT
SOS2	Affinity Capture-Western, Two-hybrid, anti bait coimmunoprecipitation, fluorescence technology, peptide array	direct interaction, physical, physical association	10940929, 17474147, (Europe PMC)	0.60	BioGRID, IntAct
SPEN	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SUV39H2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SYK	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	7831290, 8657103, (Europe PMC)	0.46	BioGRID, IntAct, MINT
TDRD1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
TESPA1	anti bait coimmunoprecipitation	association	22561606, (Europe PMC)	0.35	IntAct
TGOLN2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
THEMIS	anti bait coimmunoprecipitation, pull down	association, physical association	21189249, 23460737, (Europe PMC)	0.46, 0.50	IntAct
TRAIP	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
VIL1	anti bait coimmunoprecipitation, fluorescent resonance energy transfer	physical association	16921170, 17229814, (Europe PMC)	0.66	IntAct
WAS	Reconstituted Complex, pull down	physical, physical association	8805332, 8824280, 8892607, (Europe PMC)	0.40	BioGRID, IntAct
ZP2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct

Visualize Download

Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
AGTR1	pull down	association	9516477, (Europe PMC)	0.35	IntAct, MINT
AKT1	Affinity Capture-Western, Biochemical Activity, Reconstituted Complex, anti bait coimmunoprecipitation, pull down	direct interaction, physical, physical association	16525023, (Europe PMC)	0.60	BioGRID, IntAct, MINT
AXL	coimmunoprecipitation, far western blotting	association	9178760, (Europe PMC)	0.46	IntAct, MINT
DDIT4	anti tag coimmunoprecipitation	association	19557001, (Europe PMC)	0.35	IntAct, MINT
EGFR	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, cross-linking study, far western blotting, protein array, pull down	association, direct interaction, physical, physical association	11983899, 12061819, 12803489, 14568990, 16273093, 19605547, 24797263, 7693694, 7993895, 9020117, 9207933, 9756944, (Europe PMC)	0.85	BioGRID, IntAct, MINT
ERBB2	Affinity Capture-Western, Co-fractionation, Protein-peptide, protein array	direct interaction, physical	16273093, 1676673, 1683701, (Europe PMC)	0.44	BioGRID, IntAct, MINT
ERBB3	Protein-peptide, protein array	direct interaction, physical	16273093, (Europe PMC)	0.44	BioGRID, IntAct, MINT
FGFR1	Biochemical Activity, Co-localization, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, bioluminescence resonance energy transfer, isothermal titration calorimetry, protein kinase assay, proximity ligation assay, pull down	association, direct interaction, phosphorylation reaction, physical, physical association	15117958, 1656221, 20932831, 23063561, 25241761, 8321198, 9660748, (Europe PMC)	0.87	BioGRID, IntAct, MINT
GRB2	Affinity Capture-Western, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	10940929, 16038803, 21706016, 7629168, 9020117, 9281317, (Europe PMC)	0.56	BioGRID, IntAct, MINT
INSR	Protein-peptide, coimmunoprecipitation, cross-linking study, fluorescence microscopy, pull down	colocalization, direct interaction, physical, physical association	11796522, 14568990, 22974441, 9593725, (Europe PMC)	0.80	BioGRID, IntAct, MINT
KDR	Reconstituted Complex, pull down	association, physical	12598525, 9398617, (Europe PMC)	0.35	BioGRID, IntAct, MINT
KIT	Co-localization, Reconstituted Complex, coimmunoprecipitation, fluorescence polarization spectroscopy, proximity ligation assay	association, direct interaction, physical, physical association	11071635, 24728074, 25241761, 7536744, 7537096, (Europe PMC)	0.70	BioGRID, IntAct, MINT
LAT	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, FRET, Reconstituted Complex, anti bait coimmunoprecipitation, coimmunoprecipitation, pull down, surface plasmon resonance	association, direct interaction, physical, physical association	10811803, 11368773, 16467851, 16938345, 24642916, 27221712, 9489702, 9729044, (Europe PMC)	0.81	BioGRID, IntAct, MINT
LCP2	Affinity Capture-MS, Affinity Capture-Western, FRET, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	11390650, 15929943, 16467851, 21725281, (Europe PMC)	0.56	BioGRID, IntAct, MINT
NELL1	phage display	physical association	21723284, (Europe PMC)	0.40	IntAct, MINT
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 1715690, 25921289, 8384556, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
PDGFRA	Affinity Capture-Western, Biochemical Activity, Co-localization, Reconstituted Complex, experimental interaction detection, proximity ligation assay	association, physical, physical association	25241761, 7535778, 7682895, (Europe PMC)	0.51	BioGRID, IntAct, MINT
PDGFRB	Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, nuclear magnetic resonance, proximity ligation assay	association, direct interaction, physical, physical association	11896612, 1396585, 15641795, 22974441, 23063561, 23397142, 8443409, (Europe PMC)	0.82	BioGRID, IntAct, MINT
PIK3R1	pull down	physical association	9020117, (Europe PMC)	0.40	IntAct, MINT
PLCG1	biochemical	dephosphorylation reaction	11434923, (Europe PMC)	0.44	IntAct, MINT
PLD1	atomic force microscopy	direct interaction	19323535, (Europe PMC)	0.36	IntAct, MINT
PTPN11	pull down	physical association	9020117, (Europe PMC)	0.40	IntAct, MINT
RAC1	anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down	direct interaction, physical association	19264842, (Europe PMC)	0.64	IntAct, MINT
RASA1	Affinity Capture-Western, pull down	physical, physical association	8977179, 9020117, 9743338, (Europe PMC)	0.40	BioGRID, IntAct, MINT
RET	Co-localization, Reconstituted Complex, competition binding, proximity ligation assay	association, physical, physical association	25241761, 8628282, (Europe PMC)	0.56	BioGRID, IntAct, MINT
RHOU	pull down	physical association	15556869, (Europe PMC)	0.40	IntAct, MINT
SCARB2	pull down	direct interaction	14570588, (Europe PMC)	0.44	IntAct, MINT
SH3BP2	Far Western, Reconstituted Complex, pull down	association, physical	11390470, 15345594, 9846481, (Europe PMC)	0.53	BioGRID, IntAct, MINT
SOS1	Affinity Capture-Western, Reconstituted Complex, fluorescence technology, peptide array, pull down	direct interaction, physical, physical association	10913276, 10940929, 17474147, 9020117, (Europe PMC)	0.67	BioGRID, IntAct, MINT
SYK	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	7831290, 8657103, (Europe PMC)	0.46	BioGRID, IntAct, MINT

Visualize Download

Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
ABI1	array technology	direct interaction	20598684, (Europe PMC)	0.44	IntAct, MINT
ABL1	Reconstituted Complex, peptide array	physical, physical association	10708759, 17474147, (Europe PMC)	0.40	BioGRID, IntAct
ABL2	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
ADNP	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AFF2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AGTR1	pull down	association	9516477, (Europe PMC)	0.35	IntAct, MINT
AIRE	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AKAP2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
AKT1	Affinity Capture-Western, Biochemical Activity, Reconstituted Complex, anti bait coimmunoprecipitation, pull down	direct interaction, physical, physical association	16525023, (Europe PMC)	0.60	BioGRID, IntAct, MINT
ALK	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex	physical	11888936, 14968112, 9819383, (Europe PMC)	NA	BioGRID
AR	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
ARHGAP32	Affinity Capture-Western	physical	12454018, (Europe PMC)	NA	BioGRID
ARHGEF11	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
ARHGEF2	Affinity Capture-Western	physical	19805522, (Europe PMC)	NA	BioGRID
ASAP1	anti bait coimmunoprecipitation, fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
ASAP2	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
AXL	coimmunoprecipitation, far western blotting	association	9178760, (Europe PMC)	0.46	IntAct, MINT
BAG3	Affinity Capture-Western, Reconstituted Complex	physical	10980614, 21233200, (Europe PMC)	NA	BioGRID
BICRA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
BLNK	Affinity Capture-Western	physical	10684856, (Europe PMC)	NA	BioGRID
CACNB3	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CAMK2A	Affinity Capture-Western	physical	18292392, (Europe PMC)	NA	BioGRID
CAST	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CAV1	Affinity Capture-Western, protein array, pull down	association, direct interaction, physical	20808760, (Europe PMC)	0.52	BioGRID, IntAct
CBL	Affinity Capture-MS, Affinity Capture-Western, Co-localization, FRET, Far Western, Reconstituted Complex, proximity ligation assay	physical, physical association	12061819, 12803489, 12941616, 16467851, 16503409, 17372230, 25241761, 9712732, (Europe PMC)	0.40	BioGRID, IntAct
CCDC120	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CD22	Affinity Capture-Western, coimmunoprecipitation	association, physical, physical association	8627166, (Europe PMC)	0.50	BioGRID, IntAct
CD244	pull down, surface plasmon resonance	association, direct interaction	24642916, (Europe PMC)	0.52	IntAct
CHAF1A	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CKAP5	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CSMD2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
CTPS1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
DDIT4	anti tag coimmunoprecipitation	association	19557001, (Europe PMC)	0.35	IntAct, MINT
DGKZ	Affinity Capture-Western	physical	12890670, (Europe PMC)	NA	BioGRID
DLGAP1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DLGAP3	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DLX4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DOK1	Reconstituted Complex	physical	11071635, (Europe PMC)	NA	BioGRID
DOK2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
DPP7	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
DTNBP1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
DUSP15	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
EBI-1108795	anti bait coimmunoprecipitation	association	14968112, (Europe PMC)	0.35	IntAct
EEF1A1	Affinity Capture-Western, Far Western, Protein-peptide, Reconstituted Complex, Two-hybrid	physical	11886851, 12898421, (Europe PMC)	NA	BioGRID
EFS	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
EGFR	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, cross-linking study, far western blotting, protein array, pull down	association, direct interaction, physical, physical association	11983899, 12061819, 12803489, 14568990, 16273093, 19605547, 24797263, 7693694, 7993895, 9020117, 9207933, 9756944, (Europe PMC)	0.85	BioGRID, IntAct, MINT
EHD4	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
EPHB2	Two-hybrid	physical	9632142, (Europe PMC)	NA	BioGRID
EPOR	PCA	physical	15644415, (Europe PMC)	NA	BioGRID
EPX	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
ERBB2	Affinity Capture-Western, Co-fractionation, Protein-peptide, protein array	direct interaction, physical	16273093, 1676673, 1683701, (Europe PMC)	0.44	BioGRID, IntAct, MINT
ERBB3	Protein-peptide, protein array	direct interaction, physical	16273093, (Europe PMC)	0.44	BioGRID, IntAct, MINT
EXTL3	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
F2RL2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FANCA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FAS	anti bait coimmunoprecipitation	association	20696918, (Europe PMC)	0.35	IntAct
FCGR2B	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
FCGR2C	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FGFR1	Biochemical Activity, Co-localization, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, bioluminescence resonance energy transfer, isothermal titration calorimetry, protein kinase assay, proximity ligation assay, pull down	association, direct interaction, phosphorylation reaction, physical, physical association	15117958, 1656221, 20932831, 23063561, 25241761, 8321198, 9660748, (Europe PMC)	0.87	BioGRID, IntAct, MINT
FGFR2	Affinity Capture-Western, Co-localization, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, fluorescent resonance energy transfer, microscale thermophoresis, proximity ligation assay, pull down	association, direct interaction, physical, physical association	15629145, 24440983, 25241761, (Europe PMC)	0.40, 0.70	BioGRID, IntAct
FLNA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FLNB	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FLNC	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
FLT1	Reconstituted Complex, Two-hybrid, proximity ligation assay	physical, physical association	23397142, 9398617, (Europe PMC)	0.40	BioGRID, IntAct
FYB1	pull down	association	22074159, (Europe PMC)	0.35	IntAct
GAB1	Affinity Capture-Western, Far Western, fluorescence polarization spectroscopy	direct interaction, physical	11507676, 24728074, 8596638, (Europe PMC)	0.44	BioGRID, IntAct
GAB2	Reconstituted Complex	physical	10391903, (Europe PMC)	NA	BioGRID
GAS2L1	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
GHR	Reconstituted Complex, peptide array	physical, physical association	17474147, 9632636, (Europe PMC)	0.40	BioGRID, IntAct
GIT1	Affinity Capture-Western, Reconstituted Complex	physical	14523024, (Europe PMC)	NA	BioGRID
GRB2	Affinity Capture-Western, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	10940929, 16038803, 21706016, 7629168, 9020117, 9281317, (Europe PMC)	0.56	BioGRID, IntAct, MINT
GSN	Reconstituted Complex	physical	9164868, (Europe PMC)	NA	BioGRID
GTF3C4	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
HAVCR2	anti bait coimmunoprecipitation, pull down	association	26492563, (Europe PMC)	0.46	IntAct
HCK	proximity ligation assay	physical association	23397142, (Europe PMC)	0.40	IntAct
HNRNPK	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
HNRNPL	Affinity Capture-RNA	physical	28611215, (Europe PMC)	NA	BioGRID
HSCB	anti bait coimmunoprecipitation	association	28380382, (Europe PMC)	0.35	IntAct
IBTK	Affinity Capture-Western	physical	18596081, (Europe PMC)	NA	BioGRID
ID4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
IL3RA	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
INSR	Protein-peptide, coimmunoprecipitation, cross-linking study, fluorescence microscopy, pull down	colocalization, direct interaction, physical, physical association	11796522, 14568990, 22974441, 9593725, (Europe PMC)	0.80	BioGRID, IntAct, MINT
IRS2	Affinity Capture-Western, Protein-peptide	physical	22974441, 9535722, (Europe PMC)	NA	BioGRID
ISG20L2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
ITK	Affinity Capture-Western, Biochemical Activity, Reconstituted Complex	physical	10586033, 12163161, (Europe PMC)	NA	BioGRID
JAK1	Affinity Capture-Western	physical	14978237, (Europe PMC)	NA	BioGRID
JAK2	Affinity Capture-Western, peptide array	physical, physical association	14978237, 17474147, (Europe PMC)	0.40	BioGRID, IntAct
KCNJ5	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
KDR	Reconstituted Complex, pull down	association, physical	12598525, 9398617, (Europe PMC)	0.35	BioGRID, IntAct, MINT
KHDRBS1	Affinity Capture-Western, Reconstituted Complex	physical	10467411, 11960376, 8977179, 9743338, (Europe PMC)	NA	BioGRID
KHDRBS1	coimmunoprecipitation, pull down	physical association	7537265, 9045636, (Europe PMC)	0.59	IntAct
KHDRBS2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
KIT	Co-localization, Reconstituted Complex, coimmunoprecipitation, fluorescence polarization spectroscopy, proximity ligation assay	association, direct interaction, physical, physical association	11071635, 24728074, 25241761, 7536744, 7537096, (Europe PMC)	0.70	BioGRID, IntAct, MINT
LAT	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, FRET, Reconstituted Complex, anti bait coimmunoprecipitation, coimmunoprecipitation, pull down, surface plasmon resonance	association, direct interaction, physical, physical association	10811803, 11368773, 16467851, 16938345, 24642916, 27221712, 9489702, 9729044, (Europe PMC)	0.81	BioGRID, IntAct, MINT
LAT2	Affinity Capture-Western	physical	12514734, (Europe PMC)	NA	BioGRID
LCP2	Affinity Capture-MS, Affinity Capture-Western, FRET, Reconstituted Complex, anti tag coimmunoprecipitation, pull down	association, physical, physical association	11390650, 15929943, 16467851, 21725281, (Europe PMC)	0.56	BioGRID, IntAct, MINT
LDLRAD4	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
LIG3	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
LIMD1	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
LTK	Affinity Capture-Western	physical	8084603, (Europe PMC)	NA	BioGRID
LZTS2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
MAP4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
MAP4K1	anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.66	IntAct
MCMBP	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
MEPE	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
MET	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
MST1R	Affinity Capture-Western	physical	8918464, (Europe PMC)	NA	BioGRID
MVB12B	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
NCAM1	Reconstituted Complex	physical	23061666, (Europe PMC)	NA	BioGRID
NCKIPSD	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
NELFB	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
NELL1	phage display	physical association	21723284, (Europe PMC)	0.40	IntAct, MINT
NFAT5	anti tag coimmunoprecipitation	physical association	20080774, (Europe PMC)	0.40	IntAct
NPEPL1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
NPM1	Affinity Capture-Western, Reconstituted Complex	physical	9819383, (Europe PMC)	NA	BioGRID
NTMT1	Co-fractionation	physical	22939629, (Europe PMC)	NA	BioGRID
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 1715690, 25921289, 8384556, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
NTRK2	Reconstituted Complex, Two-hybrid	physical	10092678, 12074588, (Europe PMC)	NA	BioGRID
NTRK3	Reconstituted Complex	physical	10092678, (Europe PMC)	NA	BioGRID
NXF1	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
PAK1	Reconstituted Complex	physical	12085993, (Europe PMC)	NA	BioGRID
PDGFA	Affinity Capture-Western	physical	8443409, (Europe PMC)	NA	BioGRID
PDGFRA	Affinity Capture-Western, Biochemical Activity, Co-localization, Reconstituted Complex, experimental interaction detection, proximity ligation assay	association, physical, physical association	25241761, 7535778, 7682895, (Europe PMC)	0.51	BioGRID, IntAct, MINT
PDGFRB	Affinity Capture-Western, Protein-peptide, coimmunoprecipitation, nuclear magnetic resonance, proximity ligation assay	association, direct interaction, physical, physical association	11896612, 1396585, 15641795, 22974441, 23063561, 23397142, 8443409, (Europe PMC)	0.82	BioGRID, IntAct, MINT
PDIA2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
PECAM1	Far Western, Reconstituted Complex	physical	10350061, (Europe PMC)	NA	BioGRID
PFKP	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PHACTR2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
PICALM	Reconstituted Complex	physical	10926122, (Europe PMC)	NA	BioGRID
PIK3R1	pull down	physical association	9020117, (Europe PMC)	0.40	IntAct, MINT
PKN2	Reconstituted Complex	physical	8910519, (Europe PMC)	NA	BioGRID
PLCG1	biochemical	dephosphorylation reaction	11434923, (Europe PMC)	0.44	IntAct, MINT
PLCG2	Co-localization, proximity ligation assay	physical, physical association	25241761, (Europe PMC)	0.40	BioGRID, IntAct
PLD1	atomic force microscopy	direct interaction	19323535, (Europe PMC)	0.36	IntAct, MINT
PLD2	Affinity Capture-Western, Reconstituted Complex	physical	12646582, (Europe PMC)	NA	BioGRID
PLXNB1	Affinity Capture-Western	physical	19805522, (Europe PMC)	NA	BioGRID
PLXNB2	Affinity Capture-Western	physical	19805522, (Europe PMC)	NA	BioGRID
PML	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation	physical	17419608, (Europe PMC)	NA	BioGRID
PPFIA4	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
PRKD1	Affinity Capture-Western	physical	8885868, (Europe PMC)	NA	BioGRID
PRKN	Affinity Capture-Western	physical	18671761, (Europe PMC)	NA	BioGRID
PTK2	Affinity Capture-Western, proximity ligation assay	physical, physical association	10430888, 23397142, (Europe PMC)	0.40	BioGRID, IntAct
PTPN11	pull down	physical association	9020117, (Europe PMC)	0.40	IntAct, MINT
PTPN6	Affinity Capture-Western	physical	27221712, (Europe PMC)	NA	BioGRID
PTPRJ	Biochemical Activity	physical	11259588, (Europe PMC)	NA	BioGRID
PYGB	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
RAB11A	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
RAC1	anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down	direct interaction, physical association	19264842, (Europe PMC)	0.64	IntAct, MINT
RACK1	Far Western	physical	8290562, (Europe PMC)	NA	BioGRID
RAG1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RASA1	Affinity Capture-Western, pull down	physical, physical association	8977179, 9020117, 9743338, (Europe PMC)	0.40	BioGRID, IntAct, MINT
RET	Co-localization, Reconstituted Complex, competition binding, proximity ligation assay	association, physical, physical association	25241761, 8628282, (Europe PMC)	0.56	BioGRID, IntAct, MINT
RGS7	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RHOA	Affinity Capture-Western, Reconstituted Complex	physical	12071848, (Europe PMC)	NA	BioGRID
RHOU	pull down	physical association	15556869, (Europe PMC)	0.40	IntAct, MINT
RIC8A	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
RIN3	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
RNF40	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
RPL13	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RPL38	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
RRAS	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
RYR1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SARNP	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
SCARB2	pull down	direct interaction	14570588, (Europe PMC)	0.44	IntAct, MINT
SEC24B	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SELE	Affinity Capture-Western	physical	12960351, (Europe PMC)	NA	BioGRID
SERPINC1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SH2B3	Affinity Capture-Western	physical	8649391, (Europe PMC)	NA	BioGRID
SH2D1B	pull down, surface plasmon resonance	association, direct interaction	24642916, (Europe PMC)	0.52	IntAct
SH3BP2	Far Western, Reconstituted Complex, pull down	association, physical	11390470, 15345594, 9846481, (Europe PMC)	0.53	BioGRID, IntAct, MINT
SHANK2	fluorescence technology, peptide array, pull down	direct interaction, physical association	17474147, (Europe PMC)	0.60	IntAct
SHANK3	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
SHB	Affinity Capture-Western	physical	10488157, (Europe PMC)	NA	BioGRID
SHC1	Affinity Capture-Western	physical	8662733, (Europe PMC)	NA	BioGRID
SKIV2L	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
SLC23A1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SNX11	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
SNX17	fluorescence technology, peptide array	direct interaction, physical association	17474147, (Europe PMC)	0.54	IntAct
SNX7	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SOS1	Affinity Capture-Western, Reconstituted Complex, fluorescence technology, peptide array, pull down	direct interaction, physical, physical association	10913276, 10940929, 17474147, 9020117, (Europe PMC)	0.67	BioGRID, IntAct, MINT
SOS2	Affinity Capture-Western, Two-hybrid, anti bait coimmunoprecipitation, fluorescence technology, peptide array	direct interaction, physical, physical association	10940929, 17474147, (Europe PMC)	0.60	BioGRID, IntAct
SPEN	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SPRY1	Affinity Capture-Western	physical	19915061, (Europe PMC)	NA	BioGRID
SRC	Affinity Capture-Western	physical	7510703, (Europe PMC)	NA	BioGRID
STRAP	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
SUV39H2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
SYK	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	7831290, 8657103, (Europe PMC)	0.46	BioGRID, IntAct, MINT
SYNCRIP	Reconstituted Complex	physical	9341187, (Europe PMC)	NA	BioGRID
TDRD1	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
TEKT2	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
TESPA1	anti bait coimmunoprecipitation	association	22561606, (Europe PMC)	0.35	IntAct
TGOLN2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
THEMIS	anti bait coimmunoprecipitation, pull down	association, physical association	21189249, 23460737, (Europe PMC)	0.46, 0.50	IntAct
TIPRL	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
TNK1	Reconstituted Complex	physical	10873601, (Europe PMC)	NA	BioGRID
TRAIP	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct
TRPM7	Reconstituted Complex	physical	11941371, (Europe PMC)	NA	BioGRID
TTC9B	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TUB	Affinity Capture-Western, Reconstituted Complex	physical	10455176, (Europe PMC)	NA	BioGRID
UBR7	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
UCHL5	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
UNC45A	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
VAV1	Affinity Capture-MS, Affinity Capture-Western, FRET	physical	16467851, 9891995, (Europe PMC)	NA	BioGRID
VIL1	anti bait coimmunoprecipitation, fluorescent resonance energy transfer	physical association	16921170, 17229814, (Europe PMC)	0.66	IntAct
WAS	Reconstituted Complex, pull down	physical, physical association	8805332, 8824280, 8892607, (Europe PMC)	0.40	BioGRID, IntAct
WDR61	Co-fractionation	physical	22863883, (Europe PMC)	NA	BioGRID
ZAP70	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex	physical	16467851, 7629168, 8906806, (Europe PMC)	NA	BioGRID
ZNF785	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
ZP2	peptide array	physical association	17474147, (Europe PMC)	0.40	IntAct

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PLCG1