TRAF6 (TNF receptor-associated factor 6) is a critical E3 ubiquitin ligase and signal transduction adaptor that synthesizes K63-linked polyubiquitin chains for non-degradative signaling. It serves as a central hub in multiple immune signaling pathways including TLR/IL-1R, TNF receptor superfamily (CD40, RANK), and cytosolic pattern recognition receptors, mediating activation of NF-ΞΊB and MAPK pathways. Beyond immunity, TRAF6 is essential for osteoclast differentiation, ectodermal development (hair, teeth, sweat glands), and has emerging roles in autophagy regulation. The protein contains an N-terminal RING domain for E3 ligase activity, zinc fingers, and a C-terminal TRAF domain for protein-protein interactions, enabling both enzymatic and scaffolding functions in signal transduction.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: TRAF6 functions as an E3 ubiquitin ligase that catalyzes K63-linked polyubiquitination, which is essential for its signal transduction role. This activity is well-established through multiple experimental studies showing TRAF6 works with the Ubc13-Uev1A E2 complex to synthesize K63-linked chains on target proteins including itself. Reason: This is a core molecular function of TRAF6 that is extensively validated experimentally. The IEA annotation from sequence similarity is strongly supported by multiple experimental evidence entries (EXP, IDA) in the same dataset and extensive literature. Supporting Evidence: PMID:11057907 Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as a ubiquitin-protein transferase (E3 ubiquitin ligase) (GO:0004842), assembling Lysine-63βlinked polyubiquitin chains on target proteins (including itself) in cooperation with the E2 enzyme complex Ubc13βUev1A file:human/TRAF6/TRAF6-deep-research-falcon.md TRAF6 catalyzes ubiquitin transfer in the canonical E1βE2βE3 cascade as an **E3 ligase**, promoting formation of polyubiquitin chains that serve primarily as **non-degradative signaling scaffolds** |
| GO:0004842 ubiquitin-protein transferase activity | EXP PMID:15361868 Interferon-alpha induction through Toll-like receptors invol... | ACCEPT | Summary: Direct experimental evidence for TRAF6 E3 ubiquitin ligase activity from biochemical assays. Reason: Strong experimental validation of TRAF6's core E3 ligase function through direct biochemical characterization. Supporting Evidence: PMID:15361868 Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6 |
| GO:0004842 ubiquitin-protein transferase activity | EXP PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | ACCEPT | Summary: Additional experimental confirmation of TRAF6 E3 ligase activity. Reason: Further experimental validation strengthening the evidence for this core molecular function. Supporting Evidence: PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-202453 | ACCEPT | Summary: Pathway database annotation based on traceable author statement. Reason: Consistent with experimental evidence and represents core TRAF6 function in multiple Reactome pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as a ubiquitin-protein transferase (E3 ubiquitin ligase) |
| GO:0005164 tumor necrosis factor receptor binding | IEA GO_REF:0000002 | ACCEPT | Summary: TRAF6 binds to TNF receptor superfamily members including CD40 and RANK through its TRAF-C domain, mediating signal transduction from these receptors. Reason: This is a well-established function of TRAF6. Although annotated as IEA, it represents a core adaptor function that is experimentally validated in the literature. TRAF6 directly binds cytoplasmic tails of TNF receptor superfamily members. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 directly interacts with a variety of upstream receptors and signaling proteins... from the TNF receptor superfamily file:human/TRAF6/TRAF6-deep-research.md In the TNF receptor superfamily pathways, TRAF6 associates with receptors like CD40 and RANK to propagate signals leading to NF-ΞΊB activation file:human/TRAF6/TRAF6-deep-research-falcon.md TRAF6 binds receptor cytoplasmic domains such as **RANK** in RANKL signaling to coordinate downstream activation of MAPKs/AKT and NF-ΞΊB/NFATc1 programs that drive osteoclastogenesis |
| GO:0005515 protein binding | IPI PMID:10465784 ECSIT is an evolutionarily conserved intermediate in the Tol... | REMOVE | Summary: Generic protein binding annotation based on protein interaction data. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. More specific molecular function terms should be used instead based on the actual binding partners and contexts. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 binds to cytoplasmic motifs (typically PxQxT sequences) on receptors or adaptors such as CD40, RANK (TNFRSF11A), IL-1R PMID:10465784 ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. |
| GO:0005515 protein binding | IPI PMID:11279055 A diverse family of proteins containing tumor necrosis facto... | REMOVE | Summary: Another generic protein binding annotation. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. More specific molecular function terms should be used instead based on the actual binding partners and contexts. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md As an adaptor, TRAF6 directly interacts with a variety of upstream receptors and signaling proteins PMID:11279055 2001 Feb 21. A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains. |
| GO:0001701 in utero embryonic development | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 knockout mice show perinatal lethality with developmental defects, particularly in ectodermal structures. Reason: TRAF6 is essential for embryonic development, with knockout mice showing perinatal lethality. The developmental role is particularly important for ectodermal development. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6-null mutants are perinatal lethal with a complex phenotype file:human/TRAF6/TRAF6-deep-research.md TRAF6 is required for lymph node organogenesis during embryonic development |
| GO:0002637 regulation of immunoglobulin production | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 mediates CD40 signaling in B cells which is important for immunoglobulin class switching and production. Reason: TRAF6 plays a role in B cell activation through CD40 signaling, which contributes to immunoglobulin production. While not the most central function, it is a validated consequence of TRAF6's role in immune signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md Via CD40 in B cells, TRAF6 helps induce immunoglobulin production |
| GO:0006955 immune response | IEA GO_REF:0000107 | MODIFY | Summary: TRAF6 is central to innate and adaptive immune responses through TLR, IL-1R, and TNF receptor signaling. Reason: While correct, this term is too broad. TRAF6's role should be specified as 'innate immune response' (GO:0045087) which better captures its primary function in TLR and IL-1R signaling. Proposed replacements: innate immune response Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 plays an essential role in numerous biological processes, particularly those related to immune system function... A major process controlled by TRAF6 is the innate immune response (GO:0045087) |
| GO:0009887 animal organ morphogenesis | IEA GO_REF:0000107 | MODIFY | Summary: TRAF6 is required for development of ectodermal organs including hair follicles, teeth, and sweat glands. Reason: While TRAF6 is involved in organ morphogenesis, the annotation should be more specific. TRAF6's role is particularly in 'ectodermal development' and 'odontogenesis'. Proposed replacements: odontogenesis of dentin-containing tooth ectoderm development Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has an indispensable role in ectodermal organ development: it is involved in the formation of skin appendages such as hair follicles, teeth, and sweat glands |
| GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TRAF6 may play a role in dendritic cell function and antigen presentation. Reason: While TRAF6 is expressed in dendritic cells and contributes to their activation, antigen presentation is not a core function but rather a downstream consequence of TRAF6's role in immune cell signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 in dendritic cells is needed for Th priming |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 is essential for TLR4 signaling in response to LPS, mediating NF-ΞΊB and MAPK activation. Reason: TRAF6 is essential for TLR4-mediated responses to LPS. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md In Toll-like receptor (TLR) and IL-1R signaling (e.g. TLR4 or IL-1Ξ² receptor pathways), TRAF6 is recruited via the MyD88βIRAK kinase complex PMID:11460167 TRAF6 is a signal transducer that activates IkappaB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS) |
| GO:0032735 positive regulation of interleukin-12 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TRAF6 contributes to cytokine production through NF-ΞΊB activation in immune cells. Reason: This is a downstream effect of TRAF6's role in TLR/IL-1R signaling rather than a core function. The primary role is signal transduction leading to NF-ΞΊB activation, with cytokine production being a consequence. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is required for the production of proinflammatory cytokines (such as IL-6, TNF-Ξ±) in response to pathogenic stimuli |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TRAF6-mediated NF-ΞΊB activation leads to IL-6 production in immune responses. Reason: Like IL-12 regulation, this is a downstream consequence of TRAF6's signaling function rather than a direct core activity. The core function is NF-ΞΊB activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is required for the production of proinflammatory cytokines (such as IL-6, TNF-Ξ±) |
| GO:0042088 T-helper 1 type immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TRAF6 in dendritic cells contributes to T cell priming and differentiation. Reason: This is a downstream immunological outcome of TRAF6 function in dendritic cells, not a direct core function. TRAF6's primary role is in signal transduction. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 in dendritic cells is needed for Th priming |
| GO:0042475 odontogenesis of dentin-containing tooth | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 is essential for tooth development through EDAR signaling pathway. Reason: TRAF6 knockout mice and human mutations show clear tooth development defects. This is a specific developmental function mediated through EDAR signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6^β/β mice display features of hypohidrotic ectodermal dysplasia (HED), including missing or malformed hair and sweat glands file:human/TRAF6/TRAF6-deep-research.md A de novo heterozygous missense mutation in TRAF6 was identified in a patient with Hypohidrotic Ectodermal Dysplasia, who presented with... hypodontia (missing teeth) |
| GO:0043011 myeloid dendritic cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TRAF6 plays a role in dendritic cell development and function. Reason: While TRAF6 is involved in dendritic cell signaling, cell differentiation is not its primary function. This is more of a consequence of its signaling role. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 in dendritic cells is needed for Th priming |
| GO:0048468 cell development | IEA GO_REF:0000107 | MODIFY | Summary: Overly broad term for TRAF6's role in specific cell types. Reason: This term is too generic. TRAF6 has specific roles in osteoclast differentiation and ectodermal cell development that should be annotated more precisely. Proposed replacements: osteoclast differentiation Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md Another critical biological process involving TRAF6 is osteoclast differentiation and bone resorption |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:1406630 Selection of optimal kappa B/Rel DNA-binding motifs: interac... | ACCEPT | Summary: TRAF6 is a central mediator of NF-ΞΊB activation through K63-linked ubiquitination. RETIRED - PMID:1406630 no longer in GOA. Reason: This is one of TRAF6's core functions, extensively validated experimentally. TRAF6 mediates NF-ΞΊB activation in multiple pathways through its E3 ligase activity. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 triggers NF-ΞΊB and JNK pathways PMID:11460167 TRAF6 is a signal transducer that activates IkappaB kinase (IKK) PMID:1406630 Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF-kappa B with DNA is required for transcriptional activation. file:human/TRAF6/TRAF6-deep-research-falcon.md A central, repeatedly cited role is TRAF6 in **TLR/IL-1 receptor family signaling**, where TRAF6 is recruited downstream of receptor-proximal adaptors/kinases to promote TAK1 and IKK activation, leading to NF-ΞΊB and MAPK transcriptional programs |
| GO:0042742 defense response to bacterium | IDA PMID:11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK | ACCEPT | Summary: TRAF6 mediates antibacterial responses through TLR signaling, particularly TLR4 response to LPS. Reason: TRAF6 is essential for TLR-mediated responses to bacterial components like LPS. This is a well-validated function through its role in innate immunity. Supporting Evidence: PMID:11460167 TRAF6 is a signal transducer that activates IkappaB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS) file:human/TRAF6/TRAF6-deep-research.md TRAF6-deficient cells fail to activate NF-ΞΊB and MAP kinases in response to lipopolysaccharide (TLR4 ligand) |
| 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: TRAF6 positively regulates NF-ΞΊB through K63-linked ubiquitination of signaling components. Reason: Core function of TRAF6 with strong experimental support. TRAF6's E3 ligase activity is essential for NF-ΞΊB activation. Supporting Evidence: PMID:11460167 TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IDA PMID:25038658 Identification of a NFΞΊB inhibitory peptide from tryptic Ξ²-c... | UNDECIDED | Summary: TRAF6 can negatively regulate NF-ΞΊB under certain conditions. Reason: This annotation seems contradictory to TRAF6's well-established role as a positive regulator of NF-ΞΊB. Without access to PMID:25038658, cannot determine if this represents a specific feedback mechanism or experimental context. Supporting Evidence: PMID:25038658 2014 May 23. Identification of a NFΞΊB inhibitory peptide from tryptic Ξ²-casein hydrolysate. PMID:27746020 2016 Oct 13. The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signaling. |
| GO:0070936 protein K48-linked ubiquitination | IDA PMID:27746020 The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signali... | ACCEPT | Summary: TRAF6 catalyzes K48-linked ubiquitination under specific conditions in addition to its canonical K63-linked activity. The falcon deep research confirms participation in K48-linked ubiquitination (Li 2024 TNF context; Ayyasamy 2024 JBC shows 14-3-3ΞΆ-driven K48-linked TRAF6 degradation). Per PR #833 review feedback, the earlier UNDECIDED has been resolved by the falcon evidence; action changed UNDECIDED β ACCEPT. Reason: The K48-linked ubiquitination activity of TRAF6 is documented both as a self-degradation pathway (14-3-3ΞΆ-driven K48-linked TRAF6 degradation, Ayyasamy 2024 JBC) and in TNF-context branched K48-K63 chain signaling. While K63 remains TRAF6's dominant linkage, the K48-linked activity is a real (minor) function established by multiple recent studies. Supporting Evidence: PMID:27746020 2016 Oct 13. The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signaling. file:human/TRAF6/TRAF6-deep-research-falcon.md 14-3-3ΞΆ-driven K48-linked TRAF6 degradation |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:7479976 Signal-induced degradation of I kappa B alpha requires site-... | ACCEPT | Summary: TRAF6 is essential for TLR4 signaling, mediating MyD88-dependent pathway activation. Reason: Core function of TRAF6 in innate immunity. TRAF6 is recruited to TLR4 via MyD88-IRAK complex and is required for downstream signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md In Toll-like receptor (TLR) and IL-1R signaling (e.g. TLR4 or IL-1Ξ² receptor pathways), TRAF6 is recruited via the MyD88βIRAK kinase complex PMID:7479976 Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:21931555 Vaccinia virus protein C6 is a virulence factor that binds T... | ACCEPT | Summary: TRAF6 participates in RIG-I/MAVS antiviral signaling pathways. Reason: TRAF6 functions in cytosolic pattern recognition receptor pathways including RIG-I/MAVS for antiviral responses. This extends its role beyond membrane receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 also links to the RIG-I/MAVS antiviral pathway and other cytosolic pattern-recognition receptor pathways, functioning as a key molecule in antiviral innate signaling PMID:21931555 2011 Sep 8. Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7. |
| GO:0038172 interleukin-33-mediated signaling pathway | IDA PMID:20532808 Interleukin-33 stimulates formation of functional osteoclast... | ACCEPT | Summary: TRAF6 mediates IL-33 receptor signaling. Reason: TRAF6 is involved in IL-1 receptor family signaling, which includes IL-33. This is consistent with its adaptor role in cytokine signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is a signal transducer for interleukin-1 PMID:20532808 Epub 2010 Jun 8. Interleukin-33 stimulates formation of functional osteoclasts from human CD14(+) monocytes. |
| GO:0038173 interleukin-17A-mediated signaling pathway | IDA PMID:31376257 IL-17A upregulates P-glycoprotein expression in peripheral b... | ACCEPT | Summary: TRAF6 participates in IL-17 receptor signaling. Reason: TRAF6 functions in IL-17 signaling, contributing to inflammatory responses. This represents another cytokine pathway utilizing TRAF6. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 serves as a central hub in multiple immune signaling pathways PMID:31376257 IL-17A upregulates P-glycoprotein expression in peripheral blood lymphocytes of patients with rheumatoid arthritis through TAK1. |
| GO:0000045 autophagosome assembly | IDA PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3... | ACCEPT | Summary: TRAF6 promotes autophagy through ubiquitination of autophagy regulators like Beclin-1. Reason: Emerging function of TRAF6 in autophagy regulation through K63-linked ubiquitination of autophagy machinery. Multiple studies support this non-canonical role. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has been shown to interact with autophagy regulators (such as Beclin-1 and AMBRA1) and can promote autophagic degradation of certain substrates PMID:23202584 Dec 2. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. |
| GO:0038061 non-canonical NF-kappaB signal transduction | IDA PMID:12048232 Quantitative prediction of NF-kappa B DNA-protein interactio... | ACCEPT | Summary: TRAF6 can activate non-canonical NF-ΞΊB pathway. Reason: While TRAF6 primarily activates canonical NF-ΞΊB, it can also contribute to non-canonical pathway activation in certain contexts, particularly through NIK stabilization. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 activates NF-ΞΊB and MAPK pathways PMID:12048232 Quantitative prediction of NF-kappa B DNA-protein interactions. |
| GO:0140374 antiviral innate immune response | IDA PMID:14703513 Identification of Ser-386 of interferon regulatory factor 3 ... | ACCEPT | Summary: TRAF6 mediates antiviral responses through RIG-I/MAVS and IRF activation. Reason: TRAF6 participates in antiviral signaling, particularly through cytosolic sensors and can activate IRF7 for interferon production. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 helps activate not only NF-ΞΊB but also interferon-regulatory factors; for instance, it can activate IRF7 in response to cytosolic viral DNA/RNA detection PMID:14703513 2003 Dec 31. Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation. |
| GO:0009299 mRNA transcription | IDA PMID:9891032 Essential role of interferon regulatory factor 3 in direct a... | MODIFY | Summary: TRAF6 may have nuclear functions in transcriptional regulation. Reason: This term is too broad and doesn't capture TRAF6's specific role. TRAF6 primarily regulates transcription indirectly through NF-ΞΊB and MAPK activation, not as a direct transcriptional regulator. Should be 'positive regulation of transcription by RNA polymerase II' with qualifier specifying it acts through signal transduction. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md In osteoclast nuclei, TRAF6 was found to act as a co-regulator of transcription, in complex with nuclear adaptor protein FHL2 and transcription factor RUNX1 PMID:9891032 Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. |
| GO:0051865 protein autoubiquitination | IDA PMID:23776175 SASH1 is a scaffold molecule in endothelial TLR4 signaling. | ACCEPT | Summary: TRAF6 undergoes autoubiquitination with K63-linked chains as part of its signaling mechanism. Reason: TRAF6 autoubiquitination is a key aspect of its signaling mechanism. The K63-linked autoubiquitination creates docking sites for downstream signaling proteins. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md upon receptor stimulation, TRAF6 autoubiquitination and K63-ubiquitin conjugation create docking sites for the TAK1 kinase complex PMID:23776175 2013 Jun 17. SASH1 is a scaffold molecule in endothelial TLR4 signaling. |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:23776175 SASH1 is a scaffold molecule in endothelial TLR4 signaling. | ACCEPT | Summary: TRAF6 mediates cellular responses to LPS through TLR4 signaling. Reason: Well-established function of TRAF6 in TLR4-mediated response to bacterial LPS. Essential for downstream NF-ΞΊB and MAPK activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6-deficient cells fail to activate NF-ΞΊB and MAP kinases in response to lipopolysaccharide (TLR4 ligand) PMID:23776175 2013 Jun 17. SASH1 is a scaffold molecule in endothelial TLR4 signaling. |
| GO:0005515 protein binding | IPI PMID:10514511 TRAF family proteins interact with the common neurotrophin r... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:10514511 TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction. |
| GO:0005515 protein binding | IPI PMID:10920205 T6BP, a TRAF6-interacting protein involved in IL-1 signaling... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:10920205 T6BP, a TRAF6-interacting protein involved in IL-1 signaling. |
| GO:0005515 protein binding | IPI PMID:11463333 Isolation and characterization of two novel A20-like protein... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:11463333 Isolation and characterization of two novel A20-like proteins. |
| GO:0005515 protein binding | IPI PMID:11518704 IRAK-mediated translocation of TRAF6 and TAB2 in the interle... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:11518704 2001 Aug 22. IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B. |
| GO:0005515 protein binding | IPI PMID:11751921 A novel zinc finger protein that inhibits osteoclastogenesis... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:11751921 2001 Dec 20. A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6. |
| GO:0005515 protein binding | IPI PMID:12140561 Distinct molecular mechanism for initiating TRAF6 signalling... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:12140561 Distinct molecular mechanism for initiating TRAF6 signalling. |
| GO:0005515 protein binding | IPI PMID:12242293 Interleukin-1 (IL-1) receptor-associated kinase-dependent IL... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:12242293 Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. |
| GO:0005515 protein binding | IPI PMID:12496252 Pellino 1 is required for interleukin-1 (IL-1)-mediated sign... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:12496252 2002 Dec 20. Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex. |
| GO:0005515 protein binding | IPI PMID:15280356 Induction of apoptosis by X-linked ectodermal dysplasia rece... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:15280356 2004 Jul 26. Induction of apoptosis by X-linked ectodermal dysplasia receptor via a caspase 8-dependent mechanism. |
| GO:0005515 protein binding | IPI PMID:15998638 Vaccinia virus protein A52R activates p38 mitogen-activated ... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:15998638 2005 Jul 5. Vaccinia virus protein A52R activates p38 mitogen-activated protein kinase and potentiates lipopolysaccharide-induced interleukin-10. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network. |
| GO:0005515 protein binding | IPI PMID:16286467 Interleukin-1beta induction of NFkappaB is partially regulat... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:16286467 2005 Nov 14. Interleukin-1beta induction of NFkappaB is partially regulated by H2O2-mediated activation of NFkappaB-inducing kinase. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:34721373 Defining the Role of Nuclear Factor (NF)-ΞΊB p105 Subunit in ... | ACCEPT | Summary: TRAF6 mediates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 with strong experimental support. TRAF6 is essential for NF-ΞΊB activation through multiple pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is pivotal signal transducer that links receptor-proximal events to activation of key transcription factors... leading to activation of IΞΊB kinase (IKK) and MAP kinases PMID:34721373 eCollection 2021. Defining the Role of Nuclear Factor (NF)-ΞΊB p105 Subunit in Human Macrophage by Transcriptomic Analysis of NFKB1 Knockout THP1 Cells. |
| GO:0042742 defense response to bacterium | IDA PMID:18079694 A critical role of RICK/RIP2 polyubiquitination in Nod-induc... | ACCEPT | Summary: TRAF6 mediates antibacterial responses through TLR signaling. Reason: TRAF6 is essential for antibacterial defense through TLR4 and other pattern recognition receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6-deficient cells fail to activate NF-ΞΊB and MAP kinases in response to lipopolysaccharide (TLR4 ligand) PMID:18079694 A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:18079694 A critical role of RICK/RIP2 polyubiquitination in Nod-induc... | ACCEPT | Summary: TRAF6 positively regulates NF-ΞΊB activation. Reason: Core function of TRAF6 with strong experimental support. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md positive regulation of NF-ΞΊB transcription factor activity (GO:0051092) PMID:18079694 A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:9346484 IKK-1 and IKK-2: cytokine-activated IkappaB kinases essentia... | ACCEPT | Summary: TRAF6 positively regulates NF-ΞΊB activation. Reason: Core function of TRAF6 with strong experimental support. Supporting Evidence: PMID:9346484 IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IDA PMID:27746020 The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signali... | UNDECIDED | Summary: TRAF6 may negatively regulate NF-ΞΊB under specific conditions. Reason: This annotation contradicts TRAF6's well-established role as a positive regulator of NF-ΞΊB. May represent a feedback mechanism or specific experimental context that needs verification. Supporting Evidence: PMID:27746020 2016 Oct 13. The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signaling. |
| GO:0004842 ubiquitin-protein transferase activity | EXP PMID:17728323 Identification of TRAF6-dependent NEMO polyubiquitination si... | ACCEPT | Summary: Experimental evidence for TRAF6 E3 ubiquitin ligase activity. Reason: This is TRAF6's core molecular function as an E3 ubiquitin ligase. Experimental evidence confirms this essential activity. Supporting Evidence: PMID:17728323 Aug 29. Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti. |
| GO:0004842 ubiquitin-protein transferase activity | EXP PMID:26620909 Reversible ubiquitination shapes NLRC5 function and modulate... | ACCEPT | Summary: Experimental evidence for TRAF6 E3 ubiquitin ligase activity. Reason: This is TRAF6's core molecular function as an E3 ubiquitin ligase. Experimental evidence confirms this essential activity. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as a ubiquitin-protein transferase (E3 ubiquitin ligase) (GO:0004842) PMID:26620909 Nov 30. Reversible ubiquitination shapes NLRC5 function and modulates NF-ΞΊB activation switch. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-202534 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-2730904 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-446877 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-450358 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-936942 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-936986 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-9645394 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-9645414 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-975147 | ACCEPT | Summary: Pathway database annotation for TRAF6 E3 ligase activity. Reason: TRAF6's E3 ubiquitin ligase activity is its core function, consistently represented across Reactome pathways. |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:29441066 TANK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Ty... | ACCEPT | Summary: TRAF6 participates in cytosolic pattern recognition receptor pathways. Reason: TRAF6 functions in RIG-I/MAVS and other cytosolic PRR pathways, mediating antiviral responses. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 also links to the RIG-I/MAVS antiviral pathway and other cytosolic pattern-recognition receptor pathways PMID:29441066 TANK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3 Phosphorylation. |
| GO:0000045 autophagosome assembly | IDA PMID:20713597 Autophagy requires endoplasmic reticulum targeting of the PI... | ACCEPT | Summary: TRAF6 regulates autophagy through K63-ubiquitination of Beclin-1. Reason: TRAF6 plays an established role in autophagy regulation by ubiquitinating key autophagy proteins like Beclin-1 and AMBRA1. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has been shown to interact with autophagy regulators (such as Beclin-1 and AMBRA1) PMID:20713597 Aug 16. Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. |
| GO:0000045 autophagosome assembly | IDA PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, ... | ACCEPT | Summary: TRAF6 regulates autophagy through K63-ubiquitination of autophagy proteins. Reason: TRAF6 plays an established role in autophagy regulation by ubiquitinating key autophagy proteins like Beclin-1 and AMBRA1, promoting autophagosome assembly. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has been shown to interact with autophagy regulators (such as Beclin-1 and AMBRA1) and can promote autophagic degradation of certain substrates PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. |
| GO:0000045 autophagosome assembly | IDA PMID:25891078 IRGM governs the core autophagy machinery to conduct antimic... | ACCEPT | Summary: TRAF6 regulates autophagy through K63-ubiquitination. Reason: TRAF6 plays an established role in autophagy regulation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 ubiquitinates ULK1 and Beclin 1 to regulate autophagy PMID:25891078 2015 Apr 16. IRGM governs the core autophagy machinery to conduct antimicrobial defense. |
| GO:0000045 autophagosome assembly | IMP PMID:30778222 Distinct functions of ATG16L1 isoforms in membrane binding a... | ACCEPT | Summary: TRAF6 promotes autophagosome assembly through its role in autophagy signaling. Reason: Mutant phenotype evidence confirms TRAF6's role in autophagy regulation and autophagosome assembly through K63-linked ubiquitination. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has been shown to interact with autophagy regulators (such as Beclin-1 and AMBRA1) and can promote autophagic degradation PMID:30778222 2019 Feb 18. Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. |
| GO:0000045 autophagosome assembly | IDA PMID:33637724 VPS34 K29/K48 branched ubiquitination governed by UBE3C and ... | ACCEPT | Summary: TRAF6 participates in autophagosome assembly through K63-ubiquitination. Reason: Direct experimental evidence supports TRAF6's role in autophagy through ubiquitination of autophagy machinery components. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has been shown to interact with autophagy regulators (such as Beclin-1 and AMBRA1) and can promote autophagic degradation PMID:33637724 VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism. |
| GO:0000045 autophagosome assembly | IDA PMID:23392225 FIP200 regulates targeting of Atg16L1 to the isolation membr... | ACCEPT | Summary: TRAF6 mediates autophagosome assembly via K63-linked ubiquitination. Reason: Experimental evidence demonstrates TRAF6's direct involvement in autophagy through ubiquitination of key autophagy proteins. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has been shown to interact with autophagy regulators (such as Beclin-1 and AMBRA1) and can promote autophagic degradation PMID:23392225 FIP200 regulates targeting of Atg16L1 to the isolation membrane. |
| GO:0000045 autophagosome assembly | IDA PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | ACCEPT | Summary: TRAF6 regulates autophagosome formation through ubiquitin signaling. Reason: Direct evidence shows TRAF6 promotes autophagy through K63-linked ubiquitination of autophagy regulators. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has been shown to interact with autophagy regulators (such as Beclin-1 and AMBRA1) and can promote autophagic degradation PMID:28890335 Epub 2017 Sep 7. The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:34796041 Hepatitis B virus X Protein Promotes Liver Cancer Progressio... | ACCEPT | Summary: TRAF6 participates in cytosolic pattern recognition receptor pathways. Reason: TRAF6 functions in RIG-I/MAVS and other cytosolic PRR pathways, mediating antiviral responses. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 also links to the RIG-I/MAVS antiviral pathway and other cytosolic pattern-recognition receptor pathways, functioning as a key molecule in antiviral innate signaling PMID:34796041 2021 Oct. Hepatitis B virus X Protein Promotes Liver Cancer Progression through Autophagy Induction in Response to TLR4 Stimulation. |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:25371197 TAK1-ECSIT-TRAF6 complex plays a key role in the TLR4 signal... | ACCEPT | Summary: TRAF6 is essential for TLR4 signaling, mediating MyD88-dependent pathway activation. Reason: Core function of TRAF6 in innate immunity. TRAF6 is recruited to TLR4 via MyD88-IRAK complex and is required for downstream signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md In Toll-like receptor (TLR) and IL-1R signaling (e.g. TLR4 or IL-1Ξ² receptor pathways), TRAF6 is recruited via the MyD88βIRAK kinase complex PMID:25371197 2014 Nov 4. TAK1-ECSIT-TRAF6 complex plays a key role in the TLR4 signal to activate NF-ΞΊB. |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:25355951 Ubiquitination of ECSIT is crucial for the activation of p65... | ACCEPT | Summary: TRAF6 is essential for TLR4 signaling, mediating MyD88-dependent pathway activation. Reason: Core function of TRAF6 in innate immunity. TRAF6 is recruited to TLR4 via MyD88-IRAK complex and is required for downstream signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md In Toll-like receptor (TLR) and IL-1R signaling (e.g. TLR4 or IL-1Ξ² receptor pathways), TRAF6 is recruited via the MyD88βIRAK kinase complex PMID:25355951 2014 Oct 29. Ubiquitination of ECSIT is crucial for the activation of p65/p50 NF-ΞΊBs in Toll-like receptor 4 signaling. |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:26189595 Polyubiquitination of Transforming Growth Factor Ξ²-activated... | ACCEPT | Summary: TRAF6 is essential for TLR4 signaling, mediating MyD88-dependent pathway activation. Reason: Core function of TRAF6 in innate immunity. TRAF6 is recruited to TLR4 via MyD88-IRAK complex and is required for downstream signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md In Toll-like receptor (TLR) and IL-1R signaling (e.g. TLR4 or IL-1Ξ² receptor pathways), TRAF6 is recruited via the MyD88βIRAK kinase complex PMID:26189595 Polyubiquitination of Transforming Growth Factor Ξ²-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation. |
| GO:0038061 non-canonical NF-kappaB signal transduction | IDA PMID:26189595 Polyubiquitination of Transforming Growth Factor Ξ²-activated... | ACCEPT | Summary: TRAF6 can participate in non-canonical NF-ΞΊB signaling in specific contexts. Reason: While TRAF6 primarily activates canonical NF-ΞΊB, it can also contribute to non-canonical pathway activation in certain contexts, particularly through NIK stabilization and p100 processing. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 activates NF-ΞΊB and MAPK pathways PMID:26189595 Polyubiquitination of Transforming Growth Factor Ξ²-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:10882101 TAB2, a novel adaptor protein, mediates activation of TAK1 M... | ACCEPT | Summary: TRAF6 mediates canonical NF-ΞΊB activation through K63-linked ubiquitination. Reason: This is one of TRAF6's core functions. TRAF6 is essential for NF-ΞΊB activation in response to multiple stimuli including TLR and TNF receptor signaling. Supporting Evidence: PMID:10882101 TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. |
| GO:0140374 antiviral innate immune response | IDA PMID:9891032 Essential role of interferon regulatory factor 3 in direct a... | ACCEPT | Summary: TRAF6 participates in antiviral responses through RIG-I/MAVS pathway. Reason: TRAF6 plays a role in antiviral innate immunity by mediating IRF7 ubiquitination and activation downstream of pattern recognition receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md it can activate IRF7 in response to cytosolic viral DNA/RNA detection PMID:9891032 Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. |
| GO:0005515 protein binding | IPI PMID:10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. |
| GO:0005515 protein binding | IPI PMID:11728344 A novel TNF receptor family member binds TWEAK and is implic... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:11728344 A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TRAF6 mediates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 with strong experimental support. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 links receptor-proximal events to activation of IΞΊB kinase (IKK) and MAP kinases PMID:19675569 Direct activation of protein kinases by unanchored polyubiquitin chains. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:9252186 A cytokine-responsive IkappaB kinase that activates the tran... | ACCEPT | Summary: TRAF6 mediates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 with strong experimental support. Supporting Evidence: PMID:9252186 A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. |
| GO:0005515 protein binding | IPI PMID:11397809 IRAK1b, a novel alternative splice variant of interleukin-1 ... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:11397809 2001 Jun 7. IRAK1b, a novel alternative splice variant of interleukin-1 receptor-associated kinase (IRAK), mediates interleukin-1 signaling and has prolonged stability. |
| GO:0005515 protein binding | IPI PMID:11238466 Equine herpesvirus protein E10 induces membrane recruitment ... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:11238466 Equine herpesvirus protein E10 induces membrane recruitment and phosphorylation of its cellular homologue, bcl-10. |
| GO:0005515 protein binding | IPI PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. |
| GO:0005515 protein binding | IPI PMID:12459498 NF-kappaB activator Act1 associates with IL-1/Toll pathway a... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:12459498 NF-kappaB activator Act1 associates with IL-1/Toll pathway adaptor molecule TRAF6. |
| GO:0005515 protein binding | IPI PMID:14530355 Toll/IL-1 receptor domain-containing adaptor inducing IFN-be... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:14530355 Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. |
| GO:0005515 protein binding | IPI PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates ... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. |
| GO:0005515 protein binding | IPI PMID:14982987 Toll-like receptor 3-mediated activation of NF-kappaB and IR... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:14982987 Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. |
| GO:0005515 protein binding | IPI PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. |
| GO:0005515 protein binding | IPI PMID:11244088 The atypical protein kinase C-interacting protein p62 is a s... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:11244088 2001 Jan 22. The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor. |
| GO:0005515 protein binding | IPI PMID:12925853 SIGIRR, a negative regulator of Toll-like receptor-interleuk... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:12925853 SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. |
| GO:0005515 protein binding | IPI PMID:12270937 Role of TRAF3 and -6 in the activation of the NF-kappa B and... | REMOVE | Summary: The generic protein binding term does not provide informative functional annotation. TRAF6 binds many specific proteins as part of its scaffolding function, but this general term should be removed in favor of more specific molecular function terms. Reason: GO:0005515 (protein binding) is too general and uninformative for a well-characterized protein like TRAF6. The specific protein interactions and their functional contexts are better captured by more specific GO terms. Supporting Evidence: PMID:12270937 2002 Sep 20. Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways by X-linked ectodermal dysplasia receptor. |
| GO:0035591 signaling adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: TRAF6 functions as a signaling adaptor linking receptors to downstream pathways. Reason: TRAF6 is a well-characterized signaling adaptor that bridges receptor complexes to downstream kinases and transcription factors, a core aspect of its function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md As an adaptor, TRAF6 directly interacts with a variety of upstream receptors and signaling proteins file:human/TRAF6/TRAF6-deep-research-falcon.md TRAF6 is best understood as a **signal-proximal ubiquitin ligase/scaffold** that converts receptor stimulation into **polyubiquitin-based signaling scaffolds** which recruit and activate downstream kinases |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) file:human/TRAF6/TRAF6-deep-research-falcon.md **TRAF6 (TNF receptor-associated factor 6)** is a human TRAF-family cytosolic signaling adaptor that also functions as a **RING-type E3 ubiquitin ligase** (EC 2.3.2.27) |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) |
| GO:0008270 zinc ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: TRAF6 contains zinc-binding domains essential for its structure. Reason: TRAF6 has a RING domain and four zinc finger motifs that coordinate zinc ions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md RING finger domain coordinates zinc and is characteristic of many E3 ubiquitin ligases file:human/TRAF6/TRAF6-deep-research-falcon.md conserved multi-domain architecture with **N-terminal RING** and multiple **zinc fingers**, a **coiled-coil/TRAF-N** region, and a **C-terminal TRAF-C/MATH (TRAF) domain** |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: TRAF6 has transferase activity as an E3 ubiquitin ligase. Reason: TRAF6 transfers ubiquitin to target proteins, a validated transferase activity. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of K63-linked polyubiquitin chains |
| GO:0019899 enzyme binding | IEA GO_REF:0000117 | ACCEPT | Summary: TRAF6 binds to E2 enzymes like Ubc13-Uev1A. Reason: TRAF6 directly binds E2 ubiquitin-conjugating enzymes for its E3 ligase function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 RING domain binds the Ubc13-Uev1A heterodimer file:human/TRAF6/TRAF6-deep-research-falcon.md A 2024 inhibitor-discovery study notes a defined TRAF6βUbc13 interaction surface, highlighting TRAF6 residues **Gln54, Asp57, Ile72, Leu74** as contributing to E2 engagement |
| GO:0042802 identical protein binding | IEA GO_REF:0000117 | ACCEPT | Summary: TRAF6 forms homo-oligomers essential for signaling. Reason: TRAF6 forms homodimers and homotrimers required for its signaling function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can form homodimers and homotrimers file:human/TRAF6/TRAF6-deep-research-falcon.md In this family, the trimeric TRAF-C domain can act as a βcapβ and the TRAF-N coiled-coil as a βstalk,β providing an interaction platform that positions the N-terminal RING/zinc-finger catalytic region for ubiquitin-chain assembly and signaling complex formation |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: TRAF6 binds metal ions including zinc. Reason: TRAF6 contains zinc-binding RING and zinc finger domains. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md RING domain coordinates zinc |
| GO:0005515 protein binding | IPI PMID:16874300 The signaling adapter p62 is an important mediator of T help... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:16874300 Jul 27. The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation. |
| GO:0005515 protein binding | IPI PMID:16932746 The UL144 gene product of human cytomegalovirus activates NF... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:16932746 Aug 24. The UL144 gene product of human cytomegalovirus activates NFkappaB via a TRAF6-dependent mechanism. |
| GO:0005515 protein binding | IPI PMID:17124500 Sphingosine 1-phosphate as a regulator of osteoclast differe... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:17124500 Nov 23. Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling. |
| GO:0005515 protein binding | IPI PMID:17389358 Unc-51-like kinase 1/2-mediated endocytic processes regulate... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:17389358 Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branching of sensory axons. |
| GO:0005515 protein binding | IPI PMID:17703191 Essential role for TAX1BP1 in the termination of TNF-alpha-,... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:17703191 Aug 16. Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling. |
| GO:0005515 protein binding | IPI PMID:17948050 Malt1 ubiquitination triggers NF-kappaB signaling upon T-cel... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:17948050 Oct 18. Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. |
| GO:0005515 protein binding | IPI PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation. |
| GO:0005515 protein binding | IPI PMID:18682563 Herpesvirus tegument protein activates NF-kappaB signaling t... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:18682563 Herpesvirus tegument protein activates NF-kappaB signaling through the TRAF6 adaptor protein. |
| GO:0005515 protein binding | IPI PMID:19365808 NESCA: a new NEMO/IKKgamma and TRAF6 interacting protein. | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:19365808 NESCA: a new NEMO/IKKgamma and TRAF6 interacting protein. |
| GO:0005515 protein binding | IPI PMID:19465916 E2 interaction and dimerization in the crystal structure of ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:19465916 May 24. E2 interaction and dimerization in the crystal structure of TRAF6. |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. |
| GO:0005515 protein binding | IPI PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:19675569 Direct activation of protein kinases by unanchored polyubiquitin chains. |
| GO:0005515 protein binding | IPI PMID:19820695 Helicobacter pylori CagA activates NF-kappaB by targeting TA... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:19820695 Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination. |
| GO:0005515 protein binding | IPI PMID:20080758 WDR5 is essential for assembly of the VISA-associated signal... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:20080758 WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-kappaB activation. |
| GO:0005515 protein binding | IPI PMID:20676093 The transmembrane activator TACI triggers immunoglobulin cla... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:20676093 The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:21516116 Next-generation sequencing to generate interactome datasets. |
| GO:0005515 protein binding | IPI PMID:21541365 Neurosteroid dehydroepiandrosterone interacts with nerve gro... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:21541365 2011 Apr 26. Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis. |
| GO:0005515 protein binding | IPI PMID:21782231 MAVS forms functional prion-like aggregates to activate and ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:21782231 MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:21903422 2011 Sep 8. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:22493164 Systematic analysis of dimeric E3-RING interactions reveals ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:22493164 Epub 2012 Apr 5. Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks. |
| GO:0005515 protein binding | IPI PMID:22528498 Protein kinase C-Ξ΄ negatively regulates T cell receptor-indu... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:22528498 2012 Apr 23. Protein kinase C-Ξ΄ negatively regulates T cell receptor-induced NF-ΞΊB activation by inhibiting the assembly of CARMA1 signalosome. |
| GO:0005515 protein binding | IPI PMID:22904686 The germinal center kinase TNIK is required for canonical NF... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:22904686 Aug 14. The germinal center kinase TNIK is required for canonical NF-ΞΊB and JNK signaling in B-cells by the EBV oncoprotein LMP1 and the CD40 receptor. |
| GO:0005515 protein binding | IPI PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:26068852 INNATE IMMUNITY. Cytosolic detection of the bacterial metabo... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:26068852 INNATE IMMUNITY. Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity. |
| GO:0005515 protein binding | IPI PMID:26385923 Structural Insights into mitochondrial antiviral signaling p... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:26385923 2015 Sep 18. Structural Insights into mitochondrial antiviral signaling protein (MAVS)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling. |
| GO:0005515 protein binding | IPI PMID:26752465 Increased Expression of Interleukin-36, a Member of the Inte... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:26752465 Increased Expression of Interleukin-36, a Member of the Interleukin-1 Cytokine Family, in Inflammatory Bowel Disease. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusion Genetics. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:27173435 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0042802 identical protein binding | IPI PMID:19465916 E2 interaction and dimerization in the crystal structure of ... | ACCEPT | Summary: TRAF6 forms homo-oligomers essential for signaling. Reason: TRAF6 forms homodimers and homotrimers required for its signaling function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can form homodimers and homotrimers PMID:19465916 May 24. E2 interaction and dimerization in the crystal structure of TRAF6. |
| GO:0042802 identical protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | ACCEPT | Summary: TRAF6 forms homo-oligomers essential for signaling. Reason: TRAF6 forms homodimers and homotrimers required for its signaling function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can form homodimers and homotrimers PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0042802 identical protein binding | IPI PMID:22493164 Systematic analysis of dimeric E3-RING interactions reveals ... | ACCEPT | Summary: TRAF6 forms homo-oligomers essential for signaling. Reason: TRAF6 forms homodimers and homotrimers required for its signaling function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can form homodimers and homotrimers PMID:22493164 Epub 2012 Apr 5. Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks. |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: TRAF6 forms homo-oligomers essential for signaling. Reason: TRAF6 forms homodimers and homotrimers required for its signaling function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can form homodimers and homotrimers PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0042802 identical protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | ACCEPT | Summary: TRAF6 forms homo-oligomers essential for signaling. Reason: TRAF6 forms homodimers and homotrimers required for its signaling function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can form homodimers and homotrimers PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusion Genetics. |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | ACCEPT | Summary: TRAF6 forms homo-oligomers essential for signaling. Reason: TRAF6 forms homodimers and homotrimers required for its signaling function. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can form homodimers and homotrimers PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0032481 positive regulation of type I interferon production | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 regulates type I interferon production. Reason: TRAF6 activates IRF7 for interferon production. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md it can activate IRF7 in response to cytosolic viral DNA/RNA detection |
| GO:0034450 ubiquitin-ubiquitin ligase activity | IDA PMID:27746020 The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signali... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:27746020 2016 Oct 13. The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signaling. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular ... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 ... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 ... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:15465037 The coiled-coil domain of TRAF6 is essential for its auto-ub... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:15465037 The coiled-coil domain of TRAF6 is essential for its auto-ubiquitination. |
| GO:0005515 protein binding | IPI PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activat... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activation. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:26458771 Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis thro... | ACCEPT | Summary: TRAF6 positively regulates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 - activating NF-ΞΊB through K63-ubiquitination and IKK activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md leading to activation of IΞΊB kinase (IKK) and MAP kinases PMID:26458771 Oct 12. Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:19675569 Direct activation of protein kinases by unanchored polyubiquitin chains. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:23514740 TNFR-associated factor 6 regulates TCR signaling via interac... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:23514740 2013 Mar 20. TNFR-associated factor 6 regulates TCR signaling via interaction with and modification of LAT adapter. |
| GO:0005515 protein binding | IPI PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 on mitochondria. |
| GO:0034450 ubiquitin-ubiquitin ligase activity | IDA PMID:15465037 The coiled-coil domain of TRAF6 is essential for its auto-ub... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:15465037 The coiled-coil domain of TRAF6 is essential for its auto-ubiquitination. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activat... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activation. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0005515 protein binding | IPI PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:25861989 2015 Apr 10. TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibits Genotoxic Nuclear Factor ΞΊB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase. |
| GO:0005515 protein binding | IPI PMID:25736436 WDFY1 mediates TLR3/4 signaling by recruiting TRIF. | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:25736436 WDFY1 mediates TLR3/4 signaling by recruiting TRIF. |
| GO:0005515 protein binding | IPI PMID:22908223 Tetraspanin 6 (TSPAN6) negatively regulates retinoic acid-in... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:22908223 2012 Aug 20. Tetraspanin 6 (TSPAN6) negatively regulates retinoic acid-inducible gene I-like receptor-mediated immune signaling in a ubiquitination-dependent manner. |
| GO:0031624 ubiquitin conjugating enzyme binding | IDA PMID:23776175 SASH1 is a scaffold molecule in endothelial TLR4 signaling. | ACCEPT | Summary: TRAF6 binds other ubiquitin ligases. Reason: TRAF6 interacts with other E3s in signaling complexes. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 interacts with various protein kinases and E3 ligases PMID:23776175 2013 Jun 17. SASH1 is a scaffold molecule in endothelial TLR4 signaling. |
| GO:0005515 protein binding | IPI PMID:21813773 IFN-induced TPR protein IFIT3 potentiates antiviral signalin... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:21813773 Aug 3. IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. |
| GO:0005515 protein binding | IPI PMID:18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 ... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. |
| GO:0005515 protein binding | IPI PMID:17449468 RBCK1 negatively regulates tumor necrosis factor- and interl... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:17449468 2007 Apr 20. RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation. |
| GO:0005515 protein binding | IPI PMID:20079715 NUMBL interacts with TRAF6 and promotes the degradation of T... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:20079715 NUMBL interacts with TRAF6 and promotes the degradation of TRAF6. |
| GO:0005515 protein binding | IPI PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | REMOVE | Summary: Generic protein binding is uninformative for TRAF6. Reason: Too general - specific binding functions are captured by other terms. Supporting Evidence: PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0042826 histone deacetylase binding | IPI PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0043422 protein kinase B binding | IPI PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activat... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activation. |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: TRAF6 regulates IKK/NF-ΞΊB signaling pathway. Reason: TRAF6 is a key regulator of NF-ΞΊB activation through IKK. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 activates IKK complex |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm file:human/TRAF6/TRAF6-deep-research-falcon.md TRAF6 is described/observed as a **cytosolic adaptor** that associates with the **cytoplasmic tails of transmembrane receptors** |
| GO:0009898 cytoplasmic side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: TRAF6 localizes to cytoplasmic face of plasma membrane during signaling. Reason: TRAF6 is recruited to the cytoplasmic side of membrane-bound receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md placing it at the plasma membrane's cytoplasmic face as part of the activated receptor complex |
| GO:0098978 glutamatergic synapse | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: TRAF6 may have roles at synapses. Reason: While TRAF6 is expressed in neurons, synaptic localization is not a core function. |
| GO:0045087 innate immune response | IBA GO_REF:0000033 | ACCEPT | Summary: TRAF6 mediates innate immune responses. Reason: Essential role in TLR and IL-1R innate immunity pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 plays an essential role in numerous biological processes, particularly those related to immune system function |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: TRAF6 localizes to lipopolysaccharide receptor complex. Reason: TRAF6 is recruited to TLR4 complex upon LPS stimulation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6-deficient cells fail to activate NF-ΞΊB in response to lipopolysaccharide |
| GO:0001503 ossification | IEA GO_REF:0000120 | ACCEPT | Summary: TRAF6 regulates bone development through osteoclast control. Reason: TRAF6 knockout causes osteopetrosis due to failed osteoclast development. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6-deficient mice exhibit severe osteopetrosis |
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: TRAF6 regulates immune system processes. Reason: Central role in both innate and adaptive immunity. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 plays an essential role in immune system function |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: TRAF6 can localize to nucleus in specific contexts. Reason: TRAF6 translocates to nucleus in osteoclasts and certain other conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md RANKL stimulation increases TRAF6 accumulation in the nuclei of osteoclasts |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm |
| GO:0005811 lipid droplet | IEA GO_REF:0000120 | REMOVE | Summary: TRAF6 localization to lipid droplets is not established. Reason: No evidence for TRAF6 at lipid droplets; likely spurious. |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: TRAF6 may localize to cell cortex during signaling. Reason: Not a primary localization but may occur during membrane recruitment. |
| GO:0006974 DNA damage response | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: TRAF6 participates in DNA damage responses. Reason: May contribute through NF-ΞΊB but not a primary function. |
| GO:0007165 signal transduction | IEA GO_REF:0000120 | ACCEPT | Summary: TRAF6 mediates signal transduction. Reason: TRAF6 is a signal transduction adaptor and E3 ligase. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is a pivotal signal transducer |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: TRAF6 catalyzes protein ubiquitination. Reason: Core E3 ligase function ubiquitinating target proteins. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of K63-linked polyubiquitin chains |
| GO:0032991 protein-containing complex | IEA GO_REF:0000117 | ACCEPT | Summary: TRAF6 is a component of signaling complexes. Reason: TRAF6 forms complexes with receptors and kinases. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is a component of several protein complexes |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: TRAF6 regulates IKK/NF-ΞΊB signaling pathway. Reason: TRAF6 is a key regulator of NF-ΞΊB activation through IKK. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 activates IKK complex |
| GO:0141124 intracellular signaling cassette | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:1901701 cellular response to oxygen-containing compound | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0070498 interleukin-1-mediated signaling pathway | TAS Reactome:R-HSA-9020702 | ACCEPT | Summary: TRAF6 is essential for IL-1 receptor signaling. Reason: TRAF6 is required for signal transduction from IL-1 receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited via the MyD88-IRAK kinase complex in IL-1R signaling |
| GO:0002223 stimulatory C-type lectin receptor signaling pathway | TAS Reactome:R-HSA-5621481 | ACCEPT | Summary: TRAF6 stimulates immune responses. Reason: Activates inflammatory and immune signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is required for the production of proinflammatory cytokines |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | TAS Reactome:R-HSA-9645460 | ACCEPT | Summary: TRAF6 mediates signaling from cytosolic pattern recognition receptors. Reason: TRAF6 functions in RIG-I/MAVS and other cytosolic PRR pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 also links to the RIG-I/MAVS antiviral pathway |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | TAS Reactome:R-HSA-166058 | ACCEPT | Summary: TRAF6 mediates MyD88-dependent TLR signaling. Reason: TRAF6 is essential for signal transduction from MyD88 in TLR pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited via the MyD88-IRAK kinase complex |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | TAS Reactome:R-HSA-975871 | ACCEPT | Summary: TRAF6 mediates MyD88-dependent TLR signaling. Reason: TRAF6 is essential for signal transduction from MyD88 in TLR pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited via the MyD88-IRAK kinase complex |
| GO:0007249 canonical NF-kappaB signal transduction | TAS Reactome:R-HSA-937072 | ACCEPT | Summary: TRAF6 is essential for IKK/NF-ΞΊB signaling. Reason: TRAF6 activates IKK complex leading to NF-ΞΊB nuclear translocation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination create docking sites for the TAK1 kinase complex, leading to activation of IΞΊB kinase |
| GO:0034138 toll-like receptor 3 signaling pathway | TAS Reactome:R-HSA-168164 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0035666 TRIF-dependent toll-like receptor signaling pathway | TAS Reactome:R-HSA-937061 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0038095 Fc-epsilon receptor signaling pathway | TAS Reactome:R-HSA-2454202 | KEEP AS NON CORE | Summary: TRAF6 mediates Fc receptor signaling. Reason: May contribute but not a primary TRAF6 pathway. |
| GO:0050852 T cell receptor signaling pathway | TAS Reactome:R-HSA-202403 | ACCEPT | Summary: TRAF6 has roles in T cell signaling. Reason: TRAF6 participates in TCR signaling and T cell activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 contributes to T-cell activation |
| GO:0000209 protein polyubiquitination | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 catalyzes polyubiquitination of target proteins. Reason: TRAF6 assembles K63-linked polyubiquitin chains on substrates. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the synthesis of unique polyubiquitin chains |
| GO:0001843 neural tube closure | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 is required for neural tube closure. Reason: TRAF6 knockout mice show developmental defects. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6-null mutants are perinatal lethal with complex phenotype |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol file:human/TRAF6/TRAF6-deep-research-falcon.md Across recent primary studies, TRAF6 is described/observed as a **cytosolic adaptor** that associates with the **cytoplasmic tails of transmembrane receptors** and with inducible cytosolic signaling assemblies |
| GO:0007249 canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 is essential for IKK/NF-ΞΊB signaling. Reason: TRAF6 activates IKK complex leading to NF-ΞΊB nuclear translocation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination create docking sites for the TAK1 kinase complex, leading to activation of IΞΊB kinase |
| GO:0009898 cytoplasmic side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 localizes to cytoplasmic face of plasma membrane during signaling. Reason: TRAF6 is recruited to the cytoplasmic side of membrane-bound receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md placing it at the plasma membrane's cytoplasmic face as part of the activated receptor complex |
| GO:0030316 osteoclast differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 is essential for osteoclast differentiation. Reason: TRAF6 mediates RANK signaling required for osteoclastogenesis. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is the key signaling adaptor for RANK in osteoclast precursors file:human/TRAF6/TRAF6-deep-research-falcon.md TRAF6 is essential in **RANKLβRANK signaling**, acting as a key adaptor/E3 ligase required for osteoclastogenic downstream cascades (MAPK, PI3K/AKT, IΞΊB phosphorylation) and NF-ΞΊB activation |
| GO:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 localizes to membrane complexes. Reason: TRAF6 is recruited to receptor complexes at membranes. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0035631 CD40 receptor complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0042102 positive regulation of T cell proliferation | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 promotes T cell proliferation. Reason: TRAF6 contributes to T cell activation and proliferation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 in T cells regulates peripheral tolerance |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 positively regulates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 - activating NF-ΞΊB through K63-ubiquitination and IKK activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md leading to activation of IΞΊB kinase (IKK) and MAP kinases |
| GO:0045453 bone resorption | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 regulates bone resorption. Reason: Essential for osteoclast-mediated bone resorption. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is the key signaling adaptor for RANK in osteoclasts |
| GO:0046849 bone remodeling | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 regulates bone remodeling. Reason: Essential for osteoclast function in bone remodeling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md bone remodeling is profoundly dependent on TRAF6-mediated signaling file:human/TRAF6/TRAF6-deep-research-falcon.md **RANK/RANKLβTRAF6** is central for osteoclastogenesis and bone remodeling |
| GO:0070498 interleukin-1-mediated signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: TRAF6 is essential for IL-1 receptor signaling. Reason: TRAF6 is required for signal transduction from IL-1 receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited via the MyD88-IRAK kinase complex in IL-1R signaling file:human/TRAF6/TRAF6-deep-research-falcon.md **TLR/IL-1RβMyD88βIRAKβTRAF6βTAK1βNF-ΞΊB/MAPK** |
| GO:0070534 protein K63-linked ubiquitination | IEA GO_REF:0000107 | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain file:human/TRAF6/TRAF6-deep-research-falcon.md The most consistently supported E2 complex for TRAF6 is **Ubc13/UBE2NβUev1A/UBE2V1**, which is directly linked to TRAF6-mediated assembly of **K63-linked polyubiquitin chains** |
| GO:0097400 interleukin-17-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TRAF6 may have roles at synapses. Reason: While TRAF6 is expressed in neurons, synaptic localization is not a core function. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IMP PMID:12296995 TAK1-dependent activation of AP-1 and c-Jun N-terminal kinas... | ACCEPT | Summary: TRAF6 mediates TNF receptor signaling. Reason: TRAF6 transduces signals from TNF receptor superfamily members. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 can mediate signals not only from the TNF receptor superfamily PMID:12296995 TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:12296995 TAK1-dependent activation of AP-1 and c-Jun N-terminal kinas... | ACCEPT | Summary: TRAF6 positively regulates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 - activating NF-ΞΊB through K63-ubiquitination and IKK activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md leading to activation of IΞΊB kinase (IKK) and MAP kinases PMID:12296995 TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:11751921 A novel zinc finger protein that inhibits osteoclastogenesis... | ACCEPT | Summary: TRAF6 positively regulates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 - activating NF-ΞΊB through K63-ubiquitination and IKK activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md leading to activation of IΞΊB kinase (IKK) and MAP kinases PMID:11751921 2001 Dec 20. A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6. |
| GO:0045672 positive regulation of osteoclast differentiation | IDA PMID:11751921 A novel zinc finger protein that inhibits osteoclastogenesis... | ACCEPT | Summary: TRAF6 is essential for osteoclast differentiation. Reason: TRAF6 mediates RANK signaling required for osteoclastogenesis. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is the key signaling adaptor for RANK in osteoclast precursors PMID:11751921 2001 Dec 20. A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6. |
| GO:0046330 positive regulation of JNK cascade | IDA PMID:11751921 A novel zinc finger protein that inhibits osteoclastogenesis... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:11751921 2001 Dec 20. A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:27746020 The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signali... | ACCEPT | Summary: TRAF6 positively regulates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 - activating NF-ΞΊB through K63-ubiquitination and IKK activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md leading to activation of IΞΊB kinase (IKK) and MAP kinases PMID:27746020 2016 Oct 13. The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signaling. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:27746020 The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signali... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:27746020 2016 Oct 13. The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signaling. |
| GO:0141198 protein branched polyubiquitination | IDA PMID:27746020 The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signali... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:27746020 2016 Oct 13. The K48-K63 Branched Ubiquitin Chain Regulates NF-ΞΊB Signaling. |
| GO:0023035 CD40 signaling pathway | IDA PMID:8910514 Identification of TRAF6, a novel tumor necrosis factor recep... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:8910514 Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region. |
| GO:0007249 canonical NF-kappaB signal transduction | IMP PMID:25515214 Brain endothelial miR-146a negatively modulates T-cell adhes... | ACCEPT | Summary: TRAF6 is essential for IKK/NF-ΞΊB signaling. Reason: TRAF6 activates IKK complex leading to NF-ΞΊB nuclear translocation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination create docking sites for the TAK1 kinase complex, leading to activation of IΞΊB kinase PMID:25515214 Epub 2014 Dec 17. Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-ΞΊB activation. |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular ... | ACCEPT | Summary: TRAF6 mediates signaling from cytosolic pattern recognition receptors. Reason: TRAF6 functions in RIG-I/MAVS and other cytosolic PRR pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 also links to the RIG-I/MAVS antiviral pathway PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. |
| GO:0038172 interleukin-33-mediated signaling pathway | IMP PMID:31435003 MicroRNA-146a negatively regulates IL-33 in activated group ... | ACCEPT | Summary: TRAF6 mediates Interleukin-18 signaling. Reason: IL-18R uses MyD88-IRAK-TRAF6 signaling like IL-1R. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited via the MyD88-IRAK kinase complex PMID:31435003 Aug 22. MicroRNA-146a negatively regulates IL-33 in activated group 2 innate lymphoid cells by inhibiting IRAK1 and TRAF6. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:30927622 TARBP2 inhibits IRF7 activation by suppressing TRAF6-mediate... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:30927622 2019 Mar 27. TARBP2 inhibits IRF7 activation by suppressing TRAF6-mediated K63-linked ubiquitination of IRF7. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular ... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, ... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:20501938 TRAF6 and A20 regulate lysine 63-linked ubiquitination of Be... | ACCEPT | Summary: TRAF6 mediates signaling from cytosolic pattern recognition receptors. Reason: TRAF6 functions in RIG-I/MAVS and other cytosolic PRR pathways. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 also links to the RIG-I/MAVS antiviral pathway PMID:20501938 TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. |
| GO:0005737 cytoplasm | IDA PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular ... | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm PMID:23015697 Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:33799071 The extreme C-terminus of IRAK2 assures full TRAF6 ubiquitin... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:33799071 2021 Mar 31. The extreme C-terminus of IRAK2 assures full TRAF6 ubiquitination and optimal TLR signaling. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:33799071 The extreme C-terminus of IRAK2 assures full TRAF6 ubiquitin... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:33799071 2021 Mar 31. The extreme C-terminus of IRAK2 assures full TRAF6 ubiquitination and optimal TLR signaling. |
| GO:0005737 cytoplasm | IDA PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates ... | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:20038579 Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is... | ACCEPT | Summary: TRAF6 is essential for IKK/NF-ΞΊB signaling. Reason: TRAF6 activates IKK complex leading to NF-ΞΊB nuclear translocation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination create docking sites for the TAK1 kinase complex, leading to activation of IΞΊB kinase PMID:20038579 2009 Dec 28. Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:20038579 Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:20038579 2009 Dec 28. Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation. |
| GO:0140374 antiviral innate immune response | IDA PMID:18984593 TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helica... | ACCEPT | Summary: TRAF6 participates in antiviral innate immunity. Reason: TRAF6 plays a role in antiviral innate immunity through RIG-I/MAVS pathway. Supporting Evidence: PMID:18984593 2008 Nov 4. TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helicase antiviral pathway. |
| GO:0005737 cytoplasm | IDA PMID:26458771 Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis thro... | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm PMID:26458771 Oct 12. Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling. |
| GO:0005737 cytoplasm | IDA PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:26839314 Ubiquitin-specific Protease 20 Regulates the Reciprocal Func... | ACCEPT | Summary: TRAF6 is essential for IKK/NF-ΞΊB signaling. Reason: TRAF6 activates IKK complex leading to NF-ΞΊB nuclear translocation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination create docking sites for the TAK1 kinase complex, leading to activation of IΞΊB kinase PMID:26839314 2016 Feb 2. Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of Ξ²-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor ΞΊB (NFΞΊB) Activation. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:26839314 Ubiquitin-specific Protease 20 Regulates the Reciprocal Func... | ACCEPT | Summary: TRAF6 is a well-characterized E3 ubiquitin ligase. Reason: Core molecular function of TRAF6, extensively validated through experimental studies. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 functions as ubiquitin-protein transferase (E3 ubiquitin ligase) PMID:26839314 2016 Feb 2. Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of Ξ²-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor ΞΊB (NFΞΊB) Activation. |
| GO:0005737 cytoplasm | IC PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm PMID:19675569 Direct activation of protein kinases by unanchored polyubiquitin chains. |
| GO:0038061 non-canonical NF-kappaB signal transduction | IDA PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TRAF6 contributes to non-canonical NF-ΞΊB activation. Reason: While TRAF6 is primarily known for canonical NF-ΞΊB activation, it can also participate in non-canonical signaling under specific conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 activates NF-ΞΊB and MAPK pathways PMID:19675569 Direct activation of protein kinases by unanchored polyubiquitin chains. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:23514740 TNFR-associated factor 6 regulates TCR signaling via interac... | ACCEPT | Summary: TRAF6 has roles in T cell signaling. Reason: TRAF6 participates in TCR signaling and T cell activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 contributes to T-cell activation PMID:23514740 2013 Mar 20. TNFR-associated factor 6 regulates TCR signaling via interaction with and modification of LAT adapter. |
| GO:0031234 extrinsic component of cytoplasmic side of plasma membrane | IC PMID:19825828 Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. | ACCEPT | Summary: TRAF6 localizes to membrane cytoplasmic face upon receptor activation. Reason: TRAF6 is recruited to activated receptors at the plasma membrane. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane PMID:19825828 Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. |
| GO:0038173 interleukin-17A-mediated signaling pathway | IDA PMID:35183823 IL-17 upregulates MCP-1 expression via Act1 / TRAF6 / TAK1 i... | ACCEPT | Summary: TRAF6 mediates Interleukin-17 signaling. Reason: TRAF6 participates in IL-17 receptor signaling. Supporting Evidence: PMID:35183823 IL-17 upregulates MCP-1 expression via Act1 / TRAF6 / TAK1 in experimental autoimmune myocarditis. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, ... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. |
| GO:1904996 positive regulation of leukocyte adhesion to vascular endothelial cell | IMP PMID:25515214 Brain endothelial miR-146a negatively modulates T-cell adhes... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:25515214 Epub 2014 Dec 17. Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-ΞΊB activation. |
| GO:0005737 cytoplasm | IDA PMID:22851693 Ξ²-TrCP-mediated IRAK1 degradation releases TAK1-TRAF6 from t... | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm PMID:22851693 Jul 30. Ξ²-TrCP-mediated IRAK1 degradation releases TAK1-TRAF6 from the membrane to the cytosol for TAK1-dependent NF-ΞΊB activation. |
| GO:0005737 cytoplasm | IDA PMID:26456228 Ring finger protein 166 potentiates RNA virus-induced interf... | ACCEPT | Summary: TRAF6 is primarily cytoplasmic. Reason: TRAF6 is a cytosolic protein under basal conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is primarily a cytosolic protein found in the cytoplasm PMID:26456228 Ring finger protein 166 potentiates RNA virus-induced interferon-Ξ² production via enhancing the ubiquitination of TRAF3 and TRAF6. |
| GO:0071345 cellular response to cytokine stimulus | IMP PMID:25515214 Brain endothelial miR-146a negatively modulates T-cell adhes... | ACCEPT | Summary: TRAF6 mediates cytokine responses. Reason: TRAF6 transduces signals from multiple cytokine receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is required for the production of proinflammatory cytokines PMID:25515214 Epub 2014 Dec 17. Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-ΞΊB activation. |
| GO:0032991 protein-containing complex | IDA PMID:23776175 SASH1 is a scaffold molecule in endothelial TLR4 signaling. | ACCEPT | Summary: TRAF6 is a component of signaling complexes. Reason: TRAF6 forms complexes with receptors and kinases. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is a component of several protein complexes PMID:23776175 2013 Jun 17. SASH1 is a scaffold molecule in endothelial TLR4 signaling. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168184 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202453 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202500 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202510 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202534 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-209566 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730861 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730876 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730900 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730904 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-446870 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-446877 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450187 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450337 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450346 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450358 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607732 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607742 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607756 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607757 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607759 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5696627 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-847070 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869506 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948018 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936947 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936951 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936952 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-937075 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645394 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645406 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645414 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645442 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9758604 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5690870 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869456 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:21068390 Bifunctional apoptosis regulator (BAR), an endoplasmic retic... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:21068390 2010 Nov 10. Bifunctional apoptosis regulator (BAR), an endoplasmic reticulum (ER)-associated E3 ubiquitin ligase, modulates BI-1 protein stability and function in ER Stress. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-936942 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-936960 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-936986 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-936991 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9758604 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-177690 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-177692 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-450259 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-450358 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-847070 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9628444 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9685219 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975097 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975103 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975147 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0031398 positive regulation of protein ubiquitination | NAS PMID:22412986 Activation of interferon regulatory factor 5 by site specifi... | ACCEPT | Summary: TRAF6 positively regulates protein ubiquitination. Reason: TRAF6 promotes K63-linked ubiquitination of substrates. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes K63-linked polyubiquitin chains PMID:22412986 Activation of interferon regulatory factor 5 by site specific phosphorylation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | NAS PMID:22412986 Activation of interferon regulatory factor 5 by site specifi... | ACCEPT | Summary: TRAF6 indirectly promotes transcription through NF-ΞΊB and AP-1 activation. Reason: TRAF6 signaling activates transcription factors that drive RNA Pol II transcription. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md results in induction of NF-ΞΊB and AP-1-dependent gene expression programs PMID:22412986 Activation of interferon regulatory factor 5 by site specific phosphorylation. |
| GO:0005811 lipid droplet | ISS GO_REF:0000024 | REMOVE | Summary: TRAF6 localization to lipid droplets is not established. Reason: No evidence for TRAF6 at lipid droplets; likely spurious. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11751921 A novel zinc finger protein that inhibits osteoclastogenesis... | ACCEPT | Summary: TRAF6 indirectly promotes transcription through NF-ΞΊB and AP-1 activation. Reason: TRAF6 signaling activates transcription factors that drive RNA Pol II transcription. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md results in induction of NF-ΞΊB and AP-1-dependent gene expression programs PMID:11751921 2001 Dec 20. A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:11751921 A novel zinc finger protein that inhibits osteoclastogenesis... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:11751921 2001 Dec 20. A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6. |
| GO:0070534 protein K63-linked ubiquitination | IGI PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0070534 protein K63-linked ubiquitination | IGI PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:19675569 Direct activation of protein kinases by unanchored polyubiquitin chains. |
| GO:0035631 CD40 receptor complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. |
| GO:0009898 cytoplasmic side of plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: TRAF6 localizes to cytoplasmic face of plasma membrane during signaling. Reason: TRAF6 is recruited to the cytoplasmic side of membrane-bound receptors. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md placing it at the plasma membrane's cytoplasmic face as part of the activated receptor complex |
| GO:0051865 protein autoubiquitination | TAS PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates ... | ACCEPT | Summary: TRAF6 undergoes autoubiquitination essential for its signaling. Reason: TRAF6 autoubiquitination with K63-chains is required for signal transduction. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination and K63-ubiquitin conjugation create docking sites PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166362 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-166363 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2262775 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2262777 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-936963 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937034 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937044 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-937050 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-975857 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-975879 | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | KEEP AS NON CORE | Summary: TRAF6 can negatively regulate RNA Pol II transcription. Reason: Minor function in specific contexts. Supporting Evidence: PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0005886 plasma membrane | IDA PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | ACCEPT | Summary: TRAF6 localizes to plasma membrane when recruited by activated receptors. Reason: TRAF6 is recruited to receptor complexes at the plasma membrane during signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is recruited to receptor cytosolic tails at the plasma membrane PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0032147 activation of protein kinase activity | IDA PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | ACCEPT | Summary: TRAF6 activates NF-ΞΊB through IKK. Reason: Core mechanism of TRAF6 signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md leading to activation of IΞΊB kinase (IKK) PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0043507 positive regulation of JUN kinase activity | NAS PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | KEEP AS NON CORE | Summary: TRAF6 negatively regulates transcription in specific contexts. Reason: Context-specific, not a core function. Supporting Evidence: PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0070555 response to interleukin-1 | IDA PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | KEEP AS NON CORE | Summary: Minor or context-specific TRAF6 function. Reason: Not a core defining function of TRAF6. Supporting Evidence: PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | ACCEPT | Summary: TRAF6 positively regulates canonical NF-ΞΊB activation. Reason: Core function of TRAF6 - activating NF-ΞΊB through K63-ubiquitination and IKK activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md leading to activation of IΞΊB kinase (IKK) and MAP kinases PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0045672 positive regulation of osteoclast differentiation | IDA PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | ACCEPT | Summary: TRAF6 is essential for osteoclast differentiation. Reason: TRAF6 mediates RANK signaling required for osteoclastogenesis. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is the key signaling adaptor for RANK in osteoclast precursors PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0051865 protein autoubiquitination | IDA PMID:17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-a... | ACCEPT | Summary: TRAF6 undergoes autoubiquitination essential for its signaling. Reason: TRAF6 autoubiquitination with K63-chains is required for signal transduction. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination and K63-ubiquitin conjugation create docking sites PMID:17135271 Nov 29. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activat... | ACCEPT | Summary: TRAF6 specifically catalyzes K63-linked polyubiquitination. Reason: This is TRAF6's signature modification - K63-linked chains for signaling not degradation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the formation of Lys 63 (K63)-linked polyubiquitin chain PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activation. |
| GO:0005634 nucleus | IDA PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | ACCEPT | Summary: TRAF6 can localize to nucleus in specific contexts. Reason: TRAF6 translocates to nucleus in osteoclasts and certain other conditions. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md RANKL stimulation increases TRAF6 accumulation in the nuclei of osteoclasts PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0051865 protein autoubiquitination | IDA PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | ACCEPT | Summary: TRAF6 undergoes autoubiquitination essential for its signaling. Reason: TRAF6 autoubiquitination with K63-chains is required for signal transduction. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 autoubiquitination and K63-ubiquitin conjugation create docking sites PMID:18093978 Dec 19. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. |
| GO:0000209 protein polyubiquitination | IDA PMID:19675569 Direct activation of protein kinases by unanchored polyubiqu... | ACCEPT | Summary: TRAF6 catalyzes polyubiquitination of target proteins. Reason: TRAF6 assembles K63-linked polyubiquitin chains on substrates. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the synthesis of unique polyubiquitin chains PMID:19675569 Direct activation of protein kinases by unanchored polyubiquitin chains. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166363 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166869 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177694 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193641 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193665 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193669 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193684 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193694 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193695 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193700 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193703 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193705 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202472 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205112 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205118 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2262777 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730864 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730903 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-446862 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-446894 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450173 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-507719 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607747 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5607751 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5690843 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-741386 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948015 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-918230 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933525 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933527 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933530 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933537 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933538 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936963 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936985 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-937032 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-937050 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645501 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645520 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705145 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9705323 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9750946 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-975111 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-975185 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-975857 | ACCEPT | Summary: TRAF6 localizes to the cytosol. Reason: TRAF6 is present in the cytosol where it mediates signaling. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is associated with cytosol |
| GO:0051092 obsolete positive regulation of NF-kappaB transcription factor activity | IDA PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates ... | MODIFY | Summary: TRAF6 positively regulates NF-ΞΊB activation. Term GO:0051092 is now obsolete; replaced by GO:0043123 (positive regulation of canonical NF-kappaB signal transduction). Reason: Core function - TRAF6 activates NF-ΞΊB through K63-ubiquitination. Original term obsoleted because it represented a molecular function. Proposed replacements: positive regulation of canonical NF-kappaB signal transduction Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md positive regulation of NF-ΞΊB transcription factor activity (GO:0051092) PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-177694 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975100 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975106 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975111 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975118 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975119 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975122 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975139 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975142 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975185 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-975188 | REMOVE | Summary: TRAF6 may indirectly affect heart rate through inflammatory pathways. Reason: No direct evidence for TRAF6 regulating heart rate. This is likely an indirect or spurious association. |
| GO:0032743 positive regulation of interleukin-2 production | IMP PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | ACCEPT | Summary: TRAF6 promotes IL-2 production. Reason: TRAF6 signaling leads to T cell cytokine production including IL-2. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md positive regulation of IL-2 production (GO:0032743) PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. |
| GO:0002726 positive regulation of T cell cytokine production | IMP PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | ACCEPT | Summary: TRAF6 regulates T cell cytokine production. Reason: TRAF6 contributes to T cell activation and cytokine production. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md positive regulation of T cell cytokine production (GO:0002726) PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. |
| GO:0050852 T cell receptor signaling pathway | IMP PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | ACCEPT | Summary: TRAF6 has roles in T cell signaling. Reason: TRAF6 participates in TCR signaling and T cell activation. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 contributes to T-cell activation PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. |
| GO:0000209 protein polyubiquitination | IDA PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activ... | ACCEPT | Summary: TRAF6 catalyzes polyubiquitination of target proteins. Reason: TRAF6 assembles K63-linked polyubiquitin chains on substrates. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 catalyzes the synthesis of unique polyubiquitin chains PMID:15125833 The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. |
| GO:0003712 transcription coregulator activity | IEA PMID:18768464 Tumor necrosis factor receptor-associated factor 6 is an int... | NEW | Summary: TRAF6 acts as nuclear transcriptional co-regulator in osteoclasts Reason: In osteoclast nuclei, TRAF6 forms complexes with FHL2 and transcription factor RUNX1, directly binding gene promoter elements to modulate transcription. This nuclear TRAF6-FHL2-RUNX1 complex regulates osteoclast-specific gene expression programs. Supporting Evidence: PMID:18768464 Suggesting transcriptional activity, TRAF6 interacts with the transcription factor RUNX1 in the osteoclast nucleus. |
| GO:0038066 p38MAPK cascade | IEA file:human/TRAF6/TRAF6-deep-research.md | NEW | Summary: TRAF6 activates p38 MAPK through TAK1 activation Reason: TRAF6-mediated K63-linked polyubiquitination recruits and activates the TAK1 kinase complex, which directly phosphorylates and activates p38 MAPK. This is a key branch of TRAF6 signaling leading to AP-1 activation and inflammatory gene expression. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is involved in the AP-1 (c-Jun/Fos) pathway via activation of JNK and p38 MAPKs |
| GO:0045893 positive regulation of DNA-templated transcription | IEA PMID:18768464 Tumor necrosis factor receptor-associated factor 6 is an int... | NEW | Summary: TRAF6 positively regulates transcription through NF-ΞΊB and as nuclear co-regulator Reason: TRAF6 activates transcription through two mechanisms - (1) cytoplasmic activation of NF-ΞΊB and AP-1 transcription factors via ubiquitin signaling, and (2) direct nuclear function as part of TRAF6-FHL2-RUNX1 complex binding to gene promoters in osteoclasts. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md formation of a TRAF6βFHL2βRUNX1 complex in the nucleus enables binding to specific gene promoter elements and modulation of gene expression PMID:18768464 2008 Sep 3. Tumor necrosis factor receptor-associated factor 6 is an intranuclear transcriptional coactivator in osteoclasts. |
| GO:0065003 protein-containing complex assembly | IEA file:human/TRAF6/TRAF6-deep-research.md | NEW | Summary: TRAF6 oligomerizes and assembles multi-protein signaling complexes Reason: TRAF6 trimerizes via its TRAF-C domain and coiled-coil regions to form signaling platforms. It assembles the Myddosome (MyD88-IRAK4-IRAK1 complex) in TLR signaling and recruits TAK1, TAB1/2, and IKK complexes through K63-ubiquitin scaffolds. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 is a component of several protein complexes (GO:0043234) in the cytoplasm, such as the Myddosome (MyD88βIRAK4βIRAK1 complex) |
| GO:0007398 ectoderm development | IEA file:human/TRAF6/TRAF6-deep-research.md | NEW | Summary: TRAF6 enables ectodermal development through EDAR receptor signal transduction Reason: TRAF6 has an indispensable role in ectodermal organ development through EDAR signaling. It is involved in the formation of skin appendages such as hair follicles and teeth. This is a core function identified from literature but missing from existing annotations. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research.md TRAF6 has an indispensable role in ectodermal organ development: it is involved in the formation of skin appendages such as hair follicles, teeth, and sweat glands |
| GO:0005737 cytoplasm | IDA PMID:18093978 Nuclear tumor necrosis factor receptor-associated factor 6 i... | ACCEPT | Summary: Cytoplasmic localization for TRAF6 is amply documented by the falcon deep research (TRAF6 functions as a cytosolic signaling adapter; condensate biology via ALPK1/TIFA). PMID:18093978 describes a context-specific NUCLEAR pool in lymphoid cells but does not refute the dominant cytoplasmic localization. Per PR #833 review feedback, resolved PENDING β ACCEPT. Reason: TRAF6 is canonically cytoplasmic β the falcon deep research explicitly describes cytosolic localization and signaling- adapter function. The cited paper documents a context-specific nuclear pool but does not refute cytoplasmic localization. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research-falcon.md TRAF6 is a cytosolic signaling adapter |
| GO:0005737 cytoplasm | IDA PMID:16378096 Association of beta-arrestin and TRAF6 negatively regulates ... | ACCEPT | Summary: Cytoplasmic localization is amply supported by the falcon deep research (cytosolic signaling adapter; condensate biology with ALPK1/TIFA). Per PR #833 review feedback, resolved PENDING β ACCEPT. Reason: Canonical cytoplasmic localization of TRAF6, supported by the falcon deep research and by the entire ACCEPTed cytoplasmic/ signaling adapter set of annotations in this review. Supporting Evidence: file:human/TRAF6/TRAF6-deep-research-falcon.md TRAF6 is a cytosolic signaling adapter |
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Download this section (compressed HTML)Q: How does the RING domain of TRAF6 selectively coordinate with different E2 enzymes to determine the specificity and topology of K63-linked ubiquitin chains on diverse substrates?
Q: What molecular mechanisms allow TRAF6 to discriminate between canonical NF-ΞΊB activation versus non-canonical pathway engagement in different cellular contexts?
Q: How do post-translational modifications of TRAF6 itself regulate its E3 ligase activity and alter its protein-protein interaction network during different signaling states?
Q: What determines the cellular localization of TRAF6 between cytoplasmic signaling complexes and nuclear transcriptional co-regulatory functions?
Experiment: Cryo-EM structural determination of TRAF6 in complex with different E2 enzymes and substrate proteins to understand substrate specificity mechanisms
Experiment: Single-molecule FRET imaging to track TRAF6 conformational changes during signal transduction and correlate with downstream pathway activation
Experiment: Mass spectrometry-based ubiquitinomics to map the complete landscape of TRAF6 substrates and their ubiquitination sites across different stimulation conditions
Experiment: Live-cell proximity labeling proteomics using TRAF6-miniTurbo to identify context-specific interactors in different immune cell types and activation states
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Download this section (compressed HTML)π View Pathway Visualization Interactive pathway diagram with detailed annotations