TYK2 is a Janus kinase (JAK) family non-receptor tyrosine kinase with N-terminal FERM and SH2-like domains, a regulatory pseudokinase domain and a C-terminal tyrosine kinase domain. It lacks a transmembrane segment and binds constitutively, via its FERM-SH2 module, to membrane-proximal box1/box2 motifs in the intracellular domains of specific cytokine receptor chains (IFNAR1, IL12RB1, IL10RB, IL13RA1), so it acts on the cytoplasmic face of the plasma membrane. Upon cytokine-induced receptor dimerization TYK2 is activated with its partner JAK (JAK1 or JAK2), phosphorylates receptor tyrosines to create STAT docking sites, and phosphorylates STAT proteins, driving type I interferon, IL-10 family, IL-12 and IL-23 signaling. It is also required for normal IFNAR1 surface expression. TYK2 deficiency causes immunodeficiency with susceptibility to mycobacterial and viral infections, and TYK2 variants are associated with autoimmune disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to protein kinase activity. Reason: Correct but general; TYK2 is a non-membrane spanning protein tyrosine kinase (GO:0004715). Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:1386289 A protein tyrosine kinase in the interferon alpha/beta signa... | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:1386289 tyk2 links the interferon alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:7526154 Direct binding to and tyrosine phosphorylation of the alpha ... | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte... | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:8232552 The reciprocal interdependence between JAK1 and Tyk2 activities in the interferon-alpha pathway |
| GO:0004713 protein tyrosine kinase activity | IC PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ... | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:7543512 IL-10 treatment of both T cells and monocytes results in the ligand-induced tyrosine phosphorylation of tyk2 and Jak1 |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:10542297 Catalytically active TYK2 is essential for interferon-beta-m... | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:10542297 catalytically active TYK2 is required for IFN-beta-mediated tyrosine phosphorylation of STAT3 and IFNAR-1 in intact cells |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit |
| GO:0004713 protein tyrosine kinase activity | TAS PMID:7528775 Interleukin 12 (IL-12) induces tyrosine phosphorylation of J... | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:7528775 IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2 and JAK2 |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-909730 | MODIFY | Summary: TYK2 is a Janus-family tyrosine kinase that phosphorylates receptor chains (IFNAR1) and STATs. Reason: Correct but general; TYK2 lacks a transmembrane segment and the more specific term non-membrane spanning protein tyrosine kinase activity (GO:0004715), already carried by the gene, is supported. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: Reactome:R-HSA-909730 PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of non-membrane spanning PTK activity for the JAK family. Reason: Matches direct biochemical evidence for TYK2. Supporting Evidence: PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit PMID:7657660 Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701 |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:7526154 Direct binding to and tyrosine phosphorylation of the alpha ... | ACCEPT | Summary: Core catalytic activity: cytoplasmic (non-receptor) tyrosine kinase that phosphorylates IFNAR1, other receptor chains and STATs. Reason: Direct in vitro kinase assays (IFNAR1, STAT1 Tyr701) and kinase-dead complementation establish this activity; TYK2 has no transmembrane domain. Supporting Evidence: PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:7657660 Phosphorylation and activation of the DNA binding activity o... | ACCEPT | Summary: Core catalytic activity: cytoplasmic (non-receptor) tyrosine kinase that phosphorylates IFNAR1, other receptor chains and STATs. Reason: Direct in vitro kinase assays (IFNAR1, STAT1 Tyr701) and kinase-dead complementation establish this activity; TYK2 has no transmembrane domain. Supporting Evidence: PMID:7657660 Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701 |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte... | ACCEPT | Summary: Core catalytic activity: cytoplasmic (non-receptor) tyrosine kinase that phosphorylates IFNAR1, other receptor chains and STATs. Reason: Direct in vitro kinase assays (IFNAR1, STAT1 Tyr701) and kinase-dead complementation establish this activity; TYK2 has no transmembrane domain. Supporting Evidence: PMID:8232552 The reciprocal interdependence between JAK1 and Tyk2 activities in the interferon-alpha pathway |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) ... | ACCEPT | Summary: Core catalytic activity: cytoplasmic (non-receptor) tyrosine kinase that phosphorylates IFNAR1, other receptor chains and STATs. Reason: Direct in vitro kinase assays (IFNAR1, STAT1 Tyr701) and kinase-dead complementation establish this activity; TYK2 has no transmembrane domain. Supporting Evidence: PMID:8605876 We demonstrate that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core catalytic activity: cytoplasmic (non-receptor) tyrosine kinase that phosphorylates IFNAR1, other receptor chains and STATs. Reason: Direct in vitro kinase assays (IFNAR1, STAT1 Tyr701) and kinase-dead complementation establish this activity; TYK2 has no transmembrane domain. Supporting Evidence: PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit PMID:7657660 Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701 |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | TAS PMID:2216457 tyk2, prototype of a novel class of non-receptor tyrosine ki... | ACCEPT | Summary: Core catalytic activity: cytoplasmic (non-receptor) tyrosine kinase that phosphorylates IFNAR1, other receptor chains and STATs. Reason: Direct in vitro kinase assays (IFNAR1, STAT1 Tyr701) and kinase-dead complementation establish this activity; TYK2 has no transmembrane domain. Supporting Evidence: PMID:2216457 Hydrophobicity analysis of our sequence does not identify a transmembrane domain |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | TAS Reactome:R-HSA-6788582 | ACCEPT | Summary: Core catalytic activity: cytoplasmic (non-receptor) tyrosine kinase that phosphorylates IFNAR1, other receptor chains and STATs. Reason: Direct in vitro kinase assays (IFNAR1, STAT1 Tyr701) and kinase-dead complementation establish this activity; TYK2 has no transmembrane domain. Supporting Evidence: Reactome:R-HSA-6788582 PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit |
| GO:0005131 growth hormone receptor binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference of growth hormone receptor binding for JAK family. Reason: TYK2 co-immunoprecipitates with GHR in human liver, but GH signaling is primarily JAK2-mediated; peripheral to TYK2 core cytokine signaling. Supporting Evidence: PMID:10502458 Jak1, Jak2 and Tyk2 were associated with the GHR in this tissue |
| GO:0005131 growth hormone receptor binding | IPI PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and T... | KEEP AS NON CORE | Summary: TYK2 co-immunoprecipitates with GHR in human liver. Reason: Supported binding, but GHR signaling is mainly via JAK2; non-core for TYK2. Supporting Evidence: PMID:10502458 Jak1, Jak2 and Tyk2 were associated with the GHR in this tissue |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24704786 Structural basis of recognition of interferon-Ξ± receptor by ... | MODIFY | Summary: Crystal structure of TYK2 FERM-SH2 bound to the IFNAR1 box2 intracellular motif. Reason: The interaction is specific receptor binding: TYK2 binds the intracellular domain of the type I interferon receptor chain IFNAR1, so type I interferon receptor binding is the informative term. Proposed replacements: type I interferon receptor binding Supporting Evidence: PMID:24704786 in complex with a so-called 'box2'-containing intracellular peptide motif from the interferon-Ξ± receptor chain 1 (IFNAR1) PMID:7526154 the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26175413 CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibi... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32953130 SARS-CoV-2 N protein antagonizes type I interferon signaling... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34521819 TODO: Fetch title | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the interaction is not disputed, but the assay does not establish a more informative molecular function. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding inferred from the kinase domain. Reason: True (ATP is the phosphate donor of the kinase reaction) but ancillary to the catalytic activity. Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling |
| GO:0005634 nucleus | IDA PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and T... | KEEP AS NON CORE | Summary: Immunohistochemical detection in human liver nuclei. Reason: Curator IDA retained; nuclear TYK2 is not part of the established signaling mechanism, which occurs at receptor complexes in the cytoplasm. Supporting Evidence: PMID:10502458 Using Western blot analysis and immunohistochemistry, we demonstrate that Jak1, Jak2, Jak3 and Tyk2 are present in human liver. |
| GO:0005737 cytoplasm | IDA PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and T... | KEEP AS NON CORE | Summary: Immunohistochemical detection in liver cytoplasm. Reason: Correct; the method does not resolve membrane-associated versus soluble pools. Function is at the cytoplasmic face of the plasma membrane. Supporting Evidence: PMID:10502458 Using Western blot analysis and immunohistochemistry, we demonstrate that Jak1, Jak2, Jak3 and Tyk2 are present in human liver. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-447130 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-447130 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-447226 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-447226 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-447252 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-447252 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-448661 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-448661 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-449811 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-449811 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6784006 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6784006 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6784319 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6784319 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6784323 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6784323 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6784324 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6784324 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6784791 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6784791 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6785762 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6785762 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6785821 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6785821 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786050 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6786050 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786070 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6786070 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786110 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6786110 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786114 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6786114 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786118 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6786118 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6788571 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6788571 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6788582 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6788582 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6788628 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-6788628 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8854645 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8854645 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950128 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950128 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950269 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950269 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950340 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950340 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950423 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950423 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950441 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950441 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950448 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950448 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950485 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950485 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950518 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950518 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950537 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950537 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950757 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8950757 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8952749 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8952749 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8952807 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8952807 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8952823 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8952823 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8981093 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8981093 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8986480 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8986480 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8986985 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8986985 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8986994 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8986994 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8986995 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8986995 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987014 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987014 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987033 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987033 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987040 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987040 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987042 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987042 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987070 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987070 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987080 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987080 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987105 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987105 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987132 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987132 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987202 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987202 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987223 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987223 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987230 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987230 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987236 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987236 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987255 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987255 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987266 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-8987266 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909718 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909718 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909719 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909719 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909722 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909722 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909724 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909724 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909726 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909726 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909729 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909729 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909730 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909730 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909732 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-909732 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9674816 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-9674816 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9678737 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-9678737 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705738 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-9705738 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9707977 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-9707977 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9851114 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-9851114 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-997309 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-997309 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-997311 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-997311 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005829 cytosol | TAS Reactome:R-HSA-997314 | KEEP AS NON CORE | Summary: Reactome/PAINT place TYK2 in the cytosol. Reason: TYK2 is a soluble cytoplasmic protein, but its functional pool is bound to the intracellular domains of cytokine receptors at the cytoplasmic face of the plasma membrane (GO:0031234); cytosol is correct for the unbound pool but peripheral to function. Supporting Evidence: Reactome:R-HSA-997314 PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0005886 plasma membrane | NAS PMID:1495999 Molecular basis of the membrane-anchored and two soluble iso... | MODIFY | Summary: TYK2 associates with the plasma membrane via cytokine receptor intracellular domains. Reason: Correct but general: TYK2 is not an integral membrane protein; it is a peripheral protein bound to receptor ICDs on the cytoplasmic side of the plasma membrane (GO:0031234, already carried by the gene). It is not exposed at the cell surface. Proposed replacements: extrinsic component of cytoplasmic side of plasma membrane Supporting Evidence: PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors PMID:34813358 the intracellular domains (ICDs) of which are associated with the kinases TYK2 and JAK1, respectively |
| GO:0005886 plasma membrane | TAS PMID:34813358 IFNAR1 and IFNAR2 play distinct roles in initiating type I i... | MODIFY | Summary: TYK2 associates with the plasma membrane via cytokine receptor intracellular domains. Reason: Correct but general: TYK2 is not an integral membrane protein; it is a peripheral protein bound to receptor ICDs on the cytoplasmic side of the plasma membrane (GO:0031234, already carried by the gene). It is not exposed at the cell surface. Proposed replacements: extrinsic component of cytoplasmic side of plasma membrane Supporting Evidence: PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors PMID:34813358 the intracellular domains (ICDs) of which are associated with the kinases TYK2 and JAK1, respectively |
| GO:0005895 interleukin-5 receptor complex | NAS PMID:1495999 Molecular basis of the membrane-anchored and two soluble iso... | UNDECIDED | Summary: NAS linking TYK2 to the IL-5 receptor complex. Reason: The cited paper concerns IL5RA isoforms and its abstract does not mention TYK2; IL-5 receptor signaling is reported to use JAK1/JAK2. Cannot verify the basis for this statement. Supporting Evidence: PMID:9516124 JAK2 and JAK1 were associated with hIL-5Ralpha and betac |
| GO:0006468 protein phosphorylation | TAS PMID:2216457 tyk2, prototype of a novel class of non-receptor tyrosine ki... | MODIFY | Summary: Early sequence analysis predicted a kinase involved in protein phosphorylation. Reason: Correct but general; TYK2 phosphorylates tyrosine residues on receptors and STATs, supported by direct assays. Proposed replacements: peptidyl-tyrosine phosphorylation Supporting Evidence: PMID:2216457 Hydrophobicity analysis of our sequence does not identify a transmembrane domain PMID:7657660 Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701 |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IDA PMID:7526154 Direct binding to and tyrosine phosphorylation of the alpha ... | ACCEPT | Summary: TYK2 mediates cytokine receptor signaling via JAK-STAT. Reason: Core process: TYK2 phosphorylates receptor chains and STATs downstream of type I IFN, IL-10, IL-12 and IL-23 family receptors. Supporting Evidence: PMID:7526154 These data support the hypothesis that the Tyk2 protein functions as part of a receptor complex to initiate intracellular signaling in response to type I IFNs. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IDA PMID:7657660 Phosphorylation and activation of the DNA binding activity o... | ACCEPT | Summary: TYK2 mediates cytokine receptor signaling via JAK-STAT. Reason: Core process: TYK2 phosphorylates receptor chains and STATs downstream of type I IFN, IL-10, IL-12 and IL-23 family receptors. Supporting Evidence: PMID:7657660 Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701 |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte... | ACCEPT | Summary: TYK2 mediates cytokine receptor signaling via JAK-STAT. Reason: Core process: TYK2 phosphorylates receptor chains and STATs downstream of type I IFN, IL-10, IL-12 and IL-23 family receptors. Supporting Evidence: PMID:8232552 The reciprocal interdependence between JAK1 and Tyk2 activities in the interferon-alpha pathway |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IDA PMID:8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) ... | ACCEPT | Summary: TYK2 mediates cytokine receptor signaling via JAK-STAT. Reason: Core process: TYK2 phosphorylates receptor chains and STATs downstream of type I IFN, IL-10, IL-12 and IL-23 family receptors. Supporting Evidence: PMID:8605876 We demonstrate that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IDA PMID:9516124 JAK2 and JAK1 constitutively associate with an interleukin-5... | ACCEPT | Summary: TYK2 mediates cytokine receptor signaling via JAK-STAT. Reason: Core process: TYK2 phosphorylates receptor chains and STATs downstream of type I IFN, IL-10, IL-12 and IL-23 family receptors. Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IEA GO_REF:0000117 | ACCEPT | Summary: TYK2 mediates cytokine receptor signaling via JAK-STAT. Reason: Core process: TYK2 phosphorylates receptor chains and STATs downstream of type I IFN, IL-10, IL-12 and IL-23 family receptors. Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 |
| GO:0008283 cell population proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic ortholog transfer of cell population proliferation. Reason: Proliferation is a downstream, context-dependent consequence of cytokine signaling, not a process TYK2 directly executes. Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling |
| GO:0009898 cytoplasmic side of plasma membrane | IC PMID:7528775 Interleukin 12 (IL-12) induces tyrosine phosphorylation of J... | MODIFY | Summary: TYK2 acts at the cytoplasmic side of the plasma membrane, bound to receptor ICDs. Reason: Correct but the term should specify a peripheral (extrinsic) association: TYK2 is a soluble kinase docked on receptor intracellular domains. Proposed replacements: extrinsic component of cytoplasmic side of plasma membrane Supporting Evidence: PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors PMID:7528775 IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2 and JAK2 |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to membrane. Reason: Too general; TYK2 is a peripheral protein on the cytoplasmic side of the plasma membrane bound to cytokine receptors. Proposed replacements: extrinsic component of cytoplasmic side of plasma membrane Supporting Evidence: PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0019221 cytokine-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of cytokine-mediated signaling. Reason: Appropriate summary-level process for a kinase shared by many cytokine receptors (type I IFN, IL-10, IL-12, IL-23 families). Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling |
| GO:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic mapping to cytokine-mediated signaling. Reason: Consistent with direct evidence. Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling |
| GO:0019221 cytokine-mediated signaling pathway | TAS Reactome:R-HSA-6785807 | ACCEPT | Summary: Reactome cytokine signaling. Reason: Consistent with direct evidence. Supporting Evidence: Reactome:R-HSA-6785807 file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling |
| GO:0019897 extrinsic component of plasma membrane | TAS PMID:34813358 IFNAR1 and IFNAR2 play distinct roles in initiating type I i... | MODIFY | Summary: TYK2 associates with the plasma membrane via the IFNAR1 ICD. Reason: Correct but refine to the cytoplasmic side: TYK2 is extrinsic to the inner leaflet, not exposed extracellularly. Proposed replacements: extrinsic component of cytoplasmic side of plasma membrane Supporting Evidence: PMID:34813358 the intracellular domains (ICDs) of which are associated with the kinases TYK2 and JAK1, respectively PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference of cell differentiation. Reason: Plausible downstream role (e.g. IL-12/IL-23 driven T-helper differentiation) but indirect relative to the kinase signaling function. Supporting Evidence: PMID:7528775 IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2 and JAK2 |
| GO:0031234 extrinsic component of cytoplasmic side of plasma membrane | IC PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ... | ACCEPT | Summary: TYK2 is bound to IL-10 and IL-12 receptor intracellular domains at the cytoplasmic face of the plasma membrane. Reason: Correct peripheral membrane location for the functional pool of a JAK kinase; no extracellular exposure. Supporting Evidence: PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors PMID:34813358 the intracellular domains (ICDs) of which are associated with the kinases TYK2 and JAK1, respectively |
| GO:0031234 extrinsic component of cytoplasmic side of plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: UniProt mapping to extrinsic component of cytoplasmic side of plasma membrane. Reason: Correct and specific. Supporting Evidence: PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference of intracellular signal transduction. Reason: True in a broad sense but less informative than the cell surface receptor JAK-STAT pathway terms accepted here. Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro mapping to intracellular signal transduction. Reason: As above. Supporting Evidence: file:human/TYK2/TYK2-uniprot.txt Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling |
| GO:0035722 interleukin-12-mediated signaling pathway | IDA PMID:7528775 Interleukin 12 (IL-12) induces tyrosine phosphorylation of J... | ACCEPT | Summary: IL-12 induces tyrosine phosphorylation of TYK2 in T cells. Reason: TYK2 associates with IL12RB1 and is required for IL-12 signaling. Supporting Evidence: PMID:7528775 IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2 and JAK2 file:human/TYK2/TYK2-uniprot.txt Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 |
| GO:0038043 interleukin-5-mediated signaling pathway | NAS PMID:7888666 Interleukin-5 signaling in human eosinophils involves JAK2 t... | UNDECIDED | Summary: NAS linking TYK2 to IL-5 signaling in eosinophils. Reason: The cited abstract reports only JAK2 phosphorylation in response to IL-5; TYK2 involvement could not be verified. Supporting Evidence: PMID:7888666 IL-5 induced rapid and transient tyrosine phosphorylation of JAK2. |
| GO:0038155 interleukin-23-mediated signaling pathway | IDA PMID:7528775 Interleukin 12 (IL-12) induces tyrosine phosphorylation of J... | ACCEPT | Summary: TYK2 participates in IL-23 receptor signaling. Reason: IL-23 shares the TYK2-associated IL12RB1 chain with IL-12; curator IDA from the cited paper retained. Supporting Evidence: PMID:7528775 IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2 and JAK2 file:human/TYK2/TYK2-uniprot.txt Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 |
| GO:0042102 positive regulation of T cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer of positive regulation of T cell proliferation. Reason: Downstream consequence of IL-12/IL-23 signaling; peripheral. Supporting Evidence: PMID:7528775 IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2 and JAK2 |
| GO:0060333 type II interferon-mediated signaling pathway | IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte... | UNDECIDED | Summary: IDA for TYK2 in type II interferon signaling. Reason: The cited abstract assigns IFN-gamma signaling to JAK1 and JAK2, with TYK2 linked to the IFN-alpha pathway. Without full text, TYK2 involvement in IFN-gamma signaling cannot be verified. Supporting Evidence: PMID:8232552 between JAK1 and JAK2 in the interferon-gamma pathway |
| GO:0060337 type I interferon-mediated signaling pathway | IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte... | ACCEPT | Summary: TYK2 is required for type I interferon signaling. Reason: Core: TYK2 is bound to IFNAR1, phosphorylates it and STATs, and genetic complementation of the 11.1 mutant restores IFN-alpha response. Supporting Evidence: PMID:8232552 The reciprocal interdependence between JAK1 and Tyk2 activities in the interferon-alpha pathway PMID:1386289 tyk2 links the interferon alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes |
| GO:0060337 type I interferon-mediated signaling pathway | TAS Reactome:R-HSA-909733 | ACCEPT | Summary: Reactome type I IFN signaling. Reason: Consistent with core function. Supporting Evidence: Reactome:R-HSA-909733 PMID:1386289 tyk2 links the interferon alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference of GH receptor JAK-STAT signaling. Reason: TYK2 associates with GHR but GH signaling is primarily JAK2-dependent; non-core. Supporting Evidence: PMID:10502458 Jak1, Jak2 and Tyk2 were associated with the GHR in this tissue |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | Summary: Detected in a B-cell exosome proteome. Reason: High-throughput detection only; TYK2 is a cytoplasmic kinase and not a physiological exosome or extracellular protein. Supporting Evidence: PMID:20458337 identified 539 proteins PMID:24704786 lack a transmembrane component and instead constitutively associate with membrane proximal peptide motifs found on the intracellular side of cytokine receptors |
| GO:0140105 interleukin-10-mediated signaling pathway | IDA PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ... | ACCEPT | Summary: IL-10 induces tyrosine phosphorylation of TYK2. Reason: TYK2 associates with IL10RB and transmits IL-10 signals. Supporting Evidence: PMID:7543512 IL-10 treatment of both T cells and monocytes results in the ligand-induced tyrosine phosphorylation of tyk2 and Jak1 file:human/TYK2/TYK2-uniprot.txt Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 |
| GO:1900182 positive regulation of protein localization to nucleus | IDA PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v... | KEEP AS NON CORE | Summary: TYK2 promotes STAT nuclear accumulation. Reason: Downstream consequence of STAT phosphorylation; peripheral to kinase function. Supporting Evidence: |
| GO:1900182 positive regulation of protein localization to nucleus | IDA PMID:8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) ... | KEEP AS NON CORE | Summary: IFNAR1 phosphorylation by TYK2 enables STAT docking and nuclear translocation. Reason: Downstream consequence of TYK2 kinase activity; peripheral. Supporting Evidence: PMID:8605876 We demonstrate that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1. |
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Download this section (compressed HTML)Q: Does TYK2 contribute to IFN-gamma or IL-5 signaling in primary human cells, or are these pathways strictly JAK1/JAK2-dependent?
Q: How does the pseudokinase domain-mediated autoinhibition differ between TYK2 bound to IFNAR1 versus IL12RB1, and how do allosteric inhibitors (deucravacitinib) exploit this?
Experiment: Compare IFN-gamma and IL-5 induced STAT phosphorylation in TYK2-null versus kinase-dead TYK2 primary human cells to resolve the unverified pathway assignments.
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