TBK1 (TANK-binding kinase 1) is a cytoplasmic non-canonical IKB kinase (IKK)-related serine/threonine protein kinase. Its domain architecture comprises an N-terminal protein kinase domain, a ubiquitin-like domain (ULD), a scaffold/dimerization domain, and a C-terminal coiled-coil region that mediates homodimerization; the active kinase is generated by trans-autophosphorylation at Ser172. TBK1 is a master kinase of innate antiviral immunity: downstream of cytoplasmic nucleic-acid sensors (RIG-I/MDA5 via MAVS; cGAS via STING1) and endosomal Toll-like receptors (TLR3/TLR4 via TRIF/TICAM1), TBK1 phosphorylates these adaptor proteins on their pLxIS motif to recruit and then phosphorylate the transcription factors IRF3 and IRF7, driving their dimerization, nuclear translocation, and induction of type I interferons (IFN-alpha/IFN-beta) and other antiviral/pro-inflammatory genes. It is the kinase effector of the cGAS-STING DNA-sensing pathway and was originally identified as an NF-kappaB-activating kinase (binding the adaptor TANK), phosphorylating RELA/NFKBIA/IKBKB under particular conditions. TBK1 is also a central kinase of selective autophagy: it phosphorylates the autophagy cargo receptors OPTN/optineurin (Ser177), SQSTM1/p62, NDP52/CALCOCO2 and TAX1BP1 to enhance their ubiquitin- and LC3-binding and drive mitophagy and antibacterial xenophagy, and it phosphorylates SMCR8 (in the C9orf72-SMCR8 complex) and the ATG8 proteins MAP1LC3C and GABARAPL2 to promote autophagosome maturation. TBK1 assembles into kinase complexes with scaffolding adaptors AZI2/NAP1, TANK and TBKBP1/SINTBAD. Additional context-dependent roles include bidirectional regulation of mTORC1/mTORC2 signaling, AKT1 activation, and immune cell differentiation. TBK1 activity is antagonized by numerous viral proteins, and human mutations cause familial ALS/frontotemporal dementia (haploinsufficiency), normal-tension/primary open-angle glaucoma, herpes-simplex encephalopathy, and autoinflammatory disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm: the core compartment where TBK1 assembles into signaling complexes and phosphorylates its substrates. Reason: Core cytoplasmic localization, experimentally supported. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0002218 activation of innate immune response | IBA GO_REF:0000033 | ACCEPT | Summary: Activation of innate immune response: core process; TBK1 activation is a central node in innate antiviral signaling. Reason: Core biological process directly supported by experimental evidence. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0032481 positive regulation of type I interferon production | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0002218 activation of innate immune response | IEA GO_REF:0000117 | ACCEPT | Summary: Activation of innate immune response: core process; TBK1 activation is a central node in innate antiviral signaling. Reason: Core biological process directly supported by experimental evidence. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding by the kinase domain, part of the catalytic mechanism of TBK1. Reason: Correct and integral to the core protein kinase activity. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm: the core compartment where TBK1 assembles into signaling complexes and phosphorylates its substrates. Reason: Core cytoplasmic localization, experimentally supported. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0006952 defense response | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Defense response: a generic parent of TBK1's specific antiviral/innate-immune role. Reason: Correct but generic; the specific antiviral-innate-immune-response and type-I-IFN-production terms capture the core function more precisely. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0016239 positive regulation of macroautophagy | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of macroautophagy: core process; TBK1 phosphorylates autophagy receptors (OPTN Ser177) and SMCR8 to promote selective autophagy and autophagosome maturation. Reason: Core biological process directly demonstrated (OPTN, SMCR8, ATG8 phosphorylation). Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy |
| GO:0032008 positive regulation of TOR signaling | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of TOR signaling (IEA): generic mTOR-pathway parent; secondary/pleiotropic. Reason: Generic and context-dependent; non-core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR |
| GO:0032728 positive regulation of interferon-beta production | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of interferon-beta production: a specific, core output of TBK1-mediated IRF3 activation. Reason: Core biological process; TBK1 induces IFN-beta via IRF3. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of canonical NF-kappaB signal transduction: the founding role of TBK1 (TANK-binding kinase) as an IKK-related NF-kappaB-activating kinase. Reason: Well-supported biological process; TBK1 was identified as an NF-kappaB-activating IKK-related kinase and phosphorylates RELA/NFKBIA/IKBKB under particular conditions. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus |
| GO:0051707 response to other organism | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Response to other organism: a generic parent of TBK1's specific antiviral/innate-immune role. Reason: Correct but generic; the specific antiviral-innate-immune-response and type-I-IFN-production terms capture the core function more precisely. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005515 protein binding | IPI PMID:14743216 A physical and functional map of the human TNF-alpha/NF-kapp... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:15841462 Interaction between the HCV NS3 protein and the host TBK1 pr... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:16306936 Critical role of TRAF3 in the Toll-like receptor-dependent a... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:17568778 SINTBAD, a novel component of innate antiviral immunity, sha... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:17599067 Involvement of the ubiquitin-like domain of TBK1/IKK-i kinas... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:18307994 Enhanced binding of TBK1 by an optineurin mutant that causes... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:18583960 The DEAD-box helicase DDX3X is a critical component of the T... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:18724357 STING is an endoplasmic reticulum adaptor that facilitates i... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:19153231 Ebola virus protein VP35 impairs the function of interferon ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:19380580 Severe acute respiratory syndrome coronavirus M protein inhi... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:19416887 ISG56 is a negative-feedback regulator of virus-triggered si... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:20098747 Expanding the substantial interactome of NEMO using protein ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:21931555 Vaccinia virus protein C6 is a virulence factor that binds T... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:22000020 Activation of STAT6 by STING is critical for antiviral innat... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:23096996 Hepatitis C virus NS2 protease inhibits host cell antiviral ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:23542348 Hepatitis C virus NS4B blocks the interaction of STING and T... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:24509444 Suppression of innate antiviral response by severe acute res... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:24622840 SARS coronavirus papain-like protease inhibits the type I in... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:24643253 MAVS protein is attenuated by rotavirus nonstructural protei... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:24696485 Murine gammaherpesvirus 68 encoding open reading frame 11 ta... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:24807708 RIOK3 is an adaptor protein required for IRF3-mediated antiv... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:25803835 Haploinsufficiency of TBK1 causes familial ALS and fronto-te... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:27086836 The TBK1-binding domain of optineurin promotes type I interf... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:27094905 Middle East respiratory syndrome coronavirus M protein suppr... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:27135603 A TRAF-like motif of the inducible costimulator ICOS control... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:29251827 Quantitative Proteomics Identified TTC4 as a TBK1 Interactor... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:32353859 A SARS-CoV-2 protein interaction map reveals targets for dru... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:32979938 Evasion of Type I Interferon by SARS-CoV-2. | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:33060197 Comparative host-coronavirus protein interaction networks re... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:33372174 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:33707416 SARS-CoV-2 non-structural protein 13 (nsp13) hijacks host de... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:34084167 SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Produ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:34166398 SARS-CoV-2 viral proteins NSP1 and NSP13 inhibit interferon ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pat... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Nucleic acid binding, transferred electronically from the mouse ortholog (Ensembl Compara). TBK1 is a protein serine/threonine kinase; there is no experimental support for it being a sequence-nonspecific nucleic-acid-binding protein. Reason: Electronic ortholog transfer with no experimental basis for TBK1; biologically implausible as a molecular function for this protein kinase. Flagged as over-annotation (electronic, not experimental). Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression, transferred electronically from the mouse ortholog. The documented role of TBK1 is to positively drive antiviral/inflammatory gene expression (IFNs) via IRF3/IRF7; a generic negative-regulation term mischaracterizes the core function. Reason: Overly generic electronic ortholog transfer that does not reflect the documented positive, IRF-driven transcriptional role; flagged as over-annotation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB |
| GO:0019903 protein phosphatase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein phosphatase binding, inferred by orthology (IEA/ISS). Relates to regulation of TBK1 phosphorylation status; not a core function. Reason: Orthology-based interaction property; non-core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Identical protein binding (homodimerization), inferred electronically from the mouse ortholog. TBK1 does homodimerize via its C-terminal coiled-coil, but the term is uninformative. Reason: Real homodimerization but the term is uninformative; the coiled-coil-mediated dimerization is better described at the structural level. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt and a C-terminal coiled-coil region mediating homodimerization. |
| GO:0060340 positive regulation of type I interferon-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of type I interferon-mediated signaling pathway (IEA ortholog). Same caveat as GO:0060337 - TBK1's documented role is in IFN induction rather than downstream IFN-receptor signaling. Reason: Orthology-based; imprecise relative to TBK1's induction role. Non-core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:1904417 positive regulation of xenophagy | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of xenophagy: TBK1 phosphorylates OPTN on Ser177 to drive selective autophagy of cytosolic bacteria (e.g. Salmonella). Reason: Core biological process directly demonstrated for antibacterial (xeno)phagy. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy |
| GO:1904515 positive regulation of TORC2 signaling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of TORC2 signaling (ISS/IEA, by orthology): TBK1 promotes mTORC2-dependent AKT1 activation. Secondary/pleiotropic role. Reason: Orthology-based, secondary role; non-core relative to innate immunity/autophagy. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Acts as a positive regulator of the mTORC2 complex by mediating phosphorylation of MTOR |
| GO:0016236 macroautophagy | TAS Reactome:R-HSA-5205685 | KEEP AS NON CORE | Summary: Macroautophagy (Reactome PINK1-PRKN mitophagy TAS). A generic parent of TBK1's specific positive-regulatory autophagy role. Reason: Correct but generic; the positive-regulation-of-macroautophagy/xenophagy terms capture the core function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy |
| GO:0032481 positive regulation of type I interferon production | TAS Reactome:R-HSA-1834941 | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0032481 positive regulation of type I interferon production | TAS Reactome:R-HSA-3270619 | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:27035970 Phosphorylation of OPTN by TBK1 enhances its binding to Ub c... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-2396007 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-3249371 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-933525 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleoplasm (IDA, immunofluorescence/HPA): a minor pool. TBK1 is predominantly cytoplasmic and acts there. Reason: Minor/secondary localization; the dominant functional pool is cytoplasmic. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:15485837 NAK is recruited to the TNFR1 complex in a TNFalpha-dependen... | ACCEPT | Summary: Cytoplasm: the core compartment where TBK1 assembles into signaling complexes and phosphorylates its substrates. Reason: Core cytoplasmic localization, experimentally supported. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:32298923 E3 ubiquitin ligase ASB8 negatively regulates interferon via... | ACCEPT | Summary: Cytoplasm: the core compartment where TBK1 assembles into signaling complexes and phosphorylates its substrates. Reason: Core cytoplasmic localization, experimentally supported. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0106310 protein serine kinase activity | EXP PMID:10783893 NAK is an IkappaB kinase-activating kinase. | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:14703513 Identification of Ser-386 of interferon regulatory factor 3 ... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:15367631 Activation of TBK1 and IKKvarepsilon kinases by vesicular st... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:18583960 The DEAD-box helicase DDX3X is a critical component of the T... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:21138416 Novel cross-talk within the IKK family controls innate immun... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:21270402 TANK-binding kinase 1 attenuates PTAP-dependent retroviral b... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:21464307 IkappaB kinase epsilon and TANK-binding kinase 1 activate AK... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:21617041 Phosphorylation of the autophagy receptor optineurin restric... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:29150432 The IKK-related kinase TBK1 activates mTORC1 directly in res... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:31530866 TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Se... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0106310 protein serine kinase activity | EXP PMID:31709703 TBK1-mediated phosphorylation of LC3C and GABARAP-L2 control... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0051607 defense response to virus | NAS PMID:17142768 NAK-associated protein 1 participates in both the TLR3 and t... | ACCEPT | Summary: Defense response to virus: a core, well-supported biological process; TBK1 is essential for antiviral defense via IRF3/type I IFN. Reason: Core biological process strongly supported across the literature. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0051607 defense response to virus | NAS PMID:21931631 Functional dissection of the TBK1 molecular network. | ACCEPT | Summary: Defense response to virus: a core, well-supported biological process; TBK1 is essential for antiviral defense via IRF3/type I IFN. Reason: Core biological process strongly supported across the literature. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0051607 defense response to virus | NAS PMID:24622840 SARS coronavirus papain-like protease inhibits the type I in... | ACCEPT | Summary: Defense response to virus: a core, well-supported biological process; TBK1 is essential for antiviral defense via IRF3/type I IFN. Reason: Core biological process strongly supported across the literature. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0060337 type I interferon-mediated signaling pathway | NAS PMID:17142768 NAK-associated protein 1 participates in both the TLR3 and t... | KEEP AS NON CORE | Summary: Type I interferon-mediated signaling pathway. TBK1 acts in IFN *induction* (driving IRF3/IFN gene expression) rather than in downstream IFN-receptor (JAK/STAT) signaling that this term most precisely denotes. Reason: Correct pathway context but imprecise: TBK1's role is upstream IFN induction; the positive-regulation-of-type-I-IFN-production terms capture the core function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0060337 type I interferon-mediated signaling pathway | NAS PMID:21931631 Functional dissection of the TBK1 molecular network. | KEEP AS NON CORE | Summary: Type I interferon-mediated signaling pathway. TBK1 acts in IFN *induction* (driving IRF3/IFN gene expression) rather than in downstream IFN-receptor (JAK/STAT) signaling that this term most precisely denotes. Reason: Correct pathway context but imprecise: TBK1's role is upstream IFN induction; the positive-regulation-of-type-I-IFN-production terms capture the core function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:1902554 serine/threonine protein kinase complex | NAS PMID:17142768 NAK-associated protein 1 participates in both the TLR3 and t... | ACCEPT | Summary: Serine/threonine protein kinase complex: TBK1 functions within kinase complexes (e.g. the TBK1-IKKepsilon-NAP1/TANK/SINTBAD complexes). Reason: Core cellular component; TBK1 acts as part of ser/thr kinase complexes with its adaptors. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes |
| GO:1902554 serine/threonine protein kinase complex | NAS PMID:21931631 Functional dissection of the TBK1 molecular network. | ACCEPT | Summary: Serine/threonine protein kinase complex: TBK1 functions within kinase complexes (e.g. the TBK1-IKKepsilon-NAP1/TANK/SINTBAD complexes). Reason: Core cellular component; TBK1 acts as part of ser/thr kinase complexes with its adaptors. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes |
| GO:1902554 serine/threonine protein kinase complex | NAS PMID:24622840 SARS coronavirus papain-like protease inhibits the type I in... | ACCEPT | Summary: Serine/threonine protein kinase complex: TBK1 functions within kinase complexes (e.g. the TBK1-IKKepsilon-NAP1/TANK/SINTBAD complexes). Reason: Core cellular component; TBK1 acts as part of ser/thr kinase complexes with its adaptors. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes |
| GO:0005515 protein binding | IPI PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:29441066 TANK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Ty... | ACCEPT | Summary: Cytoplasmic pattern recognition receptor signaling pathway: TBK1 functions downstream of cytoplasmic RNA/DNA sensors (RIG-I/MDA5-MAVS, cGAS-STING). Reason: Core biological process; TBK1 transduces cytoplasmic PRR signals to IRF3. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:14703513 Identification of Ser-386 of interferon regulatory factor 3 ... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005737 cytoplasm | IDA PMID:14703513 Identification of Ser-386 of interferon regulatory factor 3 ... | ACCEPT | Summary: Cytoplasm: the core compartment where TBK1 assembles into signaling complexes and phosphorylates its substrates. Reason: Core cytoplasmic localization, experimentally supported. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:22412986 Activation of interferon regulatory factor 5 by site specifi... | KEEP AS NON CORE | Summary: RNA polymerase II transcription factor binding (IRF5), recording TBK1 binding to its IRF substrate. The informative function is the kinase activity that phosphorylates IRFs. Reason: Records an IRF (substrate) interaction; subsumed by the core kinase activity and IFN-production annotations. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 |
| GO:0106310 protein serine kinase activity | IDA PMID:22412986 Activation of interferon regulatory factor 5 by site specifi... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0140896 cGAS/STING signaling pathway | TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe... | ACCEPT | Summary: cGAS/STING signaling pathway: TBK1 is the kinase recruited by activated STING1 that phosphorylates STING1 and IRF3 in the cytosolic DNA-sensing pathway. Reason: Core biological process; TBK1 is an essential kinase of the cGAS-STING axis. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 |
| GO:0004674 protein serine/threonine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:1904515 positive regulation of TORC2 signaling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of TORC2 signaling (ISS/IEA, by orthology): TBK1 promotes mTORC2-dependent AKT1 activation. Secondary/pleiotropic role. Reason: Orthology-based, secondary role; non-core relative to innate immunity/autophagy. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Acts as a positive regulator of the mTORC2 complex by mediating phosphorylation of MTOR |
| GO:0005829 cytosol | IDA PMID:21813773 IFN-induced TPR protein IFIT3 potentiates antiviral signalin... | ACCEPT | Summary: Cytosol: the core subcellular location of TBK1 signaling activity. Reason: Core cytosolic localization consistent with experimental cytoplasmic localization. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0061470 T follicular helper cell differentiation | IDA PMID:27135603 A TRAF-like motif of the inducible costimulator ICOS control... | KEEP AS NON CORE | Summary: T follicular helper cell differentiation: TBK1 participates with ICOS in TFH/TFR cell differentiation. A specialized, developmental/immunological role. Reason: Specialized pleiotropic role; non-core relative to the kinase's central innate-immune/autophagy functions. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt participates in the differentiation of T follicular regulatory cells together with the receptor ICOS |
| GO:0005515 protein binding | IPI PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcription... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0140374 antiviral innate immune response | IDA PMID:14703513 Identification of Ser-386 of interferon regulatory factor 3 ... | ACCEPT | Summary: Antiviral innate immune response: a core biological process for TBK1, which phosphorylates IRF3 (e.g. Ser-386) and the adaptors STING1/MAVS/TRIF to drive antiviral gene expression. Reason: Core biological process directly demonstrated; TBK1 is a master kinase of antiviral innate immunity. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005829 cytosol | TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe... | ACCEPT | Summary: Cytosol: the core subcellular location of TBK1 signaling activity. Reason: Core cytosolic localization consistent with experimental cytoplasmic localization. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22394562 STING specifies IRF3 phosphorylation by TBK1 in the cytosoli... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:22394562 STING specifies IRF3 phosphorylation by TBK1 in the cytosoli... | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0140374 antiviral innate immune response | IDA PMID:22394562 STING specifies IRF3 phosphorylation by TBK1 in the cytosoli... | ACCEPT | Summary: Antiviral innate immune response: a core biological process for TBK1, which phosphorylates IRF3 (e.g. Ser-386) and the adaptors STING1/MAVS/TRIF to drive antiviral gene expression. Reason: Core biological process directly demonstrated; TBK1 is a master kinase of antiviral innate immunity. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0002218 activation of innate immune response | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: Activation of innate immune response: core process; TBK1 activation is a central node in innate antiviral signaling. Reason: Core biological process directly supported by experimental evidence. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:29150432 The IKK-related kinase TBK1 activates mTORC1 directly in res... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:31530866 TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Se... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:1904262 negative regulation of TORC1 signaling | IDA PMID:31530866 TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Se... | KEEP AS NON CORE | Summary: Negative regulation of TORC1 signaling: TBK1 limits mTORC1 by phosphorylating RPTOR (Ser877). A context-dependent, secondary role opposite to its TORC1-activating role. Reason: Real but context-dependent/pleiotropic; non-core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt it limits the mTORC1 complex by promoting phosphorylation of RPTOR |
| GO:1904263 positive regulation of TORC1 signaling | IDA PMID:29150432 The IKK-related kinase TBK1 activates mTORC1 directly in res... | KEEP AS NON CORE | Summary: Positive regulation of TORC1 signaling: TBK1 activates mTORC1 in response to growth factors (MTOR phosphorylation). A context-dependent, secondary role. Reason: Real but context-dependent and pleiotropic; opposite TORC1 effects are reported depending on stimulus. Non-core relative to innate immunity/autophagy. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:28747347 TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Res... | KEEP AS NON CORE | Summary: Toll-like receptor 4 signaling pathway: TBK1 acts downstream of TLR4 (via TRIF) to activate IRF3. An upstream-pathway context for its IFN-induction role. Reason: Correct pathway context; the antiviral-innate-immune and type-I-IFN terms are the core capture. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:14703513 Identification of Ser-386 of interferon regulatory factor 3 ... | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22921120 TBK-1 promotes autophagy-mediated antimicrobial defense by c... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0010508 positive regulation of autophagy | IDA PMID:28871090 TRIM23 mediates virus-induced autophagy via activation of TB... | ACCEPT | Summary: Positive regulation of autophagy: core process driven by TBK1 phosphorylation of autophagy machinery and receptors. Reason: Core biological process directly demonstrated. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:29441066 TANK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Ty... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0032728 positive regulation of interferon-beta production | IDA PMID:31390091 TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiv... | ACCEPT | Summary: Positive regulation of interferon-beta production: a specific, core output of TBK1-mediated IRF3 activation. Reason: Core biological process; TBK1 induces IFN-beta via IRF3. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:29441066 TANK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Ty... | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:31709703 TBK1-mediated phosphorylation of LC3C and GABARAP-L2 control... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823904 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828200 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005515 protein binding | IPI PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:30354798 Ccdc61 controls centrosomal localization of Cep170 and is re... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:31662325 Phosphorylation of RAB7 by TBK1/IKKΞ΅ Regulates Innate Immune... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005737 cytoplasm | IDA PMID:29251827 Quantitative Proteomics Identified TTC4 as a TBK1 Interactor... | ACCEPT | Summary: Cytoplasm: the core compartment where TBK1 assembles into signaling complexes and phosphorylates its substrates. Reason: Core cytoplasmic localization, experimentally supported. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005515 protein binding | IPI PMID:28011935 TTLL12 Inhibits the Activation of Cellular Antiviral Signali... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | KEEP AS NON CORE | Summary: Peptidyl-serine phosphorylation: a generic process description of TBK1's kinase activity. Reason: Correct but generic; the protein serine/threonine kinase activity (MF) and the specific signaling-pathway terms are more informative. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0018107 peptidyl-threonine phosphorylation | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | KEEP AS NON CORE | Summary: Peptidyl-threonine phosphorylation: a generic process description of TBK1's kinase activity. Reason: Correct but generic; the protein serine/threonine kinase activity (MF) and the specific signaling-pathway terms are more informative. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0032479 regulation of type I interferon production | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: Regulation of type I interferon production: core regulatory role of TBK1 via adaptor and IRF3 phosphorylation. Reason: Core biological process; consistent with the positive-regulation-of-type-I-IFN annotations. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0045087 innate immune response | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: Innate immune response: core biological process for TBK1. Reason: Core biological process; TBK1 is central to innate immune signaling. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0019903 protein phosphatase binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Protein phosphatase binding, inferred by orthology (IEA/ISS). Relates to regulation of TBK1 phosphorylation status; not a core function. Reason: Orthology-based interaction property; non-core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9008684 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005515 protein binding | IPI PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0006468 protein phosphorylation | IDA PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ... | KEEP AS NON CORE | Summary: Protein phosphorylation: a generic process description of TBK1's kinase activity. Reason: Correct but generic; the protein serine/threonine kinase activity (MF) and the specific signaling-pathway terms are more informative. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005515 protein binding | IPI PMID:24560620 NLRC3, a member of the NLR family of proteins, is a negative... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0016239 positive regulation of macroautophagy | IDA PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ... | ACCEPT | Summary: Positive regulation of macroautophagy: core process; TBK1 phosphorylates autophagy receptors (OPTN Ser177) and SMCR8 to promote selective autophagy and autophagosome maturation. Reason: Core biological process directly demonstrated (OPTN, SMCR8, ATG8 phosphorylation). Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy |
| GO:0005515 protein binding | IPI PMID:25736436 WDFY1 mediates TLR3/4 signaling by recruiting TRIF. | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:25803835 Haploinsufficiency of TBK1 causes familial ALS and fronto-te... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0005515 protein binding | IPI PMID:24056301 The deubiquitylase USP33 discriminates between RALB function... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3249386 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948709 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1606327 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166245 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166271 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396002 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396007 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3249371 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3249390 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3249392 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948703 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013978 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013979 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-918229 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-918232 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933525 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933538 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9679819 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705320 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705323 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9817397 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9817411 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823906 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824892 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824894 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824897 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828205 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9840807 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005515 protein binding | IPI PMID:21813773 IFN-induced TPR protein IFIT3 potentiates antiviral signalin... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005737 cytoplasm | IDA PMID:21813773 IFN-induced TPR protein IFIT3 potentiates antiviral signalin... | ACCEPT | Summary: Cytoplasm: the core compartment where TBK1 assembles into signaling complexes and phosphorylates its substrates. Reason: Core cytoplasmic localization, experimentally supported. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005515 protein binding | IPI PMID:18636086 The tumour suppressor CYLD is a negative regulator of RIG-I-... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:21042276 Emerging roles for the non-canonical IKKs in cancer. | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0006954 inflammatory response | TAS PMID:21042276 Emerging roles for the non-canonical IKKs in cancer. | KEEP AS NON CORE | Summary: Inflammatory response (review TAS). A broad downstream consequence of TBK1 signaling. Reason: Broad/secondary process; the specific IFN and NF-kappaB signaling terms are more informative. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0007249 canonical NF-kappaB signal transduction | TAS PMID:21042276 Emerging roles for the non-canonical IKKs in cancer. | KEEP AS NON CORE | Summary: Canonical NF-kappaB signal transduction (TAS). Records TBK1's NF-kappaB-pathway involvement; the positive-regulation term is the more informative capture. Reason: Correct pathway context; subsumed by the positive-regulation-of-canonical-NF-kappaB annotation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA |
| GO:0009615 response to virus | TAS PMID:21042276 Emerging roles for the non-canonical IKKs in cancer. | KEEP AS NON CORE | Summary: Response to virus: a generic parent of TBK1's specific antiviral/innate-immune role. Reason: Correct but generic; the specific antiviral-innate-immune-response and type-I-IFN-production terms capture the core function more precisely. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0032481 positive regulation of type I interferon production | TAS PMID:21042276 Emerging roles for the non-canonical IKKs in cancer. | ACCEPT | Summary: Positive regulation of type I interferon production: core process by which TBK1 phosphorylates IRF3/IRF7 to induce IFN-alpha/IFN-beta. Reason: Core biological process; TBK1 drives type I IFN induction via IRF3/IRF7 phosphorylation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0045087 innate immune response | TAS PMID:21042276 Emerging roles for the non-canonical IKKs in cancer. | ACCEPT | Summary: Innate immune response: core biological process for TBK1. Reason: Core biological process; TBK1 is central to innate immune signaling. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 |
| GO:0032727 positive regulation of interferon-alpha production | IDA PMID:16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I... | ACCEPT | Summary: Positive regulation of interferon-alpha production: core output of TBK1/IRF7 activation in the RIG-I/MAVS (IPS-1) pathway. Reason: Core biological process; TBK1 induces IFN-alpha via IRF activation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB |
| GO:0032728 positive regulation of interferon-beta production | IDA PMID:16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I... | ACCEPT | Summary: Positive regulation of interferon-beta production: a specific, core output of TBK1-mediated IRF3 activation. Reason: Core biological process; TBK1 induces IFN-beta via IRF3. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I... | KEEP AS NON CORE | Summary: Positive regulation of transcription by RNA polymerase II: an indirect consequence of TBK1 activating IRF3/IRF7 transcription factors. Reason: Indirect (via IRF activation); non-core. The IFN-production terms capture the relevant output. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt leading to transcriptional activation of pro-inflammatory and antiviral genes |
| GO:0005515 protein binding | IPI PMID:19419966 The tyrosine kinase c-Src enhances RIG-I (retinoic acid-indu... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0005515 protein binding | IPI PMID:20174559 Optineurin negatively regulates the induction of IFNbeta in ... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0051219 phosphoprotein binding | IPI PMID:14530355 Toll/IL-1 receptor domain-containing adaptor inducing IFN-be... | KEEP AS NON CORE | Summary: Phosphoprotein binding (TRIF/TICAM1 study). A specific interaction property; uninformative as a core function. Reason: Records an interaction property; not a core function and subsumed by kinase activity. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1834939 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3249378 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-918225 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933527 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-937337 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705010 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705082 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705137 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705145 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9709831 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9709852 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9710988 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9754827 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823910 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823934 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824888 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828196 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828209 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction-step annotation. Correct core compartment, though one of many redundant per-step pathway localizations. Reason: Correct cytosolic compartment where TBK1 signaling occurs; redundant with the experimental cytosol/cytoplasm evidence but consistent and retained as core. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005515 protein binding | IPI PMID:16281057 SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- a... | KEEP AS NON CORE | Summary: IPI interaction annotation. TBK1 has a very large interactome (adaptors TANK/AZI2/SINTBAD, OPTN, STING1, MAVS, TRAF3, DDX3X, regulators, and many viral antagonists). These interactions are functionally important but bare protein binding is uninformative. Reason: Records real interactions but bare protein binding (GO:0005515) is uninformative per curation guidelines; the kinase activity and specific signaling-pathway annotations capture the function. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEP PMID:12761501 Large-scale identification and characterization of human gen... | ACCEPT | Summary: Positive regulation of canonical NF-kappaB signal transduction: the founding role of TBK1 (TANK-binding kinase) as an IKK-related NF-kappaB-activating kinase. Reason: Well-supported biological process; TBK1 was identified as an NF-kappaB-activating IKK-related kinase and phosphorylates RELA/NFKBIA/IKBKB under particular conditions. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus |
| GO:0004672 protein kinase activity | NAS PMID:10581243 NF-kappaB activation by a signaling complex containing TRAF2... | ACCEPT | Summary: TBK1 is a non-canonical IKK-related serine/threonine protein kinase; this is its core, extensively documented molecular function (trans-autophosphorylation at Ser172; phosphorylation of IRF3/IRF7, the adaptors MAVS/STING1/TICAM1, OPTN, SMCR8, ATG8s, etc.). Reason: Core molecular function directly demonstrated by multiple experimental studies. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents |
| GO:0007249 canonical NF-kappaB signal transduction | TAS PMID:10581243 NF-kappaB activation by a signaling complex containing TRAF2... | KEEP AS NON CORE | Summary: Canonical NF-kappaB signal transduction (TAS). Records TBK1's NF-kappaB-pathway involvement; the positive-regulation term is the more informative capture. Reason: Correct pathway context; subsumed by the positive-regulation-of-canonical-NF-kappaB annotation. Supporting Evidence: file:human/TBK1/TBK1-uniprot.txt functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA |
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Download this section (compressed HTML)Q: How is TBK1's substrate selection partitioned between its antiviral/IFN-induction outputs (IRF3/IRF7, STING1/MAVS/TRIF) and its selective-autophagy outputs (OPTN, NDP52, TAX1BP1, SMCR8, ATG8s) within different signaling complexes and adaptors?
Q: Given that TBK1 both activates and limits mTORC1 depending on stimulus, what determines the directionality of its mTOR regulation, and how does this intersect with its core innate-immune and autophagy roles?
Experiment: Use TBK1-knockout cells reconstituted with wild-type, kinase-dead (K38A), or Ser172-phospho-deficient TBK1, combined with phosphoproteomics under cGAS-STING, RIG-I/MAVS, TLR3/4, and mitophagy/xenophagy stimuli, to map the stimulus-specific TBK1 substrate repertoire and distinguish core IFN-induction from autophagy outputs.
Experiment: Reconstitute IRF3 and OPTN phosphorylation in vitro with purified TBK1 and the adaptors STING1/MAVS or autophagy receptors to test how adaptor pLxIS-motif phosphorylation and TBK1 oligomerization license downstream substrate phosphorylation.
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