DEPOD - human DEPhOsphorylation Database

Basic Information
Phosphatases
Pathway
Interacting Proteins
Phosphorylating Kinases

Gene Name	TYK2 (QuickGO)	Interactive visualization of TYK2 structures (A quick tutorial to explore the interctive visulaization) Representative structure: 3LXP
Synonyms	TYK2
Protein Name	TYK2
Alternative Name(s)	Non-receptor tyrosine-protein kinase TYK2;2.7.10.2;
Protein Family	Belongs to the protein kinase superfamily Tyr proteinkinase family JAK subfamily
EntrezGene ID	7297 (Comparitive Toxicogenomics)
UniProt AC (Human)	P29597 (protein sequence)
Enzyme Class	2.7.10.2 (BRENDA )
Molecular Weight	133650 Dalton
Protein Length	1187 amino acids (AA)
Genome Browsers	NCBI \| ENSG00000105397 (Ensembl) \| UCSC
Crosslinking annotations	Query our ID-mapping table
Orthologues	Quest For Orthologues (QFO) \| GeneTree \| eggNOG - KOG0197 \| eggNOG - COG0515
Phosphorylation Network	Visualize

Domain organization, Expression, Diseases

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Localization, Function, Catalytic activity and Sequence

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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)
hsa04217	Necroptosis	Necroptosis is a programmed form of necrosis. It can be initiated by different stimuli, such as tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL), interferon (IFN), LPS, viral DNA or RNA, DNA-damage agent and requires the kinase activity of receptor-interacting protein 1 (RIPK1) and RIPK3. Its execution involves ROS generation, calcium overload, the opening of the mitochondrial permeability transition pore, mitochondrial fission, inflammatory response and chromatinolysis. Necroptosis participates in many pathogenesis of diseases, including neurological diseases, retinal disorders, acute kidney injury, inflammatory diseases and microbial infections.
hsa04380	Osteoclast differentiation	The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways activated by RANK and immune receptors, whose ligands are expressed on the surface of osteoblasts. Signaling from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast.
hsa04621	NOD-like receptor signaling pathway	Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-{kappa}B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. The activated of caspase-1 regulates maturation of the pro-inflammatory cytokines IL-1B, IL-18 and drives pyroptosis.
hsa04630	Jak-STAT signaling pathway	The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. Following the binding of cytokines to their cognate receptor, STATs are activated by members of the JAK family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. In addition to the activation of STATs, JAKs mediate the recruitment of other molecules such as the MAP kinases, PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in the activation of additional transcription factors.
hsa04658	Th1 and Th2 cell differentiation	Immunity to different classes of microorganisms is orchestrated by separate lineages of effector T helper (TH)-cells, which differentiate from naive CD4+ precursor cells in response to cues provided by antigen presenting cells (APC) and include T helper type 1 (Th1) and Th2. Th1 cells are characterized by the transcription factor T-bet and signal transducer and activator of transcription (STAT) 4, and the production of IFN-gamma. These cells stimulate strong cell-mediated immune responses, particularly against intracellular pathogens. On the other hand, transcription factors like GATA-3 and STAT6 drive the generation of Th2 cells that produce IL-4, IL-5 and IL-13 and are necessary for inducing the humoral response to combat parasitic helminths (type 2 immunity) and isotype switching to IgG1 and IgE. The balance between Th1/Th2 subsets determines the susceptibility to disease states, where the improper development of Th2 cells can lead to allergy, while an overactive Th1 response can lead to autoimmunity.
hsa04659	Th17 cell differentiation	Interleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the pathogenesis of autoimmune diseases. In vivo, Th17 differentiation requires antigen presentation and co-stimulation, and activation of antigen presenting-cells (APCs) to produce TGF-beta, IL-6, IL-1, IL-23 and IL-21. This initial activation results in the activation and up-regulation of STAT3, ROR(gamma)t and other transcriptional factors in CD4+ T cells, which bind to the promoter regions of the IL-17, IL-21 and IL-22 genes and induce IL-17, IL-21 and IL-22. In contrast, the differentiation of Th17 cells and their IL-17 expression are negatively regulated by IL-2, Th2 cytokine IL-4, IL-27 and Th1 cytokine IFN-gamma through STAT5, STAT6 and STAT1 activation, respectively. Retinoid acid and the combination of IL-2 and TGF-beta upregulate Foxp3, which also downregulates cytokines like IL-17 and IL-21. The inhibition of Th17 differentiation may serve as a protective strategy to 'fine-tune' the expression IL-17 so it does not cause excessive inflammation. Thus, balanced differentiation of Th cells is crucial for immunity and host protection.
hsa05145	Toxoplasmosis	Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host.
hsa05160	Hepatitis C	Hepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the cytoplasm of the host cell and forms membrane-associated replication complexes along with non-structural proteins. Viral RNA can trigger the RIG-I pathway and interferon production during this process. Translated HCV protein products regulate immune response to inhibit the action of interferon. HCV core and NS5A proteins appear to be the most important molecules with regulatory functions that modulate transcription, cellular proliferation, and apoptosis.
hsa05162	Measles	Measles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacterial infections. Several MV proteins have been suggested to disturb host immunity. After infection of host lymphoid cells via SLAM, MV inhibits cytokine response by direct interference with host signaling systems. Three proteins (P, V, and C) associate with Jak/STAT proteins in interferon-triggered pathway and other important proteins related to apoptosis. Interaction between MV and host brings about the shift towards a Th2 response by decreasing IL-12 production and induces lymphopenia by suppressing cell proliferation.
hsa05164	Influenza A	Influenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains that cause pandemics arise from avian influenza virus by genetic reassortment among influenza viruses and two surface glycoproteins HA and NA form the basis of serologically distinct virus types. The innate immune system recognizes invaded virus through multiple mechanisms. Viral non-structural NS1 protein is a multifunctional virulence factor that interfere IFN-mediated antiviral response. It inhibits IFN production by blocking activation of transcription factors such as NF-kappa B, IRF3 and AP1. NS1 further inhibits the activation of IFN-induced antiviral genes. PB1-F2 protein is another virulence factor that induce apoptosis of infected cells, which results in life-threatening bronchiolitis.
hsa05165	Human papillomavirus infection	Human papillomavirus (HPV) is a non-enveloped, double-stranded DNA virus. HPV infect mucoal and cutaneous epithelium resulting in several types of pathologies, most notably, cervical cancer. All types of HPV share a common genomic structure and encode eight proteins: E1, E2, E4, E5, E6, and E7 (early) and L1 and L2 (late). It has been demonstrated that E1 and E2 are involved in viral transcription and replication. The functions of the E4 protein is not yet fully understood. E5, E6, and E7 act as oncoproteins. E5 inhibits the V-ATPase, prolonging EGFR signaling and thereby promoting cell proliferation. The expression of E6 and E7 not only inhibits the tumor suppressors p53 and Rb, but also alters additional signalling pathways. Among these pathways, PI3K/Akt signalling cascade plays a very important role in HPV-induced carcinogenesis. The L1 and L2 proteins form icosahedral capsids for progeny virion generation.
hsa05167	Kaposi sarcoma-associated herpesvirus infection	Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the most recently identified human tumor virus, and is associated with the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and Multicentric Castleman's disease (MCD). Like all other herpesviruses, KSHV displays two modes of life cycle, latency and lytic replication, which are characterized by the patterns of viral gene expression. Genes expressed in latency (LANA, v-cyclin, v-FLIP, Kaposins A, B and C and viral miRNAs) are mainly thought to facilitate the establishment of life long latency in its host and survival against the host innate, and adaptive immune surveillance mechanisms. Among the viral proteins shown to be expressed during lytic replication are potent signaling molecules such as vGPCR, vIL6, vIRFs, vCCLs, K1 and K15, which have been implicated experimentally in the angiogenic and inflammatory phenotype observed in KS lesions. Several of these latent viral and lytic proteins are known to transform host cells, linking KSHV with the development of severe human malignancies.
hsa05168	Herpes simplex infection	Herpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishment of latent infection in neuronal ganglia. HSV is the main cause of herpes infections that lead to the formation of characteristic blistering lesion. HSV express multiple viral accessory proteins that interfere with host immune responses and are indispensable for viral replication. Among these proteins, the immediate early (IE) gene ICP0, ICP4, and ICP27 are essential for regulation of HSV gene expression in productive infection. On the other hand, ORF P and ORF O gene are transcribed during latency and blocks the expression of the IE genes, thus maintaining latent infection.
hsa05169	Epstein-Barr virus infection	Epstein-Barr virus (EBV) is a gamma-herpes virus that widely infects human populations predominantly at an early age but remains mostly asymptomatic. EBV has been linked to a wide spectrum of human malignancies, including nasopharyngeal carcinoma and other hematologic cancers, like Hodgkin's lymphoma, Burkitt's lymphoma (BL), B-cell immunoblastic lymphoma in HIV patients, and posttransplant-associated lymphoproliferative diseases. EBV has the unique ability to establish life-long latent infection in primary human B lymphocytes. During latent infection, EBV expresses a small subset of genes, including 6 nuclear antigens (EBNA-1, -2, -3A, -3B, -3C, and -LP), 3 latent membrane proteins (LMP-1, -2A, and -2B), 2 small noncoding RNAs (EBER-1 and 2). On the basis of these latent gene expression, three different latency patterns associated with the types of cancers are recognized.

Pathway ID	Pathway Name	Pathway Description (KEGG)
R-HSA-1059683	Interleukin-6 signaling.	Interleukin-6 (IL-6) is a pleiotropic cytokine with roles in processes including immune regulation, hematopoiesis, inflammation, oncogenesis, metabolic control and sleep. It is the founding member of a family of IL-6-related cytokines such as IL-11, IL-27 leukemia inhibitory factor (LIF), cilliary neurotrophic factor (CNTF) and oncostatin M. The IL-6 receptor (IL6R) consists of an alpha subunit that specifically binds IL-6 and a beta subunit, IL6RB or gp130, which is the signaling component of all the receptors for cytokines related to IL-6. IL6R alpha exists in transmembrane and soluble forms. The transmembrane form is mainly expressed by hepatocytes, neutrophils, monocytes/macrophages, and some lymphocytes. Soluble forms of IL6R (sIL6R) are also expressed by these cells. Two major mechanisms for the production of sIL6R have been proposed. Alternative splicing generates a transcript lacking the transmembrane domain by using splicing donor and acceptor sites that flank the transmembrane domain coding region. This also introduces a frameshift leading to the incorporation of 10 additional amino acids at the C terminus of sIL6R.A second mechanism for the generation of sIL6R is the proteolytic cleavage or 'shedding' of membrane-bound IL-6R. Two proteases ADAM10 and ADAM17 are thought to contribute to this (Briso et al. 2008). sIL6R can bind IL6 and stimulate cells that express gp130 but not IL6R alpha, a process that is termed trans-signaling. This explains why many cells, including hematopoietic progenitor cells, neuronal cells, endothelial cells, smooth muscle cells, and embryonic stem cells, do not respond to IL6 alone, but show a remarkable response to IL6/sIL6R. It is clear that the trans-signaling pathway is responsible for the pro-inflammatory activities of IL-6 whereas the membrane bound receptor governs regenerative and anti-inflammatory IL-6 activitiesIL6R signal transduction is mediated by two pathways:the JAK-STAT (Janus family tyrosine kinase-signal transducer and activator of transcription) pathway and the Ras-MAPK (mitogen-activated protein kinase) pathway. Negative regulators of IL-6 signaling include SOCS (suppressor of cytokine signals) and SHP2. Within the last few years different antibodies have been developed to inhibit IL-6 activity, and the first such antibodies have been introduced into the clinic for the treatment of inflammatory diseases (Kopf et al. 2010)
R-HSA-110056	MAPK3 (ERK1) activation.	Mitogen-activated protein kinase kinase MAP2K1 (also known as MEK1) is a dual threonine and tyrosine recognition kinase that phosphorylates and activates MAPK3 (ERK1) (Ohren et al. 2004; Roskoski 2012a)
R-HSA-112411	MAPK1 (ERK2) activation.	Mitogen-activated protein kinase kinase MAP2K2 (also known as MEK2) is a dual threonine and tyrosine recognition kinase that phosphorylates and activates MAPK1 (ERK2) (Ohren et al. 2004; Roskoski 2012)
R-HSA-449836	Other interleukin signaling.	Interleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but are now known to be produced by many other cells throughout the body. They have pleiotropic effects on cells which bind them, impacting processes such as tissue growth and repair, hematopoietic homeostasis, and multiple levels of the host defense against pathogens where they are an essential part of the immune system
R-HSA-6783783	Interleukin-10 signaling.	Interleukin-10 (IL10) was originally described as a factor named cytokine synthesis inhibitory factor that inhibited T-helper (Th) 1 activation and Th1 cytokine production (Fiorentino et al. 1989). It was found to be expressed by a variety of cell types including macrophages, dendritic cell subsets, B cells, several T-cell subpopulations including Th2 and T-regulatory cells (Tregs) and Natural Killer (NK) cells (Moore et al. 2001). It is now recognized that the biological effects of IL10 are directed at antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs), its effects on T-cell development and differentiation are largely indirect via inhibition of macrophage/dendritic cell activation and maturation (Pestka et al. 2004, Mocellin et al. 2004). T cells are thought to be the main source of IL10 (Hedrich & Bream 2010). IL10 inhibits a broad spectrum of activated macrophage/monocyte functions including monokine synthesis, NO production, and expression of class II MHC and costimulatory molecules such as IL12 and CD80/CD86 (de Waal Malefyt et al. 1991, Gazzinelli et al. 1992). Studies with recombinant cytokine and neutralizing antibodies revealed pleiotropic activities of IL10 on B, T, and mast cells (de Waal Malefyt et al. 1993, Rousset et al. 1992, Thompson-Snipes et al. 1991) and provided evidence for the in vivo significance of IL10 activities (Ishida et al. 1992, 1993). IL10 antagonizes the expression of MHC class II and the co-stimulatory molecules CD80/CD86 as well as the pro-inflammatory cytokines IL1Beta, IL6, IL8, TNFalpha and especially IL12 (Fiorentino et al. 1991, D'Andrea et al. 1993). The biological role of IL10 is not limited to inactivation of APCs, it also enhances B cell, granulocyte, mast cell, and keratinocyte growth/differentiation, as well as NK-cell and CD8+ cytotoxic T-cell activation (Moore et al. 2001, Hedrich & Bream 2010). IL10 also enhances NK-cell proliferation and/or production of IFN-gamma (Cai et al. 1999). IL10-deficient mice exhibited inflammatory bowel disease (IBD) and other exaggerated inflammatory responses (Kuhn et al. 1993, Berg et al. 1995) indicating a critical role for IL10 in limiting inflammatory responses. Dysregulation of IL10 is linked with susceptibility to numerous infectious and autoimmune diseases in humans and mouse models (Hedrich & Bream 2010). IL10 signaling is initiated by binding of homodimeric IL10 to the extracellular domains of two adjoining IL10RA molecules. This tetramer then binds two IL10RB chains. IL10RB cannot bind to IL10 unless bound to IL10RA (Ding et al. 2001, Yoon et al. 2006); binding of IL10 to IL10RA without the co-presence of IL10RB fails to initiate signal transduction (Kotenko et al. 1997).IL10 binding activates the receptor-associated Janus tyrosine kinases, JAK1 and TYK2, which are constitutively bound to IL10R1 and IL10R2 respectively. In the classic model of receptor activation assembly of the receptor complex is believed to enable JAK1/TYK2 to phosphorylate and activate each other. Alternatively the binding of IL10 may cause conformational changes that allow the pseudokinase inhibitory domain of one JAK kinase to move away from the kinase domain of the other JAK within the receptor dimer-JAK complex, allowing the two kinase domains to interact and trans-activate (Waters & Brooks 2015).The activated JAK kinases phosphorylate the intracellular domains of the IL10R1 chains on specific tyrosine residues. These phosphorylated tyrosine residues and their flanking peptide sequences serve as temporary docking sites for the latent, cytosolic, transcription factor, STAT3. STAT3 transiently docks on the IL10R1 chain via its SH2 domain, and is in turn tyrosine phosphorylated by the receptor-associated JAKs. Once activated, it dissociates from the receptor, dimerizes with other STAT3 molecules, and translocates to the nucleus where it binds with high affinity to STAT-binding elements (SBEs) in the promoters of IL-10-inducible genes (Donnelly et al. 1999)
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling.	Interleukin-4 (IL4) is a principal regulatory cytokine during the immune response, crucially important in allergy and asthma (Nelms et al. 1999). When resting T cells are antigen-activated and expand in response to Interleukin-2 (IL2), they can differentiate as Type 1 (Th1) or Type 2 (Th2) T helper cells. The outcome is influenced by IL4. Th2 cells secrete IL4, which both stimulates Th2 in an autocrine fashion and acts as a potent B cell growth factor to promote humoral immunity (Nelms et al. 1999). Interleukin-13 (IL13) is an immunoregulatory cytokine secreted predominantly by activated Th2 cells. It is a key mediator in the pathogenesis of allergic inflammation. IL13 shares many functional properties with IL4, stemming from the fact that they share a common receptor subunit. IL13 receptors are expressed on human B cells, basophils, eosinophils, mast cells, endothelial cells, fibroblasts, monocytes, macrophages, respiratory epithelial cells, and smooth muscle cells, but unlike IL4, not T cells. Thus IL13 does not appear to be important in the initial differentiation of CD4 T cells into Th2 cells, rather it is important in the effector phase of allergic inflammation (Hershey et al. 2003).\n\nIL4 and IL13 induce “alternative activation” of macrophages, inducing an anti-inflammatory phenotype by signaling through IL4R alpha in a STAT6 dependent manner. This signaling plays an important role in the Th2 response, mediating anti-parasitic effects and aiding wound healing (Gordon & Martinez 2010, Loke et al. 2002)\n\nThere are two types of IL4 receptor complex (Andrews et al. 2006). Type I IL4R (IL4R1) is predominantly expressed on the surface of hematopoietic cells and consists of IL4R and IL2RG, the common gamma chain. Type II IL4R (IL4R2) is predominantly expressed on the surface of nonhematopoietic cells, it consists of IL4R and IL13RA1 and is also the type II receptor for IL13. (Obiri et al. 1995, Aman et al. 1996, Hilton et al. 1996, Miloux et al. 1997, Zhang et al. 1997). The second receptor for IL13 consists of IL4R and Interleukin-13 receptor alpha 2 (IL13RA2), sometimes called Interleukin-13 binding protein (IL13BP). It has a high affinity receptor for IL13 (Kd = 250 pmol/L) but is not sufficient to render cells responsive to IL13, even in the presence of IL4R (Donaldson et al. 1998). It is reported to exist in soluble form (Zhang et al. 1997) and when overexpressed reduces JAK-STAT signaling (Kawakami et al. 2001). It's function may be to prevent IL13 signalling via the functional IL4R:IL13RA1 receptor. IL13RA2 is overexpressed and enhances cell invasion in some human cancers (Joshi & Puri 2012).The first step in the formation of IL4R1 (IL4:IL4R:IL2RB) is the binding of IL4 with IL4R (Hoffman et al. 1995, Shen et al. 1996, Hage et al. 1999). This is also the first step in formation of IL4R2 (IL4:IL4R:IL13RA1). After the initial binding of IL4 and IL4R, IL2RB binds (LaPorte et al. 2008), to form IL4R1. Alternatively, IL13RA1 binds, forming IL4R2. In contrast, the type II IL13 complex (IL13R2) forms with IL13 first binding to IL13RA1 followed by recruitment of IL4R (Wang et al. 2009).Crystal structures of the IL4:IL4R:IL2RG, IL4:IL4R:IL13RA1 and IL13:IL4R:IL13RA1 complexes have been determined (LaPorte et al. 2008). Consistent with these structures, in monocytes IL4R is tyrosine phosphorylated in response to both IL4 and IL13 (Roy et al. 2002, Gordon & Martinez 2010) while IL13RA1 phosphorylation is induced only by IL13 (Roy et al. 2002, LaPorte et al. 2008) and IL2RG phosphorylation is induced only by IL4 (Roy et al. 2002).Both IL4 receptor complexes signal through Jak/STAT cascades. IL4R is constitutively-associated with JAK2 (Roy et al. 2002) and associates with JAK1 following binding of IL4 (Yin et al. 1994) or IL13 (Roy et al. 2002). IL2RG constitutively associates with JAK3 (Boussiotis et al. 1994, Russell et al. 1994). IL13RA1 constitutively associates with TYK2 (Umeshita-Suyama et al. 2000, Roy et al. 2002, LaPorte et al. 2008, Bhattacharjee et al. 2013). IL4 binding to IL4R1 leads to phosphorylation of JAK1 (but not JAK2) and STAT6 activation (Takeda et al. 1994, Ratthe et al. 2007, Bhattacharjee et al. 2013). IL13 binding increases activating tyrosine-99 phosphorylation of IL13RA1 but not that of IL2RG. IL4 binding to IL2RG leads to its tyrosine phosphorylation (Roy et al. 2002). IL13 binding to IL4R2 leads to TYK2 and JAK2 (but not JAK1) phosphorylation (Roy & Cathcart 1998, Roy et al. 2002).Phosphorylated TYK2 binds and phosphorylates STAT6 and possibly STAT1 (Bhattacharjee et al. 2013). A second mechanism of signal transduction activated by IL4 and IL13 leads to the insulin receptor substrate (IRS) family (Kelly-Welch et al. 2003). IL4R1 associates with insulin receptor substrate 2 and activates the PI3K/Akt and Ras/MEK/Erk pathways involved in cell proliferation, survival and translational control. IL4R2 does not associate with insulin receptor substrate 2 and consequently the PI3K/Akt and Ras/MEK/Erk pathways are not activated (Busch-Dienstfertig & González-Rodríguez 2013)
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions.	The members involved in (interleukin)-6-type cytokine signalling are the IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CTF1) and cardiotrophin-like cytokine factor 1 (CLCF1). Receptors involved in recognition of the IL-6-type cytokines can be subdivided in the non-signalling alpha-receptors (IL6R, IL 11R, and CNTFR) and the signal transducing receptors (gp130, LIFR, and OSMR). The latter associate with JAKs and become tyrosine phosphorylated in response to cytokine stimulation (Heinrich et al. 1998, 2003). IL27 and IL35 belongs to IL12 cytokine family but they share gp130 as a component of signalling receptor, along with IL-6, IL-11, LIF, OSM, CNTF, CTF1 and CLCF1
R-HSA-8854691	Interleukin-20 family signaling.	The interleukin 20 (IL20) subfamily comprises IL19, IL20, IL22, IL24 and IL26. They are members of the larger IL10 family, but have been grouped together based on their usage of common receptor subunits and similarities in their target cell profiles and biological functions. Members of the IL20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. Much of the understanding of this group of cytokines is based on IL22, which is the most studied member (Rutz et al. 2014, Akdis M et al. 2016, Longsdon et al. 2012)
R-HSA-8984722	Interleukin-35 Signalling.	Interleukin 35 (IL35) is an IL12 family cytokine produced by regulatory but not effector T-cells. It is a dimeric protein composed of IL-12RB2 and IL27RA chains. IL35 suppresses inflammatory responses of immune cells
R-HSA-9020591	Interleukin-12 signaling.	Interleukin 12 (IL-12) is heterodimeric cytokine produced by dendritic cells, macrophages and neutrophils. It is encoded by the genes Interleukin-12 subunit alpha (IL12A) and Interleukin-12 subunit beta (IL12B), which encode a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40), respectively. The active IL12 heterodimer is sometimes referred to as p70. The p35 component has homology to single-chain cytokines, while p40 is homologous to the extracellular domains of members of the haematopoietic cytokine-receptor family. The IL12 heterodimer therefore resembles a cytokine linked to a soluble receptor. \n\nIL12 is involved in the differentiation of naive T cells into Th1 cells and sometimes known as T cell-stimulating factor. IL12 enhances the cytotoxic activity of Natural Killer cells and CD8+ cytotoxic T lymphocytes. IL12 also has anti-angiogenic activity, mediated by increased production of CXCL10 via interferon gamma. \n\nThe IL12 receptor is a heterodimer formed by Interleukin-12 receptor subunit beta-1 (IL12RB1) and Interleukin-12 receptor subunit beta-2 (IL12RB2), both of which have extensive homology to IL6ST (gp130), the signal transducing receptor subunit of the IL6-like cytokine superfamily. IL-12RB2 is considered to play the key role in IL12 function, in part because its expression on activated T cells is stimulated by cytokines that promote Th1 cell development and inhibited by those that promote Th2 cells development. In addition, IL12 binding leads to IL12RB2 tyrosine phosphorylation, which provides binding sites for the kinases Non-receptor tyrosine-protein kinase TYK2 and Tyrosine-protein kinase JAK2. These activate transcription factor proteins in the Signal transducer and activator of transcription (STAT) family, particularly STAT4
R-HSA-9020933	Interleukin-23 signaling.	Interleukin-23 (IL23) is a heterodimer of Interleukin-12 subunit beta (IL12B, IL-12p40), which is shared with IL12, and Interleukin-23 subunit alpha IL23A (IL-23p19) subunit. The functional receptor for IL23 consists of Interleukin-12 receptor subunit beta-1 (IL12RB1), which is shared with the IL12 receptor, and Interleukin-23 receptor (IL23R). IL23R is mainly expresed on activated memory T cells, Natural Killer cells, monocytes/macrophage and at low levels on dendritic cells (DCs). IL23 is mainly secreted by activated macrophages and DCs in peripheral tissues such as skin, intestinal mucosa and lung. \n\nIL23 is proinlflammatory and implicated in several autoimmune inflammatory disorders such as colitis, gastritis, psoriasis and arthritis. It is similar to IL-12 both in structure and its ability to memory T cells to increase interferon-γ (IFN-γ) production and proliferation, the ability of IL-23 to induce IL-17.\n\nIL23 activates the Janus kinases JAK2 and TYK2, resulting in phosphorylation of the receptor complex, which forms the docking sites for Signal transducer and activator of transcription 3 (STAT3) and STAT4 to bind and become phosphorylated
R-HSA-9020956	Interleukin-27 signaling.	Interleukin-27 (IL27) is a heterodimeric cytokine that contains Epstein-Barr virus–induced gene 3 (EBI3) and IL27p28 (IL27). It signals through a receptor composed of Interleukin-6 receptor subunit beta (IL6ST, gp130), which is utilized by many cytokines, and Interleukin-27 receptor subunit alpha (IL27RA, WSX-1, TCCR) (Yoshida & Hunter 2015)
R-HSA-909733	Interferon alpha/beta signaling.	Type I interferons (IFNs) are composed of various genes including IFN alpha (IFNA), beta (IFNB), omega, epsilon, and kappa. In humans the IFNA genes are composed of more than 13 subfamily genes, whereas there is only one IFNB gene. The large family of IFNA/B proteins all bind to a single receptor which is composed of two distinct chains: IFNAR1 and IFNAR2. The IFNA/B stimulation of the IFNA receptor complex leads to the formation of two transcriptional activator complexes: IFNA-activated-factor (AAF), which is a homodimer of STAT1 and IFN-stimulated gene factor 3 (ISGF3), which comprises STAT1, STAT2 and a member of the IRF family, IRF9/P48. AAF mediates activation of the IRF-1 gene by binding to GAS (IFNG-activated site), whereas ISGF3 activates several IFN-inducible genes including IRF3 and IRF7
R-HSA-912694	Regulation of IFNA signaling.	There are several proteins and mechanisms involved in controlling the extent of ligand stimulation of IFNA/B signaling. These mechanisms can effect every step of the IFNA/B cascade. Dephosphorylation of JAK and STAT by SHP protein phosphatases, inhibition of STAT function in the nucleus by protein inhibitors of activated STATs (PIAS) proteins, inhibition of tyrosine kinase activity of JAKs by SOCS as well as inhibition of JAK and IFNAR2 interaction by UBP43 are few of the negative regulation mechanisms in controling type I IFN signaling

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IntAct
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Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
BAG2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
C16orf71	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CBL	Affinity Capture-Western	physical	8780698, (Europe PMC)	NA	BioGRID
CCT2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT3	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT4	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT5	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT6A	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT7	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT8	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CD79A	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CDH8	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CEP170B	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
COPS5	Affinity Capture-Western, Two-hybrid	physical	24043623, (Europe PMC)	NA	BioGRID
CRKL	Affinity Capture-Western	physical	9374471, (Europe PMC)	NA	BioGRID
DDX5	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
DNM2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
EFNB2	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
EIF2AK2	Affinity Capture-Western, Reconstituted Complex	physical	17290288, (Europe PMC)	NA	BioGRID
ELP2	Affinity Capture-Western	physical	10954736, (Europe PMC)	NA	BioGRID
FHL3	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	21516116, 25416956, (Europe PMC)	0.70	BioGRID, IntAct
FYN	Affinity Capture-Western, Reconstituted Complex	physical	9196040, (Europe PMC)	NA	BioGRID
GHR	Affinity Capture-Western	physical	10502458, (Europe PMC)	NA	BioGRID
GMNN	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
GPR156	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
HAVCR2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
HNRNPH1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
HNRNPK	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.49, 0.56	BioGRID, IntAct
HNRNPL	Affinity Capture-RNA	physical	28611215, (Europe PMC)	NA	BioGRID
HSP90AA1	Affinity Capture-Luminescence	physical	22939624, (Europe PMC)	NA	BioGRID
HSPB1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
IFNAR1	Affinity Capture-Western, Reconstituted Complex, molecular sieving, pull down	direct interaction, physical, physical association	10523853, 15337770, 15356134, 18474601, 24704786, 9733772, (Europe PMC)	0.40, 0.56	BioGRID, IntAct, MINT
IFT43	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
IL13RA1	Affinity Capture-Western	physical	10409622, (Europe PMC)	NA	BioGRID
IL4R	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
IL6ST	Affinity Capture-Western	physical	9388212, (Europe PMC)	NA	BioGRID
IRS2	Reconstituted Complex	physical	8550573, (Europe PMC)	NA	BioGRID
JAK1	Affinity Capture-Western	physical	7589562, (Europe PMC)	NA	BioGRID
JAK3	Affinity Capture-Western	physical	12207328, (Europe PMC)	NA	BioGRID
KHDRBS2	Two-hybrid, two hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	21516116, 25416956, (Europe PMC)	0.76	BioGRID, IntAct, MINT
KLF10	Affinity Capture-Western	physical	21471442, (Europe PMC)	NA	BioGRID
KRT40	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.56	BioGRID, IntAct
LGALS3BP	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
LNX1	Affinity Capture-Western	physical	22087225, (Europe PMC)	NA	BioGRID
LPAR6	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
LRP8	Affinity Capture-MS	physical	26496610, (Europe PMC)	NA	BioGRID
LRRC46	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
LYN	Reconstituted Complex	physical	9633884, (Europe PMC)	NA	BioGRID
MAS1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
MIER2	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
MOV10	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
NLGN3	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
NXF1	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
PIH1D1	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
PLAUR	Affinity Capture-Western	physical	9417082, (Europe PMC)	NA	BioGRID
PMEL	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PRMT5	Reconstituted Complex	physical	10531356, (Europe PMC)	NA	BioGRID
PROSER2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PTAFR	Affinity Capture-Western	physical	14500680, (Europe PMC)	NA	BioGRID
PTPN1	Affinity Capture-Western, coimmunoprecipitation	physical, physical association	11694501, (Europe PMC)	0.40	BioGRID, IntAct, MINT
PTPN6	Affinity Capture-Western, Biochemical Activity	physical	7629131, (Europe PMC)	NA	BioGRID
RACK1	Affinity Capture-Western, Reconstituted Complex	physical	12960323, (Europe PMC)	NA	BioGRID
RAN	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
RNF13	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
RUVBL1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
RUVBL2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
SHMT2	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
SIAH2	Affinity Capture-Western	physical	24833526, (Europe PMC)	NA	BioGRID
SIVA1	Affinity Capture-Western, Phenotypic Enhancement, Two-hybrid	genetic, physical	20727854, (Europe PMC)	NA	BioGRID
SLC2A1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
SOCS1	Affinity Capture-Western	physical	21757742, (Europe PMC)	NA	BioGRID
STAM2	Affinity Capture-Western	physical	10899310, (Europe PMC)	NA	BioGRID
STAT1	Biochemical Activity	physical	12960323, (Europe PMC)	NA	BioGRID
TCP1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TGFBR2	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
TK1	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
TMCO3	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TNFRSF13B	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TNFRSF19	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TRAF4	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.56	BioGRID, IntAct
TRIM28	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TUBA4A	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TYK2	Affinity Capture-Western	physical	7589562, (Europe PMC)	NA	BioGRID
UBE2L6	Affinity Capture-Western	physical	24833526, (Europe PMC)	NA	BioGRID
VAV1	Affinity Capture-Western	physical	10673353, (Europe PMC)	NA	BioGRID
WDR20	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
XRCC5	Affinity Capture-Western	physical	10673353, (Europe PMC)	NA	BioGRID
ZNF333	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID

Visualize Download

Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
CCT2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT3	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT4	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT5	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT6A	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT7	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT8	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CEP170B	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
DDX5	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
DNM2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
FHL3	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	21516116, 25416956, (Europe PMC)	0.70	BioGRID, IntAct
HNRNPH1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
HNRNPK	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.49, 0.56	BioGRID, IntAct
HSP90AB1	anti tag coimmunoprecipitation, luminescence based mammalian interactome mapping	physical association	22939624, (Europe PMC)	0.52	IntAct
HSPB1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
IFNAR1	Affinity Capture-Western, Reconstituted Complex, molecular sieving, pull down	direct interaction, physical, physical association	10523853, 15337770, 15356134, 18474601, 24704786, 9733772, (Europe PMC)	0.40, 0.56	BioGRID, IntAct, MINT
JAK2	anti bait coimmunoprecipitation	physical association	26175413, (Europe PMC)	0.40	IntAct
KHDRBS2	Two-hybrid, two hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	21516116, 25416956, (Europe PMC)	0.76	BioGRID, IntAct, MINT
KRT40	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.56	BioGRID, IntAct
PRKCA	anti bait coimmunoprecipitation	physical association	17290288, (Europe PMC)	0.40	IntAct, MINT
PTPN1	Affinity Capture-Western, coimmunoprecipitation	physical, physical association	11694501, (Europe PMC)	0.40	BioGRID, IntAct, MINT
RAN	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
RIPK4	anti tag coimmunoprecipitation	association	26972000, (Europe PMC)	0.35	IntAct
RUVBL1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
RUVBL2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
SLC2A1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TCP1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TK1	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
TRAF4	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.56	BioGRID, IntAct
TRIM28	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TUBA4A	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
UBE2F	two hybrid	physical association	19549727, (Europe PMC)	0.37	IntAct
WDR20	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct

Visualize Download

Interacting partner	Detection method	Interaction type	PubMed IDs	Interaction Score	Source
BAG2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
C16orf71	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CBL	Affinity Capture-Western	physical	8780698, (Europe PMC)	NA	BioGRID
CCT2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT3	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT4	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT5	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT6A	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT7	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CCT8	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
CD79A	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CDH8	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
CEP170B	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
COPS5	Affinity Capture-Western, Two-hybrid	physical	24043623, (Europe PMC)	NA	BioGRID
CRKL	Affinity Capture-Western	physical	9374471, (Europe PMC)	NA	BioGRID
DDX5	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
DNM2	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
EFNB2	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
EIF2AK2	Affinity Capture-Western, Reconstituted Complex	physical	17290288, (Europe PMC)	NA	BioGRID
ELP2	Affinity Capture-Western	physical	10954736, (Europe PMC)	NA	BioGRID
FHL3	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	21516116, 25416956, (Europe PMC)	0.70	BioGRID, IntAct
FYN	Affinity Capture-Western, Reconstituted Complex	physical	9196040, (Europe PMC)	NA	BioGRID
GHR	Affinity Capture-Western	physical	10502458, (Europe PMC)	NA	BioGRID
GMNN	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
GPR156	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
HAVCR2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
HNRNPH1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
HNRNPK	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.49, 0.56	BioGRID, IntAct
HNRNPL	Affinity Capture-RNA	physical	28611215, (Europe PMC)	NA	BioGRID
HSP90AA1	Affinity Capture-Luminescence	physical	22939624, (Europe PMC)	NA	BioGRID
HSP90AB1	anti tag coimmunoprecipitation, luminescence based mammalian interactome mapping	physical association	22939624, (Europe PMC)	0.52	IntAct
HSPB1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
IFNAR1	Affinity Capture-Western, Reconstituted Complex, molecular sieving, pull down	direct interaction, physical, physical association	10523853, 15337770, 15356134, 18474601, 24704786, 9733772, (Europe PMC)	0.40, 0.56	BioGRID, IntAct, MINT
IFT43	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
IL13RA1	Affinity Capture-Western	physical	10409622, (Europe PMC)	NA	BioGRID
IL4R	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
IL6ST	Affinity Capture-Western	physical	9388212, (Europe PMC)	NA	BioGRID
IRS2	Reconstituted Complex	physical	8550573, (Europe PMC)	NA	BioGRID
JAK1	Affinity Capture-Western	physical	7589562, (Europe PMC)	NA	BioGRID
JAK2	anti bait coimmunoprecipitation	physical association	26175413, (Europe PMC)	0.40	IntAct
JAK3	Affinity Capture-Western	physical	12207328, (Europe PMC)	NA	BioGRID
KHDRBS2	Two-hybrid, two hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	21516116, 25416956, (Europe PMC)	0.76	BioGRID, IntAct, MINT
KLF10	Affinity Capture-Western	physical	21471442, (Europe PMC)	NA	BioGRID
KRT40	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.56	BioGRID, IntAct
LGALS3BP	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
LNX1	Affinity Capture-Western	physical	22087225, (Europe PMC)	NA	BioGRID
LPAR6	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
LRP8	Affinity Capture-MS	physical	26496610, (Europe PMC)	NA	BioGRID
LRRC46	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
LYN	Reconstituted Complex	physical	9633884, (Europe PMC)	NA	BioGRID
MAS1	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
MIER2	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
MOV10	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
NLGN3	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
NXF1	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
PIH1D1	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
PLAUR	Affinity Capture-Western	physical	9417082, (Europe PMC)	NA	BioGRID
PMEL	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PRKCA	anti bait coimmunoprecipitation	physical association	17290288, (Europe PMC)	0.40	IntAct, MINT
PRMT5	Reconstituted Complex	physical	10531356, (Europe PMC)	NA	BioGRID
PROSER2	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
PTAFR	Affinity Capture-Western	physical	14500680, (Europe PMC)	NA	BioGRID
PTPN1	Affinity Capture-Western, coimmunoprecipitation	physical, physical association	11694501, (Europe PMC)	0.40	BioGRID, IntAct, MINT
PTPN6	Affinity Capture-Western, Biochemical Activity	physical	7629131, (Europe PMC)	NA	BioGRID
RACK1	Affinity Capture-Western, Reconstituted Complex	physical	12960323, (Europe PMC)	NA	BioGRID
RAN	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
RIPK4	anti tag coimmunoprecipitation	association	26972000, (Europe PMC)	0.35	IntAct
RNF13	Affinity Capture-MS	physical	26186194, 28514442, (Europe PMC)	NA	BioGRID
RUVBL1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
RUVBL2	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
SHMT2	Affinity Capture-RNA	physical	22658674, (Europe PMC)	NA	BioGRID
SIAH2	Affinity Capture-Western	physical	24833526, (Europe PMC)	NA	BioGRID
SIVA1	Affinity Capture-Western, Phenotypic Enhancement, Two-hybrid	genetic, physical	20727854, (Europe PMC)	NA	BioGRID
SLC2A1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
SOCS1	Affinity Capture-Western	physical	21757742, (Europe PMC)	NA	BioGRID
STAM2	Affinity Capture-Western	physical	10899310, (Europe PMC)	NA	BioGRID
STAT1	Biochemical Activity	physical	12960323, (Europe PMC)	NA	BioGRID
TCP1	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TGFBR2	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID
TK1	Two-hybrid, two hybrid	physical, physical association	21900206, (Europe PMC)	0.37	BioGRID, IntAct, MINT
TMCO3	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TNFRSF13B	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TNFRSF19	Affinity Capture-MS	physical	28514442, (Europe PMC)	NA	BioGRID
TRAF4	Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid	physical, physical association	25416956, (Europe PMC)	0.56	BioGRID, IntAct
TRIM28	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TUBA4A	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
TYK2	Affinity Capture-Western	physical	7589562, (Europe PMC)	NA	BioGRID
UBE2F	two hybrid	physical association	19549727, (Europe PMC)	0.37	IntAct
UBE2L6	Affinity Capture-Western	physical	24833526, (Europe PMC)	NA	BioGRID
VAV1	Affinity Capture-Western	physical	10673353, (Europe PMC)	NA	BioGRID
WDR20	Affinity Capture-MS, anti tag coimmunoprecipitation	association, physical	25852190, (Europe PMC)	0.35	BioGRID, IntAct
XRCC5	Affinity Capture-Western	physical	10673353, (Europe PMC)	NA	BioGRID
ZNF333	Affinity Capture-MS	physical	26186194, (Europe PMC)	NA	BioGRID

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TYK2