JAK3 is a Janus-family non-receptor tyrosine kinase expressed mainly in hematopoietic cells, especially lymphocytes and NK cells. Through its N-terminal FERM domain it binds the cytoplasmic tail of the common gamma chain (IL2RG) shared by the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, and it acts together with JAK1, which binds the partner receptor chains. Cytokine binding activates JAK3 by autophosphorylation, after which JAK1/JAK3 phosphorylate the receptor tails and recruited STATs, chiefly STAT5, which dimerize and enter the nucleus to regulate transcription. JAK3 is a cytoplasmic protein that acts at the inner face of the plasma membrane. Inactivating JAK3 mutations cause autosomal recessive T-B+NK- severe combined immunodeficiency, mirroring IL2RG-deficient X-linked SCID.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002731 negative regulation of dendritic cell cytokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic protein kinase activity from InterPro. Reason: Correct but too general; JAK3 is a non-membrane spanning protein tyrosine kinase, already annotated. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:18829468 Ligand-independent homomeric and heteromeric complexes betwe... | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:7973658 Interaction of IL-2R beta and gamma c chains with Jak1 and J... | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat... | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004713 protein tyrosine kinase activity | IMP PMID:18250158 Phosphorylation of human Jak3 at tyrosines 904 and 939 posit... | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004713 protein tyrosine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004713 protein tyrosine kinase activity | TAS PMID:8022790 Molecular cloning of L-JAK, a Janus family protein-tyrosine ... | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-451942 | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: JAK3 is a non-receptor tyrosine kinase activated downstream of gamma c cytokine receptors. Reason: Core catalytic activity; JAK3 is tyrosine phosphorylated and activated by IL-2-family cytokines, restores IL-2 responsiveness in JAK3-negative cells, and mutation of its autophosphorylation sites reduces kinase activity and STAT5 phosphorylation. Supporting Evidence: PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. |
| GO:0005131 growth hormone receptor binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Growth hormone receptor binding propagated from the Janus-kinase family. Reason: The JAK family as a whole binds GH receptor, but JAK3 is specialized for the common gamma chain of IL-2-family receptors; growth hormone signaling is mediated predominantly by JAK2, and there is no direct evidence that JAK3 binds GHR as a physiological partner. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN002521566 SUPPORTS SOURCE BUT NOT TARGET Ancestral node seeded by JAK2/Jak2 GHR evidence; JAK3 diverged to pair with gamma c receptors. MGI:MGI:96628 SUPPORTS SOURCE BUT NOT TARGET Mouse Jak2 GHR binding is well supported but does not establish JAK3 binding. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:9045636 Interaction between Sam68 and Src family tyrosine kinases, F... | REMOVE | Summary: High-throughput or targeted interaction reported (NAP1L1, MAGED2, Sam68, SMARCA4, SMAD4, FBXW7). Reason: Bare protein binding is uninformative under the protein-binding policy; these interactions (largely from kinase interaction screens or neo-interaction screens with cancer mutants) do not define a JAK3 function. Removal does not mean the interactions are false. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding by the kinase domain. Reason: Implied by tyrosine kinase activity; autophosphorylation sites are required for optimal ATP usage. Supporting Evidence: PMID:18250158 Y904 and Y939 were required for optimal ATP usage by Jak3 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005768 endosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Endosome/endomembrane association, by similarity or Reactome modeling of internalized receptor complexes. Reason: Receptor-bound JAK3 can accompany internalized or trafficking receptors on the cytoplasmic face of endomembranes; this is a secondary location. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005768 endosome | TAS Reactome:R-HSA-8983335 | KEEP AS NON CORE | Summary: Endosome/endomembrane association, by similarity or Reactome modeling of internalized receptor complexes. Reason: Receptor-bound JAK3 can accompany internalized or trafficking receptors on the cytoplasmic face of endomembranes; this is a secondary location. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295540 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-449115 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-449958 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450063 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-451895 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-451942 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452091 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452097 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452100 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452108 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452122 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-453104 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-453111 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-508247 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-508282 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-508292 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-508451 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-508513 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6785165 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786058 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786072 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786092 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786095 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786096 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786124 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8963734 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983003 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983063 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983298 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983300 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983335 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983371 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983374 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983378 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983384 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8985914 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9006844 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9006850 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9006870 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9006873 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9025969 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-912527 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-913374 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-913424 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-919404 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9679028 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9701485 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9701488 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9701507 | ACCEPT | Summary: JAK3 is a soluble cytoplasmic kinase. Reason: JAK3 lacks membrane-spanning segments and acts in the cytoplasm at receptor tails; Reactome places its receptor-associated reactions in the cytosol. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8985900 | MODIFY | Summary: JAK3 associates with the plasma membrane through gamma c receptor chains. Reason: True but less specific than warranted; JAK3 is a peripheral cytoplasmic-side protein, not an integral or surface-exposed membrane protein. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8985914 | MODIFY | Summary: JAK3 associates with the plasma membrane through gamma c receptor chains. Reason: True but less specific than warranted; JAK3 is a peripheral cytoplasmic-side protein, not an integral or surface-exposed membrane protein. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8985929 | MODIFY | Summary: JAK3 associates with the plasma membrane through gamma c receptor chains. Reason: True but less specific than warranted; JAK3 is a peripheral cytoplasmic-side protein, not an integral or surface-exposed membrane protein. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8985973 | MODIFY | Summary: JAK3 associates with the plasma membrane through gamma c receptor chains. Reason: True but less specific than warranted; JAK3 is a peripheral cytoplasmic-side protein, not an integral or surface-exposed membrane protein. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8985988 | MODIFY | Summary: JAK3 associates with the plasma membrane through gamma c receptor chains. Reason: True but less specific than warranted; JAK3 is a peripheral cytoplasmic-side protein, not an integral or surface-exposed membrane protein. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0007167 enzyme-linked receptor protein signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Broad pathway class covering kinase-associated cytokine receptors. Reason: Defensible grouping; specific cytokine pathways are accepted. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IEA GO_REF:0000117 | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | NAS PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0007260 tyrosine phosphorylation of STAT protein | TAS PMID:19290934 Janus kinases in immune cell signaling. | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0009898 cytoplasmic side of plasma membrane | IC PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat... | ACCEPT | Summary: JAK3 is bound to the cytoplasmic tail of the gamma c receptor chain at the inner face of the plasma membrane. Reason: JAK3 has no transmembrane segment and is recruited to the cytoplasmic membrane face by binding the C-terminal region of IL2RG; this is its functional location. Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0010561 negative regulation of glycoprotein biosynthetic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Mouse-derived negative regulation of glycoprotein biosynthesis. Reason: No mechanism links JAK3 to glycoprotein biosynthesis; the source phenotype probably reflects altered surface marker expression in Jak3-deficient cells, an indirect consequence of cytokine signaling. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0012505 endomembrane system | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Endosome/endomembrane association, by similarity or Reactome modeling of internalized receptor complexes. Reason: Receptor-bound JAK3 can accompany internalized or trafficking receptors on the cytoplasmic face of endomembranes; this is a secondary location. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: JAK3 associates with the plasma membrane through gamma c receptor chains. Reason: True but less specific than warranted; JAK3 is a peripheral cytoplasmic-side protein, not an integral or surface-exposed membrane protein. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0019221 cytokine-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0019897 extrinsic component of plasma membrane | IC PMID:7973658 Interaction of IL-2R beta and gamma c chains with Jak1 and J... | MODIFY | Summary: JAK3 is a peripheral protein of the plasma membrane via receptor binding. Reason: Correct but the association is specifically on the cytoplasmic side; the more precise term is already carried. Proposed replacements: extrinsic component of cytoplasmic side of plasma membrane Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively |
| GO:0019903 protein phosphatase binding | IPI PMID:11909529 The T cell protein tyrosine phosphatase is a negative regula... | KEEP AS NON CORE | Summary: JAK3 is a substrate of and binds the T cell protein tyrosine phosphatase TCPTP (PTPN2). Reason: Supported binding, but it reflects JAK3 being dephosphorylated by a negative regulator rather than a JAK3 function. Supporting Evidence: PMID:11909529 We have identified two members of the Janus family of tyrosine kinases (JAKs), JAK1 and JAK3, as bona fide substrates of TCPTP. |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | MODIFY | Summary: Cell differentiation propagated across the Janus family. Reason: Too general. For JAK3 the supported differentiation role is lymphoid, particularly thymic T cell development, which fails in JAK3 deficiency. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96629 SUPPORTS TRANSFER Differentiation roles are conserved across JAKs but lineage-specific; for JAK3 it is lymphocyte development. Proposed replacements: T cell differentiation in thymus Supporting Evidence: PMID:9973401 Targeted deletion of the murine Jak3 gene results in severe reduction of alphabeta and complete elimination of gammadelta lineage thymocytes and NK cells. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. |
| GO:0030183 B cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Lymphocyte development/homeostasis outcome of JAK3-dependent gamma c signaling. Reason: Jak3-deficient mice lack normal T, NK and (in mice) B cell development, and human JAK3 deficiency causes T-B+NK- SCID; these are downstream of IL-7/IL-15 receptor signaling. Supporting Evidence: PMID:9973401 Targeted deletion of the murine Jak3 gene results in severe reduction of alphabeta and complete elimination of gammadelta lineage thymocytes and NK cells. PMID:19290934 A striking phenotype associated with inactivating Jak3 mutations is severe combined immunodeficiency syndrome |
| GO:0031234 extrinsic component of cytoplasmic side of plasma membrane | IC PMID:18829468 Ligand-independent homomeric and heteromeric complexes betwe... | ACCEPT | Summary: JAK3 is bound to the cytoplasmic tail of the gamma c receptor chain at the inner face of the plasma membrane. Reason: JAK3 has no transmembrane segment and is recruited to the cytoplasmic membrane face by binding the C-terminal region of IL2RG; this is its functional location. Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0031234 extrinsic component of cytoplasmic side of plasma membrane | IC PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat... | ACCEPT | Summary: JAK3 is bound to the cytoplasmic tail of the gamma c receptor chain at the inner face of the plasma membrane. Reason: JAK3 has no transmembrane segment and is recruited to the cytoplasmic membrane face by binding the C-terminal region of IL2RG; this is its functional location. Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0031234 extrinsic component of cytoplasmic side of plasma membrane | IDA PMID:7568001 Tyrosine phosphorylation and activation of STAT5, STAT3, and... | ACCEPT | Summary: JAK3 is bound to the cytoplasmic tail of the gamma c receptor chain at the inner face of the plasma membrane. Reason: JAK3 has no transmembrane segment and is recruited to the cytoplasmic membrane face by binding the C-terminal region of IL2RG; this is its functional location. Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0031234 extrinsic component of cytoplasmic side of plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: JAK3 is bound to the cytoplasmic tail of the gamma c receptor chain at the inner face of the plasma membrane. Reason: JAK3 has no transmembrane segment and is recruited to the cytoplasmic membrane face by binding the C-terminal region of IL2RG; this is its functional location. Supporting Evidence: PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0032693 negative regulation of interleukin-10 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
| GO:0032695 negative regulation of interleukin-12 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: JAK3 acts in intracellular signaling downstream of cytokine receptors. Reason: True but too general; JAK3 acts in cell surface receptor signaling via JAK-STAT, already accepted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96628 SUPPORTS TRANSFER JAK-family signaling role is conserved; the JAK-STAT receptor pathway term is the informative level. Proposed replacements: cell surface receptor signaling pathway via JAK-STAT Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: JAK3 acts in intracellular signaling downstream of cytokine receptors. Reason: True but too general; JAK3 acts in cell surface receptor signaling via JAK-STAT, already accepted. Proposed replacements: cell surface receptor signaling pathway via JAK-STAT Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0035556 intracellular signal transduction | ISS GO_REF:0000024 | MODIFY | Summary: JAK3 acts in intracellular signaling downstream of cytokine receptors. Reason: True but too general; JAK3 acts in cell surface receptor signaling via JAK-STAT, already accepted. Proposed replacements: cell surface receptor signaling pathway via JAK-STAT Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0035723 interleukin-15-mediated signaling pathway | IDA PMID:7568001 Tyrosine phosphorylation and activation of STAT5, STAT3, and... | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0035771 interleukin-4-mediated signaling pathway | IDA PMID:7538655 JAK3 associates with the human interleukin 4 receptor and is... | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0035771 interleukin-4-mediated signaling pathway | NAS PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0038110 interleukin-2-mediated signaling pathway | IDA PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat... | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0038110 interleukin-2-mediated signaling pathway | TAS Reactome:R-HSA-9020558 | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0038111 interleukin-7-mediated signaling pathway | IDA PMID:9182906 Jak3 activation in human lymphocyte precursor cells. | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0038113 interleukin-9-mediated signaling pathway | IDA PMID:18829468 Ligand-independent homomeric and heteromeric complexes betwe... | ACCEPT | Summary: JAK3 is the gamma c-associated kinase that transduces IL-2-family cytokine signals via STATs. Reason: Direct human evidence shows JAK3 association with and activation by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, and its kinase activity is needed for STAT5 phosphorylation; JAK3 deficiency causes SCID. Supporting Evidence: PMID:7973659 Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. PMID:7973658 Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:9182906 Jak3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. PMID:18250158 A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo |
| GO:0042981 regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: JAK3 signaling supports lymphocyte survival. Reason: Jak3-dependent IL-7 signaling maintains bcl-2 and thymocyte survival; an indirect, downstream effect. Supporting Evidence: PMID:9973401 we show that bcl-2 expression and in vivo survival of immature thymocytes are greatly compromised in Jak3-/- mice |
| GO:0043029 T cell homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Lymphocyte development/homeostasis outcome of JAK3-dependent gamma c signaling. Reason: Jak3-deficient mice lack normal T, NK and (in mice) B cell development, and human JAK3 deficiency causes T-B+NK- SCID; these are downstream of IL-7/IL-15 receptor signaling. Supporting Evidence: PMID:9973401 Targeted deletion of the murine Jak3 gene results in severe reduction of alphabeta and complete elimination of gammadelta lineage thymocytes and NK cells. PMID:19290934 A striking phenotype associated with inactivating Jak3 mutations is severe combined immunodeficiency syndrome |
| GO:0043029 T cell homeostasis | TAS PMID:19290934 Janus kinases in immune cell signaling. | KEEP AS NON CORE | Summary: Lymphocyte development/homeostasis outcome of JAK3-dependent gamma c signaling. Reason: Jak3-deficient mice lack normal T, NK and (in mice) B cell development, and human JAK3 deficiency causes T-B+NK- SCID; these are downstream of IL-7/IL-15 receptor signaling. Supporting Evidence: PMID:9973401 Targeted deletion of the murine Jak3 gene results in severe reduction of alphabeta and complete elimination of gammadelta lineage thymocytes and NK cells. PMID:19290934 A striking phenotype associated with inactivating Jak3 mutations is severe combined immunodeficiency syndrome |
| GO:0045626 negative regulation of T-helper 1 cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
| GO:0046425 regulation of receptor signaling pathway via JAK-STAT | TAS PMID:19290934 Janus kinases in immune cell signaling. | MARK AS OVER ANNOTATED | Summary: Review statement placing JAK3 as a regulator of JAK-STAT signaling. Reason: JAK3 is a core component of gamma c receptor JAK-STAT signaling rather than a regulator of it; participation is captured by the accepted pathway terms. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0050863 regulation of T cell activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
| GO:0050868 negative regulation of T cell activation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: GH receptor JAK-STAT signaling propagated from the Janus-kinase family. Reason: GH receptor signaling is carried out mainly by JAK2; JAK3 activity is restricted to gamma c cytokine receptors in lymphocytes. Any GH-induced JAK3 phosphorylation in cell lines is not a defining role. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN002521566 SUPPORTS SOURCE BUT NOT TARGET Node supported by JAK2 GH signaling; JAK3 receptor specificity diverged to gamma c receptors. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | TAS PMID:19290934 Janus kinases in immune cell signaling. | MARK AS OVER ANNOTATED | Summary: Review statement listing JAK roles in GH signaling. Reason: GH receptor signaling is a JAK2 function; JAK3 acts with gamma c cytokine receptors. Supporting Evidence: file:human/JAK3/JAK3-uniprot.txt In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. |
| GO:0070232 regulation of T cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: JAK3 signaling supports lymphocyte survival. Reason: Jak3-dependent IL-7 signaling maintains bcl-2 and thymocyte survival; an indirect, downstream effect. Supporting Evidence: PMID:9973401 we show that bcl-2 expression and in vivo survival of immature thymocytes are greatly compromised in Jak3-/- mice |
| GO:0070244 negative regulation of thymocyte apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: JAK3 signaling supports lymphocyte survival. Reason: Jak3-dependent IL-7 signaling maintains bcl-2 and thymocyte survival; an indirect, downstream effect. Supporting Evidence: PMID:9973401 we show that bcl-2 expression and in vivo survival of immature thymocytes are greatly compromised in Jak3-/- mice |
| GO:0070669 response to interleukin-2 | TAS PMID:9973401 Distinct effects of Jak3 signaling on alphabeta and gammadel... | KEEP AS NON CORE | Summary: JAK3 is activated in response to gamma c cytokines. Reason: JAK3 phosphorylation in response to IL-2, IL-4, IL-9 and IL-15 is well documented; the accepted cytokine-mediated signaling pathway terms describe the core role more precisely. Supporting Evidence: PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0070670 response to interleukin-4 | IDA PMID:7538655 JAK3 associates with the human interleukin 4 receptor and is... | KEEP AS NON CORE | Summary: JAK3 is activated in response to gamma c cytokines. Reason: JAK3 phosphorylation in response to IL-2, IL-4, IL-9 and IL-15 is well documented; the accepted cytokine-mediated signaling pathway terms describe the core role more precisely. Supporting Evidence: PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0070670 response to interleukin-4 | IDA PMID:7594533 Regulation of JAK3 expression and activation in human B cell... | KEEP AS NON CORE | Summary: JAK3 is activated in response to gamma c cytokines. Reason: JAK3 phosphorylation in response to IL-2, IL-4, IL-9 and IL-15 is well documented; the accepted cytokine-mediated signaling pathway terms describe the core role more precisely. Supporting Evidence: PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0070672 response to interleukin-15 | TAS PMID:7594533 Regulation of JAK3 expression and activation in human B cell... | KEEP AS NON CORE | Summary: JAK3 is activated in response to gamma c cytokines. Reason: JAK3 phosphorylation in response to IL-2, IL-4, IL-9 and IL-15 is well documented; the accepted cytokine-mediated signaling pathway terms describe the core role more precisely. Supporting Evidence: PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:0071104 response to interleukin-9 | TAS PMID:7594533 Regulation of JAK3 expression and activation in human B cell... | KEEP AS NON CORE | Summary: JAK3 is activated in response to gamma c cytokines. Reason: JAK3 phosphorylation in response to IL-2, IL-4, IL-9 and IL-15 is well documented; the accepted cytokine-mediated signaling pathway terms describe the core role more precisely. Supporting Evidence: PMID:7568001 JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. PMID:7538655 Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. |
| GO:1903037 regulation of leukocyte cell-cell adhesion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
| GO:2000329 negative regulation of T-helper 17 cell lineage commitment | IDA PMID:20696842 CD69 association with Jak3/Stat5 proteins regulates Th17 cel... | KEEP AS NON CORE | Summary: Immune regulatory phenotype of JAK3 deficiency or inhibition. Reason: Mouse knockout and inhibitor studies show altered dendritic cell cytokine production, T helper differentiation and T cell activation; these are context-dependent consequences of gamma c (and other) cytokine signaling rather than core activities. Supporting Evidence: PMID:20696842 Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORΞ³t. |
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Experiment: Swap FERM domains between JAK3 and JAK2 and test binding to IL2RG versus GHR/EPOR and rescue of IL-2 and GH signaling in JAK3-null lymphocytes.
Type: domain swap and complementation
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