TAX1BP1 is a ubiquitin-binding adaptor protein whose best-supported role is as a selective-autophagy cargo adaptor/receptor. It helps couple ubiquitylated pathogens and ubiquitin-rich cargo condensates to upstream autophagy machinery, including TBK1/FIP200-dependent local autophagosome formation and Myosin VI-linked maturation steps. TAX1BP1 also has context-specific adaptor functions in innate immune signaling, including A20/TNFAIP3-dependent termination of inflammatory signaling and selective autophagic turnover of signaling adaptors such as TRIF. Recent work extends this to aggrephagy of MAVS aggregates and to additional selective-autophagy programs including lysophagy and STING-restraining golgiphagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred negative regulation of apoptosis. This is consistent with the original finding that TAX1BP1/TXBP151 mediates the anti-apoptotic activity of A20 in TNF- and Fas-mediated cell death, and with later work showing TAX1BP1 restrains virus-induced apoptosis by promoting Itch-mediated MAVS degradation. This is a downstream, context-dependent consequence of TAX1BP1's adaptor/selective-autophagy activities rather than its core molecular function. Reason: The IBA call is biologically supported via the A20/anti-apoptotic and MAVS-restraint contexts, but apoptosis regulation is an indirect outcome of TAX1BP1's adaptor and cargo-receptor activities, not the core conserved function. Retain as non-core. Supporting Evidence: PMID:17703191 TAX1BP1 inhibits TNF- and Fas-mediated apoptosis, and antisense TAX1BP1 inhibits the anti-apoptotic effect of A20, suggesting that TAX1BP1 may mediate the function of A20 PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS |
| GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronically transferred (Ensembl Compara, from mouse ortholog) annotation for negative regulation of TNF-mediated signaling. This is directly supported by experimental human/mouse evidence that TAX1BP1 is a negative regulator of TNF-alpha-induced NF-kappaB activation acting as an adaptor between A20 and its targets. The role is a context-specific immune-signaling function rather than the core cargo-adaptor activity. Reason: Well supported by experimental data (duplicated by the IDA row from PMID:18239685), but represents a signaling-context function rather than the core selective-autophagy role emphasized in this review. Supporting Evidence: PMID:18239685 Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation PMID:17703191 TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation. |
| GO:0019900 kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TAX1BP1 is a substrate of and physically engages the antiviral kinases TBK1 and IKBKE/IKKi, which phosphorylate it to promote its lysosomal localization and receptor function. Kinase binding is a supporting regulatory context rather than the core cargo-adaptor function. Reason: Kinase association is biologically supported (TBK1/IKBKE phosphorylate TAX1BP1), but it represents an upstream regulatory input to the selective-autophagy receptor activity rather than the core function. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md A prominent regulatory principle supported by mechanistic evidence is phosphorylation-dependent modulation of TAX1BP1 trafficking/function by antiviral kinases (...TBK1 and IKBKE/IKKi...). |
| GO:0035591 signaling adaptor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The automated adaptor term is a valid high-level description of TAX1BP1, but it is less informative than the selective-autophagy cargo-adaptor role curated separately below. Reason: Keep the broad adaptor label as non-core context. A more specific selective-autophagy cargo-adaptor annotation is added separately for the PN-focused biology. Supporting Evidence: PMID:26451915 Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy. PMID:29940186 TAX1BP1 may not only function as an autophagy receptor to recruit ubiquitylated substrates for autophagic degradation, but also serve as a Myosin VI cargo adaptor protein for mediating the maturation of autophagosome. PMID:30459273 NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronically transferred (Ensembl Compara, from rat ortholog) annotation for negative regulation of apoptosis. Duplicates the IBA call above and is consistent with experimental evidence that TAX1BP1 mediates the anti-apoptotic activity of A20 and restrains virus-induced apoptosis via MAVS turnover. This is a downstream, context-dependent consequence of TAX1BP1's adaptor/selective-autophagy activities rather than its core molecular function. Reason: Biologically supported but an indirect outcome of TAX1BP1's adaptor and cargo-receptor activities. Retain as non-core, consistent with the IBA row. Supporting Evidence: PMID:17703191 TAX1BP1 inhibits TNF- and Fas-mediated apoptosis, and antisense TAX1BP1 inhibits the anti-apoptotic effect of A20, suggesting that TAX1BP1 may mediate the function of A20 PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronically transferred (Ensembl Compara, from mouse ortholog) annotation for negative regulation of canonical NF-kappaB signaling. Directly supported by experimental human/mouse evidence that TAX1BP1 is essential for termination of NF-kappaB activation as a regulator of the A20 ubiquitin-editing complex. Duplicated by the ISS row below. Reason: Well supported experimentally but represents a context-specific immune-signaling function rather than the core selective-autophagy cargo-adaptor role. Supporting Evidence: PMID:17703191 TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation. PMID:18239685 Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation |
| GO:2000660 negative regulation of interleukin-1-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronically transferred (Ensembl Compara, from mouse ortholog) annotation for negative regulation of IL-1-mediated signaling. Directly supported by experimental evidence that TAX1BP1 negatively regulates IL-1beta-induced NF-kappaB activation via the A20 axis. Duplicated by the IDA row from PMID:18239685. Reason: Experimentally supported context-specific immune-signaling role rather than the core cargo-adaptor function. Supporting Evidence: PMID:18239685 Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation PMID:17703191 TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation. |
| GO:0005515 protein binding | IPI PMID:10920205 T6BP, a TRAF6-interacting protein involved in IL-1 signaling... | MARK AS OVER ANNOTATED | Summary: Identifies TAX1BP1 (T6BP) as a TRAF6-interacting protein in IL-1 signaling, binding via its coiled-coil region to the TRAF6 ring/zinc finger domains (interaction partner TRAF6, UniProt Q9Y4K3). The bare protein binding term is uninformative about molecular function. Reason: The underlying TAX1BP1-TRAF6 interaction is real and historically important, but GO:0005515 protein binding conveys no functional information. TAX1BP1's adaptor role is better captured by the more specific signaling adaptor and protein-macromolecule adaptor annotations elsewhere in this review. Supporting Evidence: PMID:10920205 We report the identification of a TRAF-interacting protein, T6BP, that specifically associates with TRAF6. This interaction occurs between the coiled-coil region of T6BP and the N-terminal ring finger and zinc finger domains of TRAF6. |
| GO:0005515 protein binding | IPI PMID:14697242 Chromosome 13q12 encoded Rho GTPase activating protein suppr... | UNDECIDED | Summary: IntAct-curated binary interaction (partner UniProt Q9Y3M8) supporting the bare protein binding term. The cited publication is not available in the local cache, so the biological context of the interaction cannot be verified. Reason: The supporting publication is inaccessible here, so I cannot confirm the interaction context. Regardless, GO:0005515 protein binding is an uninformative molecular function term that does not capture TAX1BP1's adaptor/receptor activity. |
| GO:0005515 protein binding | IPI PMID:15231748 Functional proteomics mapping of a human signaling pathway. | MARK AS OVER ANNOTATED | Summary: Binary interaction (partner UniProt Q9Y3C5) from a large-scale yeast two-hybrid mapping of the Smad/TGF-beta signaling network. This is a high-throughput screen with no TAX1BP1-specific functional follow-up, and the bare protein binding term is uninformative. Reason: High-throughput interaction supporting only the generic GO:0005515 term; it adds no specific molecular-function information for TAX1BP1. Supporting Evidence: PMID:15231748 We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins |
| GO:0005515 protein binding | IPI PMID:17703191 Essential role for TAX1BP1 in the termination of TNF-alpha-,... | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interactions from the foundational TAX1BP1 study (partners include A20/TNFAIP3 Q15311-related entries and TRAF6 Q9Y4K3), establishing TAX1BP1 as an A20-associated adaptor in NF-kappaB/JNK termination. The bare protein binding term conveys no molecular-function information beyond what is captured by the more specific signaling-adaptor and protein-macromolecule adaptor annotations. Reason: The underlying TAX1BP1-A20/TRAF6 interactions are real and biologically important, but GO:0005515 protein binding is uninformative. The functional content is better represented by the signaling adaptor (GO:0035591) and protein-macromolecule adaptor (GO:0030674) annotations elsewhere in this review. Supporting Evidence: PMID:17703191 Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20. |
| GO:0005515 protein binding | IPI PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th... | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interactions from the TAX1BP1-deficient mouse valvulitis study (partners include A20/TNFAIP3 and TRAF6 Q9Y4K3), underpinning the A20-bridging adaptor role. The bare protein binding term is uninformative about molecular function. Reason: Real and functionally relevant interactions (A20, TRAF6), but GO:0005515 protein binding adds no specific information. The adaptor function is captured by the signaling adaptor (GO:0035591) and protein-macromolecule adaptor (GO:0030674) annotations in this review. Supporting Evidence: PMID:18239685 Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets. |
| GO:0005515 protein binding | IPI PMID:19131965 The ubiquitin-editing enzyme A20 requires RNF11 to downregul... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction (partner Q9Y3C5, RNF11) from the study showing A20 requires RNF11 to downregulate NF-kappaB signalling. This places TAX1BP1 within the A20 ubiquitin-editing complex (with RNF11/Itch), but the bare protein binding term is uninformative. Reason: The TAX1BP1-RNF11 association within the A20 regulatory complex is meaningful, but GO:0005515 conveys no molecular-function content. The adaptor activity is captured by more specific terms elsewhere. Supporting Evidence: PMID:19131965 Here, we demonstrate a novel function of RNF11 as a negative regulator of |
| GO:0005515 protein binding | IPI PMID:21765415 The kinase IKKΞ± inhibits activation of the transcription fac... | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interaction (partner UniProt O15111, IKBKB/IKK-beta) supporting the bare protein binding term. This is consistent with TAX1BP1's documented role in the A20 ubiquitin-editing complex that restrains IKK/NF-kappaB signaling, but the generic GO:0005515 term conveys no molecular-function information. Reason: A single curated interaction supporting only the uninformative GO:0005515 protein binding term. TAX1BP1's adaptor activity is better captured by the signaling adaptor (GO:0035591) and protein-macromolecule adaptor (GO:0030674) annotations elsewhere in this review. Supporting Evidence: PMID:17703191 Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction (partner UniProt Q9Y4K3, TRAF6) from a large-scale yeast two-hybrid map of the human liver protein interaction network. This is a high-throughput screen supporting only the bare protein binding term; the TAX1BP1-TRAF6 association itself is captured by the foundational T6BP study. Reason: High-throughput interactome screen supporting only the uninformative GO:0005515 term. No TAX1BP1-specific functional follow-up; the molecular function is better described by the adaptor terms in this review. Supporting Evidence: PMID:21988832 we map the interactions of an unbiased selection of 5026 human liver expression proteins by yeast two-hybrid technology and establish a human liver protein interaction network (HLPN) composed of 3484 interactions among 2582 proteins. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interactions from a proteome-scale Y2H map of the human interactome (CCSB/HI-II-14; multiple partners). These are high-throughput systematic two-hybrid hits supporting only the bare protein binding term, with no TAX1BP1-specific functional characterization. Reason: Systematic interactome mapping supporting only the uninformative GO:0005515 term. It adds no specific molecular-function content for TAX1BP1. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction (partner UniProt P83436, COG7) from a systematic Y2H study of how alternative splicing expands protein interaction capabilities. High-throughput data supporting only the bare protein binding term. Reason: Systematic interactome screen supporting only the uninformative GO:0005515 term; no specific molecular-function information for TAX1BP1. Supporting Evidence: PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction (partner UniProt O00214, LGALS8/galectin-8) from a high-throughput interactome-perturbation study of de novo missense mutations in developmental disorders. Supports only the bare protein binding term. Reason: High-throughput screen supporting only the uninformative GO:0005515 term; no TAX1BP1-specific functional information. Supporting Evidence: PMID:29892012 An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders. |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interactions (partners include UniProt P21580/TNFAIP3-A20 and Q15025/TNIP1) from a Virotrap protein-complex map of the TNF-induced NF-kappaB signaling pathway. These are biologically coherent with TAX1BP1's A20/TNIP1 adaptor role, but the bare protein binding term is uninformative. Reason: The A20/TNIP1 associations are consistent with TAX1BP1's known NF-kappaB-restraining adaptor function, but GO:0005515 protein binding adds no molecular-function content. Captured by the signaling adaptor (GO:0035591) and protein-macromolecule adaptor (GO:0030674) annotations. Supporting Evidence: PMID:30561431 Here, we present a protein-protein interaction dataset of the TNFR1-induced signaling pathway. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interactions (partners include UniProt P83436/COG7) from a high-throughput study of how genetic variants disrupt protein interactions across the allele-frequency spectrum. Supports only the bare protein binding term. Reason: High-throughput interaction screen supporting only the uninformative GO:0005515 term; no specific molecular-function information for TAX1BP1. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interactions from the HuRI reference map of the human binary protein interactome (many partners). High-throughput systematic Y2H data supporting only the bare protein binding term. Reason: Reference interactome mapping supporting only the uninformative GO:0005515 term; no specific molecular-function information for TAX1BP1. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction (partner UniProt P28799, GRN/progranulin) from a systematic interactome map of neurodegenerative-disease proteins. This is a high-throughput hit supporting only the bare protein binding term, though it is consistent with TAX1BP1's role in aggrephagy of disease-associated aggregates. Reason: High-throughput interactome screen supporting only the uninformative GO:0005515 term; no specific molecular-function information for TAX1BP1. 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... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interactions (partners include UniProt O00214/LGALS8, P21580/TNFAIP3-A20) from the BioPlex 3.0 affinity-purification mass spectrometry interactome. High-throughput data supporting only the bare protein binding term. Reason: Proteome-scale AP-MS interactome supporting only the uninformative GO:0005515 term; no specific molecular-function information for TAX1BP1. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0000407 phagophore assembly site | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: TAX1BP1 supports cargo-proximal autophagosome initiation, but this localization is supporting context rather than the best statement of core function. Reason: Literature supports recruitment of upstream autophagy-initiation machinery around TAX1BP1-bound cargo. The more informative core curation is the selective-autophagy cargo adaptor activity itself. Supporting Evidence: PMID:33226137 TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping placing TAX1BP1 in the cytoplasm. This is correct and well supported: TAX1BP1 acts predominantly as a cytosolic selective-autophagy cargo receptor, but the broad cytoplasm term is a high-level localization rather than the most informative annotation. Reason: Accurate and uncontroversial broad localization consistent with TAX1BP1's cytosolic function. A correct, if general, cellular-component annotation. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping placing TAX1BP1 at the mitochondrion. Mitochondrial localization is context-dependent (e.g., virus-induced relocalization via MAVS, and a minor contribution to mitophagy in multi-receptor knockout rescue), not a constitutive feature of the protein. Reason: Supported only as a conditional/context-specific localization rather than a core compartment for TAX1BP1. Retain as non-core, consistent with the IDA mitochondrion row from PMID:27736772. Supporting Evidence: PMID:27736772 Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS. |
| GO:0005776 autophagosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: TAX1BP1 associates with autophagic membranes during selective autophagy, but this cellular component annotation is supporting context rather than the core activity. Reason: Valid localization that fits receptor function on autophagic membranes, yet it should not eclipse the more informative cargo-adaptor role. Supporting Evidence: PMID:26451915 This mutually exclusive binding and the association of TAX1BP1 with LC3 on the outer limiting membrane of autophagosomes may suggest a molecular mechanism for recruitment of this motor to autophagosomes. file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture, with evidence for localization to ...autophagosomes/autophagic vacuoles..., ...lysosomes... (including increased LAMP1 colocalization when phosphorylated), and likely the ...outer autophagosome membrane... through ubiquitin/myosin VI coupling. |
| GO:0000407 phagophore assembly site | EXP PMID:33226137 Receptor-mediated clustering of FIP200 bypasses the role of ... | KEEP AS NON CORE | Summary: The experimental paper supports TAX1BP1-driven local autophagosome initiation around cargo, which is compatible with phagophore assembly site localization. Reason: Useful mechanistic localization in selective autophagy, but not the main evolved function statement for the gene. Supporting Evidence: PMID:33226137 TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3. |
| GO:0000407 phagophore assembly site | EXP PMID:34471133 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in... | KEEP AS NON CORE | Summary: In vitro reconstitution shows TAX1BP1 is the main driver of FIP200 recruitment to p62-ubiquitin condensates, i.e. it nucleates autophagosome initiation at the phagophore assembly site around cargo. This supports the localization but is best treated as supporting context for the core cargo-adaptor activity. Reason: Mechanistically well supported localization at sites of cargo-coupled autophagosome initiation; duplicates the PMID:33226137 EXP row. Retain as non-core context rather than the primary functional statement. Supporting Evidence: PMID:34471133 While all three receptors interact with FIP200, TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62-ubiquitin condensates. |
| GO:0005737 cytoplasm | EXP PMID:30909570 Autophagy Promotes Infectious Particle Production of Mopeia ... | ACCEPT | Summary: In a study of autophagy during arenavirus (Mopeia/Lassa) infection, TAX1BP1 was identified as a cytoplasmic autophagy adaptor interacting with the viral Z matrix protein. This supports a cytoplasmic localization, but the broad term is a general localization statement. Reason: Correct, well-supported broad cytoplasmic localization consistent with TAX1BP1's role as a cytosolic autophagy receptor. Duplicates the cytoplasm annotations from other sources. Supporting Evidence: PMID:30909570 We identified two autophagy receptors, calcium-binding and coiled-coil domain 2 (CALCOCO 2 or NDP52) and TAX1BP1 (or CALCOCO 3), suggesting a link between autophagy and viral infection. |
| GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway | IDA PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th... | KEEP AS NON CORE | Summary: TAX1BP1 negatively regulates TNF-induced NF-kappaB signaling through the A20/TNFAIP3 axis, but this immune-signaling role is contextual relative to the gene's selective-autophagy core. Reason: Biologically sound and experimentally supported, yet it captures a signaling consequence/context rather than the PN-relevant cargo-adaptor activity emphasized in this review. Supporting Evidence: PMID:18239685 Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets. PMID:17703191 Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20. |
| GO:0035591 signaling adaptor activity | IDA PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th... | KEEP AS NON CORE | Summary: Early immune-signaling work supports TAX1BP1 as an A20-linked signaling adaptor, but that role is broader and more contextual than the selective-autophagy cargo-adaptor function. Reason: Accurate experimentally, yet not the most informative core annotation once the selective-autophagy receptor/adaptor biology is considered. Supporting Evidence: PMID:18239685 Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets. PMID:17703191 Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS-transferred annotation (from mouse ortholog Q3UKC1) for negative regulation of canonical NF-kappaB signaling. Directly supported by experimental human/mouse evidence that TAX1BP1 is essential for termination of NF-kappaB activation as a regulator of the A20 ubiquitin-editing complex. Duplicates the IEA row above. Reason: Well supported experimentally but represents a context-specific immune-signaling function rather than the core selective-autophagy cargo-adaptor role. Supporting Evidence: PMID:17703191 TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation. PMID:18239685 Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation |
| GO:2000660 negative regulation of interleukin-1-mediated signaling pathway | IDA PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th... | KEEP AS NON CORE | Summary: TAX1BP1 dampens IL-1 signaling through the A20 axis, but this is a context-specific immune-signaling role rather than the core PN function. Reason: Retain as experimentally supported context while keeping the selective-autophagy cargo-adaptor role as the primary functional summary. Supporting Evidence: PMID:17703191 The NF-kappaB transcription factor is normally transiently activated by proinflammatory cytokines and bacterial lipopolysaccharide (LPS); however, persistent NF-kappaB activation is commonly observed in inflammatory disease and malignancy. PMID:18239685 Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation |
| GO:0005737 cytoplasm | IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of... | ACCEPT | Summary: In the TRIM32-TRIF study, TAX1BP1 functions as a cytoplasmic selective- autophagy receptor that targets TRIF for autophagic degradation. This supports the broad cytoplasm localization, which is correct but general. Reason: Correct, well-supported broad cytoplasmic localization consistent with TAX1BP1's cytosolic autophagy-receptor function; duplicates other cytoplasm annotations. Supporting Evidence: PMID:28898289 TRIM32-mediated as well as poly(I:C)- and LPS-induced degradation of TRIF is inhibited by deficiency of TAX1BP1, a receptor for selective autophagy. |
| GO:0005739 mitochondrion | IDA PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating It... | KEEP AS NON CORE | Summary: TAX1BP1 can relocalize to mitochondria during virus infection through MAVS, but the accessible evidence here supports a context-dependent localization rather than a standalone core mitochondrial or mitophagy annotation. Reason: Keep the experimentally observed localization, but do not treat it as evidence that mitophagy is a core established TAX1BP1 function in this local review. Supporting Evidence: PMID:27736772 Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS. file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md A 2023 BioEssays review discusses selective autophagy receptors in oxidative stress response and cites evidence that re-expression of SARs including ...TAX1BP1 (to a lesser extent)... can restore mitophagy in a multi-receptor knockout context. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating It... | KEEP AS NON CORE | Summary: This paper supports adaptor activity in antiviral signaling via the MAVS/ITCH axis, but not the more specific selective-autophagy cargo-adaptor claim. Reason: Valid context-specific adaptor function. It should be retained separately from the autophagy cargo-adaptor curation rather than folded into the core PN call. Supporting Evidence: PMID:27736772 TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of... | KEEP AS NON CORE | Summary: In the TRIF study, TAX1BP1 clearly behaves as a selective-autophagy receptor/adaptor, but the broad adaptor term can be retained as non-core context alongside a more specific new cargo-adaptor annotation. Reason: Keep the generic adaptor term as a contextual statement while adding the more specific autophagy cargo adaptor activity call separately. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-notes.md TRIM32-mediated as well as poly(I:C)- and LPS-induced degradation of TRIF is inhibited by deficiency of TAX1BP1, a receptor for selective autophagy. file:human/TAX1BP1/TAX1BP1-notes.md TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation. |
| GO:0034144 negative regulation of toll-like receptor 4 signaling pathway | IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of... | KEEP AS NON CORE | Summary: The TRIF paper supports negative regulation of TLR3/4 signaling via selective autophagic degradation of TRIF, but this immune pathway role is contextual rather than core PN biology. Reason: Keep as a context-specific innate immune consequence of TAX1BP1-mediated selective autophagy; do not elevate it to the main conserved function. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-notes.md TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation. |
| GO:0039532 negative regulation of cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating It... | KEEP AS NON CORE | Summary: TAX1BP1 negatively modulates MAVS-dependent antiviral signaling, but this pathway annotation is context-specific. Reason: The experimental work supports antiviral signaling restraint via MAVS turnover, yet the autophagy cargo-adaptor role is the more informative core curation for PN purposes. Supporting Evidence: PMID:27736772 MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; PMID:27736772 TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression. file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md A concrete mechanistic example is ...MAVS aggrephagy...: TAX1BP1 functions as an aggrephagy receptor promoting ...MAVS aggregate clearance..., which directly reduces downstream innate immune signaling. |
| GO:1905161 protein localization to phagocytic vesicle | IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of... | UNDECIDED | Summary: The accessible abstract supports TAX1BP1-mediated selective autophagic degradation of TRIF, but it does not clearly justify this more specific vesicle-localization process term. Reason: I cannot confidently connect the currently accessible evidence to protein localization to phagocytic vesicle without fuller paper context. The more defensible local update is the autophagy cargo-adaptor reading instead. |
| GO:0160247 autophagy cargo adaptor activity | IDA PMID:26451915 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosi... | NEW | Summary: TAX1BP1 acts as a selective-autophagy cargo adaptor/receptor that links ubiquitylated cargo to the autophagy machinery. Reason: This specific molecular function is central to the PN-focused biology and is better supported than the currently seeded broad adaptor terms. The literature directly describes TAX1BP1 as an autophagy receptor/cargo adaptor in xenophagy and related selective-autophagy settings. Supporting Evidence: PMID:26451915 In summary, this work highlights the importance of TAX1BP1 as a novel autophagy receptor in myosin VI-mediated xenophagy. PMID:29940186 TAX1BP1 may not only function as an autophagy receptor to recruit ubiquitylated substrates for autophagic degradation, but also serve as a Myosin VI cargo adaptor protein for mediating the maturation of autophagosome. PMID:30459273 NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy. file:human/TAX1BP1/TAX1BP1-deep-research-openai.md the strongest evidence supports it as a selective-autophagy cargo adaptor / autophagy receptor. file:human/TAX1BP1/TAX1BP1-deep-research-manual.md TAX1BP1 is best supported as a ubiquitin-binding selective-autophagy cargo adaptor/receptor rather than as a general signaling adaptor or a dedicated mitophagy/fusion factor. file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md Across mechanistic and review-level sources, TAX1BP1 functions as a ...ubiquitin-directed adaptor/cargo receptor... that routes tagged substrates to ...lysosomal degradation... through selective autophagy (e.g., aggrephagy and lysophagy). |
| GO:0016236 macroautophagy | IDA PMID:33226137 Receptor-mediated clustering of FIP200 bypasses the role of ... | NEW | Summary: TAX1BP1 directly promotes cargo-coupled autophagosome formation and FIP200 recruitment during selective macroautophagy. Reason: The available literature supports direct involvement in macroautophagy via local autophagosome initiation around TAX1BP1-bound cargo, while more specific xenophagy is captured separately below. Supporting Evidence: PMID:33226137 TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3. file:human/TAX1BP1/TAX1BP1-notes.md TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62-ubiquitin condensates. file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md infection conditions can also route TAX1BP1 to lysosomes through an ATG8-family-independent mechanism requiring ...RB1CC1/FIP200.... |
| GO:0098792 xenophagy | IDA PMID:26451915 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosi... | NEW | Summary: TAX1BP1 is directly recruited to ubiquitylated Salmonella and is required for autophagic clearance of the pathogen. Reason: This specific selective-autophagy process annotation is missing from the seeded GOA set but is directly supported by the Salmonella study and fits the PN xenophagy context cleanly. Supporting Evidence: PMID:26451915 Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy. PMID:26451915 In summary, this work highlights the importance of TAX1BP1 as a novel autophagy receptor in myosin VI-mediated xenophagy. |
| GO:0070062 extracellular exosome | HDA PMID:18570454 Proteomic analysis of exosomes from human neural stem cells ... | MARK AS OVER ANNOTATED | Summary: High-throughput mass-spectrometry detection of TAX1BP1 in exosome preparations from human neural stem cells. This is a proteomic presence-in-fraction observation that does not reflect a known functional localization or role for TAX1BP1, which acts as a cytosolic selective-autophagy receptor. Reason: Detection in a bulk exosome proteomics dataset is prone to contamination and does not establish a biologically meaningful extracellular-exosome localization for a cytosolic ubiquitin-binding autophagy receptor. There is no functional follow-up supporting an extracellular role. Supporting Evidence: PMID:18570454 Exosomal lysates of each fraction were digested and analyzed using nanoflow LC-ESI-MS-MS for protein identification. |
| GO:0005515 protein binding | IPI PMID:15474016 A20 is a potent inhibitor of TLR3- and Sendai virus-induced ... | MARK AS OVER ANNOTATED | Summary: Curated interaction (partner UniProt P21580, TNFAIP3/A20) from a study showing A20 is a potent inhibitor of TLR3- and Sendai virus-induced NF-kappaB/IFN-beta activation. This places TAX1BP1 in the A20 axis, but the cited paper is about A20-TRIF and the bare protein binding term conveys no molecular-function information. Reason: The TAX1BP1-A20 association is biologically meaningful, but GO:0005515 protein binding is uninformative. TAX1BP1's adaptor activity is captured by the signaling adaptor (GO:0035591) and protein-macromolecule adaptor (GO:0030674) annotations elsewhere. Supporting Evidence: PMID:15474016 These data suggest that A20 targets TRIF to inhibit TLR3-mediated induction of IFN-beta transcription and functions as a feedback negative regulator for TLR3 signaling and cellular anti-viral response. |
| GO:0019900 kinase binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS-transferred kinase binding annotation. Consistent with experimental evidence that TAX1BP1 is phosphorylated by and associates with the antiviral kinases TBK1 and IKBKE/IKKi. Retain as supporting regulatory context rather than core function. Reason: Kinase association is supported, but it is an upstream regulatory input to the selective-autophagy receptor function rather than the core activity. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md A prominent regulatory principle supported by mechanistic evidence is phosphorylation-dependent modulation of TAX1BP1 trafficking/function by antiviral kinases (...TBK1 and IKBKE/IKKi...). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5693055 | ACCEPT | Summary: Reactome TAS annotation placing the TAX1BP1:A20 complex in the cytosol, where it binds RIPK1-containing complexes during NF-kappaB regulation. Cytosol is the correct major compartment for TAX1BP1. Reason: Accurate broad localization consistent with TAX1BP1's cytosolic adaptor/autophagy-receptor function. Duplicates the cytoplasm annotations. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5693108 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization, associated with the A20-mediated K48 ubiquitination of RIPK1 event in which the TAX1BP1:A20 complex participates. Cytosol is the correct major compartment. Reason: Accurate broad cytosolic localization consistent with TAX1BP1's function; duplicates the other cytosol/cytoplasm annotations. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture |
| GO:0005829 cytosol | TAS Reactome:R-HSA-937337 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization, associated with the TAX1BP1:A20 inhibition of TBK1/IKKi K63-polyubiquitination event. Cytosol is the correct major compartment for TAX1BP1. Reason: Accurate broad cytosolic localization consistent with TAX1BP1's adaptor/autophagy-receptor function; duplicates other cytosol/cytoplasm annotations. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture |
| GO:0043066 negative regulation of apoptotic process | TAS PMID:10435631 The zinc finger protein A20 interacts with a novel anti-apop... | KEEP AS NON CORE | Summary: TAS annotation for negative regulation of apoptosis, citing the original report (PMID:10435631, De Valck et al.) identifying TXBP151/TAX1BP1 as a mediator of the anti-apoptotic activity of A20. The primary paper is not in the local cache, but the same anti-apoptotic role is independently supported by accessible literature and duplicates the IBA/IEA apoptosis rows. This is a downstream, context-dependent consequence of TAX1BP1's adaptor activity rather than its core molecular function. Reason: The anti-apoptotic role (mediating A20 function) is well established by accessible follow-up work and duplicates the phylogenetic IBA call, so it is retained; but apoptosis regulation is an indirect outcome of TAX1BP1's adaptor/cargo-receptor activities, not the core conserved function. Supporting Evidence: PMID:17703191 TAX1BP1 inhibits TNF- and Fas-mediated apoptosis, and antisense TAX1BP1 inhibits the anti-apoptotic effect of A20, suggesting that TAX1BP1 may mediate the function of A20 PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS |
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Download this section (compressed HTML)Q: Does TAX1BP1 make a direct, non-redundant contribution to mitophagy in human cells, or is the current mitochondrial evidence mainly signaling- or cargo- context dependent?
Q: How general is TAX1BP1-directed golgiphagy as a negative-feedback mechanism for STING signaling, and does this represent a distinct compartment-specific selective-autophagy program relative to its xenophagy and aggrephagy roles?
Q: Is TAX1BP1 alone sufficient to execute lysophagy of damaged lysosomes in human cells, and how does phosphorylation by TBK1/IKBKE shift TAX1BP1 between aggrephagy (MAVS) and other selective-autophagy programs?
Experiment: Compare TAX1BP1 knockout/rescue with separation-of-function mutants that disrupt ubiquitin binding, FIP200 recruitment, or Myosin VI binding across xenophagy, ubiquitin-condensate autophagy, and PINK1/Parkin mitophagy assays to resolve which TAX1BP1 activities are core versus context-specific.
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