TANK (TRAF family member-associated NF-kappa-B activator; also known as I-TRAF) is a cytoplasmic adaptor/scaffold protein, lacking any catalytic activity, that organizes signaling complexes in the innate immune and NF-kappaB pathways. It was first identified as a TRAF-interacting protein that binds the TRAF-C domains of TRAF1, TRAF2 and TRAF3 and modulates TRAF-mediated signaling. Its best-established role is as one of three mutually exclusive adaptors (alongside SINTBAD/TBKBP1 and NAP1/AZI2) that constitutively bind the IKK-related kinases TBK1 and IKBKE (IKKepsilon) via a central TBK1-binding domain and bridge them into complexes that phosphorylate IRF3/IRF7, driving type I interferon production during antiviral innate immunity; TBK1 activation in response to virus or poly(I:C) depends on the TANK-TBK1 interaction. TANK is the non-catalytic subunit of the TBK1-IKKepsilon-TANK kinase complex. TANK also has a separable negative-regulatory function: in response to genotoxic stress or interleukin-1/LPS it scaffolds a deubiquitination complex containing ZC3H12A (MCPIP1) and the deubiquitinase USP10, promoting USP10-dependent deubiquitination of TRAF6 (and NEMO/IKBKG) and thereby restraining canonical NF-kappaB activation. TANK itself contains no deubiquitinase domain, so its activity in this complex is purely as an assembly scaffold. Phosphorylation of TANK by IKBKE disrupts its binding to TRAF2, providing a phospho-switch on its adaptor function. Structurally TANK contains an N-terminal coiled-coil, a TBK1/IKBKE-binding region, a TRAF-interaction motif (which engages the CD40-recognition site of TRAF3), and a C-terminal UBZ1-type zinc finger. TANK is targeted by viral proteases (encephalomyocarditis virus and Seneca Valley virus 3C proteases cleave it; vaccinia C6 binds it) as an immune-evasion strategy, underscoring its role in the antiviral interferon response.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of cytoplasmic localization from the UniProt subcellular location. TANK is a cytoplasmic adaptor, so this is correct and matches the experimental IDA cytoplasm annotation. Reason: Correct core compartment; TANK acts as a cytoplasmic adaptor, consistent with the experimental IDA cytoplasm/cytosol annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based electronic assignment of negative regulation of canonical NF-kappaB signaling. This is corroborated by the experimental IMP of the same term (PMID:25861989) where TANK scaffolds USP10-dependent TRAF6 deubiquitination to restrain NF-kappaB. Reason: Correct and supported by experimental evidence, but reflects the secondary genotoxic/IL-1 NF-kappaB-restraining role rather than TANK's core TBK1/IKK adaptor function; redundant with the IMP annotation. Supporting Evidence: PMID:25861989 TANK negatively regulates NF-kappaB activation by DNA damage via inhibiting ubiquitination of TRAF6 |
| GO:0005515 protein binding | IPI PMID:12005438 Downstream regulator TANK binds to the CD40 recognition site... | KEEP AS NON CORE | Summary: IPI interaction with TRAF3 from the crystal structure study of the TANK peptide bound to the CD40-recognition site of TRAF3. A real, functionally important interaction, but bare protein binding is uninformative. Reason: Records the real TANK-TRAF3 interaction (structurally defined), but bare protein binding is uninformative per curation guidelines; the informative adaptor function is captured by GO:0060090. Supporting Evidence: PMID:12005438 TANK binds to the CD40 recognition site on TRAF3 |
| 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 interactions (TRAF2, TRAF3, TBK1) from a TNF-alpha/NF-kappaB pathway interaction map. Bare protein binding is uninformative. Reason: Records real pathway interactions (TRAF2/TRAF3/TBK1) but bare protein binding is uninformative; the adaptor function (GO:0060090) is the informative MF. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q12933: TRAF2; NbExp=10; IntAct=EBI-356349, EBI-355744 |
| GO:0005515 protein binding | IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu... | KEEP AS NON CORE | Summary: IPI interaction with HTT (huntingtin) from a genetic-modifier interactome screen. Bare protein binding is uninformative and this partner is not connected to TANK's core function. Reason: Records a real but functionally peripheral interaction (HTT); bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; P42858: HTT; NbExp=3; IntAct=EBI-356349, EBI-466029 |
| GO:0005515 protein binding | IPI PMID:17568778 SINTBAD, a novel component of innate antiviral immunity, sha... | KEEP AS NON CORE | Summary: IPI interactions with IKBKE/IKKepsilon and TBK1 from the SINTBAD paper showing TANK shares a TBK1-binding domain with NAP1 and SINTBAD. A real, core-relevant interaction, but bare protein binding is uninformative. Reason: Records the functionally central TANK-IKBKE/TBK1 interactions, but bare protein binding is uninformative; captured by the adaptor MF (GO:0060090). Supporting Evidence: PMID:17568778 shares a TBK1-binding domain with NAP1 and TANK |
| GO:0005515 protein binding | IPI PMID:18307994 Enhanced binding of TBK1 by an optineurin mutant that causes... | KEEP AS NON CORE | Summary: IPI interaction with TBK1 reported in a study of an optineurin mutant enhancing TBK1 binding. Bare protein binding is uninformative. Reason: Records a real TBK1 interaction but bare protein binding is uninformative; the adaptor function captures this. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q9UHD2: TBK1; NbExp=14; IntAct=EBI-356349, EBI-356402 |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | KEEP AS NON CORE | Summary: IPI interaction (TRAF2) from a network analysis of the human autophagy system. Bare protein binding is uninformative. Reason: High-throughput network interaction; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q12933: TRAF2; NbExp=10; IntAct=EBI-356349, EBI-355744 |
| GO:0005515 protein binding | IPI PMID:21212807 Inducible SUMO modification of TANK alleviates its repressio... | KEEP AS NON CORE | Summary: IPI interactions with SUMO1/SUMO2 from the study showing inducible SUMOylation of TANK alleviates its repression of TLR7 signaling. Bare protein binding is uninformative, but documents a regulatory SUMO modification of TANK. Reason: Records real SUMO1/2 interactions (SUMOylation regulates TANK's repressor activity) but bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; P63165: SUMO1; NbExp=8; IntAct=EBI-356349, EBI-80140 |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | KEEP AS NON CORE | Summary: IPI interaction (TSC1) from an autism-disorder interactome study. Bare protein binding is uninformative and the partner is not core to TANK function. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q92574: TSC1; NbExp=3; IntAct=EBI-356349, EBI-1047085 |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | KEEP AS NON CORE | Summary: IPI interactions (including TRAF2, TRAF3, TBK1) from a dynamic innate-immunity interaction network regulating type I interferon production. Bare protein binding is uninformative but the partners are core-relevant. Reason: Records real innate-immune interactions but bare protein binding is uninformative; the type I IFN adaptor role is captured by GO:0032481/GO:0060090. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q9UHD2: TBK1; NbExp=14; IntAct=EBI-356349, EBI-356402 |
| GO:0005515 protein binding | IPI PMID:21931555 Vaccinia virus protein C6 is a virulence factor that binds T... | KEEP AS NON CORE | Summary: IPI interactions (vaccinia virus C6, IKBKE, TBK1) from the study showing vaccinia C6 binds TBK1 adaptor proteins to inhibit IRF3/IRF7. Bare protein binding is uninformative but supports TANK's role in the TBK1-IRF antiviral axis. Reason: Records a host-virus interaction (C6) plus TBK1/IKBKE; bare protein binding is uninformative. Supporting Evidence: PMID:21931555 binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7 |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Summary: IPI interactions from a human liver protein interaction network (includes PLK1, TRAF2, TRAF1, TBK1, NEMO). Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; P53350: PLK1; NbExp=4; IntAct=EBI-356349, EBI-476768 |
| GO:0005515 protein binding | IPI PMID:24008843 Structure homology and interaction redundancy for discoverin... | KEEP AS NON CORE | Summary: IPI interaction with a viral protein (NS) from a structure-homology virus-host interaction study. Bare protein binding is uninformative. Reason: Host-virus interaction predicted/validated by homology; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; P03495: NS; Xeno; NbExp=2; IntAct=EBI-356349, EBI-2548993 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: IPI interactions (SRSF11, TP53BP2, CEP63) from a proteome-scale human interactome map. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q05519: SRSF11; NbExp=3; IntAct=EBI-356349, EBI-1051785 |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | KEEP AS NON CORE | Summary: IPI interaction (IKBKE) from a kinase-network analysis of TRAIL-induced apoptosis. Bare protein binding is uninformative. Reason: High-throughput kinase-network interaction; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q14164: IKBKE; NbExp=5; IntAct=EBI-356349, EBI-307369 |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | KEEP AS NON CORE | Summary: IPI interaction (CEP63) from a centrosome-cilium interface interactome. Bare protein binding is uninformative and peripheral to TANK function. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q96MT8: CEP63; NbExp=4; IntAct=EBI-356349, EBI-741977 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: IPI interaction (TRAF1) from a human interactome architecture study. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q13077: TRAF1; NbExp=5; IntAct=EBI-356349, EBI-359224 |
| GO:0005515 protein binding | IPI PMID:29251827 Quantitative Proteomics Identified TTC4 as a TBK1 Interactor... | KEEP AS NON CORE | Summary: IPI interaction with TBK1 from a quantitative proteomics study of the TBK1 interactome (TTC4 study). Bare protein binding is uninformative but the TBK1 partner is core-relevant. Reason: Records the core TBK1 interaction but bare protein binding is uninformative; the adaptor function captures this. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q9UHD2: TBK1; NbExp=14; IntAct=EBI-356349, EBI-356402 |
| 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 interactions (TRAF2, TRAF3, TBK1, NEMO/IKBKG) from a TNF-induced NF-kappaB pathway interaction map. Bare protein binding is uninformative but partners are pathway-relevant. Reason: Records real NF-kappaB-pathway interactions but bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q9Y6K9: IKBKG; NbExp=7; IntAct=EBI-356349, EBI-81279 |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | KEEP AS NON CORE | Summary: IPI interaction (TBK1) from a kinase interaction network study. Bare protein binding is uninformative. Reason: High-throughput kinase-network interaction; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q9UHD2: TBK1; NbExp=14; IntAct=EBI-356349, EBI-356402 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: IPI interactions (TRAF1, TRAF2, TRAF3, TBK1, IKBKE, NEMO) from a cell-specific proteome-scale interactome. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q13114: TRAF3; NbExp=8; IntAct=EBI-356349, EBI-357631 |
| GO:0005515 protein binding | IPI PMID:34084167 SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Produ... | KEEP AS NON CORE | Summary: IPI interaction (TRAF3) from a study of SARS-CoV-2 M protein-mediated TBK1 degradation. Bare protein binding is uninformative but the host-virus innate-immune context is consistent with TANK's TBK1 axis role. Reason: Records a real interaction in an innate-immune/host-virus context but bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q13114: TRAF3; NbExp=8; IntAct=EBI-356349, EBI-357631 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: IPI interaction (NEMO/IKBKG) from a multimodal cell-map structural/functional genomics study. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Q92844; Q9Y6K9: IKBKG; NbExp=7; IntAct=EBI-356349, EBI-81279 |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: HPA immunofluorescence localization to the nucleolus. There is no functional literature placing TANK activity in the nucleolus; TANK is established as a cytoplasmic adaptor. Reason: Derived from a single high-throughput immunofluorescence dataset (GO_REF:0000052) with no supporting functional evidence; conflicts with the consistently reported cytoplasmic localization and is likely an over-annotation/staining artifact. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence localization to the cytosol, consistent with TANK's established cytoplasmic adaptor role. Reason: Correct cytosolic localization (the compartment where TANK assembles TBK1/IKK and TRAF deubiquitination complexes); kept consistent with the other cytosol annotations. The core localization is captured by the IDA cytoplasm is_active_in annotation. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0051607 defense response to virus | NAS PMID:21931631 Functional dissection of the TBK1 molecular network. | KEEP AS NON CORE | Summary: ComplexPortal author-statement assignment of antiviral defense for the TBK1-IKKepsilon-TANK complex. Consistent with TANK's role in the TBK1-IRF3/7 type I IFN antiviral axis. Reason: Correct process-level role (downstream of TANK's adaptor function in the antiviral IFN response) but broad; the core is the TBK1 adaptor/type I IFN production function. Supporting Evidence: PMID:21931631 TBK1 activation was strictly dependent on the integrity of the TBK1/TANK interaction |
| GO:0060337 type I interferon-mediated signaling pathway | NAS PMID:21931631 Functional dissection of the TBK1 molecular network. | KEEP AS NON CORE | Summary: ComplexPortal author-statement assignment of type I interferon-mediated signaling for the TBK1-IKKepsilon-TANK complex. Note this term denotes the response to interferon; TANK's documented role is in interferon induction/production rather than IFN-receptor signaling. Reason: Process is closely related to TANK's antiviral IFN role; however GO:0060337 (the response to type I IFN) is less precise for TANK than GO:0032481 (positive regulation of type I interferon production), which is the experimentally supported core BP. Supporting Evidence: PMID:21931631 TANK-binding kinase 1 (TBK1) and inducible IkappaB-kinase (IKK-i) are central regulators of type-I interferon induction |
| GO:1902554 serine/threonine protein kinase complex | NAS PMID:21931631 Functional dissection of the TBK1 molecular network. | ACCEPT | Summary: ComplexPortal assignment that TANK is part of the TBK1-IKKepsilon-TANK serine/threonine kinase complex (CPX-6089). TANK is the non-catalytic adaptor subunit of this kinase complex. Reason: Core cellular component; TANK is a bona fide subunit of the TBK1/IKKepsilon kinase complex, which is the structural basis of its adaptor function. Supporting Evidence: file:human/TANK/TANK-uniprot.txt ComplexPortal; CPX-6089; TBK1-IKKepsilon-TANK complex. |
| GO:0005737 cytoplasm | IDA PMID:21931631 Functional dissection of the TBK1 molecular network. | ACCEPT | Summary: Direct evidence (immunofluorescence) that TANK is active in the cytoplasm, where it functions as a TBK1/IKKepsilon adaptor. Core localization. Reason: Core localization with direct evidence; TANK acts as a cytoplasmic adaptor in the TBK1/IKK and TRAF-deubiquitination complexes. Supporting Evidence: PMID:21931631 the individual adaptors reside in different subcellular locations |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:21931631 Functional dissection of the TBK1 molecular network. | ACCEPT | Summary: Direct evidence that TANK promotes type I interferon production via its TBK1 adaptor function; TBK1 activation in response to virus/poly(I:C) requires the TANK-TBK1 interaction. Core biological process. Reason: Core biological process; TANK's TBK1-bridging adaptor function drives IRF3/IRF7-dependent type I IFN induction. Supporting Evidence: PMID:21931631 TBK1 activation was strictly dependent on the integrity of the TBK1/TANK interaction |
| GO:0060090 molecular adaptor activity | IDA PMID:21931631 Functional dissection of the TBK1 molecular network. | ACCEPT | Summary: Direct evidence that TANK functions as a molecular adaptor bridging TBK1/IKKepsilon into signaling complexes. This is TANK's defining core molecular function. Reason: Core molecular function; TANK is a non-catalytic adaptor that links the IKK-related kinases (and TRAFs, and the USP10/ZC3H12A DUB complex) into functional assemblies. Supporting Evidence: PMID:21931631 They are associated with three adaptor proteins called TANK, Sintbad ... and NAP1 |
| GO:0004843 cysteine-type deubiquitinase activity | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: TANK lacks a deubiquitinase domain; the contributes_to qualifier reflects that TANK scaffolds the USP10-dependent deubiquitination of TRAF6, not that TANK itself has DUB activity. The catalytic DUB is USP10. Reason: The contributes_to qualifier is acceptable for a non-catalytic scaffold that enables a complex DUB activity, but the activity resides in USP10; TANK's actual function here is better captured by molecular adaptor activity (GO:0060090) and deubiquitinase activator activity (GO:0035800). Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 |
| GO:0006974 DNA damage response | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP evidence that TANK restrains genotoxic (DNA damage-induced) NF-kappaB activation via the USP10/ZC3H12A deubiquitination complex. A real but secondary process. Reason: Experimentally supported but reflects the secondary genotoxic-stress NF-kappaB-restraining role; the term GO:0006974 is broad. The specific outcome (negative regulation of canonical NF-kappaB) is annotated separately. Supporting Evidence: PMID:25861989 TANK negatively regulates NF-kappaB activation by DNA damage via inhibiting ubiquitination of TRAF6 |
| GO:0035800 deubiquitinase activator activity | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP evidence that TANK acts as a scaffold that activates/enables USP10-dependent deubiquitination of TRAF6. This is an informative molecular function for TANK's NF-kappaB-restraining scaffold role. Reason: Real and informative MF (scaffold that activates a DUB), but reflects the secondary genotoxic/IL-1 NF-kappaB-restraining function rather than TANK's core TBK1 adaptor role. Supporting Evidence: PMID:25861989 which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-kappaB activation |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP evidence that TANK negatively regulates canonical NF-kappaB signaling; CRISPR deletion of TANK enhanced genotoxic NF-kappaB activation. This is the central outcome of TANK's scaffold role in TRAF6 deubiquitination. Reason: Well-supported, important function, but it is a context-specific (genotoxic/IL-1) negative-feedback role distinct from TANK's core positive role as a TBK1/IKK adaptor in type I IFN induction. TANK is notable for this dual (positive in IFN, negative in NF-kappaB) behavior. Supporting Evidence: PMID:25861989 CRISPR/Cas9-mediated deletion of TANK in human cells significantly enhanced NF-kappaB activation by genotoxic treatment |
| GO:0071347 cellular response to interleukin-1 | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP evidence that the TANK-MCPIP1-USP10 complex decreases TRAF6 ubiquitination in cells treated with IL-1beta, restraining the IL-1 NF-kappaB response. Reason: Real but context-specific role (IL-1 signaling) downstream of TANK's deubiquitination-scaffold function; non-core. Supporting Evidence: PMID:25861989 the TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1beta or LPS |
| GO:0071356 cellular response to tumor necrosis factor | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP-supported involvement in TNF-related NF-kappaB responses, consistent with TANK's documented modulation of TRAF2/TNFR signaling. Context-specific, non-core. Reason: Real but secondary cytokine-response role downstream of the NF-kappaB-restraining scaffold function; non-core. Supporting Evidence: file:human/TANK/TANK-uniprot.txt May control negatively TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2 |
| GO:0071479 cellular response to ionizing radiation | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP evidence linking TANK to the genotoxic-stress (ionizing radiation/DNA damage) NF-kappaB response via the USP10/TRAF6 deubiquitination axis. Reason: Real but secondary genotoxic-stress role; non-core relative to TANK's TBK1 adaptor function. Supporting Evidence: PMID:25861989 regulating cellular response to genotoxic stress |
| GO:1903003 positive regulation of protein deubiquitination | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP evidence that TANK promotes USP10-mediated deubiquitination of TRAF6 (positive regulation of protein deubiquitination). Captures TANK's scaffold function in the DUB complex. Reason: Accurate process annotation for the deubiquitination-scaffold role; non-core relative to the TBK1 adaptor function. Supporting Evidence: PMID:25861989 USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-ΞΊB |
| GO:2000158 positive regulation of ubiquitin-specific protease activity | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IMP evidence that TANK positively regulates the activity of the ubiquitin-specific protease USP10 toward TRAF6 by scaffolding it into the deubiquitination complex. Reason: Accurate process annotation for the USP10-scaffold role; non-core relative to TANK's TBK1 adaptor function. Supporting Evidence: PMID:25861989 which was essential for the USP10-dependent deubiquitination of TRAF6 |
| GO:0005515 protein binding | IPI PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IPI interactions with USP10, ZC3H12A/MCPIP1, TRAF6 and NEMO/IKBKG from the genotoxic NF-kappaB study. Functionally central interactions, but bare protein binding is uninformative. Reason: Records the real components of the TANK deubiquitination complex, but bare protein binding is uninformative; the scaffold/adaptor function captures these. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 |
| GO:0032991 protein-containing complex | IDA PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: IDA evidence that TANK is part of a protein-containing complex (the TANK-MCPIP1/ZC3H12A-USP10 deubiquitination complex). Generic complex term. Reason: Correct but maximally generic; the specific complex membership (TBK1-IKKepsilon-TANK kinase complex; TANK-USP10-ZC3H12A DUB complex) is captured by more informative annotations. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166245 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166271 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5362500 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013978 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013979 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013990 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823904 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823906 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823910 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823932 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823934 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823939 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824882 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828196 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828200 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828204 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828205 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828209 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9830706 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9830710 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:11279055 A diverse family of proteins containing tumor necrosis facto... | KEEP AS NON CORE | Summary: IPI interaction with a TRAF-domain ubiquitin ligase (TRAF family member) from a survey of TRAF-domain-containing proteins. More informative than bare protein binding (it specifies binding to a ubiquitin ligase), reflecting TANK's TRAF-interaction function. Reason: Informative MF capturing TANK's binding to TRAF E3 ligases (its original I-TRAF function), but secondary to the TBK1/IKK adaptor core; retained as non-core. Supporting Evidence: file:human/TANK/TANK-uniprot.txt Also interacts with TRAF1, TRAF2, and TRAF3 by binding to their TRAF-C domains |
| GO:0005515 protein binding | IPI PMID:21784977 Zinc finger protein tristetraprolin interacts with CCL3 mRNA... | KEEP AS NON CORE | Summary: IPI interaction (tristetraprolin/ZFP36, P26651) from a study of TTP/CCL3 mRNA and tissue inflammation. Bare protein binding is uninformative and peripheral to TANK's core function. Reason: Records a real but peripheral interaction; bare protein binding is uninformative. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBUNIT: Homodimer. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5362486 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013985 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933525 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933527 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933537 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933538 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705145 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705323 | KEEP AS NON CORE | Summary: Reactome pathway-step curation placing TANK in the cytosol within TLR/TBK1-IKKepsilon-IRF3/7 activation reactions. Correct compartment, consistent with TANK's cytoplasmic adaptor role. Reason: Correct cytosolic localization but derived from generic pathway-step context; redundant with the experimental IDA cytosol/cytoplasm annotations. Supporting Evidence: file:human/TANK/TANK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0007165 signal transduction | TAS PMID:8710854 I-TRAF is a novel TRAF-interacting protein that regulates TR... | KEEP AS NON CORE | Summary: Author-statement (original I-TRAF paper) that TANK is involved in TRAF-mediated signal transduction. Maximally generic process term. Reason: Correct but extremely generic; the specific NF-kappaB/type I IFN signaling roles are captured by more informative annotations. Supporting Evidence: PMID:8710854 I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: How is TANK's dual behaviour - positive regulation of TBK1/IKKepsilon-driven type I interferon induction versus negative regulation of canonical NF-kappaB via the USP10/ZC3H12A deubiquitination complex - partitioned between stimuli, subcellular pools, and post-translational states (phosphorylation by IKBKE, SUMOylation)?
Q: Given that TANK, SINTBAD and NAP1 compete for the same site on TBK1 and occupy distinct subcellular locations, what determines which adaptor is used for a given TBK1-dependent output (antiviral IFN versus autophagy/selective autophagy)?
Experiment: Stimulus-resolved interactome (AP-MS/proximity labeling) of endogenous TANK under viral/poly(I:C) stimulation versus genotoxic stress and IL-1 to map the switch between the TBK1-IKKepsilon kinase complex and the USP10-ZC3H12A deubiquitination complex.
Experiment: Separation-of-function mutants (TBK1-binding-deficient versus TRAF6/ZC3H12A-binding-deficient TANK) reconstituted into TANK-knockout cells to independently test the contribution of each scaffold function to type I IFN induction and NF-kappaB resolution.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)