MAP3K7 encodes TAK1 (TGF-beta-activated kinase 1), a TKL-group serine/threonine protein kinase that acts as a mitogen-activated protein kinase kinase kinase (MAP3K). TAK1 has an N-terminal kinase domain and a C-terminal region that binds the adaptors TAB2 and TAB3; the activator TAB1 binds near the kinase domain. TAK1-TAB1-TAB2/TAB3 complexes are recruited to and activated by K63-linked and unanchored polyubiquitin chains, which are bound by the TAB2/TAB3 zinc fingers, leading to autophosphorylation of the TAK1 activation loop (Thr184/Thr187/Ser192). Activated TAK1 phosphorylates MKK3/MKK6 and MKK4/MKK7, driving p38 and JNK MAP kinase cascades, and phosphorylates IKKbeta to activate canonical NF-kappaB signaling. TAK1 is the shared kinase relay downstream of TRAF6 and related ubiquitin ligases in IL-1 receptor, Toll-like receptor, TNF receptor, NOD-like receptor, antigen receptor and TGF-beta/BMP signaling, and it is inactivated by PP6/PP2A-type phosphatases. Other reported substrates include AMPK and STING. TAK1 acts mainly in the cytosol after recruitment to receptor-proximal complexes. Heterozygous MAP3K7 variants cause frontometaphyseal dysplasia 2 and cardiospondylocarpofacial syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IDA PMID:11865055 IAP suppression of apoptosis involves distinct mechanisms: t... | ACCEPT | Summary: TAK1 is the MAP3K tier of JNK and p38 MAPK cascades. Reason: TAK1 phosphorylates and activates MAP2Ks (MKK3/MKK6, MKK4/MKK7) that in turn activate p38 and JNK. Participation in the MAPK cascade is a direct, core role of the kinase. Supporting Evidence: PMID:11865055 The MAP3 kinase, TAK1, appears to be an essential component of this antiapoptotic pathway since IAP-mediated activation of JNK1, as well as protection against TNF-alpha- and ICE-induced apoptosis, is inhibited when catalytically inactive TAK1 is expressed. PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0000165 MAPK cascade | IDA PMID:8663074 A novel kinase cascade mediated by mitogen-activated protein... | ACCEPT | Summary: TAK1 is the MAP3K tier of JNK and p38 MAPK cascades. Reason: TAK1 phosphorylates and activates MAP2Ks (MKK3/MKK6, MKK4/MKK7) that in turn activate p38 and JNK. Participation in the MAPK cascade is a direct, core role of the kinase. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0000165 MAPK cascade | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic MAPK cascade annotation consistent with the experimentally established MAP3K role. Reason: ARBA/ortholog-based annotation agrees with direct experimental evidence that TAK1 acts as the MAP3K of JNK and p38 cascades. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Mg2+ is the catalytic cofactor of the TAK1 kinase domain. Reason: InterPro-based; magnesium ion binding is a generic kinase cofactor property (UniProt COFACTOR Mg2+). True but not an informative function in its own right. |
| GO:0001223 transcription coactivator binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transcription coactivator binding transferred from rat; no human evidence. Reason: Electronic ortholog transfer from rat. TAK1 is a cytoplasmic kinase and binding to transcription coactivators is not part of its established mechanism; any such interactions are context-specific and do not define its function. |
| GO:0001649 osteoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Osteoblast differentiation transferred from mouse; downstream developmental context. Reason: TAK1 signaling downstream of TGF-beta/BMP influences skeletal cell differentiation, and MAP3K7 gain-of-function causes frontometaphyseal dysplasia in humans, but TAK1 acts via its general kinase relay rather than as a dedicated osteoblast-differentiation factor. Retain as non-core. Supporting Evidence: PMID:27426733 The recurrent mutation does not destabilize TAK1, or impair its ability to homodimerize or bind TAB2, but it does increase TAK1 autophosphorylation |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TAK1 is activated by hypoxia and relays it to JNK via JIP1. Reason: Ortholog-based annotation supported in human cells: hypoxia increases TAK1 activity and TAK1-JIP1-JNK signaling shapes the hypoxic stress response. This is one of many stress inputs; non-core. Supporting Evidence: PMID:17709393 We report that TAK1 is able to form a stable complex with JIP1 and thus regulate the activation of JNK, which in turn determines the cellular stress response to hypoxia. |
| GO:0002223 stimulatory C-type lectin receptor signaling pathway | TAS Reactome:R-HSA-5621481 | KEEP AS NON CORE | Summary: Reactome places TAK1 downstream of Dectin/CLR-CARD9 signaling. Reason: TAK1 is the shared kinase relay for many receptor pathways that converge on TRAF6/K63-ubiquitin; C-type lectin receptor signaling is one such upstream context, not a TAK1-specific function. |
| GO:0002726 positive regulation of T cell cytokine production | IMP PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | KEEP AS NON CORE | Summary: TAK1 knockdown reduces TCR-induced IL-2 production. Reason: RNAi of TAK1 suppressed TCR-dependent IKK activation and IL-2 production; TAK1 acts upstream via IKK/NF-kappaB activation. Downstream cytokine output is non-core. Supporting Evidence: PMID:15125833 RNAi-mediated silencing of MALT1, TAK1, TRAF6, and TRAF2 suppressed TCR-dependent IKK activation and interleukin-2 production in T cells. |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | TAS Reactome:R-HSA-9645460 | KEEP AS NON CORE | Summary: Reactome ALPK1/TIFA pathway; TAK1 is the downstream kinase relay. Reason: TAK1 autophosphorylation within the ALPK1-TIFA-TRAF6 complex is represented in Reactome; this is one cytoplasmic PRR context in which the generic TAK1 relay operates. |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | TAS Reactome:R-HSA-166058 | ACCEPT | Summary: TAK1 is the kinase relay of MyD88-IRAK-TRAF6 signaling from TLRs/IL-1R. Reason: MyD88-dependent TLR signaling converges on TRAF6-generated K63 chains that activate the TAK1-TAB complex, which phosphorylates IKKbeta and MAP2Ks. This is one of the canonical inputs that define TAK1 function. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. PMID:19675569 free Lys 63 polyubiquitin chains, which are not conjugated to any target protein, directly activate TAK1 by binding to the ubiquitin receptor TAB2 |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | TAS Reactome:R-HSA-975871 | ACCEPT | Summary: TAK1 is the kinase relay of MyD88-IRAK-TRAF6 signaling from TLRs/IL-1R. Reason: MyD88-dependent TLR signaling converges on TRAF6-generated K63 chains that activate the TAK1-TAB complex, which phosphorylates IKKbeta and MAP2Ks. This is one of the canonical inputs that define TAK1 function. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. PMID:19675569 free Lys 63 polyubiquitin chains, which are not conjugated to any target protein, directly activate TAK1 by binding to the ubiquitin receptor TAB2 |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: TAK1 is a protein kinase (InterPro). Reason: Correct but general; the more specific Ser/Thr and MAP3K activity terms are also accepted. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:10702308 TAK1 mitogen-activated protein kinase kinase kinase is activ... | ACCEPT | Summary: TAK1 has Ser/Thr protein kinase activity, shown directly in vitro. Reason: TAK1 autophosphorylates its activation loop (Ser192, Thr184/187) and phosphorylates Ser/Thr residues on MAP2Ks, IKKbeta and other substrates (AMPK, STING Ser355). Core activity, family-wide in PTHR46716. Supporting Evidence: PMID:10702308 These results suggest that IL-1 and ectopic expression of TAB1 both activate TAK1 via autophosphorylation of Ser-192. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | ACCEPT | Summary: TAK1 has Ser/Thr protein kinase activity, shown directly in vitro. Reason: TAK1 autophosphorylates its activation loop (Ser192, Thr184/187) and phosphorylates Ser/Thr residues on MAP2Ks, IKKbeta and other substrates (AMPK, STING Ser355). Core activity, family-wide in PTHR46716. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:20538596 Autoactivation of transforming growth factor beta-activated ... | ACCEPT | Summary: TAK1 has Ser/Thr protein kinase activity, shown directly in vitro. Reason: TAK1 autophosphorylates its activation loop (Ser192, Thr184/187) and phosphorylates Ser/Thr residues on MAP2Ks, IKKbeta and other substrates (AMPK, STING Ser355). Core activity, family-wide in PTHR46716. Supporting Evidence: PMID:20538596 Co-expression of TAK1 and TAB1, but not TAB2, resulted in a functional and active TAK1-TAB1 complex capable of directly activating full-length heterotrimeric mammalian AMP-activated protein kinase (AMPK) in vitro. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the... | ACCEPT | Summary: TAK1 has Ser/Thr protein kinase activity, shown directly in vitro. Reason: TAK1 autophosphorylates its activation loop (Ser192, Thr184/187) and phosphorylates Ser/Thr residues on MAP2Ks, IKKbeta and other substrates (AMPK, STING Ser355). Core activity, family-wide in PTHR46716. Supporting Evidence: PMID:10094049 Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:37832545 TAK1 is an essential kinase for STING trafficking. | ACCEPT | Summary: TAK1 has Ser/Thr protein kinase activity, shown directly in vitro. Reason: TAK1 autophosphorylates its activation loop (Ser192, Thr184/187) and phosphorylates Ser/Thr residues on MAP2Ks, IKKbeta and other substrates (AMPK, STING Ser355). Core activity, family-wide in PTHR46716. Supporting Evidence: PMID:37832545 activated TAK1 directly mediates STING phosphorylation on serine 355 |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ser/Thr kinase activity (ARBA/ortholog); consistent with experiments. Reason: Agrees with direct biochemical evidence. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-168184 | ACCEPT | Summary: Reactome events in which activated TAK1 phosphorylates IKKbeta or MKK3/4/6/7. Reason: Reactome reactions curate TAK1 as the kinase phosphorylating IKKbeta and MAP2Ks, supported by primary literature. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-202500 | ACCEPT | Summary: Reactome events in which activated TAK1 phosphorylates IKKbeta or MKK3/4/6/7. Reason: Reactome reactions curate TAK1 as the kinase phosphorylating IKKbeta and MAP2Ks, supported by primary literature. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-202510 | ACCEPT | Summary: Reactome events in which activated TAK1 phosphorylates IKKbeta or MKK3/4/6/7. Reason: Reactome reactions curate TAK1 as the kinase phosphorylating IKKbeta and MAP2Ks, supported by primary literature. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-450337 | ACCEPT | Summary: Reactome events in which activated TAK1 phosphorylates IKKbeta or MKK3/4/6/7. Reason: Reactome reactions curate TAK1 as the kinase phosphorylating IKKbeta and MAP2Ks, supported by primary literature. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-450346 | ACCEPT | Summary: Reactome events in which activated TAK1 phosphorylates IKKbeta or MKK3/4/6/7. Reason: Reactome reactions curate TAK1 as the kinase phosphorylating IKKbeta and MAP2Ks, supported by primary literature. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-5607742 | ACCEPT | Summary: Reactome events in which activated TAK1 phosphorylates IKKbeta or MKK3/4/6/7. Reason: Reactome reactions curate TAK1 as the kinase phosphorylating IKKbeta and MAP2Ks, supported by primary literature. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-936951 | ACCEPT | Summary: Reactome events in which activated TAK1 phosphorylates IKKbeta or MKK3/4/6/7. Reason: Reactome reactions curate TAK1 as the kinase phosphorylating IKKbeta and MAP2Ks, supported by primary literature. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0004707 MAP kinase activity | IDA PMID:11865055 IAP suppression of apoptosis involves distinct mechanisms: t... | MODIFY | Summary: TAK1 is a MAP3K, not a MAPK; the assay in this paper measured JNK1 activity downstream of TAK1. Reason: Full text of PMID:11865055 shows that kinase assays used ATF-2 or MBP as substrates of immunoprecipitated JNK1; TAK1 was manipulated with a catalytically inactive mutant and acts upstream of JNK1. TAK1 does not phosphorylate transcription-factor substrates as a MAP kinase. The essence (TAK1 kinase activity in the JNK pathway) is better captured by MAP kinase kinase kinase activity. Proposed replacements: MAP kinase kinase kinase activity Supporting Evidence: PMID:11865055 After immunoprecipitation, an in vitro kinase assay was performed using ATF-2 or MBP as substrates. PMID:11865055 The MAP3 kinase, TAK1, appears to be an essential component of this antiapoptotic pathway since IAP-mediated activation of JNK1, as well as protection against TNF-alpha- and ICE-induced apoptosis, is inhibited when catalytically inactive TAK1 is expressed. |
| GO:0004708 MAP kinase kinase activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: MAP kinase kinase activity transferred from mouse; TAK1 acts one tier higher. Reason: TAK1 phosphorylates MAP2Ks (MKK3/4/6/7), i.e. it is a MAP3K. Activation of the atypical MAPK NLK by TAK1 has been reported, but direct MAP2K-type phosphorylation of a MAPK is not the established activity of human TAK1. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. PMID:15764709 Here, we show that TGF-beta-activated kinase 1 (TAK1) interacts with STAT3, that the TAK1-Nemo-like kinase (NLK) pathway is efficiently activated by IL-6 through the YXXQ motif |
| GO:0004709 MAP kinase kinase kinase activity | EXP PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | ACCEPT | Summary: Core activity: TAK1 phosphorylates and activates MKK3/MKK6 and MKK4/MKK7. Reason: Direct in vitro phosphorylation of MKK3/MKK6 and K63-ubiquitin-regulated phosphorylation of MKK6, plus activation of MKK4/SEK1. This defines TAK1 as a MAP3K. Supporting Evidence: PMID:11460167 the activity of TAK1 to phosphorylate MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63-linked polyubiquitination |
| GO:0004709 MAP kinase kinase kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000723805 (Bilateria TAK1 node); sound per PTHR46716 family review. Reason: The PAINT node is seeded by fly Tak1, rat and human TAK1; human MAP3K7 appears in WITH/FROM because of its own experimental annotations, which is expected. Human TAK1 is squarely within the clade. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0004709 MAP kinase kinase kinase activity | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | ACCEPT | Summary: Core activity: TAK1 phosphorylates and activates MKK3/MKK6 and MKK4/MKK7. Reason: Direct in vitro phosphorylation of MKK3/MKK6 and K63-ubiquitin-regulated phosphorylation of MKK6, plus activation of MKK4/SEK1. This defines TAK1 as a MAP3K. Supporting Evidence: PMID:11460167 the activity of TAK1 to phosphorylate MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63-linked polyubiquitination |
| GO:0004709 MAP kinase kinase kinase activity | IDA PMID:8663074 A novel kinase cascade mediated by mitogen-activated protein... | ACCEPT | Summary: Core activity: TAK1 phosphorylates and activates MKK3/MKK6 and MKK4/MKK7. Reason: Direct in vitro phosphorylation of MKK3/MKK6 and K63-ubiquitin-regulated phosphorylation of MKK6, plus activation of MKK4/SEK1. This defines TAK1 as a MAP3K. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0004709 MAP kinase kinase kinase activity | IDA PMID:9079627 TAK1 mediates the ceramide signaling to stress-activated pro... | ACCEPT | Summary: Core activity: TAK1 phosphorylates and activates MKK3/MKK6 and MKK4/MKK7. Reason: Direct in vitro phosphorylation of MKK3/MKK6 and K63-ubiquitin-regulated phosphorylation of MKK6, plus activation of MKK4/SEK1. This defines TAK1 as a MAP3K. Supporting Evidence: PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0004709 MAP kinase kinase kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic MAP3K annotation (EC 2.7.11.25 / InterPro MAP3K7); correct. Reason: Consistent with experiments. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0004709 MAP kinase kinase kinase activity | TAS PMID:9466656 Molecular cloning of human TAK1 and its mutational analysis ... | ACCEPT | Summary: Core activity: TAK1 phosphorylates and activates MKK3/MKK6 and MKK4/MKK7. Reason: Direct in vitro phosphorylation of MKK3/MKK6 and K63-ubiquitin-regulated phosphorylation of MKK6, plus activation of MKK4/SEK1. This defines TAK1 as a MAP3K. PMID:9466656 is the human cDNA cloning paper; the activity is supported by the primary biochemistry. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Vague signaling receptor binding from ARBA. Reason: TAK1 is recruited to receptor complexes mostly indirectly (via TRAF6, TAB2/3 and ubiquitin chains); a generic signaling receptor binding MF is uninformative and not established as direct. |
| GO:0005114 type II transforming growth factor beta receptor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Type II TGF-beta receptor binding transferred from rat; human data show TAK1 engagement via TbetaRI-TRAF6. Reason: TGF-beta activates TAK1 through TbetaRI-bound TRAF6 and K63 ubiquitination of TAK1, not via a demonstrated direct TbetaRII-TAK1 binding function. Supporting Evidence: PMID:18758450 Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6. |
| GO:0005515 protein binding | IPI PMID:10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the... | MODIFY | Summary: Interaction with the E3 ubiquitin ligase TRAF6. Reason: TRAF6 is a ubiquitin ligase whose association with TAK1 (directly or within the TAK1-TAB complex) promotes or regulates TAK1 activation by ubiquitin chains. Generic protein binding is uninformative; ubiquitin protein ligase binding captures the functional class of the interaction. This does not reject the reported interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:10094049 Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 signalling. |
| GO:0005515 protein binding | IPI PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:11865055 IAP suppression of apoptosis involves distinct mechanisms: t... | REMOVE | Summary: Generic protein binding with MAPK8/JNK1. Reason: Interaction with MAPK8/JNK1 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:11865055 The MAP3 kinase, TAK1, appears to be an essential component of this antiapoptotic pathway since IAP-mediated activation of JNK1, as well as protection against TNF-alpha- and ICE-induced apoptosis, is inhibited when catalytically inactive TAK1 is expressed. |
| GO:0005515 protein binding | IPI PMID:11865055 IAP suppression of apoptosis involves distinct mechanisms: t... | MODIFY | Summary: Interaction with the E3 ubiquitin ligase XIAP. Reason: XIAP is a ubiquitin ligase whose association with TAK1 (directly or within the TAK1-TAB complex) promotes or regulates TAK1 activation by ubiquitin chains. Generic protein binding is uninformative; ubiquitin protein ligase binding captures the functional class of the interaction. This does not reject the reported interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:11865055 The MAP3 kinase, TAK1, appears to be an essential component of this antiapoptotic pathway since IAP-mediated activation of JNK1, as well as protection against TNF-alpha- and ICE-induced apoptosis, is inhibited when catalytically inactive TAK1 is expressed. |
| GO:0005515 protein binding | IPI PMID:11865055 IAP suppression of apoptosis involves distinct mechanisms: t... | REMOVE | Summary: Generic protein binding with NAIP. Reason: Interaction with NAIP is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:11865055 The MAP3 kinase, TAK1, appears to be an essential component of this antiapoptotic pathway since IAP-mediated activation of JNK1, as well as protection against TNF-alpha- and ICE-induced apoptosis, is inhibited when catalytically inactive TAK1 is expressed. |
| GO:0005515 protein binding | IPI PMID:12496252 Pellino 1 is required for interleukin-1 (IL-1)-mediated sign... | MODIFY | Summary: Interaction with the E3 ubiquitin ligase TRAF6. Reason: TRAF6 is a ubiquitin ligase whose association with TAK1 (directly or within the TAK1-TAB complex) promotes or regulates TAK1 activation by ubiquitin chains. Generic protein binding is uninformative; ubiquitin protein ligase binding captures the functional class of the interaction. This does not reject the reported interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:12496252 The Pellino 1-IRAK-IRAK4-TRAF6 signaling complex is likely to be intermediate, located between the IL-1 receptor complex and the TAK1 complex in the IL-1 pathway. |
| GO:0005515 protein binding | IPI PMID:15075345 Reciprocal cross-talk between Nod2 and TAK1 signaling pathwa... | REMOVE | Summary: Generic protein binding with NOD2. Reason: Interaction with NOD2 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:15075345 interacts with Nod2 and is required for Nod2-mediated NF-kappaB activation |
| GO:0005515 protein binding | IPI PMID:15764709 STAT3 regulates Nemo-like kinase by mediating its interactio... | REMOVE | Summary: Generic protein binding with STAT3. Reason: Interaction with STAT3 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:15764709 Here, we show that TGF-beta-activated kinase 1 (TAK1) interacts with STAT3, that the TAK1-Nemo-like kinase (NLK) pathway is efficiently activated by IL-6 through the YXXQ motif |
| GO:0005515 protein binding | IPI PMID:16840345 Vaccinia virus B1R kinase interacts with JIP1 and modulates ... | MODIFY | Summary: Interaction with the JNK pathway scaffold JIP1 (MAPK8IP1). Reason: JIP1 is a scaffold assembling TAK1, MKK7 and JNK into a signalosome; scaffold protein binding is a more informative description than protein binding. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:16840345 MKK7 and TAK1 either bind with higher affinity or bind more stably to JIP1 |
| GO:0005515 protein binding | IPI PMID:16845370 The Yersinia enterocolitica effector YopP inhibits host cell... | REMOVE | Summary: Generic protein binding with ubiquitin (UBC). Reason: Interaction with ubiquitin (UBC) is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:16845370 YopP does not affect the interaction of TAK1, TAB1 and TAB2 but inhibits autophosphorylation of TAK1 at Thr 187 and phosphorylation of TAB1 at Ser 438. |
| GO:0005515 protein binding | IPI PMID:16845370 The Yersinia enterocolitica effector YopP inhibits host cell... | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:16845370 YopP does not affect the interaction of TAK1, TAB1 and TAB2 but inhibits autophosphorylation of TAK1 at Thr 187 and phosphorylation of TAB1 at Ser 438. |
| GO:0005515 protein binding | IPI PMID:16845370 The Yersinia enterocolitica effector YopP inhibits host cell... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:16845370 YopP does not affect the interaction of TAK1, TAB1 and TAB2 but inhibits autophosphorylation of TAK1 at Thr 187 and phosphorylation of TAB1 at Ser 438. |
| GO:0005515 protein binding | IPI PMID:17079228 Protein phosphatase 6 down-regulates TAK1 kinase activation ... | MODIFY | Summary: Interaction with PP6 catalytic subunit (PPP6C), which dephosphorylates TAK1 Thr187. Reason: PP6 binds and inactivates TAK1 by dephosphorylating the activation loop; protein phosphatase binding is more informative than protein binding. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:17079228 PP6 associated with and inactivated TAK1 by dephosphorylation of Thr-187 |
| GO:0005515 protein binding | IPI PMID:17110930 An antiapoptotic protein, c-FLIPL, directly binds to MKK7 an... | REMOVE | Summary: Generic protein binding with MAP2K7. Reason: Interaction with MAP2K7 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:17110930 inhibits the interactions of MKK7 with MAP/ERK kinase kinase 1, apoptosis-signal-regulating kinase 1, and TGFbeta-activated kinase 1 |
| GO:0005515 protein binding | IPI PMID:17158449 TAK1-dependent signaling requires functional interaction wit... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:17158449 residues 479-553 of TAK1 appear to be necessary and sufficient for TAB2/TAB3 interaction |
| GO:0005515 protein binding | IPI PMID:17363973 Retroviral oncoprotein Tax deregulates NF-kappaB by activati... | REMOVE | Summary: Generic protein binding with IKBKB. Reason: Interaction with IKBKB is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:17363973 Tax physically interacts with Tak1 and mediates the recruitment of IKK to Tak1. |
| GO:0005515 protein binding | IPI PMID:17449468 RBCK1 negatively regulates tumor necrosis factor- and interl... | MODIFY | Summary: Interaction with the E3 ubiquitin ligase RBCK1. Reason: RBCK1 is a ubiquitin ligase whose association with TAK1 (directly or within the TAK1-TAB complex) promotes or regulates TAK1 activation by ubiquitin chains. Generic protein binding is uninformative; ubiquitin protein ligase binding captures the functional class of the interaction. This does not reject the reported interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:17449468 RBCK1 physically interacts with TAB2/3 and facilitates degradation of TAB2/3 through a proteasome-dependent process. |
| GO:0005515 protein binding | IPI PMID:17709393 Vaccinia-related kinase 2 modulates the stress response to h... | REMOVE | Summary: Generic protein binding with MAP2K7. Reason: Interaction with MAP2K7 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:17709393 We report that TAK1 is able to form a stable complex with JIP1 and thus regulate the activation of JNK, which in turn determines the cellular stress response to hypoxia. |
| GO:0005515 protein binding | IPI PMID:17709393 Vaccinia-related kinase 2 modulates the stress response to h... | MODIFY | Summary: Interaction with the JNK pathway scaffold JIP1 (MAPK8IP1). Reason: JIP1 is a scaffold assembling TAK1, MKK7 and JNK into a signalosome; scaffold protein binding is a more informative description than protein binding. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:17709393 We report that TAK1 is able to form a stable complex with JIP1 and thus regulate the activation of JNK, which in turn determines the cellular stress response to hypoxia. |
| GO:0005515 protein binding | IPI PMID:18286207 Modulation of interleukin-1 transcriptional response by the ... | MODIFY | Summary: Interaction with the JNK pathway scaffold JIP1 (MAPK8IP1). Reason: JIP1 is a scaffold assembling TAK1, MKK7 and JNK into a signalosome; scaffold protein binding is a more informative description than protein binding. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:18286207 JIP1 assembles all these proteins in an oligomeric signalosome. |
| GO:0005515 protein binding | IPI PMID:18591963 GIDE is a mitochondrial E3 ubiquitin ligase that induces apo... | MODIFY | Summary: Interaction with the E3 ubiquitin ligase MUL1/GIDE. Reason: MUL1/GIDE is a ubiquitin ligase whose association with TAK1 (directly or within the TAK1-TAB complex) promotes or regulates TAK1 activation by ubiquitin chains. Generic protein binding is uninformative; ubiquitin protein ligase binding captures the functional class of the interaction. This does not reject the reported interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:18591963 only the kinase inactive mutant of TAK1, TAK1(K/W), inhibited GIDE-induced JNK activation |
| GO:0005515 protein binding | IPI PMID:18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 ... | MODIFY | Summary: Association with the type I TGF-beta receptor (TGFBR1) complex. Reason: TbetaRI engages TRAF6 to activate TAK1; the association of TAK1 with TbetaRI-containing complexes is better described with the specific receptor-binding term, although binding may be bridged by TRAF6. Proposed replacements: type I transforming growth factor beta receptor binding Supporting Evidence: PMID:18758450 Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6. |
| GO:0005515 protein binding | IPI PMID:19820695 Helicobacter pylori CagA activates NF-kappaB by targeting TA... | REMOVE | Summary: Generic protein binding with H. pylori CagA. Reason: Interaction with H. pylori CagA is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:19820695 CagA physically associates with TAK1 and enhances its activity and TAK1-induced NF-kappaB activation through the tumour necrosis factor receptor-associated factor 6-mediated, Lys 63-linked ubiquitination of TAK1. |
| GO:0005515 protein binding | IPI PMID:19820695 Helicobacter pylori CagA activates NF-kappaB by targeting TA... | REMOVE | Summary: Generic protein binding with ubiquitin (UBC). Reason: Interaction with ubiquitin (UBC) is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:19820695 CagA physically associates with TAK1 and enhances its activity and TAK1-induced NF-kappaB activation through the tumour necrosis factor receptor-associated factor 6-mediated, Lys 63-linked ubiquitination of TAK1. |
| GO:0005515 protein binding | IPI PMID:19820695 Helicobacter pylori CagA activates NF-kappaB by targeting TA... | MODIFY | Summary: Interaction with the E3 ubiquitin ligase TRAF6. Reason: TRAF6 is a ubiquitin ligase whose association with TAK1 (directly or within the TAK1-TAB complex) promotes or regulates TAK1 activation by ubiquitin chains. Generic protein binding is uninformative; ubiquitin protein ligase binding captures the functional class of the interaction. This does not reject the reported interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19820695 CagA physically associates with TAK1 and enhances its activity and TAK1-induced NF-kappaB activation through the tumour necrosis factor receptor-associated factor 6-mediated, Lys 63-linked ubiquitination of TAK1. |
| GO:0005515 protein binding | IPI PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | MODIFY | Summary: Interaction with the E3 ubiquitin ligase TRIM5. Reason: TRIM5 is a ubiquitin ligase whose association with TAK1 (directly or within the TAK1-TAB complex) promotes or regulates TAK1 activation by ubiquitin chains. Generic protein binding is uninformative; ubiquitin protein ligase binding captures the functional class of the interaction. This does not reject the reported interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:21512573 catalyses the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (also known as MAP3K7) kinase complex |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: Interaction with TAB3, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB3 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:22081109 Inhibition of autophagy by TAB2 and TAB3. | REMOVE | Summary: Interaction with TAB3, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB3 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0005515 protein binding | IPI PMID:22081109 Inhibition of autophagy by TAB2 and TAB3. | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0005515 protein binding | IPI PMID:22158122 Cysteine methylation disrupts ubiquitin-chain sensing in NF-... | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:22158122 Cysteine methylation disrupts ubiquitin-chain sensing in NF-... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:22158122 Here we show that human TAB2 and TAB3, ubiquitin-chain sensory proteins involved in NF-ΞΊB signalling, are directly inactivated by enteropathogenic Escherichia coli NleE |
| GO:0005515 protein binding | IPI PMID:22904686 The germinal center kinase TNIK is required for canonical NF... | REMOVE | Summary: Generic protein binding with TNIK. Reason: Interaction with TNIK is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:22904686 TNIK forms an activation-induced complex with the critical signaling mediators TRAF6, TAK1/TAB2, and IKKΞ², and mediates signalosome formation at LMP1. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: Generic protein binding with MAP2K7. Reason: This row comes from a high-throughput interactome screen; Interaction with MAP2K7 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:26334375 IFIT5 positively regulates NF-ΞΊB signaling through synergizi... | REMOVE | Summary: Generic protein binding with IFIT5. Reason: Interaction with IFIT5 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:26334375 Following TNF-Ξ± treatment, IFIT5 interacted with TAK1 or IKK complex and synergized the recruitment of IKK to TAK1 in a dose dependent manner. |
| GO:0005515 protein binding | IPI PMID:27426733 Mutations in MAP3K7 that Alter the Activity of the TAK1 Sign... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:27426733 The recurrent mutation does not destabilize TAK1, or impair its ability to homodimerize or bind TAB2, but it does increase TAK1 autophosphorylation |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: Generic protein binding with CDC37. Reason: This row comes from a high-throughput interactome screen; Interaction with CDC37 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:31980649 Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Generic protein binding with CDC37. Reason: This row comes from a high-throughput interactome screen; Interaction with CDC37 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Interaction with TAB3, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB3 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:33895773 RNA-induced liquid phase separation of SARS-CoV-2 nucleocaps... | REMOVE | Summary: Generic protein binding with IKBKB. Reason: Interaction with IKBKB is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:33895773 which recruits TAK1 and IKK complex, the key kinases of NF-ΞΊB signaling, to enhance NF-ΞΊB activation |
| GO:0005515 protein binding | IPI PMID:33895773 RNA-induced liquid phase separation of SARS-CoV-2 nucleocaps... | REMOVE | Summary: Generic protein binding with SARS-CoV-2 nucleoprotein. Reason: Interaction with SARS-CoV-2 nucleoprotein is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:33895773 which recruits TAK1 and IKK complex, the key kinases of NF-ΞΊB signaling, to enhance NF-ΞΊB activation |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with CDC37. Reason: This row comes from a high-throughput interactome screen; Interaction with CDC37 is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:33961781 Here we present BioPlex 3.0, the most complete model of the human interactome to date, accompanied by a second interaction network acquired in HCT116 cells. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Interaction with TAB1, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB1 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Interaction with TAB3, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB3 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005515 protein binding | IPI PMID:36179048 Novel biochemical, structural, and systems insights into inf... | REMOVE | Summary: Generic protein binding with ubiquitin (UBC). Reason: This row comes from a high-throughput interactome screen; Interaction with ubiquitin (UBC) is reported but generic protein binding conveys no functional information; where relevant the biology is captured by TAK1 kinase activity (substrates such as MAP2K7 and IKBKB) or by pathway annotations. Removal does not reject the interaction. Supporting Evidence: PMID:36179048 We used this approach to generate an integrated model of the formation principles and architecture of a large signalosome, the TNF-receptor signaling complex (TNF-RSC). |
| GO:0005515 protein binding | IPI PMID:36179048 Novel biochemical, structural, and systems insights into inf... | REMOVE | Summary: Interaction with TAB3, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB3 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0005515 protein binding | IPI PMID:36179048 Novel biochemical, structural, and systems insights into inf... | REMOVE | Summary: Interaction with TAB2, a regulatory subunit of the TAK1 complex. Reason: The TAK1-TAB2 interaction is real and central (TAK1-TAB complex), but generic protein binding is uninformative. It is captured instead by the proposed part_of GO:0097076 TGF-beta activated kinase 1 complex annotation and the TAB-dependent activation described in core functions. Removal does not reject the interaction. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: ATP binding by the kinase domain. Reason: Intrinsic to kinase catalysis (K63 catalytic lysine). |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: Detected in a sperm nucleus proteome. Reason: High-throughput proteomic detection. TAK1 can enter the nucleus in some contexts (e.g. IL-6 signaling), but its principal site of action is the cytosol. Supporting Evidence: PMID:21630459 With this approach, 403 different proteins have been identified from the isolated sperm nuclei. PMID:15764709 Here, we show that TGF-beta-activated kinase 1 (TAK1) interacts with STAT3, that the TAK1-Nemo-like kinase (NLK) pathway is efficiently activated by IL-6 through the YXXQ motif |
| GO:0005737 cytoplasm | IC PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TAK1 acts in the cytoplasm. Reason: TAK1 complex activation and its phosphorylation of IKK and MAP2Ks occur in the cytoplasm/cytosol. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005737 cytoplasm | IC PMID:34871740 TNF-Ξ±-induced E3 ligase, TRIM15 inhibits TNF-Ξ±-regulated NF-... | ACCEPT | Summary: TAK1 acts in the cytoplasm. Reason: TAK1 complex activation and its phosphorylation of IKK and MAP2Ks occur in the cytoplasm/cytosol. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005737 cytoplasm | IDA PMID:12242293 Interleukin-1 (IL-1) receptor-associated kinase-dependent IL... | ACCEPT | Summary: TAK1 acts in the cytoplasm. Reason: TAK1 complex activation and its phosphorylation of IKK and MAP2Ks occur in the cytoplasm/cytosol. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: TAK1 acts in the cytoplasm. Reason: TAK1 complex activation and its phosphorylation of IKK and MAP2Ks occur in the cytoplasm/cytosol. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | IDA PMID:12242293 Interleukin-1 (IL-1) receptor-associated kinase-dependent IL... | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168184 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177690 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202500 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202510 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730861 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730876 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730900 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4332356 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4332388 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-446870 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450187 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450337 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450346 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357860 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607732 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607742 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607757 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607759 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5696534 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-688985 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-706479 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-727819 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-847070 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936947 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936951 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936960 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936991 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-937075 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645406 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645442 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-975097 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9755757 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9758604 | ACCEPT | Summary: Cytosolic localization of TAK1 complexes. Reason: TAK1 is activated in the cytosol after release of TRAF6-TAK1-TAB complexes from receptor complexes; Reactome curates the cytosolic TAK1 complex in many reactions. Supporting Evidence: PMID:12242293 The formation of complex III and its interaction with additional cytosolic factors lead to the activation of TAK1, resulting in NF-kappaB and JNK activation. |
| GO:0005886 plasma membrane | EXP PMID:12242293 Interleukin-1 (IL-1) receptor-associated kinase-dependent IL... | KEEP AS NON CORE | Summary: TAK1-TAB1-TAB2 preassociate at the plasma membrane before IL-1 stimulation. Reason: Membrane association reflects recruitment to receptor-proximal complexes; activation occurs after translocation to the cytosol. Supporting Evidence: PMID:12242293 IRAK then brings TRAF6 to TAK1, TAB1, and TAB2, which are preassociated on the membrane before stimulation to form the membrane-associated complex II. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence plasma membrane signal. Reason: Consistent with recruitment to receptor complexes; non-core location. Supporting Evidence: PMID:12242293 IRAK then brings TRAF6 to TAK1, TAB1, and TAB2, which are preassociated on the membrane before stimulation to form the membrane-associated complex II. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular location plasma membrane. Reason: Consistent with transient receptor-proximal recruitment; non-core. Supporting Evidence: PMID:12242293 IRAK then brings TRAF6 to TAK1, TAB1, and TAB2, which are preassociated on the membrane before stimulation to form the membrane-associated complex II. |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Inferred from a rat histone kinase annotation; no human evidence. Reason: Inter-ontology inference from histone kinase activity, itself transferred from rat. No human evidence places TAK1 in chromatin remodeling; its detection in the ATAC complex is not functional evidence of histone phosphorylation. |
| GO:0006954 inflammatory response | IDA PMID:34017102 TRIM26 positively regulates the inflammatory immune response... | KEEP AS NON CORE | Summary: TAK1 activation drives inflammatory cytokine induction. Reason: TAK1 activation, enhanced by TRIM26-mediated TAB1 ubiquitination, is required for proinflammatory cytokine induction; inflammatory response is a downstream organismal outcome. Supporting Evidence: PMID:34017102 Knockout of Trim26 inhibited TAK1 activation and downstream kinases activation, thus decreasing the induction of proinflammatory cytokines following LPS, TNF-Ξ±, and IL-1Ξ² stimulation. |
| GO:0006955 immune response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA immune response from the Bilateria TAK1 node; sound but broad. Reason: The PTHR46716 family review judges this IBA sound (fly Tak1 in Imd immunity; vertebrate IL-1/TLR signaling) but explicitly recommends treating it as non-core; the informative processes are the kinase cascades. Supporting Evidence: PMID:10882101 The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated signaling pathway. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: Signal transduction (InterPro MAP3K7 signature). Reason: Correct but general. Supporting Evidence: PMID:10882101 The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated signaling pathway. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | TAS PMID:9466656 Molecular cloning of human TAK1 and its mutational analysis ... | ACCEPT | Summary: TAK1 mediates non-Smad TGF-beta signaling to p38/JNK. Reason: TAK1 was discovered as a TGF-beta/BMP-activated MAP3K and TGF-beta activates TAK1 via TbetaRI-TRAF6; one of the defining upstream inputs. Supporting Evidence: PMID:8533096 kinase activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic protein PMID:18758450 Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:10882101 TAB2, a novel adaptor protein, mediates activation of TAK1 M... | ACCEPT | Summary: TAK1 participates in canonical NF-kappaB signaling by phosphorylating IKKbeta. Reason: The TAK1 complex is the IKK-activating kinase of canonical NF-kappaB signaling downstream of IL-1, TLR and TNF receptors. Supporting Evidence: PMID:10882101 The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated signaling pathway. PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TAK1 participates in canonical NF-kappaB signaling by phosphorylating IKKbeta. Reason: The TAK1 complex is the IKK-activating kinase of canonical NF-kappaB signaling downstream of IL-1, TLR and TNF receptors. Supporting Evidence: PMID:19675569 free Lys 63 polyubiquitin chains, which are not conjugated to any target protein, directly activate TAK1 by binding to the ubiquitin receptor TAB2 PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:22158122 Cysteine methylation disrupts ubiquitin-chain sensing in NF-... | ACCEPT | Summary: TAK1 participates in canonical NF-kappaB signaling by phosphorylating IKKbeta. Reason: The TAK1 complex is the IKK-activating kinase of canonical NF-kappaB signaling downstream of IL-1, TLR and TNF receptors. Supporting Evidence: PMID:22158122 Here we show that human TAB2 and TAB3, ubiquitin-chain sensory proteins involved in NF-ΞΊB signalling, are directly inactivated by enteropathogenic Escherichia coli NleE PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:34871740 TNF-Ξ±-induced E3 ligase, TRIM15 inhibits TNF-Ξ±-regulated NF-... | ACCEPT | Summary: TAK1 participates in canonical NF-kappaB signaling by phosphorylating IKKbeta. Reason: The TAK1 complex is the IKK-activating kinase of canonical NF-kappaB signaling downstream of IL-1, TLR and TNF receptors. Supporting Evidence: PMID:34871740 TRIM15 interacts with TAK1 and inhibits its K63-linked ubiquitination, thus NF-ΞΊB activity. PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:35952808 TRIM56 positively regulates TNFΞ±-induced NF-ΞΊB signaling by ... | ACCEPT | Summary: TAK1 participates in canonical NF-kappaB signaling by phosphorylating IKKbeta. Reason: The TAK1 complex is the IKK-activating kinase of canonical NF-kappaB signaling downstream of IL-1, TLR and TNF receptors. Supporting Evidence: PMID:35952808 TRIM56 enhanced the ubiquitination of TAK1, specifically enhanced the M1-linked polyubiquitin chains to TAK1, leading to the tight interactions of the TAK1-IKKΞ± complex. PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007249 canonical NF-kappaB signal transduction | TAS Reactome:R-HSA-9014325 | ACCEPT | Summary: TAK1 participates in canonical NF-kappaB signaling by phosphorylating IKKbeta. Reason: The TAK1 complex is the IKK-activating kinase of canonical NF-kappaB signaling downstream of IL-1, TLR and TNF receptors. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007249 canonical NF-kappaB signal transduction | TAS Reactome:R-HSA-937072 | ACCEPT | Summary: TAK1 participates in canonical NF-kappaB signaling by phosphorylating IKKbeta. Reason: The TAK1 complex is the IKK-activating kinase of canonical NF-kappaB signaling downstream of IL-1, TLR and TNF receptors. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007252 I-kappaB phosphorylation | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | MARK AS OVER ANNOTATED | Summary: TAK1 phosphorylates IKK, which in turn phosphorylates IkappaB. Reason: TAK1 is upstream: it activates IKK, and IKK phosphorylates IkappaB. Annotating TAK1 to I-kappaB phosphorylation overstates its direct role; positive regulation of canonical NF-kappaB signaling and canonical NF-kappaB signal transduction capture it. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0007254 JNK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: IBA JNK cascade from the Bilateria TAK1 node; sound. Reason: Fly and mammalian seeds show TAK1 as MAP3K upstream of MKK4/7-JNK. Human TAK1 is a seed (expected, not circular). Supporting Evidence: PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0007254 JNK cascade | IDA PMID:9079627 TAK1 mediates the ceramide signaling to stress-activated pro... | ACCEPT | Summary: TAK1 activates SEK1/MKK4 and JNK. Reason: Direct experimental support. Supporting Evidence: PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0007254 JNK cascade | IEA GO_REF:0000107 | ACCEPT | Summary: JNK cascade (mouse ortholog transfer); consistent. Reason: Consistent with human data. Supporting Evidence: PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0007254 JNK cascade | TAS Reactome:R-HSA-450321 | ACCEPT | Summary: Reactome: activated TAK1 mediates JNK activation. Reason: Consistent with direct MKK4/7 phosphorylation. Supporting Evidence: PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0008349 MAP kinase kinase kinase kinase activity | IEA GO_REF:0000107 | MODIFY | Summary: MAP4K activity reflects TAK1 autophosphorylation events, not phosphorylation of a separate MAP3K. Reason: The Reactome reactions cited are "Auto phosphorylation of TAK1" / "Activation of recruited TAK1"; mapping a MAP3K autophosphorylating itself to MAP kinase kinase kinase kinase activity misrepresents its activity. The underlying Ser/Thr autophosphorylation is captured by protein serine/threonine kinase activity. The early report of TAK1 phosphorylating the MAP3K NIK (PMID:10094049) is not the basis of the modern model, where TAK1 phosphorylates IKKbeta directly. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:10702308 These results suggest that IL-1 and ectopic expression of TAB1 both activate TAK1 via autophosphorylation of Ser-192. PMID:10838074 Autophosphorylation of two threonine residues in the activation loop of TAK1 was necessary for TAK1 activation. |
| GO:0008349 MAP kinase kinase kinase kinase activity | TAS Reactome:R-HSA-177692 | MODIFY | Summary: MAP4K activity reflects TAK1 autophosphorylation events, not phosphorylation of a separate MAP3K. Reason: The Reactome reactions cited are "Auto phosphorylation of TAK1" / "Activation of recruited TAK1"; mapping a MAP3K autophosphorylating itself to MAP kinase kinase kinase kinase activity misrepresents its activity. The underlying Ser/Thr autophosphorylation is captured by protein serine/threonine kinase activity. The early report of TAK1 phosphorylating the MAP3K NIK (PMID:10094049) is not the basis of the modern model, where TAK1 phosphorylates IKKbeta directly. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:10702308 These results suggest that IL-1 and ectopic expression of TAB1 both activate TAK1 via autophosphorylation of Ser-192. PMID:10838074 Autophosphorylation of two threonine residues in the activation loop of TAK1 was necessary for TAK1 activation. |
| GO:0008349 MAP kinase kinase kinase kinase activity | TAS Reactome:R-HSA-936991 | MODIFY | Summary: MAP4K activity reflects TAK1 autophosphorylation events, not phosphorylation of a separate MAP3K. Reason: The Reactome reactions cited are "Auto phosphorylation of TAK1" / "Activation of recruited TAK1"; mapping a MAP3K autophosphorylating itself to MAP kinase kinase kinase kinase activity misrepresents its activity. The underlying Ser/Thr autophosphorylation is captured by protein serine/threonine kinase activity. The early report of TAK1 phosphorylating the MAP3K NIK (PMID:10094049) is not the basis of the modern model, where TAK1 phosphorylates IKKbeta directly. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:10702308 These results suggest that IL-1 and ectopic expression of TAB1 both activate TAK1 via autophosphorylation of Ser-192. PMID:10838074 Autophosphorylation of two threonine residues in the activation loop of TAK1 was necessary for TAK1 activation. |
| GO:0008349 MAP kinase kinase kinase kinase activity | TAS Reactome:R-HSA-9645442 | MODIFY | Summary: MAP4K activity reflects TAK1 autophosphorylation events, not phosphorylation of a separate MAP3K. Reason: The Reactome reactions cited are "Auto phosphorylation of TAK1" / "Activation of recruited TAK1"; mapping a MAP3K autophosphorylating itself to MAP kinase kinase kinase kinase activity misrepresents its activity. The underlying Ser/Thr autophosphorylation is captured by protein serine/threonine kinase activity. The early report of TAK1 phosphorylating the MAP3K NIK (PMID:10094049) is not the basis of the modern model, where TAK1 phosphorylates IKKbeta directly. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:10702308 These results suggest that IL-1 and ectopic expression of TAB1 both activate TAK1 via autophosphorylation of Ser-192. PMID:10838074 Autophosphorylation of two threonine residues in the activation loop of TAK1 was necessary for TAK1 activation. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-177690 | KEEP AS NON CORE | Summary: TAK1 complex recruited to endosomal TLR3/7/8/9 signaling complexes (Reactome). Reason: Recruitment to endosome-associated TLR-TRIF/MyD88-TRAF6 complexes is a context of TAK1 activation, not its site of kinase action on IKK/MAP2Ks. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-177692 | KEEP AS NON CORE | Summary: TAK1 complex recruited to endosomal TLR3/7/8/9 signaling complexes (Reactome). Reason: Recruitment to endosome-associated TLR-TRIF/MyD88-TRAF6 complexes is a context of TAK1 activation, not its site of kinase action on IKK/MAP2Ks. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-847070 | KEEP AS NON CORE | Summary: TAK1 complex recruited to endosomal TLR3/7/8/9 signaling complexes (Reactome). Reason: Recruitment to endosome-associated TLR-TRIF/MyD88-TRAF6 complexes is a context of TAK1 activation, not its site of kinase action on IKK/MAP2Ks. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975097 | KEEP AS NON CORE | Summary: TAK1 complex recruited to endosomal TLR3/7/8/9 signaling complexes (Reactome). Reason: Recruitment to endosome-associated TLR-TRIF/MyD88-TRAF6 complexes is a context of TAK1 activation, not its site of kinase action on IKK/MAP2Ks. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975103 | KEEP AS NON CORE | Summary: TAK1 complex recruited to endosomal TLR3/7/8/9 signaling complexes (Reactome). Reason: Recruitment to endosome-associated TLR-TRIF/MyD88-TRAF6 complexes is a context of TAK1 activation, not its site of kinase action on IKK/MAP2Ks. |
| GO:0010508 positive regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of autophagy (rat ortholog). Reason: TAB2/TAB3 switch from Beclin 1 to TAK1 upon autophagy induction, and autophagy stimulation requires TAK1 and IKK; TAK1 can also activate AMPK. Context-dependent, non-core. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. PMID:20538596 Co-expression of TAK1 and TAB1, but not TAB2, resulted in a functional and active TAK1-TAB1 complex capable of directly activating full-length heterotrimeric mammalian AMP-activated protein kinase (AMPK) in vitro. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression (rat ortholog); vague. Reason: Uninformative and not supported by human evidence as a direct TAK1 role. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Postsynaptic density (mouse ortholog proteomics-type annotation). Reason: No human evidence that TAK1 acts at the postsynaptic density; likely incidental detection. |
| GO:0016239 positive regulation of macroautophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of macroautophagy transferred from mouse. Reason: TAK1-dependent autophagy induction (via TAB2/3-Beclin 1 switch, AMPK) is context-specific; non-core. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0016239 positive regulation of macroautophagy | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of macroautophagy transferred from mouse. Reason: TAK1-dependent autophagy induction (via TAB2/3-Beclin 1 switch, AMPK) is context-specific; non-core. Supporting Evidence: PMID:22081109 Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. |
| GO:0016301 kinase activity | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | ACCEPT | Summary: Kinase activity of the TAK1 complex. Reason: Correct; general parent of the Ser/Thr and MAP3K terms. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Protein kinase binding (ARBA). Reason: TAK1 binds its kinase substrates (MAP2Ks, IKKbeta) and regulators; true but secondary to its catalytic function. Supporting Evidence: PMID:17363973 Tax physically interacts with Tak1 and mediates the recruitment of IKK to Tak1. |
| GO:0030971 receptor tyrosine kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Receptor tyrosine kinase binding (mouse ortholog; Ror2). Reason: TAK1 interacts with and phosphorylates the Ror2 intracellular domain; peripheral role in Wnt co-receptor regulation. Supporting Evidence: PMID:18762249 a MAP3K, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich (STP) domain. |
| GO:0030971 receptor tyrosine kinase binding | IPI PMID:18762249 Wnt-ligand-dependent interaction of TAK1 (TGF-beta-activated... | KEEP AS NON CORE | Summary: TAK1 binds and phosphorylates the RTK Ror2. Reason: Experimental interaction with a defined functional consequence (Ror2 phosphorylation); non-core. Supporting Evidence: PMID:18762249 a MAP3K, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich (STP) domain. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding (rat ortholog). Reason: TAK1 associates with TRAF6 and other E3s that activate it; true, secondary to kinase function. Supporting Evidence: PMID:10094049 Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 signalling. |
| GO:0032743 positive regulation of interleukin-2 production | IMP PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | KEEP AS NON CORE | Summary: TAK1 knockdown reduces TCR-induced IL-2 production. Reason: Downstream cytokine output of TAK1-IKK signaling; non-core. Supporting Evidence: PMID:15125833 RNAi-mediated silencing of MALT1, TAK1, TRAF6, and TRAF2 suppressed TCR-dependent IKK activation and interleukin-2 production in T cells. |
| GO:0034138 toll-like receptor 3 signaling pathway | TAS Reactome:R-HSA-168164 | KEEP AS NON CORE | Summary: TLR3 cascade (Reactome). Reason: TLR3-TRIF-TRAF6 recruits TAK1 for NF-kappaB (not IRF3) activation; one upstream context. Supporting Evidence: PMID:14982987 DN-TRAF6 and DN-TAK1 blocked poly(I.C)-induced NF-kappaB but not IRF3 activation |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:25371197 TAK1-ECSIT-TRAF6 complex plays a key role in the TLR4 signal... | KEEP AS NON CORE | Summary: TLR4 signaling via a TAK1-ECSIT-TRAF6 complex. Reason: Experimental support; TLR4 is one of many receptor inputs to TAK1. Supporting Evidence: PMID:25371197 ECSIT formed a high molecular endogenous complex including TAK1 and TRAF6, in which ECSIT interacted with each protein and regulated TAK1 activity, leading to the activation of NF-ΞΊB. |
| GO:0035173 histone kinase activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Histone kinase activity transferred from rat. Reason: No human evidence for TAK1 phosphorylating histones; TAK1 substrates are MAP2Ks, IKKbeta and signaling proteins. Presence in the ATAC complex does not establish histone kinase activity. Supporting Evidence: PMID:18838386 the stress- and TGFbeta-activated protein kinase (TAK1/MAP3K7) and MAP3-kinase regulator (MBIP) |
| GO:0035666 TRIF-dependent toll-like receptor signaling pathway | TAS Reactome:R-HSA-937061 | KEEP AS NON CORE | Summary: TRIF-dependent TLR signaling (Reactome). Reason: TRIF recruits TRAF6-TAK1-TAB2 for NF-kappaB activation; one upstream context. Supporting Evidence: PMID:14982987 DN-TRAF6 and DN-TAK1 blocked poly(I.C)-induced NF-kappaB but not IRF3 activation |
| GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway | TAS Reactome:R-HSA-168638 | KEEP AS NON CORE | Summary: NOD1/2 signaling (Reactome). Reason: TAK1 is required for NOD2-mediated NF-kappaB activation downstream of RIPK2 ubiquitination; one upstream context. Supporting Evidence: PMID:15075345 interacts with Nod2 and is required for Nod2-mediated NF-kappaB activation |
| GO:0038066 p38MAPK cascade | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | ACCEPT | Summary: TAK1 phosphorylates MKK6 to activate p38. Reason: Direct experimental support from reconstitution. Supporting Evidence: PMID:11460167 the activity of TAK1 to phosphorylate MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63-linked polyubiquitination |
| GO:0038066 p38MAPK cascade | TAS Reactome:R-HSA-450302 | ACCEPT | Summary: Reactome: activated TAK1 mediates p38 MAPK activation. Reason: Consistent with MKK3/6 phosphorylation. Supporting Evidence: PMID:8663074 MKK3 was also shown to be a good substrate for TAK1 in vitro. |
| GO:0038095 Fc-epsilon receptor signaling pathway | TAS Reactome:R-HSA-2454202 | KEEP AS NON CORE | Summary: Fc-epsilon receptor signaling (Reactome). Reason: Mast cell FcERI signaling engages the CARMA-BCL10-MALT1-TRAF6-TAK1 axis; one upstream context. |
| GO:0038172 interleukin-33-mediated signaling pathway | IDA PMID:20532808 Interleukin-33 stimulates formation of functional osteoclast... | KEEP AS NON CORE | Summary: IL-33 induces TAK1 phosphorylation in human monocytes. Reason: Correlative evidence (TAK1 phosphorylation) for IL-33/ST2 signaling via TRAF6; one upstream context. Supporting Evidence: PMID:20532808 These included Syk, phospholipase CΞ³2, Gab2, MAP kinases, TAK-1, and NF-ΞΊB. |
| GO:0038173 interleukin-17A-mediated signaling pathway | IDA PMID:31376257 IL-17A upregulates P-glycoprotein expression in peripheral b... | KEEP AS NON CORE | Summary: IL-17A effects on P-gp blocked by a TAK1 inhibitor. Reason: Pharmacological evidence that IL-17A signaling to P-gp requires TAK1 activity; one upstream context. Supporting Evidence: PMID:31376257 Upregulated expression of P-gp mRNA and efflux potential of P-gp were inhibited by TAK1 or ERK inhibitors in RA peripheral blood lymphocytes. |
| GO:0042742 defense response to bacterium | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | MARK AS OVER ANNOTATED | Summary: Defense response to bacterium from a biochemical reconstitution study. Reason: PMID:11460167 reconstitutes TRAF6-dependent TAK1 activation of IKK/MKK6 in vitro; defense response to bacterium is an organismal outcome several steps removed. TAK1 contributes to antibacterial responses through generic NF-kappaB/MAPK relay; the term overstates this paper. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0042770 signal transduction in response to DNA damage | TAS PMID:24936062 F-box only protein 31 (FBXO31) negatively regulates p38 mito... | MARK AS OVER ANNOTATED | Summary: DNA damage signal transduction (TAS from an FBXO31/MKK6 paper). Reason: The cited study concerns FBXO31-mediated MKK6 degradation after genotoxic stress; TAK1 participation in DNA damage signaling is not established by it. Non-specific. Supporting Evidence: PMID:24936062 FBXO31 binds to MKK6 and mediates its Lys-48-linked polyubiquitination and degradation |
| GO:0042802 identical protein binding | IPI PMID:27426733 Mutations in MAP3K7 that Alter the Activity of the TAK1 Sign... | KEEP AS NON CORE | Summary: TAK1 homodimerizes. Reason: Homodimerization reported (and preserved in FMD P485L mutant); TAK1 autoactivation is intermolecular. Non-core MF. Supporting Evidence: PMID:27426733 The recurrent mutation does not destabilize TAK1, or impair its ability to homodimerize or bind TAB2, but it does increase TAK1 autophosphorylation |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from Bilateria TAK1 node; correct for human (vertebrate) TAK1. Reason: Family review flags nematode-branch pruning only; human TAK1 activates IKK and is unaffected. Human MAP3K7 in WITH/FROM reflects its own experimental grounding. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | ACCEPT | Summary: TAK1 complex phosphorylates and activates IKK. Reason: Direct experimental evidence. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic; consistent with experiments. Reason: Consistent with direct IKK activation. Supporting Evidence: PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:14982987 Toll-like receptor 3-mediated activation of NF-kappaB and IR... | ACCEPT | Summary: Dominant-negative TAK1 blocks TLR3-induced NF-kappaB. Reason: Experimental support for TAK1 driving NF-kappaB activation downstream of TRIF-TRAF6. Supporting Evidence: PMID:14982987 DN-TRAF6 and DN-TAK1 blocked poly(I.C)-induced NF-kappaB but not IRF3 activation |
| GO:0043276 anoikis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Anoikis (mouse ortholog). Reason: TAK1 influences cell survival/death decisions (e.g. via NF-kappaB and RIPK1 control); anoikis is a context-specific downstream outcome. |
| GO:0043276 anoikis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Anoikis (mouse ortholog). Reason: TAK1 influences cell survival/death decisions (e.g. via NF-kappaB and RIPK1 control); anoikis is a context-specific downstream outcome. |
| GO:0043408 regulation of MAPK cascade | IDA PMID:22158122 Cysteine methylation disrupts ubiquitin-chain sensing in NF-... | KEEP AS NON CORE | Summary: Regulation of MAPK cascade (from NleE/TAB2-3 study). Reason: TAK1 is itself a component (MAP3K) of MAPK cascades; "regulation of" is acceptable but redundant with accepted cascade terms. Supporting Evidence: PMID:22158122 Here we show that human TAB2 and TAB3, ubiquitin-chain sensory proteins involved in NF-ΞΊB signalling, are directly inactivated by enteropathogenic Escherichia coli NleE |
| GO:0043410 positive regulation of MAPK cascade | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade (ARBA). Reason: Redundant with the accepted MAPK cascade terms; TAK1 is a cascade member. |
| GO:0043507 positive regulation of JUN kinase activity | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | ACCEPT | Summary: TAK1 activates JNK via MKK4/MKK7. Reason: Consistent with TAK1 activating the JNK pathway in a ubiquitin-dependent manner. Supporting Evidence: PMID:11460167 the activity of TAK1 to phosphorylate MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63-linked polyubiquitination |
| GO:0045787 positive regulation of cell cycle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell cycle (rat ortholog). Reason: Indirect, context-dependent consequence of signaling; no human evidence. |
| GO:0045793 positive regulation of cell size | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell size (rat ortholog; cardiac hypertrophy context). Reason: Indirect organ/cell-level outcome of signaling; not a direct TAK1 function. |
| GO:0050852 T cell receptor signaling pathway | NAS PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | KEEP AS NON CORE | Summary: TCR signaling (NAS). Reason: TAK1 mediates TCR-induced IKK activation downstream of BCL10-MALT1-TRAF6; one upstream context. Supporting Evidence: PMID:15125833 RNAi-mediated silencing of MALT1, TAK1, TRAF6, and TRAF2 suppressed TCR-dependent IKK activation and interleukin-2 production in T cells. |
| GO:0050852 T cell receptor signaling pathway | TAS Reactome:R-HSA-202403 | KEEP AS NON CORE | Summary: TCR signaling (Reactome). Reason: As above; one upstream context. Supporting Evidence: PMID:15125833 RNAi-mediated silencing of MALT1, TAK1, TRAF6, and TRAF2 suppressed TCR-dependent IKK activation and interleukin-2 production in T cells. |
| GO:0051403 stress-activated MAPK cascade | IDA PMID:9079627 TAK1 mediates the ceramide signaling to stress-activated pro... | ACCEPT | Summary: TAK1 mediates stress (ceramide) signaling to SAPK/JNK. Reason: Direct experimental support. Supporting Evidence: PMID:9079627 Ceramide itself stimulated the kinase activity of TAK1. PMID:9079627 Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. |
| GO:0060348 bone development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Bone development (mouse ortholog). Reason: Skeletal phenotypes (mouse; human FMD from MAP3K7 variants) reflect TAK1 signaling in skeletal cells; downstream developmental outcome. Supporting Evidence: PMID:27426733 The recurrent mutation does not destabilize TAK1, or impair its ability to homodimerize or bind TAB2, but it does increase TAK1 autophosphorylation |
| GO:0060546 negative regulation of necroptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of necroptosis (mouse ortholog). Reason: TAK1 restrains RIPK1-dependent cell death downstream of TNF (UniProt notes RIPK1 Ser321 phosphorylation); context-dependent, non-core. |
| GO:0070498 interleukin-1-mediated signaling pathway | IMP PMID:10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the... | ACCEPT | Summary: TAK1 is required for IL-1-induced NF-kappaB activation. Reason: Kinase-inactive TAK1 blocks IL-1-mediated NF-kappaB activation; TAK1 is the kinase relay of the IL-1R-MyD88-TRAF6 pathway. Supporting Evidence: PMID:10094049 Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 signalling. PMID:10882101 The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated signaling pathway. |
| GO:0070498 interleukin-1-mediated signaling pathway | TAS Reactome:R-HSA-9020702 | ACCEPT | Summary: Reactome IL-1 signaling. Reason: Consistent with the IL-1R-TRAF6-TAK1 axis. Supporting Evidence: PMID:10882101 The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated signaling pathway. |
| GO:0071356 cellular response to tumor necrosis factor | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to TNF (rat ortholog). Reason: TAK1 is activated by TNF via TAB2/TAB3 binding to ubiquitinated RIP1; the response term is broader than TAK1 role in TNF signaling. Supporting Evidence: PMID:15327770 We also show that TAB2 binds to polyubiquitinated RIP following TNFalpha stimulation. PMID:14633987 These results suggest that TAB2 and TAB3 function redundantly as mediators of TAK1 activation in IL-1 and TNF signal transduction. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to hypoxia (rat ortholog). Reason: Supported by human TAK1-JIP1-JNK hypoxia signaling; non-core. Supporting Evidence: PMID:17709393 We report that TAK1 is able to form a stable complex with JIP1 and thus regulate the activation of JNK, which in turn determines the cellular stress response to hypoxia. |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cellular response to TGF-beta (ARBA). Reason: Consistent with TAK1 as a TGF-beta-activated kinase; broad response term. Supporting Evidence: PMID:8533096 kinase activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic protein |
| GO:0097110 scaffold protein binding | IDA PMID:23776175 SASH1 is a scaffold molecule in endothelial TLR4 signaling. | KEEP AS NON CORE | Summary: TAK1 binds the TLR4 scaffold SASH1. Reason: Experimental; SASH1 assembles TRAF6, TAK1 and IKKs downstream of TLR4 in endothelium. Peripheral MF. Supporting Evidence: PMID:23776175 functions as a scaffold molecule to independently bind TRAF6, TAK1, IΞΊB kinase Ξ±, and IΞΊB kinase Ξ² |
| GO:0106310 protein serine kinase activity | EXP PMID:10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the... | ACCEPT | Summary: Protein serine kinase activity of TAK1. Reason: TAK1 phosphorylates serine residues (e.g. activation-loop Ser192, MKK6/IKKbeta activation-loop serines, STING Ser355). Supporting Evidence: PMID:10094049 Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. |
| GO:0106310 protein serine kinase activity | EXP PMID:10838074 Phosphorylation-dependent activation of TAK1 mitogen-activat... | ACCEPT | Summary: Protein serine kinase activity of TAK1. Reason: TAK1 phosphorylates serine residues (e.g. activation-loop Ser192, MKK6/IKKbeta activation-loop serines, STING Ser355). Supporting Evidence: PMID:10838074 Autophosphorylation of two threonine residues in the activation loop of TAK1 was necessary for TAK1 activation. |
| GO:0106310 protein serine kinase activity | EXP PMID:12589052 Transforming growth factor-beta1 (TGF-beta)-induced apoptosi... | ACCEPT | Summary: Protein serine kinase activity of TAK1. Reason: TAK1 phosphorylates serine residues (e.g. activation-loop Ser192, MKK6/IKKbeta activation-loop serines, STING Ser355). Supporting Evidence: PMID:12589052 Ectopic expression of wild-type TAK1 promoted TGF-beta1-induced phosphorylation of p38 and apoptosis, whereas dominant negative TAK1 reduced TGF-beta1-induced phosphorylation of p38 and apoptosis. |
| GO:0106310 protein serine kinase activity | EXP PMID:37832545 TAK1 is an essential kinase for STING trafficking. | ACCEPT | Summary: Protein serine kinase activity of TAK1. Reason: TAK1 phosphorylates serine residues (e.g. activation-loop Ser192, MKK6/IKKbeta activation-loop serines, STING Ser355). Supporting Evidence: PMID:37832545 activated TAK1 directly mediates STING phosphorylation on serine 355 |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based protein serine kinase activity. Reason: Consistent with experiments. Supporting Evidence: PMID:37832545 activated TAK1 directly mediates STING phosphorylation on serine 355 |
| GO:0120283 protein serine/threonine kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein Ser/Thr kinase binding (rat ortholog). Reason: TAK1 binds Ser/Thr kinase substrates (MKK7, IKKbeta); secondary to kinase activity. Supporting Evidence: PMID:17363973 Tax physically interacts with Tak1 and mediates the recruitment of IKK to Tak1. |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNA-binding TF binding (rat ortholog). Reason: TAK1 interacts with STAT3 in IL-6 signaling, where STAT3 scaffolds TAK1-NLK; peripheral. Supporting Evidence: PMID:15764709 Here, we show that TGF-beta-activated kinase 1 (TAK1) interacts with STAT3, that the TAK1-Nemo-like kinase (NLK) pathway is efficiently activated by IL-6 through the YXXQ motif |
| GO:0140672 ATAC complex | IDA PMID:18838386 Human ATAC Is a GCN5/PCAF-containing acetylase complex with ... | KEEP AS NON CORE | Summary: TAK1 co-purifies with the human ATAC acetyltransferase complex. Reason: Biochemical co-purification with MBIP; functional significance for TAK1 unknown. Non-core. Supporting Evidence: PMID:18838386 the stress- and TGFbeta-activated protein kinase (TAK1/MAP3K7) and MAP3-kinase regulator (MBIP) |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IMP PMID:10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the... | MARK AS OVER ANNOTATED | Summary: Based on the 1999 TAK1-NIK model. Reason: PMID:10094049 proposed TAK1 phosphorylates NIK to activate IKKalpha in IL-1 signaling. The subsequent model (TAK1 complex directly phosphorylates IKKbeta) superseded this, and NIK-driven non-canonical NF-kappaB is generally TAK1-independent. Retaining TAK1 in non-canonical NF-kappaB as a direct positive regulator overstates the evidence; the abstract-only cache prevents full adjudication, so this is not removed. Supporting Evidence: PMID:10094049 Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. PMID:11460167 We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. |
| GO:1902554 serine/threonine protein kinase complex | IPI PMID:22158122 Cysteine methylation disrupts ubiquitin-chain sensing in NF-... | ACCEPT | Summary: ComplexPortal: TAK1 is part of a Ser/Thr protein kinase complex (TAK1-TAB). Reason: TAK1-TAB1-TAB2/TAB3 is a Ser/Thr kinase complex. ComplexPortal uses this generic term; the specific GO:0097076 TGF-beta activated kinase 1 complex is proposed as NEW (and is not currently an is_a child of GO:1902554 in GO). Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. |
| GO:1904385 cellular response to angiotensin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Angiotensin / vascular smooth muscle annotations transferred from rat. Reason: Rat studies link TAK1 to angiotensin II-induced vascular smooth muscle responses; these are tissue-specific downstream outcomes of a general signaling kinase, without human evidence. |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Angiotensin / vascular smooth muscle annotations transferred from rat. Reason: Rat studies link TAK1 to angiotensin II-induced vascular smooth muscle responses; these are tissue-specific downstream outcomes of a general signaling kinase, without human evidence. |
| GO:1904754 positive regulation of vascular associated smooth muscle cell migration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Angiotensin / vascular smooth muscle annotations transferred from rat. Reason: Rat studies link TAK1 to angiotensin II-induced vascular smooth muscle responses; these are tissue-specific downstream outcomes of a general signaling kinase, without human evidence. |
| GO:1990450 linear polyubiquitin binding | IDA PMID:35952808 TRIM56 positively regulates TNFΞ±-induced NF-ΞΊB signaling by ... | UNDECIDED | Summary: Linear polyubiquitin binding from a TRIM56 study (abstract only). Reason: The abstract describes TRIM56 enhancing M1-linked chains conjugated to TAK1, i.e. covalent modification rather than demonstrated non-covalent linear-chain binding by TAK1. In the TAK1 complex, ubiquitin binding is performed by TAB2/TAB3 NZF domains. Without full text this cannot be adjudicated. Supporting Evidence: PMID:35952808 TRIM56 enhanced the ubiquitination of TAK1, specifically enhanced the M1-linked polyubiquitin chains to TAK1, leading to the tight interactions of the TAK1-IKKΞ± complex. PMID:15327770 We also show that TAB2 binds to polyubiquitinated RIP following TNFalpha stimulation. |
| GO:1990776 response to angiotensin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Angiotensin / vascular smooth muscle annotations transferred from rat. Reason: Rat studies link TAK1 to angiotensin II-induced vascular smooth muscle responses; these are tissue-specific downstream outcomes of a general signaling kinase, without human evidence. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of ROS metabolic process (mouse ortholog). Reason: TAK1 deficiency leads to ROS accumulation in mouse tissues; indirect, non-core. |
| GO:0097076 transforming growth factor beta activated kinase 1 complex | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. | NEW | Summary: TAK1 is the catalytic subunit of the TAK1-TAB1-TAB2/TAB3 complex (TRIKA2). Reason: The purified IKK-activating factor TRIKA2 is composed of TAK1, TAB1 and TAB2; TAB3 substitutes for TAB2. GO:0097076 is defined as exactly this complex (catalytic TAK1 plus TAB regulatory subunits) but currently carries no annotations in GOA; ComplexPortal annotates TAK1 to the generic GO:1902554. This is a component membership, not a pathway-participation claim, so the NEW process bar does not apply; the PTHR46716 family review scopes GO:0097076 to SF1. Supporting Evidence: PMID:11460167 Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. PMID:8638164 TAB1 and TAK1 were co-immunoprecipitated from mammalian cells. PMID:14633987 These results suggest that TAB2 and TAB3 function redundantly as mediators of TAK1 activation in IL-1 and TNF signal transduction. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: GO:0097076 (TGF-beta activated kinase 1 complex) has no annotations in GOA, and ComplexPortal annotates TAK1-TAB complexes to the generic GO:1902554 serine/threonine protein kinase complex. Should GO:0097076 be made is_a GO:1902554 (it is currently only under GO:1902911 protein kinase complex) and used for TAK1, TAB1, TAB2 and TAB3?
Q: Is the 1999 TAK1-NIK-IKKalpha model (basis of the non-canonical NF-kappaB IMP annotation) still supported, or should TAK1 annotations to non-canonical NF-kappaB be retired in favour of direct IKKbeta activation?
Q: Which substrate-specific outputs of TAK1 (MKK3/6, MKK4/7, IKKbeta, AMPK, STING) are selected by TAB1 versus TAB2/TAB3-containing complexes in a given receptor context?
Experiment: Reconstitute TAK1-TAB1, TAK1-TAB2 and TAK1-TAB3 complexes with defined K63, M1 and hybrid unanchored chains and measure phosphorylation kinetics on MKK4, MKK6, MKK7 and IKKbeta.
Hypothesis: Ubiquitin chain architecture and TAB composition tune TAK1 substrate selection between MAPK and IKK branches.
Experiment: Compare kinase activity, autophosphorylation and substrate phosphorylation of FMD-associated MAP3K7 variants (P485L, E70Q, V100E, G168R) with wild type in patient-derived fibroblasts.
Hypothesis: The recurrent P485L variant enhances TAB-dependent autoactivation without altering TAB2 binding, biasing downstream signaling.
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