DEPOD - human DEPhOsphorylation Database

Basic Information
Phosphatases
Pathway
Interacting Proteins
Phosphorylating Kinases

Gene Name	SHC1 (QuickGO)	Interactive visualization of SHC1 structures (A quick tutorial to explore the interctive visulaization) Representative structure: 1WCP
Synonyms	SHC1, SHC, SHCA
Protein Name	SHC1
Alternative Name(s)	SHC-transforming protein 1;SHC-transforming protein 3;SHC-transforming protein A;Src homology 2 domain-containing-transforming protein C1;SH2 domain protein C1;
Protein Family	noSimilarity_annotations
EntrezGene ID	6464 (Comparitive Toxicogenomics)
UniProt AC (Human)	P29353 (protein sequence)
Enzyme Class	N/A
Molecular Weight	62822 Dalton
Protein Length	583 amino acids (AA)
Genome Browsers	NCBI \| ENSG00000160691 (Ensembl) \| UCSC
Crosslinking annotations	Query our ID-mapping table
Orthologues	Quest For Orthologues (QFO) \| GeneTree \| eggNOG - KOG3697 \| eggNOG - ENOG410XTJN
Phosphorylation Network	Visualize

Domain organization, Expression, Diseases

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Localization, Function, Catalytic activity and Sequence

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Localization (UniProt annotation)
Cytoplasm Isoform p46Shc: Mitochondrion matrix Note=Localized to the mitochondriamatrix Targeting of isoform p46Shc to mitochondria is mediated byits first 32 amino acids, which behave as a bona fidemitochondrial targeting sequence Isoform p52Shc and isoformp66Shc, that contain the same sequence but more internallylocated, display a different subcellular localization Isoform p66Shc: Mitochondrion Note=In case of oxidative conditions, phosphorylation at 'Ser-36'of isoform p66Shc, leads to mitochondrial accumulation
Function (UniProt annotation)
Signaling adapter that couples activated growth factorreceptors to signaling pathways Participates in a signalingcascade initiated by activated KIT and KITLG/SCF Isoform p46Shcand isoform p52Shc, once phosphorylated, couple activated receptortyrosine kinases to Ras via the recruitment of the GRB2/SOScomplex and are implicated in the cytoplasmic propagation ofmitogenic signals Isoform p46Shc and isoform p52Shc may thusfunction as initiators of the Ras signaling cascade in variousnon-neuronal systems Isoform p66Shc does not mediate Rasactivation, but is involved in signal transduction pathways thatregulate the cellular response to oxidative stress and life spanIsoform p66Shc acts as a downstream target of the tumor suppressorp53 and is indispensable for the ability of stress-activated p53to induce elevation of intracellular oxidants, cytochrome crelease and apoptosis The expression of isoform p66Shc has beencorrelated with life span (By similarity) Participates insignaling downstream of the angiopoietin receptor TEK/TIE2, andplays a role in the regulation of endothelial cell migration andsprouting angiogenesis
Catalytic Activity (UniProt annotation)
N/A
Protein Sequence
MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCSFFPRMSNLRLANPAGGRPGS KGEPGRAADDGEGIVGAAMPDSGPLPLLQDMNKLSGGGGRRTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGV SYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSS LNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPP KLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPLGGVVDMRLREGAAPGAARPTAPNAQTPSHLGATLPVGQPV GGDPEVRKQMPPPPPCPGRELFDDPSYVNVQNLDKARQAVGGAGPPNPAINGSAPRDLFDMKPFEDALRVPPPPQSVSMA EQLRGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHM DNHLPIISAGSELCLQQPVERKL

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)
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.
hsa01522	Endocrine resistance	Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. The most commonly used endocrine therapy agents are selective estrogen receptor modulators (SERMs, e.g. tamoxifen), estrogen synthesis inhibitors (e.g. aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane), and selective estrogen receptor down-regulators (SERDs, e.g. fulvestrant). However, resistance to these agents has become a major clinical obstacle. Mechanisms of endocrine resistance include loss of ER-alpha expression, altered expression of coactivators or coregulators that play a critical role in ER-mediated gene transcription, ligand-independent growth factor signaling cascades that activate kinases and ER-phosphorylation, altered availability of active tamoxifen metabolites regulated by drug-metabolizing enzymes, such as CYP2D6, and deregulation of the cell cycle and apoptotic machinery.
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).
hsa04062	Chemokine signaling pathway	Inflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for the cell trafficking and thus are vital for protective host response. In addition, chemokines regulate plethora of biological processes of hematopoietic cells to lead cellular activation, differentiation and survival.The chemokine signal is transduced by chemokine receptors (G-protein coupled receptors) expressed on the immune cells. After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. Various members of small GTPases are involved in this process. Induction of nitric oxide and production of reactive oxygen species are as well regulated by chemokine signal via calcium mobilization and diacylglycerol production.
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.
hsa04510	Focal adhesion	Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the actin cytoskeleton; a prerequisite for changes in cell shape and motility, and gene expression. Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signalling.
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.
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.
hsa04910	Insulin signaling pathway	Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR.Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK) and mitogenic responses in the form of gene transcription. SHC is another substrate of INSR. When tyrosine phosphorylated, SHC associates with GRB2 and can thus activate the RAS/MAPK pathway independently of IRS-1.
hsa04915	Estrogen signaling pathway	Estrogens are steroid hormones that regulate a plethora of physiological processes in mammals, including reproduction, cardiovascular protection, bone integrity, cellular homeostasis, and behavior. Estrogen mediates its cellular actions through two signaling pathways classified as nuclear-initiated steroid signalingand membrane-initiated steroid signaling. In the nuclearpathway, estrogen binds either ERalpha or ERbeta, which in turn translocates to the nucleus, binds DNA at ERE elements and activates the expression of ERE-dependent genes. In membranepathway, Estrogen can exert its actions through a subpopulation of ER at the plasma membrane (mER) or novel G-protein coupled E2 receptors (GPER). Upon activation of these receptors various signaling pathways (i.e. Ca2+, cAMP, protein kinase cascades) are rapidly activated and ultimately influence downstream transcription factors.
hsa04917	Prolactin signaling pathway	Prolactin (PRL) is a polypeptide hormone known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, growth and development, endocrinology and metabolism, brain and behavior, and immunomodulation. PRL mediates its action through PRLR, a transmembrane protein of the hematopoietin cytokine receptor superfamily. At the protein level, the long PRLR isoform (long-R) and several short PRLR isoforms (short-R) have been detected. Acting through the long-R, PRL activates many signaling cascades including Jak2/Stat, the major cascade, Src kinase, phosphatidylinositol-3-kinase (PI3K)/AKT, and mitogen-activated protein kinase (MAPK) pathways. PRL cannot activate Jak2/Stat5 through the short-R, but can activate pathways including MAPK and PI3K pathways.
hsa04926	Relaxin signaling pathway	Human relaxin-2 (relaxin), originally identified as a peptidic hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic and angiogenic effects in both males and females. It belongs to the so-called relaxin peptide family which includes the insulin-like peptides INSL3 and INSL5, and relaxin-3 (H3) as well as relaxin. INSL3 has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. These members of relaxin peptide family exert such effects binding to different kinds of receptors, classified as relaxin family peptide (RXFP) receptors: RXFP1, RXFP2, RXFP3, and RXFP4. These G protein-coupled receptors predominantly bind relaxin, INSL3, relaxin-3, and INSL-5, respectively. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Both RXFP3 and RXFP4 inhibit cAMP production, and RXFP3 activate MAP kinases.
hsa05034	Alcoholism	Alcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the rewarding effects of alcohol, dopaminergic ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) have been identified. Acute exposure to alcohol stimulates dopamine release into the NAc, which activates D1 receptors, stimulating PKA signaling and subsequent CREB-mediated gene expression, whereas chronic alcohol exposure leads to an adaptive downregulation of this pathway, in particular of CREB function. The decreased CREB function in the NAc may promote the intake of drugs of abuse to achieve an increase in reward and thus may be involved in the regulation of positive affective states of addiction. PKA signaling also affects NMDA receptor activity and may play an important role in neuroadaptation in response to chronic alcohol exposure.
hsa05100	Bacterial invasion of epithelial cells	Many pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. Invasive bacteria induce their own uptake by non-phagocytic host cells (e.g. epithelial cells) using two mechanisms referred to as zipper model and trigger model. Listeria, Staphylococcus, Streptococcus, and Yersinia are examples of bacteria that enter using the zipper model. These bacteria express proteins on their surfaces that interact with cellular receptors, initiating signalling cascades that result in close apposition of the cellular membrane around the entering bacteria. Shigella and Salmonella are the examples of bacteria entering cells using the trigger model. These bacteria use type III secretion systems to inject protein effectors that interact with the actin cytoskeleton.
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.
hsa05220	Chronic myeloid leukemia	Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the chronic phase of CML, progression to blast crisis requires other molecular changes. Common secondary abnormalities include mutations in TP53, RB, and p16/INK4A, or overexpression of genes such as EVI1. Additional chromosome translocations are also observed,such as t(3;21)(q26;q22), which generates AML1-EVI1.
hsa05224	Breast cancer	Breast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. The molecular subtypes of breast cancer, which are based on the presence or absence of hormone receptors (estrogen and progesterone subtypes) and human epidermal growth factor receptor-2 (HER2), include: hormone receptor positive and HER2 negative (luminal A subtype), hormone receptor positive and HER2 positive (luminal B subtype), hormone receptor negative and HER2 positive (HER2 positive), and hormone receptor negative and HER2 negative (basal-like or triple-negative breast cancers (TNBCs)). Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumours, HER2 activates the PI3K/AKT and the RAS/RAF/MAPK pathways, and stimulate cell growth, survival and differentiation. In patients suffering from TNBC, the deregulation of various signalling pathways (Notch and Wnt/beta-catenin), EGFR protein have been confirmed. In the case of breast cancer only 8% of all cancers are hereditary, a phenomenon linked to genetic changes in BRCA1 or BRCA2. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers.
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.
hsa05226	Gastric cancer	Gastric cancer (GC) is one of the world's most common cancers. According to Lauren's histological classification gastric cancer is divided into two distinct histological groups - the intestinal and diffuse types. Several genetic changes have been identified in intestinal-type GC. The intestinal metaplasia is characterized by mutations in p53 gene, reduced expression of retinoic acid receptor beta (RAR-beta) and hTERT expression. Gastric adenomas furthermore display mutations in the APC gene, reduced p27 expression and cyclin E amplification. In addition, amplification and overexpression of c-ErbB2, reduced TGF-beta receptor type I (TGFBRI) expression and complete loss of p27 expression are commonly observed in more advanced GC. The main molecular changes observed in diffuse-type GCs include loss of E-cadherin function by mutations in CDH1 and amplification of MET and FGFR2F.

Pathway ID	Pathway Name	Pathway Description (KEGG)
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-1250196	SHC1 events in ERBB2 signaling.	All ERBB2 heterodimers, ERBB2:EGFR, ERBB2:ERBB3 and ERBB2:ERBB4, are able to activate RAF/MAP kinase cascade by recruiting SHC1 (Pinkas-Kramarski et al. 1996, Sepp-Lorenzino et al. 1996) to phosphorylated C-tail tyrosine residues in either EGFR (Y1148 and Y1173), ERBB2 (Y1196, Y1221, Y1222 and Y1248), ERBB3 (Y1328) or ERBB4 (Y1188 and Y1242 in JM-A CYT1 isoform, Y1178 and Y1232 in JM-B CYT1 isoform, Y1172 and Y1226 in JM-A CYT2 isoform). SHC1 recruitment is followed by phosphorylation (Segatto et al. 1993, Soler et al. 1994), and the phosphorylated SHC1 recruits GRB2:SOS1 complex (Xie et al. 1995), which leads to SOS1-mediated guanyl-nucleotide exchange on RAS (Xie et al. 1995) and downstream activation of RAF and MAP kinases
R-HSA-1250347	SHC1 events in ERBB4 signaling.	All splicing isoforms of ERBB4 possess two tyrosine residues in the C-tail that serve as docking sites for SHC1 (Kaushansky et al. 2008, Pinkas-Kramarski et al. 1996, Cohen et al. 1996). Once bound to ERBB4, SHC1 becomes phosphorylated on tyrosine residues by the tyrosine kinase activity of ERBB4, which enables it to recruit the complex of GRB2 and SOS1, resulting in the guanyl-nucleotide exchange on RAS and activation of RAF and MAP kinase cascade (Kainulainen et al. 2000)
R-HSA-167044	Signalling to RAS.	Signalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation of MAPK found in NGF-treated cells
R-HSA-180336	SHC1 events in EGFR signaling.	GRB2 can bind EGFR directly or through another SH2-containing protein, SHC1. This association leads to RAS activation
R-HSA-210993	Tie2 Signaling.	The Tie2/Tek receptor tyrosine kinase plays a pivotal role in vascular and hematopoietic development and is expressed exclusively on endothelial lineage. Tie2 interacts with a group of ligands belonging to angiopoietin family and undergoes activation.These ligands show opposing actions, angiopoietin 1 and angiopoietin 4 stimulate the Tie2 phosphorylation and angiopoietin 2 inhibits it. Upon tyrosine phosphorylation Tie2 acts as a scaffold for various signaling proteins involved in different signal transduction cascades that can effect survival of endothelium and angiogenic sprout formation
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-2428933	SHC-related events triggered by IGF1R.	Phosphorylated IGF1R binds and phosphorylates SHC1 (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parrella et al. 2010, Siddle et al. 2012). Phosphorylated SHC then binds GRB:SOS, which activates RAS-RAF-MAPK signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization.	The lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell calcium responses. Both LAT and NTAL are expressed and phosphorylated following engagement of FCERI on mast cells. NTAL is functionally and topographically different from LAT. There is a considerable debate on the role of NTAL in mast cell. Depending on the circumstances, NTAL appears to have a dual role as positive and negative regulator of MC responses elicited via FCERI. Studies conducted in bone marrow-derived mast cells (BMMCs) of mice lacking NTAL displayed enhanced FCERI-mediated tyrosine phosphorylation of several substrates, calcium response, degranulation, and cytokine production. This indicated that NTAL negatively regulates FCERI-mediated degranulation. However, in mice lacking both LAT and NTAL showed severe block in FCERI-mediated signaling than BMMCs deficient in LAT alone, suggesting that NTAL also shares a redundant function with LAT to play a positive role (Draberova et al. 2007, Orr & McVicar. 2011, Zhu et al. 2004, Volna et al. 2004)
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-354192	Integrin alphaIIb beta3 signaling.	At the sites of vascular injury bioactive molecules such as thrombin, ADP, collagen, fibrinogen and thrombospondin are generated, secreted or exposed. These stimuli activate platelets, converting the major platelet integrin alphaIIbbeta3 from a resting state to an active conformation, in a process termed integrin priming or 'inside-out signalling'. Integrin activation refers to the change required to enhance ligand-binding activity. The activated alphaIIbbeta3 interacts with the fibrinogen and links platelets together in an aggregate to form a platelet plug. AlphaIIbbeta3 bound to fibrin generates more intracellular signals (outside-in signalling), causing further platelet activation and platelet-plug retraction. In the resting state the alpha and beta tails are close together. This interaction keeps the membrane proximal regions in a bent conformation that maintains alphaIIbbeta3 in a low affinity state. Integrin alphaIIbbeta3 is released from its inactive state by interaction with the protein talin. Talin interacts with the beta3 cytoplasmic domain and disrupts the salt bridge between the alpha and beta chains. This separation in the cytoplasmic regions triggers the conformational change in the extracellular domain that increases its affinity to fibrinogen. Much of talin exists in an inactive cytosolic pool, and the Rap1 interacting adaptor molecule (RIAM) is implicated in talin activation and translocation to beta3 integrin cytoplasmic domain
R-HSA-381038	XBP1(S) activates chaperone genes.	Xbp-1 (S) binds the sequence CCACG in ER Stress Responsive Elements (ERSE, consensus sequence CCAAT (N)9 CCACG) located upstream from many genes. The ubiquitous transcription factor NF-Y, a heterotrimer, binds the CCAAT portion of the ERSE and together the IRE1-alpha: NF-Y complex activates transcription of a set of chaperone genes including DNAJB9, EDEM, RAMP4, p58IPK, and others. This results in an increase in protein folding activity in the ER
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling.	The Interleukin-3 (IL-3), IL-5 and Granulocyte-macrophage colony stimulating factor (GM-CSF) receptors form a family of heterodimeric receptors that have specific alpha chains but share a common beta subunit, often referred to as the common beta (Bc). Both subunits contain extracellular conserved motifs typical of the cytokine receptor superfamily. The cytoplasmic domains have limited similarity with other cytokine receptors and lack detectable catalytic domains such as tyrosine kinase domains. IL-3 is a 20-26 kDa product of CD4+ T cells that acts on the most immature marrow progenitors. IL-3 is capable of inducing the growth and differentiation of multi-potential hematopoietic stem cells, neutrophils, eosinophils, megakaryocytes, macrophages, lymphoid and erythroid cells. IL-3 has been used to support the proliferation of murine cell lines with properties of multi-potential progenitors, immature myeloid as well as T and pre-B lymphoid cells (Miyajima et al. 1992). IL-5 is a hematopoietic growth factor responsible for the maturation and differentiation of eosinophils. It was originally defined as a T-cell-derived cytokine that triggers activated B cells for terminal differentiation into antibody-secreting plasma cells. It also promotes the generation of cytotoxic T-cells from thymocytes. IL-5 induces the expression of IL-2 receptors (Kouro & Takatsu 2009). GM-CSF is produced by cells (T-lymphocytes, tissue macrophages, endothelial cells, mast cells) found at sites of inflammatory responses. It stimulates the growth and development of progenitors of granulocytes and macrophages, and the production and maturation of dendritic cells. It stimulates myeloblast and monoblast differentiation, synergises with Epo in the proliferation of erythroid and megakaryocytic progenitor cells, acts as an autocrine mediator of growth for some types of acute myeloid leukemia, is a strong chemoattractant for neutrophils and eosinophils. It enhances the activity of neutrophils and macrophages. Under steady-state conditions GM-CSF is not essential for the production of myeloid cells, but it is required for the proper development of alveolar macrophages, otherwise, pulmonary alvelolar proteinosis (PAP) develops. A growing body of evidence suggests that GM-CSF plays a key role in emergency hematopoiesis (predominantly myelopoiesis) in response to infection, including the production of granulocytes and macrophages in the bone marrow and their maintenance, survival, and functional activation at sites of injury or insult (Hercus et al. 2009). All three receptors have alpha chains that bind their specific ligands with low affinity (de Groot et al. 1998). Bc then associates with the alpha chain forming a high affinity receptor (Geijsen et al. 2001), though the in vivo receptor is likely be a higher order multimer as recently demonstrated for the GM-CSF receptor (Hansen et al. 2008). The receptor chains lack intrinsic kinase activity, instead they interact with and activate signaling kinases, notably Janus Kinase 2 (JAK2). These phosphorylate the common beta subunit, allowing recruitment of signaling molecules such as Shc, the phosphatidylinositol 3-kinases (PI3Ks), and the Signal Transducers and Activators of Transcription (STATs). The cytoplasmic domain of Bc has two distinct functional domains: the membrane proximal region mediates the induction of proliferation-associated genes such as c-myc, pim-1 and oncostatin M. This region binds multiple signal-transducing proteins including JAK2 (Quelle et al. 1994), STATs, c-Src and PI3 kinase (Rao and Mufson, 1995). The membrane distal domain is required for cytokine-induced growth inhibition and is necessary for the viability of hematopoietic cells (Inhorn et al. 1995). This region interacts with signal-transducing proteins such as Shc (Inhorn et al. 1995) and SHP and mediates the transcriptional activation of c-fos, c-jun, c-Raf and p70S6K (Reddy et al. 2000).Figure reproduced by permission from Macmillan Publishers Ltd: Leukemia, WL Blalock et al. 13:1109-1166, copyright 1999. Note that residue numbering in this diagram refers to the mature Common beta chain with signal peptide removed
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-5654688	SHC-mediated cascade:FGFR1.	The exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction with the receptor has not been demonstrated. Co-precipitation of p46 and p52 with the FGFR2 IIIc receptor has been reported, but this interaction is thought to be indirect, possibly mediated by SRC. Consistent with this, co-precipitation of SHC1 and FGFR1 IIIc is seen in mammalian cells expressing v-SRC. The p66 isoform of SHC1 has also been co-precipitated with FGFR3, but this occurs independently of receptor stimulation, and the p66 isoform not been shown to undergo FGF-dependent phosphorylation. SHC1 has been shown to associate with GRB2 and SOS1 in response to FGF stimulation, suggesting that the recruitment of SHC1 may contribute to activation of the MAPK cascade downstream of FGFR
R-HSA-5654699	SHC-mediated cascade:FGFR2.	The exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction with the receptor has not been demonstrated. Co-precipitation of p46 and p52 with the FGFR2 IIIc receptor has been reported, but this interaction is thought to be indirect, possibly mediated by SRC. Consistent with this, co-precipitation of SHC1 and FGFR1 IIIc is seen in mammalian cells expressing v-SRC. The p66 isoform of SHC1 has also been co-precipitated with FGFR3, but this occurs independently of receptor stimulation, and the p66 isoform not been shown to undergo FGF-dependent phosphorylation. SHC1 has been shown to associate with GRB2 and SOS1 in response to FGF stimulation, suggesting that the recruitment of SHC1 may contribute to activation of the MAPK cascade downstream of FGFR
R-HSA-5654704	SHC-mediated cascade:FGFR3.	The exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction with the receptor has not been demonstrated. Co-precipitation of p46 and p52 with the FGFR2 IIIc receptor has been reported, but this interaction is thought to be indirect, possibly mediated by SRC. Consistent with this, co-precipitation of SHC1 and FGFR1 IIIc is seen in mammalian cells expressing v-SRC. The p66 isoform of SHC1 has also been co-precipitated with FGFR3, but this occurs independently of receptor stimulation, and the p66 isoform not been shown to undergo FGF-dependent phosphorylation. SHC1 has been shown to associate with GRB2 and SOS1 in response to FGF stimulation, suggesting that the recruitment of SHC1 may contribute to activation of the MAPK cascade downstream of FGFR
R-HSA-5654719	SHC-mediated cascade:FGFR4.	The exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction with the receptor has not been demonstrated. Co-precipitation of p46 and p52 with the FGFR2 IIIc receptor has been reported, but this interaction is thought to be indirect, possibly mediated by SRC. Consistent with this, co-precipitation of SHC1 and FGFR1 IIIc is seen in mammalian cells expressing v-SRC. The p66 isoform of SHC1 has also been co-precipitated with FGFR3, but this occurs independently of receptor stimulation, and the p66 isoform not been shown to undergo FGF-dependent phosphorylation. SHC1 has been shown to associate with GRB2 and SOS1 in response to FGF stimulation, suggesting that the recruitment of SHC1 may contribute to activation of the MAPK cascade downstream of FGFR
R-HSA-5673001	RAF/MAP kinase cascade.	The RAS-RAF-MEK-ERK pathway regulates processes such as proliferation, differentiation, survival, senescence and cell motility in response to growth factors, hormones and cytokines, among others. Binding of these stimuli to receptors in the plasma membrane promotes the GEF-mediated activation of RAS at the plasma membrane and initiates the three-tiered kinase cascade of the conventional MAPK cascades. GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation (reviewed in Cseh et al, 2014; Roskoski, 2010; McKay and Morrison, 2007; Wellbrock et al, 2004). Activated RAF phosphorylates the MAPK kinase proteins MEK1 and MEK2 (also known as MAP2K1 and MAP2K2), which in turn phophorylate the proline-directed kinases ERK1 and 2 (also known as MAPK3 and MAPK1) (reviewed in Roskoski, 2012a, b; Kryiakis and Avruch, 2012). Activated ERK proteins may undergo dimerization and have identified targets in both the nucleus and the cytosol; consistent with this, a proportion of activated ERK protein relocalizes to the nucleus in response to stimuli (reviewed in Roskoski 2012b; Turjanski et al, 2007; Plotnikov et al, 2010; Cargnello et al, 2011). Although initially seen as a linear cascade originating at the plasma membrane and culminating in the nucleus, the RAS/RAF MAPK cascade is now also known to be activated from various intracellular location. Temporal and spatial specificity of the cascade is achieved in part through the interaction of pathway components with numerous scaffolding proteins (reviewed in McKay and Morrison, 2007; Brown and Sacks, 2009). The importance of the RAS/RAF MAPK cascade is highlighted by the fact that components of this pathway are mutated with high frequency in a large number of human cancers. Activating mutations in RAS are found in approximately one third of human cancers, while ~8% of tumors express an activated form of BRAF (Roberts and Der, 2007; Davies et al, 2002; Cantwell-Dorris et al, 2011)
R-HSA-74749	Signal attenuation.	Now with the complete receptor-ligand dissociation and subsequent degradation of insulin in the endosomal lumen, the endosomally associated protein tyrosine phosphatases (PTPs) complete the receptor dephosphorylation. So too are all the receptor substrates dephosphorylated leading to the collapse of the signalling complexes and signal attenuation
R-HSA-74751	Insulin receptor signalling cascade.	Autophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the autophosphorylation of the insulin receptor is its internalisation into an endosome, which downregulates its signalling activity
R-HSA-8851805	MET activates RAS signaling.	Activated MET receptor recruits the RAS guanyl nucleotide exchange factor (GEF) SOS1 indirectly, either through the GRB2 adapter (Ponzetto et al. 1994, Fournier et al. 1996, Shen and Novak 1997, Besser et al. 1997), GAB1 (Weidner et al. 1996) or SHC1 and GRB2 (Pelicci et al. 1995), or RANBP9 (Wang et al. 2002, Wang et al. 2004). Association of SOS1 with the activated MET receptor complex leads to exchange of GDP to GTP on RAS and activation of RAS signaling (Pelicci et al. 1995, Besser et al. 1997, Shen and Novak 1997, Wang et al. 2004).PTPN11 (SHP2) may contribute to activation of RAS signaling downstream of MET (Schaeper et al. 2000, Furcht et al. 2014).Sustained activation of MAPK1 (ERK2) and MAPK3 (ERK1) downstream of MET-activated RAS may require MET endocytosis and signaling from endosomes (Peschard et al. 2001, Hammond et al. 2001, Petrelli et al. 2002, Kermorgant and Parker 2008).Binding of MET to MUC20 or RANBP10 interferes with RAS activation (Higuchi et al. 2004, Wang et al. 2004)
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-8983432	Interleukin-15 signaling.	The high affinity Interleukin-15 receptor is a heterotrimer of Interleukin-15 receptor subunit alpha (IL15RA), Interleukin-2 receptor subunit beta (IL2RB, CD122) and Cytokine receptor common subunit gamma (IL2RG, CD132). IL2RB and IL2RG are also components of the Interleukin-2 (IL2) receptor. Treatment of human T cells with Interleukin-15 (IL15) results in tyrosine phosphorylation of Tyrosine-protein kinase JAK1 (JAK1, Janus kinase 1) and Tyrosine-protein kinase JAK3 (JAK3, Janus kinase 3) (Johnston et al. 1995, Winthrop 2017). IL15 can signal by a process termed 'trans presentation', where IL15 bound by IL15 on one cell is trans-presented to IL2RB:IL2RG on another cell (Dubois et al. 2002) but can also participate in more 'traditional' cis signaling (Wu et al. 2008, Mishra et al. 2014) where all the three receptors are present on the same cell. \nStimulation of lymphocytes by IL15 release MAPK activation through GAB2/SHP2/SHC (GRB2-associated-binding protein 2/Tyrosine-protein phosphatase non-receptor type 11/SHC transforming protein 1 or 2) cascade activation (Gadina et al. 2000)
R-HSA-9020558	Interleukin-2 signaling.	Interleukin-2 (IL-2) is a cytokine that is produced by T cells in response to antigen stimulation. Originally, IL-2 was discovered because of its potent growth factor activity on activated T cells in vitro and was therefore named 'T cell growth factor' (TCGF). However, the generation of IL-2- and IL-2 receptor-deficient mice revealed that IL-2 also plays a regulatory role in the immune system by suppressing autoimmune responses. Two main mechanisms have been identified that explain this suppressive function: (1) IL-2 sensitizes activated T cells for activation-induced cell death (AICD) and (2) IL-2 is critical for the survival and function of regulatory T cells (Tregs), which possess potent immunosuppressive properties.IL-2 signaling occurs when IL-2 binds to the heterotrimeric high-affinity IL-2 receptor (IL-2R), which consists of alpha, beta and gamma chains. The IL-2R was identified in 1981 via radiolabeled ligand binding (Robb et al. 1981). The IL-2R alpha chain was identified in 1982 (Leonard et al.), the beta chain in 1986/7 (Sharon et al. 1986, Teshigawara et al. 1987) and the IL-2R gamma chain in 1992 (Takeshita et al.). The high affinity of IL-2 binding to the IL-2R is created by a very rapid association rate to the IL-2R alpha chain, combined with a much slower dissociation rate contributed by the combination of the IL-2R beta and gamma chains (Wang & Smith 1987). After antigen stimulation, T cells upregulate the high-affinity IL-2R alpha chain; IL-2R alpha captures IL-2 and this complex then associates with the constitutively expressed IL-2R beta and gamma chains. The IL-2R gamma chain is shared by several other members of the cytokine receptor superfamily including IL-4, IL-7, IL-9, IL-15 and IL-21 receptors, and consequently is often referred to as the Common gamma chain (Gamma-c).\nThe tyrosine kinases Jak1 and Jak3, which are constitutively associated with IL-2R beta and Gamma-c respectively, are activated resulting in phosphorylation of three critical tyrosine residues in the IL-2R beta cytoplasmic tail. These phosphorylated residues enable recruitment of the adaptor molecule Shc, activating the MAPK and PI3K pathways, and the transcription factor STAT5. After phosphorylation, STAT5 forms dimers that translocate to the nucleus and initiate gene expression. While STAT5 activation is critical for IL-2 function in most cell types, the contribution of the PI3K/Akt pathway differs between distinct T cell subsets. In Tregs for example, PI3K/Akt is not involved in IL-2 signaling and this may explain some of the different functional outcomes of IL-2 signaling in Tregs vs. effector T cells
R-HSA-9026519	Activated NTRK2 signals through RAS.	Activation of the neurotrophin receptor NTRK2 (TRKB) by BDNF or NTF4 triggers downstream RAS signaling. The best studied mechanism for activation of RAS signaling downstream of NTRK2 is through SHC1-mediated recruitment of the GRB2:SOS1 complex, triggering SOS1-mediated guanine nucleotide exchange on RAS and formation of active RAS:GTP complexes (Minichiello et al. 1998, McCarthy and Feinstein 1999, Yuen and Mobley 1999)
R-HSA-9034864	Activated NTRK3 signals through RAS.	Upon activation by NTF3 (NT-3), the receptor tyrosine kinase NTRK3 (TRKC) triggers RAS signaling through adaptor proteins SHC1 and GRB2 (Marsh and Palfrey 1996, Gunn-Moore et al. 1997, Yuen and Mobley 1999). ERK activation downstream of NTRK3 may increase cell motility through WAVE. The mechanism is not known (Gromnitza et al. 2018)
R-HSA-912526	Interleukin receptor SHC signaling.	Phosphorylation of Shc at three tyrosine residues, 239, 240 (Gotoh et al. 1996) and 317 (Salcini et al. 1994) involves unidentified tyrosine kinases presumed to be part of the activated receptor complex. These phosphorylated tyrosines subsequently bind SH2 signaling proteins such as Grb2, Gab2 and SHIP that are involved in the regulation of different signaling pathways. Grb2 can associate with the guanosine diphosphate-guanosine triphosphate exchange factor Sos1, leading to Ras activation and regulation of cell proliferation. Downstream signals are mediated via the Raf-MEK-Erk pathway.Grb2 can also associate through Gab2 with PI3K and with SHIP.Figure reproduced from Gu, H. et al. 2000. Mol. Cell. Biol. 20(19):7109-7120Copyright American Society for Microbiology. All Rights Reserved
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
ACACA	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ACLY	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ACTA1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ACTB	Affinity Capture-MS	physical	19380743, 24189400, (Europe PMC)	NA	BioGRID
ACTG1	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
ACTN4	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
AIFM1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ALK	Affinity Capture-Western	physical	11888936, (Europe PMC)	NA	BioGRID
AMD1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
ANXA2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
AP1B1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
AP2A1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, 28514442, (Europe PMC)	0.53	BioGRID, IntAct
AP2A2	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, tandem affinity purification	association, physical	19380743, 24189400, 8617812, (Europe PMC)	0.53	BioGRID, IntAct
AP2B1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
AP2M1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.53	BioGRID, IntAct
APP	Affinity Capture-Western, Reconstituted Complex, coimmunoprecipitation, pull down	physical, physical association	11877420, 12485888, (Europe PMC)	0.59	BioGRID, IntAct, MINT
ARAP1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ARHGAP32	Affinity Capture-Western	physical	12446789, (Europe PMC)	NA	BioGRID
ARHGEF5	Affinity Capture-MS, Affinity Capture-Western, anti bait coimmunoprecipitation, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.46	BioGRID, IntAct
ATAD3B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
BCR	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
C11orf58	Two-hybrid	physical	21900206, (Europe PMC)	NA	BioGRID
CAD	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CALCOCO2	Two-hybrid, two hybrid pooling approach	physical, physical association	16189514, (Europe PMC)	0.37	BioGRID, IntAct
CALD1	Affinity Capture-Western	physical	10559276, (Europe PMC)	NA	BioGRID
CBL	Affinity Capture-MS, Affinity Capture-Western, coimmunoprecipitation, pull down, tandem affinity purification	association, physical, physical association	10025673, 10570290, 15677445, 19380743, 8621719, 8662998, 8950973, 9434624, 9461587, 9541596, (Europe PMC)	0.77	BioGRID, IntAct, MINT
CBLB	Affinity Capture-Western	physical	9614102, (Europe PMC)	NA	BioGRID
CBLC	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
CCT2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CCT6A	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CD22	Affinity Capture-Western	physical	10748054, (Europe PMC)	NA	BioGRID
CDC25C	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CDC5L	Affinity Capture-MS, anti bait coimmunoprecipitation	association, physical	20467437, (Europe PMC)	0.35	BioGRID, IntAct, MINT
CDH5	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	11950700, (Europe PMC)	0.54	BioGRID, IntAct, MINT
CEACAM1	Affinity Capture-Western	physical	11694516, (Europe PMC)	NA	BioGRID
CEP170	Proximity Label-MS, proximity-dependent biotin identification	association, physical	26638075, (Europe PMC)	0.35	BioGRID, IntAct
CLIC4	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
CLTC	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CORO1C	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CORO2B	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CRK	Affinity Capture-MS, Affinity Capture-Western, proximity ligation assay, tandem affinity purification	association, physical, physical association	10464310, 19380743, 23397142, 9617486, (Europe PMC)	0.56	BioGRID, IntAct
CRKL	Affinity Capture-Western	physical	9344843, (Europe PMC)	NA	BioGRID
CSF1R	Affinity Capture-Western	physical	10025673, (Europe PMC)	NA	BioGRID
CSF2RB	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	10704825, 16437163, (Europe PMC)	0.53	BioGRID, IntAct, MINT
CSF3R	Affinity Capture-Western, Far Western, PCA, Protein-peptide, Reconstituted Complex	physical	14557262, 17001306, 9824671, (Europe PMC)	NA	BioGRID
CSK	Affinity Capture-MS, Reconstituted Complex, tandem affinity purification	association, physical	12048194, 19380743, (Europe PMC)	0.35	BioGRID, IntAct
DAG1	Affinity Capture-Western, Reconstituted Complex	physical	11724572, (Europe PMC)	NA	BioGRID
DDB1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
DDR1	Reconstituted Complex	physical	9659899, (Europe PMC)	NA	BioGRID
DDR2	Affinity Capture-Western, Two-hybrid, coimmunoprecipitation, two hybrid	physical, physical association	11884411, (Europe PMC)	0.51	BioGRID, IntAct, MINT
DDX5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
DNAJA1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
DNAJA2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
DNM2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
DOK1	Affinity Capture-Western, Protein-peptide	physical	10822173, 22974441, (Europe PMC)	NA	BioGRID
DOK2	Affinity Capture-Western	physical	10822173, (Europe PMC)	NA	BioGRID
DUSP23	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
EEF1A1P5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
EGFR	Affinity Capture-Luminescence, Affinity Capture-MS, Affinity Capture-Western, PCA, Protein-peptide, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, coimmunoprecipitation, competition binding, experimental interaction detection, luminescence based mammalian interactome mapping, protein array, protein kinase assay, pull down, tandem affinity purification, ubiquitin reconstruction, x-ray crystallography	association, direct interaction, phosphorylation reaction, physical, physical association	10049786, 10595738, 10635327, 10766863, 11370743, 11408594, 15657067, 16273093, 16729043, 18271526, 19531499, 20473329, 20935677, 21278788, 23178716, 23799367, 23956138, 24189400, 24430869, 24658140, 24797263, 25402006, 26551075, 28065597, 7506413, 7518560, 7542744, 8034616, 8662998, 8810340, 9130710, 9544989, 9756944, (Europe PMC)	0.58, 0.97	BioGRID, IntAct, MINT
ELP1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
EPHA2	Affinity Capture-Western, Reconstituted Complex	physical	12400011, (Europe PMC)	NA	BioGRID
EPOR	Affinity Capture-Western	physical	8400282, (Europe PMC)	NA	BioGRID
EPS8	Affinity Capture-Western, Reconstituted Complex	physical	7791787, (Europe PMC)	NA	BioGRID
ERBB2	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, Two-hybrid, protein array, pull down, ubiquitin reconstruction	association, direct interaction, physical, physical association	10085134, 16273093, 16729043, 16843263, 24658140, 28065597, 9710588, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB3	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, protein array, pull down, tandem affinity purification, ubiquitin reconstruction	association, direct interaction, physical, physical association	11546794, 16273093, 16729043, 24189400, 24658140, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB4	Affinity Capture-MS, Protein-peptide, protein array, pull down, ubiquitin reconstruction	direct interaction, physical, physical association	16273093, 16729043, 24658140, (Europe PMC)	0.37, 0.61	BioGRID, IntAct, MINT
ERRFI1	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
ESR1	Affinity Capture-Western, Reconstituted Complex, anti tag coimmunoprecipitation	physical, physical association	11773443, 20935677, (Europe PMC)	0.40	BioGRID, IntAct
FAM118B	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
FASN	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
FCGR2B	Affinity Capture-Western, pull down	association, physical	10382761, 8940017, (Europe PMC)	0.35	BioGRID, IntAct, MINT
FGFR1	Reconstituted Complex	physical	7559490, (Europe PMC)	NA	BioGRID
FLT1	Two-hybrid	physical	10749680, (Europe PMC)	NA	BioGRID
FLT4	Affinity Capture-Western, Reconstituted Complex	physical	7970715, 8662748, 9927207, (Europe PMC)	NA	BioGRID
GAB1	Affinity Capture-Western, Far Western, fluorescence polarization spectroscopy	direct interaction, physical	14982882, 24728074, 9804835, (Europe PMC)	0.44	BioGRID, IntAct
GAB2	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	10704825, 11782427, 12135708, 14982882, (Europe PMC)	0.54	BioGRID, IntAct, MINT
GAREM1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
GEMIN7	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
GFAP	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
GH1	Biochemical Activity	physical	7535773, (Europe PMC)	NA	BioGRID
GHR	Reconstituted Complex	physical	7535773, (Europe PMC)	NA	BioGRID
GRB2	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, Protein-peptide, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, bimolecular fluorescence complementation, coimmunoprecipitation, isothermal titration calorimetry, pull down, surface plasmon resonance, tandem affinity purification, x-ray crystallography	association, direct interaction, physical, physical association	10049786, 10080542, 10477741, 10570290, 11302736, 11370743, 11505033, 11792427, 11827484, 11964172, 12149229, 12213123, 12441060, 12485888, 12577067, 12898421, 15688026, 15812354, 16371368, 16520382, 19380743, 21706016, 21725358, 22974441, 23178716, 24189400, 24430869, 25416956, 26551075, 7514169, 7524086, 7535773, 7537740, 7559490, 7650032, 8112292, 8195171, 8294403, 8491186, 8621719, 8647288, 8662733, 8662998, 8663178, 8810340, 8939605, 8940013, 8950973, 8995379, 9032244, 9045692, 9083103, 9126968, 9129019, 9175774, 9254595, 9434624, 9541596, 9544989, 9886492, 9927207, (Europe PMC)	0.40, 0.52, 0.97	BioGRID, IntAct, MINT
HAX1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HIF1A	Affinity Capture-Western	physical	12114320, (Europe PMC)	NA	BioGRID
HMOX2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
HNRNPA2B1	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
HNRNPH1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HNRNPU	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
HSP90AA1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSP90AB1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA1A	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
HSPA1B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA1L	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA6	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA8	Affinity Capture-MS	physical	19380743, 24189400, (Europe PMC)	NA	BioGRID
HSPA9	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
IARS	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
IGF1R	Affinity Capture-Western, Two-hybrid, far western blotting, two hybrid	physical, physical association	14764897, 15629149, 16113100, 24051437, 7541045, 7559507, 8776723, (Europe PMC)	0.37, 0.51	BioGRID, IntAct
IGHG1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
IL2RB	Affinity Capture-Western, Reconstituted Complex	physical	10602027, 8294403, (Europe PMC)	NA	BioGRID
IL2RG	Affinity Capture-Western	physical	8643566, (Europe PMC)	NA	BioGRID
IL4R	Affinity Capture-Western, Reconstituted Complex	physical	10652211, 11714803, (Europe PMC)	NA	BioGRID
IL6ST	Affinity Capture-Western, Reconstituted Complex	physical	9126968, (Europe PMC)	NA	BioGRID
ILK	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
INPP5D	Affinity Capture-Western, pull down	direct interaction, physical	10194451, 10704825, 10822173, 10900203, 12024011, 12149229, 15470047, 8643691, (Europe PMC)	0.44	BioGRID, IntAct, MINT
INPPL1	Affinity Capture-MS, Affinity Capture-Western, tandem affinity purification	association, physical	10194451, 11349134, 19380743, 9660833, (Europe PMC)	0.35	BioGRID, IntAct
INSR	Reconstituted Complex, Two-hybrid, pull down, two hybrid	physical, physical association	10803466, 15629149, 7499194, 9593725, (Europe PMC)	0.57	BioGRID, IntAct, MINT
IQGAP1	Affinity Capture-MS, fluorescence microscopy	colocalization, physical	19380743, 20075861, (Europe PMC)	0.27	BioGRID, IntAct, MINT
ITGAV	Affinity Capture-Western	physical	19889638, (Europe PMC)	NA	BioGRID
ITGB1	Affinity Capture-Western	physical	19889638, (Europe PMC)	NA	BioGRID
ITGB3	Affinity Capture-Western, Protein-peptide	physical	10896934, 19889638, (Europe PMC)	NA	BioGRID
ITGB4	Far Western	physical	11044453, (Europe PMC)	NA	BioGRID
JAK2	Reconstituted Complex	physical	7535773, 9126968, (Europe PMC)	NA	BioGRID
KDR	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical, physical association	10319320, 11950700, 12214271, (Europe PMC)	0.56	BioGRID, IntAct, MINT
KRAS	Synthetic Lethality	genetic	26627737, (Europe PMC)	NA	BioGRID
KRT1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT10	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT13	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT14	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT16	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT17	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT3	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT4	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT6A	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT77	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT9	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
LCP2	Affinity Capture-Western, coimmunoprecipitation	physical, physical association	9716598, (Europe PMC)	0.40	BioGRID, IntAct, MINT
LGALS3BP	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
LRP1	Affinity Capture-Western, Reconstituted Complex	physical	11854294, 12789267, (Europe PMC)	NA	BioGRID
LRRK1	Affinity Capture-MS	physical	20697350, (Europe PMC)	NA	BioGRID
LTK	Affinity Capture-Western	physical	7650032, (Europe PMC)	NA	BioGRID
LYN	Affinity Capture-Western, pull down	direct interaction, physical	7516469, 7650013, (Europe PMC)	0.44	BioGRID, IntAct, MINT
MAPK1	Affinity Capture-Western, fluorescent resonance energy transfer, isothermal titration calorimetry, pull down, x ray scattering	direct interaction, physical, physical association	10996427, 23584453, (Europe PMC)	0.40, 0.62	BioGRID, IntAct
MAPK6	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
MAPKAPK2	Affinity Capture-Western, Biochemical Activity, Two-hybrid	physical	15094067, (Europe PMC)	NA	BioGRID
MAT1A	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
MET	Affinity Capture-Western, fluorescence polarization spectroscopy	direct interaction, physical	24728074, 9660480, (Europe PMC)	0.44	BioGRID, IntAct
MOV10	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
MRPL44	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
MST1R	Affinity Capture-Western	physical	8918464, (Europe PMC)	NA	BioGRID
MYH10	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
MYH11	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
MYH14	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
MYH9	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
MYO1C	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
MYO1D	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
NGFR	Affinity Capture-Western	physical	7541035, (Europe PMC)	NA	BioGRID
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 12446789, 25921289, 8183561, 8226808, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
NTRK2	Reconstituted Complex	physical	10092678, (Europe PMC)	NA	BioGRID
NTRK3	Reconstituted Complex	physical	10092678, (Europe PMC)	NA	BioGRID
NUDT21	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
NXF1	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
OSGEP	Two-hybrid	physical	21900206, (Europe PMC)	NA	BioGRID
OXT	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PAG1	Reconstituted Complex	physical	10790433, (Europe PMC)	NA	BioGRID
PDGFRB	Affinity Capture-Western	physical	8195171, (Europe PMC)	NA	BioGRID
PEAK1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PIK3C2B	Reconstituted Complex	physical	11533253, (Europe PMC)	NA	BioGRID
PIK3R1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, coimmunoprecipitation, proximity ligation assay, pull down, tandem affinity purification	association, physical, physical association	16135792, 16219545, 19380743, 19889638, 23397142, 7537361, 8621719, 8662998, 9541596, (Europe PMC)	0.83	BioGRID, IntAct, MINT
PIK3R2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PLCG1	Affinity Capture-Western	physical	8662733, (Europe PMC)	NA	BioGRID
PLCG2	Affinity Capture-Western	physical	10623845, 12135708, (Europe PMC)	NA	BioGRID
PLS3	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PLSCR1	Affinity Capture-Western, Reconstituted Complex	physical	12009895, 12871937, (Europe PMC)	NA	BioGRID
PPP1R8	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PPP1R9B	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PRDX1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
PRKCD	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, tandem affinity purification	association, physical	12024011, 19380743, (Europe PMC)	0.35	BioGRID, IntAct
PRKDC	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
PRKRA	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
PRMT5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
PRSS3	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
PSPH	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PSTPIP2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PTK2	Affinity Capture-Western	physical	11980671, (Europe PMC)	NA	BioGRID
PTPN12	Affinity Capture-MS, Affinity Capture-Western, Proximity Label-MS, Reconstituted Complex, Two-hybrid, tandem affinity purification, two hybrid array	association, physical, physical association	19380743, 24189400, 24412244, 27880917, 28514442, 7929214, 8626541, (Europe PMC)	0.66	BioGRID, IntAct, MINT
RAB3GAP2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
RAPGEF1	Affinity Capture-Western	physical	9344843, (Europe PMC)	NA	BioGRID
RASAL2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
RET	Affinity Capture-Western, Reconstituted Complex, pull down	physical, physical association	15677445, 8183561, 9047384, (Europe PMC)	0.40	BioGRID, IntAct, MINT
RFFL	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
RMDN1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
RPS19	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
RUVBL1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
RUVBL2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
S100A7	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
S100A8	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
S100A9	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
SCLT1	Proximity Label-MS, proximity-dependent biotin identification	association, physical	26638075, (Europe PMC)	0.35	BioGRID, IntAct
SEC16A	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
SH2B2	Reconstituted Complex	physical	9233773, (Europe PMC)	NA	BioGRID
SHC1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
SHC2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
SHCBP1	Affinity Capture-Western, Reconstituted Complex, Two-hybrid	physical	10086341, (Europe PMC)	NA	BioGRID
SOS1	Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation, tandem affinity purification	association, physical, physical association	10025673, 10570290, 10675333, 10783152, 16371368, 19380743, 7559490, 8950973, 9344843, 9544989, (Europe PMC)	0.56	BioGRID, IntAct, MINT
SOS2	Affinity Capture-MS, Affinity Capture-Western	physical	10675333, 19380743, (Europe PMC)	NA	BioGRID
SPTA1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
SPTAN1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
SPTBN1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
STAT5A	Affinity Capture-Western, proximity ligation assay	physical, physical association	10996427, 23397142, (Europe PMC)	0.40	BioGRID, IntAct
STAT5B	Affinity Capture-Western	physical	10996427, (Europe PMC)	NA	BioGRID
STXBP1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
SUV39H2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
TEC	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TIMM50	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TRIM15	PCA	physical	25450970, (Europe PMC)	NA	BioGRID
TUBA1A	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA1B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA1C	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA4B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA8	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBAL3	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB2B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB3	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB4B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB6	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
UBASH3B	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.53	BioGRID, IntAct
USP15	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
USP9X	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
USP9Y	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
VARS	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
VAV3	Affinity Capture-Western	physical	11094073, (Europe PMC)	NA	BioGRID
XPO1	Affinity Capture-MS	physical	26673895, (Europe PMC)	NA	BioGRID
ZAP70	Affinity Capture-Western, Biochemical Activity, anti tag coimmunoprecipitation	physical, physical association	15688026, 23267066, 9685404, (Europe PMC)	0.40	BioGRID, IntAct, MINT

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Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
AP2A2	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, tandem affinity purification	association, physical	19380743, 24189400, 8617812, (Europe PMC)	0.53	BioGRID, IntAct
AP2B1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
AP2M1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.53	BioGRID, IntAct
APP	Affinity Capture-Western, Reconstituted Complex, coimmunoprecipitation, pull down	physical, physical association	11877420, 12485888, (Europe PMC)	0.59	BioGRID, IntAct, MINT
AR	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
ARHGEF5	Affinity Capture-MS, Affinity Capture-Western, anti bait coimmunoprecipitation, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.46	BioGRID, IntAct
BUB1	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
CAD	tandem affinity purification	association	19380743, (Europe PMC)	0.35	IntAct
CALCOCO2	Two-hybrid, two hybrid pooling approach	physical, physical association	16189514, (Europe PMC)	0.37	BioGRID, IntAct
CBL	Affinity Capture-MS, Affinity Capture-Western, coimmunoprecipitation, pull down, tandem affinity purification	association, physical, physical association	10025673, 10570290, 15677445, 19380743, 8621719, 8662998, 8950973, 9434624, 9461587, 9541596, (Europe PMC)	0.77	BioGRID, IntAct, MINT
CBLC	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
CD247	nuclear magnetic resonance	association	7544002, (Europe PMC)	0.35	IntAct, MINT
CD3E	pull down	association	11855827, (Europe PMC)	0.35	IntAct, MINT
CDC5L	Affinity Capture-MS, anti bait coimmunoprecipitation	association, physical	20467437, (Europe PMC)	0.35	BioGRID, IntAct, MINT
CDH5	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	11950700, (Europe PMC)	0.54	BioGRID, IntAct, MINT
CEACAM1	pull down	association	11694516, (Europe PMC)	0.35	IntAct, MINT
CEP170	Proximity Label-MS, proximity-dependent biotin identification	association, physical	26638075, (Europe PMC)	0.35	BioGRID, IntAct
CRK	Affinity Capture-MS, Affinity Capture-Western, proximity ligation assay, tandem affinity purification	association, physical, physical association	10464310, 19380743, 23397142, 9617486, (Europe PMC)	0.56	BioGRID, IntAct
CSF2RB	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	10704825, 16437163, (Europe PMC)	0.53	BioGRID, IntAct, MINT
CSK	Affinity Capture-MS, Reconstituted Complex, tandem affinity purification	association, physical	12048194, 19380743, (Europe PMC)	0.35	BioGRID, IntAct
DDR2	Affinity Capture-Western, Two-hybrid, coimmunoprecipitation, two hybrid	physical, physical association	11884411, (Europe PMC)	0.51	BioGRID, IntAct, MINT
DNAJA2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
DNM2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
DUSP23	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
EGFR	Affinity Capture-Luminescence, Affinity Capture-MS, Affinity Capture-Western, PCA, Protein-peptide, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, coimmunoprecipitation, competition binding, experimental interaction detection, luminescence based mammalian interactome mapping, protein array, protein kinase assay, pull down, tandem affinity purification, ubiquitin reconstruction, x-ray crystallography	association, direct interaction, phosphorylation reaction, physical, physical association	10049786, 10595738, 10635327, 10766863, 11370743, 11408594, 15657067, 16273093, 16729043, 18271526, 19531499, 20473329, 20935677, 21278788, 23178716, 23799367, 23956138, 24189400, 24430869, 24658140, 24797263, 25402006, 26551075, 28065597, 7506413, 7518560, 7542744, 8034616, 8662998, 8810340, 9130710, 9544989, 9756944, (Europe PMC)	0.58, 0.97	BioGRID, IntAct, MINT
ELP1	tandem affinity purification	association	19380743, (Europe PMC)	0.35	IntAct
ERBB2	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, Two-hybrid, protein array, pull down, ubiquitin reconstruction	association, direct interaction, physical, physical association	10085134, 16273093, 16729043, 16843263, 24658140, 28065597, 9710588, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB3	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, protein array, pull down, tandem affinity purification, ubiquitin reconstruction	association, direct interaction, physical, physical association	11546794, 16273093, 16729043, 24189400, 24658140, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB4	Affinity Capture-MS, Protein-peptide, protein array, pull down, ubiquitin reconstruction	direct interaction, physical, physical association	16273093, 16729043, 24658140, (Europe PMC)	0.37, 0.61	BioGRID, IntAct, MINT
ERRFI1	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
ESR1	Affinity Capture-Western, Reconstituted Complex, anti tag coimmunoprecipitation	physical, physical association	11773443, 20935677, (Europe PMC)	0.40	BioGRID, IntAct
EZR	proximity-dependent biotin identification	association	29568061, (Europe PMC)	0.35	IntAct
FAM118B	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
FASTKD3	tandem affinity purification	association	20869947, (Europe PMC)	0.35	IntAct
FBXW7	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
FCGR1A	experimental interaction detection	phosphorylation reaction	9716598, (Europe PMC)	0.31	IntAct, MINT
FCGR2B	Affinity Capture-Western, pull down	association, physical	10382761, 8940017, (Europe PMC)	0.35	BioGRID, IntAct, MINT
FYN	pull down	direct interaction	7516469, (Europe PMC)	0.44	IntAct, MINT
GAB1	Affinity Capture-Western, Far Western, fluorescence polarization spectroscopy	direct interaction, physical	14982882, 24728074, 9804835, (Europe PMC)	0.44	BioGRID, IntAct
GAB2	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	10704825, 11782427, 12135708, 14982882, (Europe PMC)	0.54	BioGRID, IntAct, MINT
GEMIN7	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
GRAP	pull down	association	8995379, (Europe PMC)	0.35	IntAct, MINT
GRB2	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, Protein-peptide, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, bimolecular fluorescence complementation, coimmunoprecipitation, isothermal titration calorimetry, pull down, surface plasmon resonance, tandem affinity purification, x-ray crystallography	association, direct interaction, physical, physical association	10049786, 10080542, 10477741, 10570290, 11302736, 11370743, 11505033, 11792427, 11827484, 11964172, 12149229, 12213123, 12441060, 12485888, 12577067, 12898421, 15688026, 15812354, 16371368, 16520382, 19380743, 21706016, 21725358, 22974441, 23178716, 24189400, 24430869, 25416956, 26551075, 7514169, 7524086, 7535773, 7537740, 7559490, 7650032, 8112292, 8195171, 8294403, 8491186, 8621719, 8647288, 8662733, 8662998, 8663178, 8810340, 8939605, 8940013, 8950973, 8995379, 9032244, 9045692, 9083103, 9126968, 9129019, 9175774, 9254595, 9434624, 9541596, 9544989, 9886492, 9927207, (Europe PMC)	0.40, 0.52, 0.97	BioGRID, IntAct, MINT
HMOX2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
HNRNPA2B1	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
IGF1R	Affinity Capture-Western, Two-hybrid, far western blotting, two hybrid	physical, physical association	14764897, 15629149, 16113100, 24051437, 7541045, 7559507, 8776723, (Europe PMC)	0.37, 0.51	BioGRID, IntAct
ILK	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
INPP5D	Affinity Capture-Western, pull down	direct interaction, physical	10194451, 10704825, 10822173, 10900203, 12024011, 12149229, 15470047, 8643691, (Europe PMC)	0.44	BioGRID, IntAct, MINT
INPPL1	Affinity Capture-MS, Affinity Capture-Western, tandem affinity purification	association, physical	10194451, 11349134, 19380743, 9660833, (Europe PMC)	0.35	BioGRID, IntAct
INSR	Reconstituted Complex, Two-hybrid, pull down, two hybrid	physical, physical association	10803466, 15629149, 7499194, 9593725, (Europe PMC)	0.57	BioGRID, IntAct, MINT
IQGAP1	Affinity Capture-MS, fluorescence microscopy	colocalization, physical	19380743, 20075861, (Europe PMC)	0.27	BioGRID, IntAct, MINT
KDR	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical, physical association	10319320, 11950700, 12214271, (Europe PMC)	0.56	BioGRID, IntAct, MINT
KIT	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
KRT18	fluorescence microscopy	colocalization	12577067, (Europe PMC)	0.27	IntAct
LCP2	Affinity Capture-Western, coimmunoprecipitation	physical, physical association	9716598, (Europe PMC)	0.40	BioGRID, IntAct, MINT
LRRK1	anti tag coimmunoprecipitation	association	24947832, (Europe PMC)	0.35	IntAct
LYN	Affinity Capture-Western, pull down	direct interaction, physical	7516469, 7650013, (Europe PMC)	0.44	BioGRID, IntAct, MINT
MAPK1	Affinity Capture-Western, fluorescent resonance energy transfer, isothermal titration calorimetry, pull down, x ray scattering	direct interaction, physical, physical association	10996427, 23584453, (Europe PMC)	0.40, 0.62	BioGRID, IntAct
MAPK6	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
MET	Affinity Capture-Western, fluorescence polarization spectroscopy	direct interaction, physical	24728074, 9660480, (Europe PMC)	0.44	BioGRID, IntAct
MRPL44	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
MYH9	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
MYO1C	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
MYO1D	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 12446789, 25921289, 8183561, 8226808, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
NUDT21	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
OSGEP	two hybrid	physical association	21900206, (Europe PMC)	0.37	IntAct, MINT
PIK3R1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, coimmunoprecipitation, proximity ligation assay, pull down, tandem affinity purification	association, physical, physical association	16135792, 16219545, 19380743, 19889638, 23397142, 7537361, 8621719, 8662998, 9541596, (Europe PMC)	0.83	BioGRID, IntAct, MINT
PIK3R2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PPP1R9B	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PRKCD	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, tandem affinity purification	association, physical	12024011, 19380743, (Europe PMC)	0.35	BioGRID, IntAct
PRKRA	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
PRSS3	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
PSTPIP2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PTPN12	Affinity Capture-MS, Affinity Capture-Western, Proximity Label-MS, Reconstituted Complex, Two-hybrid, tandem affinity purification, two hybrid array	association, physical, physical association	19380743, 24189400, 24412244, 27880917, 28514442, 7929214, 8626541, (Europe PMC)	0.66	BioGRID, IntAct, MINT
RB1	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
RET	Affinity Capture-Western, Reconstituted Complex, pull down	physical, physical association	15677445, 8183561, 9047384, (Europe PMC)	0.40	BioGRID, IntAct, MINT
S100A8	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
S100A9	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
SCLT1	Proximity Label-MS, proximity-dependent biotin identification	association, physical	26638075, (Europe PMC)	0.35	BioGRID, IntAct
SEC16A	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
SHC1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
SIRT4 {ECO:0000255\|HAMAP-Rule:MF_03161,	anti tag coimmunoprecipitation	association	25525879, (Europe PMC)	0.35	IntAct
SMAD4	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
SMAP	two hybrid	physical association	21900206, (Europe PMC)	0.37	IntAct, MINT
SOS1	Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation, tandem affinity purification	association, physical, physical association	10025673, 10570290, 10675333, 10783152, 16371368, 19380743, 7559490, 8950973, 9344843, 9544989, (Europe PMC)	0.56	BioGRID, IntAct, MINT
SPTA1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
SRC	protein kinase assay	phosphorylation reaction	26551075, (Europe PMC)	0.44	IntAct
STAT5A	Affinity Capture-Western, proximity ligation assay	physical, physical association	10996427, 23397142, (Europe PMC)	0.40	BioGRID, IntAct
SUV39H2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
TEK	coimmunoprecipitation, pull down	association	14665640, (Europe PMC)	0.46	IntAct, MINT
TGFBR2	coimmunoprecipitation	association	17440088, (Europe PMC)	0.35	IntAct, MINT
UBASH3B	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.53	BioGRID, IntAct
USP9X	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
USP9Y	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
YWHAZ	coimmunoprecipitation	association	11342545, 19218246, (Europe PMC)	0.53	IntAct, MINT
ZAP70	Affinity Capture-Western, Biochemical Activity, anti tag coimmunoprecipitation	physical, physical association	15688026, 23267066, 9685404, (Europe PMC)	0.40	BioGRID, IntAct, MINT

Visualize Download

Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
BUB1	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
CBL	Affinity Capture-MS, Affinity Capture-Western, coimmunoprecipitation, pull down, tandem affinity purification	association, physical, physical association	10025673, 10570290, 15677445, 19380743, 8621719, 8662998, 8950973, 9434624, 9461587, 9541596, (Europe PMC)	0.77	BioGRID, IntAct, MINT
CBLC	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
CD247	nuclear magnetic resonance	association	7544002, (Europe PMC)	0.35	IntAct, MINT
CD3E	pull down	association	11855827, (Europe PMC)	0.35	IntAct, MINT
CDC5L	Affinity Capture-MS, anti bait coimmunoprecipitation	association, physical	20467437, (Europe PMC)	0.35	BioGRID, IntAct, MINT
CDH5	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	11950700, (Europe PMC)	0.54	BioGRID, IntAct, MINT
CEACAM1	pull down	association	11694516, (Europe PMC)	0.35	IntAct, MINT
CSF2RB	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	10704825, 16437163, (Europe PMC)	0.53	BioGRID, IntAct, MINT
DDR2	Affinity Capture-Western, Two-hybrid, coimmunoprecipitation, two hybrid	physical, physical association	11884411, (Europe PMC)	0.51	BioGRID, IntAct, MINT
DUSP23	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
EGFR	Affinity Capture-Luminescence, Affinity Capture-MS, Affinity Capture-Western, PCA, Protein-peptide, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, coimmunoprecipitation, competition binding, experimental interaction detection, luminescence based mammalian interactome mapping, protein array, protein kinase assay, pull down, tandem affinity purification, ubiquitin reconstruction, x-ray crystallography	association, direct interaction, phosphorylation reaction, physical, physical association	10049786, 10595738, 10635327, 10766863, 11370743, 11408594, 15657067, 16273093, 16729043, 18271526, 19531499, 20473329, 20935677, 21278788, 23178716, 23799367, 23956138, 24189400, 24430869, 24658140, 24797263, 25402006, 26551075, 28065597, 7506413, 7518560, 7542744, 8034616, 8662998, 8810340, 9130710, 9544989, 9756944, (Europe PMC)	0.58, 0.97	BioGRID, IntAct, MINT
ERBB2	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, Two-hybrid, protein array, pull down, ubiquitin reconstruction	association, direct interaction, physical, physical association	10085134, 16273093, 16729043, 16843263, 24658140, 28065597, 9710588, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB3	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, protein array, pull down, tandem affinity purification, ubiquitin reconstruction	association, direct interaction, physical, physical association	11546794, 16273093, 16729043, 24189400, 24658140, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB4	Affinity Capture-MS, Protein-peptide, protein array, pull down, ubiquitin reconstruction	direct interaction, physical, physical association	16273093, 16729043, 24658140, (Europe PMC)	0.37, 0.61	BioGRID, IntAct, MINT
FAM118B	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
FBXW7	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
FCGR1A	experimental interaction detection	phosphorylation reaction	9716598, (Europe PMC)	0.31	IntAct, MINT
FCGR2B	Affinity Capture-Western, pull down	association, physical	10382761, 8940017, (Europe PMC)	0.35	BioGRID, IntAct, MINT
FYN	pull down	direct interaction	7516469, (Europe PMC)	0.44	IntAct, MINT
GAB2	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	10704825, 11782427, 12135708, 14982882, (Europe PMC)	0.54	BioGRID, IntAct, MINT
GEMIN7	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
GRAP	pull down	association	8995379, (Europe PMC)	0.35	IntAct, MINT
GRB2	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, Protein-peptide, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, bimolecular fluorescence complementation, coimmunoprecipitation, isothermal titration calorimetry, pull down, surface plasmon resonance, tandem affinity purification, x-ray crystallography	association, direct interaction, physical, physical association	10049786, 10080542, 10477741, 10570290, 11302736, 11370743, 11505033, 11792427, 11827484, 11964172, 12149229, 12213123, 12441060, 12485888, 12577067, 12898421, 15688026, 15812354, 16371368, 16520382, 19380743, 21706016, 21725358, 22974441, 23178716, 24189400, 24430869, 25416956, 26551075, 7514169, 7524086, 7535773, 7537740, 7559490, 7650032, 8112292, 8195171, 8294403, 8491186, 8621719, 8647288, 8662733, 8662998, 8663178, 8810340, 8939605, 8940013, 8950973, 8995379, 9032244, 9045692, 9083103, 9126968, 9129019, 9175774, 9254595, 9434624, 9541596, 9544989, 9886492, 9927207, (Europe PMC)	0.40, 0.52, 0.97	BioGRID, IntAct, MINT
HMOX2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
ILK	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
INPP5D	Affinity Capture-Western, pull down	direct interaction, physical	10194451, 10704825, 10822173, 10900203, 12024011, 12149229, 15470047, 8643691, (Europe PMC)	0.44	BioGRID, IntAct, MINT
INSR	Reconstituted Complex, Two-hybrid, pull down, two hybrid	physical, physical association	10803466, 15629149, 7499194, 9593725, (Europe PMC)	0.57	BioGRID, IntAct, MINT
IQGAP1	Affinity Capture-MS, fluorescence microscopy	colocalization, physical	19380743, 20075861, (Europe PMC)	0.27	BioGRID, IntAct, MINT
KDR	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical, physical association	10319320, 11950700, 12214271, (Europe PMC)	0.56	BioGRID, IntAct, MINT
LCP2	Affinity Capture-Western, coimmunoprecipitation	physical, physical association	9716598, (Europe PMC)	0.40	BioGRID, IntAct, MINT
LYN	Affinity Capture-Western, pull down	direct interaction, physical	7516469, 7650013, (Europe PMC)	0.44	BioGRID, IntAct, MINT
MAPK6	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
MRPL44	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 12446789, 25921289, 8183561, 8226808, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
NUDT21	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
OSGEP	two hybrid	physical association	21900206, (Europe PMC)	0.37	IntAct, MINT
PIK3R1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, coimmunoprecipitation, proximity ligation assay, pull down, tandem affinity purification	association, physical, physical association	16135792, 16219545, 19380743, 19889638, 23397142, 7537361, 8621719, 8662998, 9541596, (Europe PMC)	0.83	BioGRID, IntAct, MINT
PRKRA	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
PTPN12	Affinity Capture-MS, Affinity Capture-Western, Proximity Label-MS, Reconstituted Complex, Two-hybrid, tandem affinity purification, two hybrid array	association, physical, physical association	19380743, 24189400, 24412244, 27880917, 28514442, 7929214, 8626541, (Europe PMC)	0.66	BioGRID, IntAct, MINT
RB1	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
RET	Affinity Capture-Western, Reconstituted Complex, pull down	physical, physical association	15677445, 8183561, 9047384, (Europe PMC)	0.40	BioGRID, IntAct, MINT
SMAD4	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
SMAP	two hybrid	physical association	21900206, (Europe PMC)	0.37	IntAct, MINT
SOS1	Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation, tandem affinity purification	association, physical, physical association	10025673, 10570290, 10675333, 10783152, 16371368, 19380743, 7559490, 8950973, 9344843, 9544989, (Europe PMC)	0.56	BioGRID, IntAct, MINT
SUV39H2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
TEK	coimmunoprecipitation, pull down	association	14665640, (Europe PMC)	0.46	IntAct, MINT
TGFBR2	coimmunoprecipitation	association	17440088, (Europe PMC)	0.35	IntAct, MINT
YWHAZ	coimmunoprecipitation	association	11342545, 19218246, (Europe PMC)	0.53	IntAct, MINT
ZAP70	Affinity Capture-Western, Biochemical Activity, anti tag coimmunoprecipitation	physical, physical association	15688026, 23267066, 9685404, (Europe PMC)	0.40	BioGRID, IntAct, MINT

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Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
ACACA	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ACLY	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ACTA1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ACTB	Affinity Capture-MS	physical	19380743, 24189400, (Europe PMC)	NA	BioGRID
ACTG1	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
ACTN4	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
AIFM1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ALK	Affinity Capture-Western	physical	11888936, (Europe PMC)	NA	BioGRID
AMD1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
ANXA2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
AP1B1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
AP2A1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, 28514442, (Europe PMC)	0.53	BioGRID, IntAct
AP2A2	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, tandem affinity purification	association, physical	19380743, 24189400, 8617812, (Europe PMC)	0.53	BioGRID, IntAct
AP2B1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
AP2M1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.53	BioGRID, IntAct
APP	Affinity Capture-Western, Reconstituted Complex, coimmunoprecipitation, pull down	physical, physical association	11877420, 12485888, (Europe PMC)	0.59	BioGRID, IntAct, MINT
AR	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
ARAP1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ARHGAP32	Affinity Capture-Western	physical	12446789, (Europe PMC)	NA	BioGRID
ARHGEF5	Affinity Capture-MS, Affinity Capture-Western, anti bait coimmunoprecipitation, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.46	BioGRID, IntAct
ATAD3B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
BCR	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
BUB1	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
C11orf58	Two-hybrid	physical	21900206, (Europe PMC)	NA	BioGRID
CAD	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CAD	tandem affinity purification	association	19380743, (Europe PMC)	0.35	IntAct
CALCOCO2	Two-hybrid, two hybrid pooling approach	physical, physical association	16189514, (Europe PMC)	0.37	BioGRID, IntAct
CALD1	Affinity Capture-Western	physical	10559276, (Europe PMC)	NA	BioGRID
CBL	Affinity Capture-MS, Affinity Capture-Western, coimmunoprecipitation, pull down, tandem affinity purification	association, physical, physical association	10025673, 10570290, 15677445, 19380743, 8621719, 8662998, 8950973, 9434624, 9461587, 9541596, (Europe PMC)	0.77	BioGRID, IntAct, MINT
CBLB	Affinity Capture-Western	physical	9614102, (Europe PMC)	NA	BioGRID
CBLC	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
CCT2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CCT6A	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CD22	Affinity Capture-Western	physical	10748054, (Europe PMC)	NA	BioGRID
CD247	nuclear magnetic resonance	association	7544002, (Europe PMC)	0.35	IntAct, MINT
CD3E	pull down	association	11855827, (Europe PMC)	0.35	IntAct, MINT
CDC25C	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CDC5L	Affinity Capture-MS, anti bait coimmunoprecipitation	association, physical	20467437, (Europe PMC)	0.35	BioGRID, IntAct, MINT
CDH5	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	11950700, (Europe PMC)	0.54	BioGRID, IntAct, MINT
CEACAM1	Affinity Capture-Western	physical	11694516, (Europe PMC)	NA	BioGRID
CEACAM1	pull down	association	11694516, (Europe PMC)	0.35	IntAct, MINT
CEP170	Proximity Label-MS, proximity-dependent biotin identification	association, physical	26638075, (Europe PMC)	0.35	BioGRID, IntAct
CLIC4	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
CLTC	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CORO1C	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
CORO2B	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CRK	Affinity Capture-MS, Affinity Capture-Western, proximity ligation assay, tandem affinity purification	association, physical, physical association	10464310, 19380743, 23397142, 9617486, (Europe PMC)	0.56	BioGRID, IntAct
CRKL	Affinity Capture-Western	physical	9344843, (Europe PMC)	NA	BioGRID
CSF1R	Affinity Capture-Western	physical	10025673, (Europe PMC)	NA	BioGRID
CSF2RB	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical	10704825, 16437163, (Europe PMC)	0.53	BioGRID, IntAct, MINT
CSF3R	Affinity Capture-Western, Far Western, PCA, Protein-peptide, Reconstituted Complex	physical	14557262, 17001306, 9824671, (Europe PMC)	NA	BioGRID
CSK	Affinity Capture-MS, Reconstituted Complex, tandem affinity purification	association, physical	12048194, 19380743, (Europe PMC)	0.35	BioGRID, IntAct
DAG1	Affinity Capture-Western, Reconstituted Complex	physical	11724572, (Europe PMC)	NA	BioGRID
DDB1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
DDR1	Reconstituted Complex	physical	9659899, (Europe PMC)	NA	BioGRID
DDR2	Affinity Capture-Western, Two-hybrid, coimmunoprecipitation, two hybrid	physical, physical association	11884411, (Europe PMC)	0.51	BioGRID, IntAct, MINT
DDX5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
DNAJA1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
DNAJA2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
DNM2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
DOK1	Affinity Capture-Western, Protein-peptide	physical	10822173, 22974441, (Europe PMC)	NA	BioGRID
DOK2	Affinity Capture-Western	physical	10822173, (Europe PMC)	NA	BioGRID
DUSP23	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
EEF1A1P5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
EGFR	Affinity Capture-Luminescence, Affinity Capture-MS, Affinity Capture-Western, PCA, Protein-peptide, Reconstituted Complex, Two-hybrid, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, coimmunoprecipitation, competition binding, experimental interaction detection, luminescence based mammalian interactome mapping, protein array, protein kinase assay, pull down, tandem affinity purification, ubiquitin reconstruction, x-ray crystallography	association, direct interaction, phosphorylation reaction, physical, physical association	10049786, 10595738, 10635327, 10766863, 11370743, 11408594, 15657067, 16273093, 16729043, 18271526, 19531499, 20473329, 20935677, 21278788, 23178716, 23799367, 23956138, 24189400, 24430869, 24658140, 24797263, 25402006, 26551075, 28065597, 7506413, 7518560, 7542744, 8034616, 8662998, 8810340, 9130710, 9544989, 9756944, (Europe PMC)	0.58, 0.97	BioGRID, IntAct, MINT
ELP1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
ELP1	tandem affinity purification	association	19380743, (Europe PMC)	0.35	IntAct
EPHA2	Affinity Capture-Western, Reconstituted Complex	physical	12400011, (Europe PMC)	NA	BioGRID
EPOR	Affinity Capture-Western	physical	8400282, (Europe PMC)	NA	BioGRID
EPS8	Affinity Capture-Western, Reconstituted Complex	physical	7791787, (Europe PMC)	NA	BioGRID
ERBB2	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, Two-hybrid, protein array, pull down, ubiquitin reconstruction	association, direct interaction, physical, physical association	10085134, 16273093, 16729043, 16843263, 24658140, 28065597, 9710588, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB3	Affinity Capture-MS, Affinity Capture-Western, Protein-peptide, protein array, pull down, tandem affinity purification, ubiquitin reconstruction	association, direct interaction, physical, physical association	11546794, 16273093, 16729043, 24189400, 24658140, 9756944, (Europe PMC)	0.37, 0.70	BioGRID, IntAct, MINT
ERBB4	Affinity Capture-MS, Protein-peptide, protein array, pull down, ubiquitin reconstruction	direct interaction, physical, physical association	16273093, 16729043, 24658140, (Europe PMC)	0.37, 0.61	BioGRID, IntAct, MINT
ERRFI1	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
ESR1	Affinity Capture-Western, Reconstituted Complex, anti tag coimmunoprecipitation	physical, physical association	11773443, 20935677, (Europe PMC)	0.40	BioGRID, IntAct
EZR	proximity-dependent biotin identification	association	29568061, (Europe PMC)	0.35	IntAct
FAM118B	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
FASN	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
FASTKD3	tandem affinity purification	association	20869947, (Europe PMC)	0.35	IntAct
FBXW7	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
FCGR1A	experimental interaction detection	phosphorylation reaction	9716598, (Europe PMC)	0.31	IntAct, MINT
FCGR2B	Affinity Capture-Western, pull down	association, physical	10382761, 8940017, (Europe PMC)	0.35	BioGRID, IntAct, MINT
FGFR1	Reconstituted Complex	physical	7559490, (Europe PMC)	NA	BioGRID
FLT1	Two-hybrid	physical	10749680, (Europe PMC)	NA	BioGRID
FLT4	Affinity Capture-Western, Reconstituted Complex	physical	7970715, 8662748, 9927207, (Europe PMC)	NA	BioGRID
FYN	pull down	direct interaction	7516469, (Europe PMC)	0.44	IntAct, MINT
GAB1	Affinity Capture-Western, Far Western, fluorescence polarization spectroscopy	direct interaction, physical	14982882, 24728074, 9804835, (Europe PMC)	0.44	BioGRID, IntAct
GAB2	Affinity Capture-Western, coimmunoprecipitation, pull down	direct interaction, physical, physical association	10704825, 11782427, 12135708, 14982882, (Europe PMC)	0.54	BioGRID, IntAct, MINT
GAREM1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
GEMIN7	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
GFAP	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
GH1	Biochemical Activity	physical	7535773, (Europe PMC)	NA	BioGRID
GHR	Reconstituted Complex	physical	7535773, (Europe PMC)	NA	BioGRID
GRAP	pull down	association	8995379, (Europe PMC)	0.35	IntAct, MINT
GRB2	Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, Protein-peptide, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, bimolecular fluorescence complementation, coimmunoprecipitation, isothermal titration calorimetry, pull down, surface plasmon resonance, tandem affinity purification, x-ray crystallography	association, direct interaction, physical, physical association	10049786, 10080542, 10477741, 10570290, 11302736, 11370743, 11505033, 11792427, 11827484, 11964172, 12149229, 12213123, 12441060, 12485888, 12577067, 12898421, 15688026, 15812354, 16371368, 16520382, 19380743, 21706016, 21725358, 22974441, 23178716, 24189400, 24430869, 25416956, 26551075, 7514169, 7524086, 7535773, 7537740, 7559490, 7650032, 8112292, 8195171, 8294403, 8491186, 8621719, 8647288, 8662733, 8662998, 8663178, 8810340, 8939605, 8940013, 8950973, 8995379, 9032244, 9045692, 9083103, 9126968, 9129019, 9175774, 9254595, 9434624, 9541596, 9544989, 9886492, 9927207, (Europe PMC)	0.40, 0.52, 0.97	BioGRID, IntAct, MINT
HAX1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HIF1A	Affinity Capture-Western	physical	12114320, (Europe PMC)	NA	BioGRID
HMOX2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
HNRNPA2B1	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
HNRNPH1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HNRNPU	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
HSP90AA1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSP90AB1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA1A	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
HSPA1B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA1L	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA6	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
HSPA8	Affinity Capture-MS	physical	19380743, 24189400, (Europe PMC)	NA	BioGRID
HSPA9	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
IARS	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
IGF1R	Affinity Capture-Western, Two-hybrid, far western blotting, two hybrid	physical, physical association	14764897, 15629149, 16113100, 24051437, 7541045, 7559507, 8776723, (Europe PMC)	0.37, 0.51	BioGRID, IntAct
IGHG1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
IL2RB	Affinity Capture-Western, Reconstituted Complex	physical	10602027, 8294403, (Europe PMC)	NA	BioGRID
IL2RG	Affinity Capture-Western	physical	8643566, (Europe PMC)	NA	BioGRID
IL4R	Affinity Capture-Western, Reconstituted Complex	physical	10652211, 11714803, (Europe PMC)	NA	BioGRID
IL6ST	Affinity Capture-Western, Reconstituted Complex	physical	9126968, (Europe PMC)	NA	BioGRID
ILK	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
INPP5D	Affinity Capture-Western, pull down	direct interaction, physical	10194451, 10704825, 10822173, 10900203, 12024011, 12149229, 15470047, 8643691, (Europe PMC)	0.44	BioGRID, IntAct, MINT
INPPL1	Affinity Capture-MS, Affinity Capture-Western, tandem affinity purification	association, physical	10194451, 11349134, 19380743, 9660833, (Europe PMC)	0.35	BioGRID, IntAct
INSR	Reconstituted Complex, Two-hybrid, pull down, two hybrid	physical, physical association	10803466, 15629149, 7499194, 9593725, (Europe PMC)	0.57	BioGRID, IntAct, MINT
IQGAP1	Affinity Capture-MS, fluorescence microscopy	colocalization, physical	19380743, 20075861, (Europe PMC)	0.27	BioGRID, IntAct, MINT
ITGAV	Affinity Capture-Western	physical	19889638, (Europe PMC)	NA	BioGRID
ITGB1	Affinity Capture-Western	physical	19889638, (Europe PMC)	NA	BioGRID
ITGB3	Affinity Capture-Western, Protein-peptide	physical	10896934, 19889638, (Europe PMC)	NA	BioGRID
ITGB4	Far Western	physical	11044453, (Europe PMC)	NA	BioGRID
JAK2	Reconstituted Complex	physical	7535773, 9126968, (Europe PMC)	NA	BioGRID
KDR	Affinity Capture-Western, coimmunoprecipitation, pull down	association, physical, physical association	10319320, 11950700, 12214271, (Europe PMC)	0.56	BioGRID, IntAct, MINT
KIT	fluorescence polarization spectroscopy	direct interaction	24728074, (Europe PMC)	0.44	IntAct
KRAS	Synthetic Lethality	genetic	26627737, (Europe PMC)	NA	BioGRID
KRT1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT10	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT13	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT14	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT16	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT17	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT18	fluorescence microscopy	colocalization	12577067, (Europe PMC)	0.27	IntAct
KRT2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT3	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT4	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT6A	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT77	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
KRT9	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
LCP2	Affinity Capture-Western, coimmunoprecipitation	physical, physical association	9716598, (Europe PMC)	0.40	BioGRID, IntAct, MINT
LGALS3BP	Affinity Capture-MS	physical	24189400, (Europe PMC)	NA	BioGRID
LRP1	Affinity Capture-Western, Reconstituted Complex	physical	11854294, 12789267, (Europe PMC)	NA	BioGRID
LRRK1	Affinity Capture-MS	physical	20697350, (Europe PMC)	NA	BioGRID
LRRK1	anti tag coimmunoprecipitation	association	24947832, (Europe PMC)	0.35	IntAct
LTK	Affinity Capture-Western	physical	7650032, (Europe PMC)	NA	BioGRID
LYN	Affinity Capture-Western, pull down	direct interaction, physical	7516469, 7650013, (Europe PMC)	0.44	BioGRID, IntAct, MINT
MAPK1	Affinity Capture-Western, fluorescent resonance energy transfer, isothermal titration calorimetry, pull down, x ray scattering	direct interaction, physical, physical association	10996427, 23584453, (Europe PMC)	0.40, 0.62	BioGRID, IntAct
MAPK6	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
MAPKAPK2	Affinity Capture-Western, Biochemical Activity, Two-hybrid	physical	15094067, (Europe PMC)	NA	BioGRID
MAT1A	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
MET	Affinity Capture-Western, fluorescence polarization spectroscopy	direct interaction, physical	24728074, 9660480, (Europe PMC)	0.44	BioGRID, IntAct
MOV10	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
MRPL44	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
MST1R	Affinity Capture-Western	physical	8918464, (Europe PMC)	NA	BioGRID
MYH10	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
MYH11	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
MYH14	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
MYH9	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
MYO1C	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
MYO1D	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
NGFR	Affinity Capture-Western	physical	7541035, (Europe PMC)	NA	BioGRID
NTRK1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, Two-hybrid, coimmunoprecipitation, competition binding	association, physical	10092678, 10708759, 12446789, 25921289, 8183561, 8226808, 9856458, (Europe PMC)	0.46	BioGRID, IntAct, MINT
NTRK2	Reconstituted Complex	physical	10092678, (Europe PMC)	NA	BioGRID
NTRK3	Reconstituted Complex	physical	10092678, (Europe PMC)	NA	BioGRID
NUDT21	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
NXF1	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
OSGEP	Two-hybrid	physical	21900206, (Europe PMC)	NA	BioGRID
OSGEP	two hybrid	physical association	21900206, (Europe PMC)	0.37	IntAct, MINT
OXT	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PAG1	Reconstituted Complex	physical	10790433, (Europe PMC)	NA	BioGRID
PDGFRB	Affinity Capture-Western	physical	8195171, (Europe PMC)	NA	BioGRID
PEAK1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PIK3C2B	Reconstituted Complex	physical	11533253, (Europe PMC)	NA	BioGRID
PIK3R1	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, coimmunoprecipitation, proximity ligation assay, pull down, tandem affinity purification	association, physical, physical association	16135792, 16219545, 19380743, 19889638, 23397142, 7537361, 8621719, 8662998, 9541596, (Europe PMC)	0.83	BioGRID, IntAct, MINT
PIK3R2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PLCG1	Affinity Capture-Western	physical	8662733, (Europe PMC)	NA	BioGRID
PLCG2	Affinity Capture-Western	physical	10623845, 12135708, (Europe PMC)	NA	BioGRID
PLS3	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PLSCR1	Affinity Capture-Western, Reconstituted Complex	physical	12009895, 12871937, (Europe PMC)	NA	BioGRID
PPP1R8	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PPP1R9B	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PRDX1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
PRKCD	Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex, tandem affinity purification	association, physical	12024011, 19380743, (Europe PMC)	0.35	BioGRID, IntAct
PRKDC	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
PRKRA	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
PRMT5	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
PRSS3	Affinity Capture-MS, tandem affinity purification	association, physical	24189400, (Europe PMC)	0.35	BioGRID, IntAct
PSPH	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
PSTPIP2	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
PTK2	Affinity Capture-Western	physical	11980671, (Europe PMC)	NA	BioGRID
PTPN12	Affinity Capture-MS, Affinity Capture-Western, Proximity Label-MS, Reconstituted Complex, Two-hybrid, tandem affinity purification, two hybrid array	association, physical, physical association	19380743, 24189400, 24412244, 27880917, 28514442, 7929214, 8626541, (Europe PMC)	0.66	BioGRID, IntAct, MINT
RAB3GAP2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
RAPGEF1	Affinity Capture-Western	physical	9344843, (Europe PMC)	NA	BioGRID
RASAL2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
RB1	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
RET	Affinity Capture-Western, Reconstituted Complex, pull down	physical, physical association	15677445, 8183561, 9047384, (Europe PMC)	0.40	BioGRID, IntAct, MINT
RFFL	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
RMDN1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
RPS19	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
RUVBL1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
RUVBL2	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
S100A7	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
S100A8	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
S100A9	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
SCLT1	Proximity Label-MS, proximity-dependent biotin identification	association, physical	26638075, (Europe PMC)	0.35	BioGRID, IntAct
SEC16A	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
SH2B2	Reconstituted Complex	physical	9233773, (Europe PMC)	NA	BioGRID
SHC1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.35	BioGRID, IntAct
SHC2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
SHCBP1	Affinity Capture-Western, Reconstituted Complex, Two-hybrid	physical	10086341, (Europe PMC)	NA	BioGRID
SIRT4 {ECO:0000255\|HAMAP-Rule:MF_03161,	anti tag coimmunoprecipitation	association	25525879, (Europe PMC)	0.35	IntAct
SMAD4	two hybrid array	physical association	24412244, (Europe PMC)	0.37	IntAct, MINT
SMAP	two hybrid	physical association	21900206, (Europe PMC)	0.37	IntAct, MINT
SOS1	Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation, tandem affinity purification	association, physical, physical association	10025673, 10570290, 10675333, 10783152, 16371368, 19380743, 7559490, 8950973, 9344843, 9544989, (Europe PMC)	0.56	BioGRID, IntAct, MINT
SOS2	Affinity Capture-MS, Affinity Capture-Western	physical	10675333, 19380743, (Europe PMC)	NA	BioGRID
SPTA1	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
SPTAN1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
SPTBN1	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
SRC	protein kinase assay	phosphorylation reaction	26551075, (Europe PMC)	0.44	IntAct
STAT5A	Affinity Capture-Western, proximity ligation assay	physical, physical association	10996427, 23397142, (Europe PMC)	0.40	BioGRID, IntAct
STAT5B	Affinity Capture-Western	physical	10996427, (Europe PMC)	NA	BioGRID
STXBP1	Co-fractionation	physical	26344197, (Europe PMC)	NA	BioGRID
SUV39H2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
TEC	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TEK	coimmunoprecipitation, pull down	association	14665640, (Europe PMC)	0.46	IntAct, MINT
TGFBR2	coimmunoprecipitation	association	17440088, (Europe PMC)	0.35	IntAct, MINT
TIMM50	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TRIM15	PCA	physical	25450970, (Europe PMC)	NA	BioGRID
TUBA1A	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA1B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA1C	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA4B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBA8	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBAL3	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB2B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB3	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB4B	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
TUBB6	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
UBASH3B	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, 24189400, (Europe PMC)	0.53	BioGRID, IntAct
USP15	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
USP9X	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
USP9Y	Affinity Capture-MS, tandem affinity purification	association, physical	19380743, (Europe PMC)	0.35	BioGRID, IntAct
VARS	Affinity Capture-MS	physical	19380743, (Europe PMC)	NA	BioGRID
VAV3	Affinity Capture-Western	physical	11094073, (Europe PMC)	NA	BioGRID
XPO1	Affinity Capture-MS	physical	26673895, (Europe PMC)	NA	BioGRID
YWHAZ	coimmunoprecipitation	association	11342545, 19218246, (Europe PMC)	0.53	IntAct, MINT
ZAP70	Affinity Capture-Western, Biochemical Activity, anti tag coimmunoprecipitation	physical, physical association	15688026, 23267066, 9685404, (Europe PMC)	0.40	BioGRID, IntAct, MINT

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SHC1