Affinage

TAX1BP1

Tax1-binding protein 1 · UniProt Q86VP1

Length
789 aa
Mass
90.9 kDa
Annotated
2026-06-10
65 papers in source corpus 33 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAX1BP1 is a multifunctional ubiquitin-binding adaptor that operates at the interface of selective autophagy and inflammatory/antiviral signaling termination (PMID:17703191, PMID:33207181). As a selective autophagy receptor, it recognizes ubiquitinated cargo through its tandem C-terminal zinc-finger (UBZ) domains—whose structures and ubiquitin-binding mechanism have been defined—and its non-canonical LIR motif engages LC3/GABARAP, while its SKICH domain recruits the FIP200/RB1CC1 autophagy-initiation machinery directly and via NAP1/SINTBAD adaptors that also bring in TBK1 (PMID:24239949, PMID:29940186, PMID:34471133, PMID:38437556, PMID:39448883). The zinc-finger ubiquitin-binding site overlaps the myosin VI binding site, so ubiquitin and myosin VI engage TAX1BP1 in a mutually exclusive manner (PMID:26451915, PMID:29940186). Through this receptor activity TAX1BP1 mediates clearance of stress-induced protein aggregates—serving as the primary aggrephagy receptor in brain (PMID:33207181)—as well as xenophagy of intracellular bacteria recruited via galectin-8 and the LAMTOR1/2 complex (PMID:30428163, PMID:34225486), and within reconstituted ubiquitin condensates it is the principal driver of FIP200 recruitment to initiate autophagosome biogenesis (PMID:34471133, PMID:39448883). In parallel, TAX1BP1 is an essential co-factor of the A20 ubiquitin-editing complex, acting as the adaptor linking A20 to its ubiquitinated substrates RIP1, TRAF6, TBK1 and IKKi to terminate NF-κB, JNK, and antiviral IRF3 signaling; this function requires IKKα-mediated phosphorylation of TAX1BP1 on Ser593/Ser624 to assemble the A20/Itch/RNF11 complex (PMID:17703191, PMID:18239685, PMID:20304918, PMID:21765415, PMID:21885437). TAX1BP1 further restrains innate immune and antiviral responses by directing degradation of signaling organelles and adaptors—recruiting E3 ligases Itch and RNF34 to ubiquitinate MAVS for autophagic clearance and restraining NLRP3 inflammasome activation (PMID:27736772, PMID:36654301, PMID:39193925), and degrading STING1 via K63-ubiquitination, ESCRT-0/HGS-dependent microautophagy and Golgiphagy (PMID:40000606, PMID:41673009). TBK1/IKKi phosphorylation of TAX1BP1 controls its own lysosomal turnover and its MAVS aggrephagy activity (PMID:39193925). Distinct from these cytoplasmic roles, TAX1BP1 functions as a nuclear receptor coactivator that complexes with the glucocorticoid receptor and p300, and supports the metabolic activation of T cells through LIR-dependent autophagy (PMID:28314591, PMID:19109394, PMID:17283140).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2007 High

    Established TAX1BP1's first defined function—as an essential regulator that enables A20 to terminate inflammatory signaling—answering whether the protein has a role in cytokine-induced NF-κB/JNK shutdown.

    Evidence TAX1BP1-deficient mouse fibroblasts with co-IP and ubiquitination assays across TNF-α/IL-1/LPS stimuli

    PMID:17703191

    Open questions at the time
    • Did not define how TAX1BP1 physically bridges A20 to substrates
    • Mechanism of A20 recruitment regulation unresolved
  2. 2008 High

    Showed that ubiquitin binding via the C-terminal zinc fingers is required for TRAF6 association and NF-κB inhibition, and that loss causes inflammatory pathology in vivo, linking the molecular adaptor activity to organismal phenotype.

    Evidence TAX1BP1-KO mice plus zinc-finger ubiquitin-binding mutagenesis and co-IP

    PMID:18239685

    Open questions at the time
    • Structural basis of ubiquitin recognition not yet defined
    • Did not address how the adaptor function is switched on
  3. 2010 High

    Extended A20/TAX1BP1 negative regulation to antiviral signaling by identifying TBK1 and IKKi as targets, answering whether the complex restrains type I interferon induction.

    Evidence Tax1bp1−/− MEFs with viral challenge, ubiquitination and IRF3 reporter assays

    PMID:20304918

    Open questions at the time
    • How TAX1BP1 disrupts TRAF3-TBK1/IKKi ubiquitination mechanistically unclear
    • Recruitment to kinase complex not defined
  4. 2011 High

    Defined the upstream activating signal—IKKα phosphorylation of Ser593/Ser624—required to assemble the A20 editing complex, and identified ABIN1 as the adaptor recruiting TAX1BP1/A20 to TBK1/IKKi, establishing how the regulatory complex is triggered.

    Evidence In vitro kinase assays, phosphosite mutagenesis, IKKα KO, and ABIN1 co-IP/domain mutagenesis

    PMID:21765415 PMID:21885437

    Open questions at the time
    • Whether other kinases phosphorylate the same sites in different contexts unaddressed
    • ABIN1 work from single lab at Medium confidence
  5. 2012 Medium

    Reframed TAX1BP1 as a bona fide selective autophagy cargo receptor, opening its second major functional domain and connecting autophagic sequestration to non-canonical NF-κB signaling.

    Evidence Autophagic flux assays and siRNA knockdown in K-Ras-dependent NSCLC

    PMID:23209807

    Open questions at the time
    • Cargo specificity not defined
    • Single-lab functional knockdown
  6. 2013 High

    Provided the structural basis for ubiquitin recognition by solving the tandem UBZ1+2 domains, revealing inter-domain conformational flexibility relevant to partner recognition.

    Evidence X-ray crystallography and NMR relaxation analysis of the tandem zinc fingers

    PMID:24239949

    Open questions at the time
    • Ubiquitin-bound complex structure not determined here
    • Functional consequence of flexibility untested
  7. 2015 High

    Demonstrated TAX1BP1 drives xenophagy of ubiquitylated Salmonella and that ubiquitin and myosin VI bind the zinc fingers mutually exclusively, defining a regulatory switch within the cargo-recognition module.

    Evidence Structural analysis, point mutagenesis, live imaging and Salmonella infection with TAX1BP1 KD

    PMID:26451915

    Open questions at the time
    • Functional consequence of myosin VI/ubiquitin competition in vivo unclear
    • How autophagy machinery is recruited downstream not addressed
  8. 2016 High

    Showed TAX1BP1 restrains virus-induced apoptosis by recruiting Itch to ubiquitinate and degrade mitochondrial MAVS, establishing organelle/adaptor targeting as a distinct antiviral-restraining mode.

    Evidence TAX1BP1-KO and Itch-KO cells with fractionation, ubiquitination and apoptosis assays during VSV/Sendai infection

    PMID:27736772

    Open questions at the time
    • Whether MAVS degradation is autophagic vs proteasomal here not fully resolved
    • Signal triggering mitochondrial relocalization undefined
  9. 2017 High

    Separated TAX1BP1's UBD-independent functions: a LIR-dependent specialized autophagy supporting T cell metabolic activation, and TRIM32-bridged selective degradation of TRIF to dampen TLR3/4 responses.

    Evidence TAX1BP1-KO T cells with LIR/UBD mutants and metabolic rescue; TRIM32-KO mice and domain mapping

    PMID:28314591 PMID:28898289

    Open questions at the time
    • How LIR-only function bypasses cargo ubiquitin recognition unclear
    • TRIM32-TAX1BP1 cargo selectivity not generalized
  10. 2018 High

    Defined at atomic resolution how the SKICH domain engages the NAP1 adaptor and how tandem zinc-finger rigidity governs myosin VI binding, mechanistically linking the autophagy-machinery-recruiting and cargo-binding modules.

    Evidence Crystal structures of SKICH/NAP1, plus NMR and biochemistry of zinc fingers with ubiquitin/myosin VI

    PMID:29940186 PMID:30459273

    Open questions at the time
    • FIP200 engagement mode not yet structurally resolved
    • Phospho-regulation of SKICH binding only evaluated with phosphomimetics
  11. 2020 High

    Identified TAX1BP1 as the primary autophagy receptor for stress-induced protein aggregate clearance, including in brain, answering which receptor handles proteotoxic aggregates.

    Evidence TAX1BP1-KO mice, iPSC-derived neurons, and comparison against OPTN/NBR1/p62/NDP52

    PMID:33207181

    Open questions at the time
    • How TAX1BP1 is selectively recruited to aggregates not defined here
    • Relationship to disease aggregates untested
  12. 2021 High

    Reconstitution and KO studies placed TAX1BP1 within a receptor hierarchy—recruited to p62/NBR1 ubiquitin condensates as the primary driver of FIP200 recruitment—and identified galectin-8 and LAMTOR1/2 as upstream sensors/recruiters for pathogen autophagy, plus RNF34 for MAVS degradation.

    Evidence In vitro reconstitution with purified proteins; CRISPR galectin-8 KO and LAMTOR KO macrophages; RNF34 KD with ubiquitination assays

    PMID:30428163 PMID:34225486 PMID:34471133 PMID:36654301

    Open questions at the time
    • How NBR1 hands TAX1BP1 to condensates mechanistically incomplete
    • RNF34/MAVS and LAMTOR findings single-lab Medium confidence
  13. 2024 High

    Resolved the SKICH-RB1CC1(FIP200) and GABARAP-LIR binding interfaces and showed RB1CC1 and NAP1 compete yet can form a ternary complex, while reconstitution showed cargo ubiquitin load acts as a switch recruiting TAX1BP1 and TBK1 (via SINTBAD) to initiate autophagosome biogenesis.

    Evidence Multiple crystal structures with biochemistry; in vitro reconstitution with domain mutagenesis and SINTBAD/NBR1 binding-site mapping

    PMID:33207181 PMID:38437556 PMID:39448883

    Open questions at the time
    • In vivo confirmation of the condensation-to-sequestration switch lacking
    • Stoichiometry of ternary TAX1BP1/NAP1/RB1CC1 complex in cells unknown
  14. 2024 High

    Established phospho-regulation of TAX1BP1's autophagy function—TBK1/IKKi redundantly phosphorylate it to drive its own lysosomal turnover and MAVS aggrephagy—and explained pathological autophagy evasion by Tau fibrils whose ubiquitins are masked by excessive p62 coating.

    Evidence KO/KI MEFs with phosphosite mutagenesis and semi-denaturing aggregate assays; in vitro reconstitution with patient-derived Tau fibrils

    PMID:38865459 PMID:39193925

    Open questions at the time
    • Physiological triggers of TAX1BP1 self-turnover unclear
    • Whether p62-masking generalizes to other fibrils untested
  15. 2025 Medium

    Extended TAX1BP1's organelle/adaptor degradation roles to STING1 (via coiled-coil/K224-ubiquitin recognition and ESCRT-0/HGS microautophagy plus Golgiphagy), to IFNAR1 (hijacked by ASFV p22), and to autophagy-independent MHC-II antigen presentation via calnexin, broadening its immunoregulatory reach.

    Evidence TAX1BP1-KO cells/macrophages with co-IP, K-to-R mutagenesis, ESCRT and Golgi assays; immunopeptidome analysis with calnexin co-IP

    PMID:36215666 PMID:40000606 PMID:40668839 PMID:41673009

    Open questions at the time
    • Each substrate characterized in single labs
    • How TAX1BP1 selects micro- vs macroautophagy routes unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAX1BP1's distinct functional outputs—A20-complex signaling termination, ubiquitin/LIR-driven cargo autophagy, and nuclear receptor coactivation—are coordinated within a cell, and how post-translational modifications partition it among these roles, remains unresolved.
  • No unified model linking the signaling and autophagy functions
  • Parkin K549 mitophagy regulation only in preprint
  • Lysophagy axis (TMEM192) supported by Low-confidence evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005764 lysosome 2 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-9612973 Autophagy 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 1
Partners
A20ITCHMAVSNBR1RB1CC1/FIP200STING1TBK1TRAF6
Complex memberships
A20 ubiquitin-editing complex (TAX1BP1/A20/Itch/RNF11)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 TAX1BP1 is essential for termination of TNF-α-, IL-1-, and LPS-mediated NF-κB and JNK signaling. In TAX1BP1-deficient mouse fibroblasts, IKK and JNK activation is elevated and persistent due to enhanced ubiquitination of RIP1 and TRAF6. In the absence of TAX1BP1, A20 is impaired in RIP1 binding and TRAF6 deubiquitination, establishing TAX1BP1 as an essential regulator of A20 function. TAX1BP1-deficient mouse fibroblasts (KO), co-immunoprecipitation, ubiquitination assays, NF-κB/JNK activation assays The EMBO journal High 17703191
2008 TAX1BP1 acts as a negative regulator of TNF-α- and IL-1β-induced NF-κB activation. Ubiquitin binding via its C-terminal zinc finger domain is required for TRAF6 association and NF-κB inhibition. TAX1BP1-KO mice develop age-dependent inflammatory cardiac valvulitis, and TAX1BP1 functions as an essential adaptor between A20 and its ubiquitinated targets. TAX1BP1-KO mice, ubiquitin-binding zinc finger domain mutagenesis, NF-κB activation assays, co-immunoprecipitation The EMBO journal High 18239685
2010 TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1 and IKKi kinases. TAX1BP1-deficient MEFs show increased IFN-β production upon viral challenge. TAX1BP1 and A20 block antiviral signaling by disrupting K63-linked polyubiquitination of TBK1/IKKi independently of A20's deubiquitination domain. TRAF3 promotes TBK1-IKKi ubiquitination upstream. A20 requires TAX1BP1 to target and inactivate TBK1 and IKKi. Tax1bp1−/− MEFs, viral challenge assays, ubiquitination assays, co-immunoprecipitation, IRF3 activation assays The Journal of biological chemistry High 20304918
2011 IKKα (but not IKKβ) phosphorylates TAX1BP1 on Ser593 and Ser624 in response to TNF or IL-1 stimulation. This phosphorylation is required for cytokine-dependent assembly of the A20 ubiquitin-editing complex (TAX1BP1, A20, Itch, RNF11) and subsequent downregulation of NF-κB canonical signaling. In vitro kinase assay, phospho-specific antibodies, IKKα KO/knockdown, co-immunoprecipitation, NF-κB reporter assays, site-directed mutagenesis (Ser593/Ser624) Nature immunology High 21765415
2011 ABIN1 interacts with TAX1BP1 and is essential for recruitment of TAX1BP1 and A20 to TBK1 and IKKi in response to poly(I:C). ABIN1 and TAX1BP1 together disrupt TRAF3-TBK1/IKKi interactions to attenuate K63-linked polyubiquitination of TBK1/IKKi. ABIN1's intact ubiquitin binding domain is required for interaction with TBK1/IKKi and IFN-β inhibition. Co-immunoprecipitation, siRNA knockdown, ABIN1 ubiquitin-binding domain mutagenesis, IFN-β reporter assays The Journal of biological chemistry Medium 21885437
2012 TAX1BP1 (as a paralogue of NDP52) functions as a bona fide cargo receptor for selective autophagy. Basal autophagy in K-Ras-dependent NSCLC is characterized by sequestration of TAX1BP1 (and NDP52), and this process promotes non-canonical NF-κB signaling in a TBK1-dependent manner. Autophagic flux assays, siRNA knockdown, non-canonical NF-κB reporter assays, TBK1 inhibition PloS one Medium 23209807
2013 Crystal and NMR solution structures of the tandem UBZ1+2 (ubiquitin-binding zinc finger) domains of TAX1BP1 were determined, revealing conformational flexibility between the two domains that may influence recognition of interacting partners including ubiquitinated signaling proteins. X-ray crystallography, NMR spectroscopy, NMR relaxation analysis Journal of molecular biology High 24239949
2015 TAX1BP1 and myosin VI are recruited to ubiquitylated Salmonella and are required for xenophagic clearance. The ubiquitin-binding site of TAX1BP1 overlaps with the myosin VI binding site (in the zinc finger domains), such that ubiquitin and myosin VI bind TAX1BP1 in a mutually exclusive manner. Point mutations in the zinc finger domains that abrogate ubiquitin binding also ablate myosin VI binding. TAX1BP1 also associates with LC3 on the outer autophagosomal membrane. Structural analysis, point mutagenesis, co-immunoprecipitation, live-cell imaging, TAX1BP1 KD, Salmonella infection assays PLoS pathogens High 26451915
2016 TAX1BP1 restrains virus-induced apoptosis by recruiting the E3 ligase Itch to MAVS on mitochondria, triggering MAVS ubiquitination and degradation. Virus infection promotes mitochondrial localization of TAX1BP1 and interaction with MAVS. Loss of TAX1BP1 or Itch results in increased MAVS protein levels and hypersensitivity to apoptosis. TAX1BP1 also undergoes degradation during RNA virus infection. TAX1BP1-KO and Itch-KO cells, co-immunoprecipitation, subcellular fractionation, apoptosis assays, ubiquitination assays, viral infection (VSV, Sendai virus) Molecular and cellular biology High 27736772
2017 TRIM32 interacts with TRIF and mediates its selective autophagic degradation via TAX1BP1. TRIM32 links TRIF and TAX1BP1 through distinct domains, and poly(I:C)/LPS-induced TRIF degradation is inhibited by TAX1BP1 deficiency. This mechanism negatively regulates TLR3/4-mediated innate immune responses. Co-immunoprecipitation, TAX1BP1-deficient cells, domain mapping, autophagic flux assays, Trim32-KO mice, cytokine measurement PLoS pathogens High 28898289
2017 TAX1BP1 drives a specialized form of autophagy required for the metabolic transition of activated T cells. TAX1BP1 binding to LC3/GABARAP via its LIR motif (but not its ubiquitin-binding domain) supports T cell proliferation and mTOR complex formation. TAX1BP1-deficient T cells stall in S phase due to bioenergetic and biosynthetic defects from defective autophagy induction and insufficient mTOR activation. TAX1BP1-KO T cells, LIR/UBD domain mutants, mTOR complex assays, metabolic assays, L-cysteine supplementation rescue Immunity High 28314591
2018 Crystal structures of the SKICH domains of NDP52 and TAX1BP1 in complex with NAP1 were determined, revealing the mechanistic basis of NAP1-SKICH interaction and a general SKICH domain binding mode. TBK1-mediated phosphorylation sites in the SKICH domains of both receptors were evaluated with respect to their NAP1 interactions. X-ray crystallography, biochemical binding assays, phosphomimetic mutant analysis Proceedings of the National Academy of Sciences of the United States of America High 30459273
2018 Biochemical, NMR, and structural analyses defined the binding mechanism of TAX1BP1's tandem zinc fingers with ubiquitin, and showed that both tandem zinc fingers and the conformational rigidity between them are required for myosin VI binding. Ubiquitin and myosin VI bind TAX1BP1 in a mutually exclusive manner. NMR spectroscopy, biochemical assays, structural analysis, mutagenesis Journal of molecular biology High 29940186
2019 LAMTOR2/LAMTOR1 complex is required for TAX1BP1-mediated xenophagy. LAMTOR1 localizes to bacterium-containing endosomes, and LAMTOR2 is recruited to damaged endosomes in a LAMTOR1-dependent manner. LAMTOR2 interacts with TAX1BP1 (and NBR1, p62) and is necessary for TAX1BP1 recruitment to pathogen-containing autophagosomes. TAX1BP1 KO reduces autolysosome formation and subsequent bacterial degradation. LAMTOR1/2 KO cells, TAX1BP1 KO cells, co-immunoprecipitation, live imaging, GAS/Salmonella infection assays, autolysosome formation assays Cellular microbiology Medium 30428163
2020 Endogenous TAX1BP1 is recruited to and required for clearance of stress-induced protein aggregates via autophagy. TAX1BP1 depletion sensitizes cells to aggregate-induced proteotoxicity. Loss of TAX1BP1 in mice results in accumulation of high molecular weight ubiquitin conjugates and premature lipofuscin accumulation in brains, establishing TAX1BP1 as the primary autophagy receptor for aggregate clearance in the brain. TAX1BP1 KO mice, siRNA knockdown, autophagy receptor comparison (OPTN, NBR1, p62, NDP52, TAX1BP1), iPSC-derived neurons, viability assays, brain histology Molecular cell High 33207181
2021 In vitro reconstitution defined that p62 is the major driver of ubiquitin condensate formation; NBR1 promotes condensation and recruits TAX1BP1 to condensates; TAX1BP1 is the main driver of FIP200 recruitment to the condensates, thereby initiating autophagic degradation. All three receptors interact with FIP200, but TAX1BP1 is the primary mediator of autophagy machinery recruitment. In vitro reconstitution with purified proteins, cell biology assays, co-IP, ubiquitin condensate formation assays Nature communications High 34471133
2021 Galectin-8 senses damaged Mtb-containing phagosomes and directly interacts with TAX1BP1. This galectin-8/TAX1BP1 interaction is necessary for efficient targeting of Mtb to selective autophagy in macrophages. Galectin-8 KO (but not galectin-3 or -9 KO alone) impairs TAX1BP1-mediated selective autophagy of Mtb. CRISPR/Cas9 KO macrophages (galectin-8-/-, galectin-3/8/9-/-), co-immunoprecipitation, confocal microscopy, Mtb replication assays mBio Medium 34225486
2021 RNF34 is recruited to interact with TAX1BP1 and facilitates autophagic degradation of MAVS through K27-linked polyubiquitination. TAX1BP1 overexpression suppresses NLRP3 mitochondrial localization by inhibiting NLRP3 interaction with MAVS. Knockdown of RNF34 nullifies TAX1BP1-mediated protection against MAVS accumulation and NLRP3 inflammasome activation. Co-immunoprecipitation, siRNA knockdown, TAX1BP1 overexpression (adenovirus), mitochondrial fractionation, ubiquitination assays, NLRP3 activation assays Science bulletin Medium 36654301
2023 TNIP1 negatively regulates mitophagy rate through an evolutionarily conserved LIR motif (binding LC3/GABARAP) and an AHD3 domain that binds TAX1BP1. TNIP1 competes with autophagy receptors for FIP200 binding in a phosphorylation-dependent manner, providing a molecular basis for its inhibitory function during mitophagy. TNIP1 KO HeLa cells, ectopic expression, LIR/AHD3 domain mutants, co-immunoprecipitation, mitophagy rate assays, ULK1 complex interaction assays Molecular cell High 36898370
2024 Crystal structure of the TAX1BP1 SKICH domain in complex with the RB1CC1 (FIP200) coiled-coil region was determined. Two distinct binding sites between TAX1BP1 and RB1CC1 were identified: the SKICH/coiled-coil interaction and a CC1-domain/Claw interaction. RB1CC1 and NAP1 compete for SKICH binding, but NAP1's FIR motif can stabilize a ternary TAX1BP1/NAP1/RB1CC1 complex. The structure of GABARAP in complex with the non-canonical LIR motif of TAX1BP1 was also determined, revealing a unique binding mode. X-ray crystallography, biochemical binding assays, mutagenesis, ternary complex formation assays Proceedings of the National Academy of Sciences of the United States of America High 38437556
2024 TBK1 and IKBKE/IKKi redundantly phosphorylate TAX1BP1 and regulate its autophagic turnover through canonical macroautophagy. TAX1BP1 phosphorylation promotes its localization to lysosomes resulting in degradation. TAX1BP1 plays a critical role in clearance of MAVS aggregates (aggrephagy), and its phosphorylation by TBK1/IKKi controls this MAVS aggrephagy function. During VSV infection, TAX1BP1 is targeted to lysosomes in an ATG8-family protein-independent manner. KO and KI MEFs, phospho-site mutagenesis, kinase assays, lysosomal localization assays, MAVS aggregate clearance assays (semi-denaturing AGE), VSV infection Autophagy High 39193925
2024 TAX1BP1 recruitment to ubiquitin-containing protein aggregates correlates with induction of autophagosome biogenesis and is not a constitutive component of condensates. TAX1BP1 is sufficient to recruit TBK1 kinase via the SINTBAD adaptor. The NBR1-TAX1BP1 binding site was defined and is adjacent to the GABARAP/LC3 interaction site. Increased ubiquitin load on condensates enhances TAX1BP1 recruitment, suggesting a cargo-sensing switch from condensation to sequestration. In vitro reconstitution, domain mutagenesis, SINTBAD interaction assays, NBR1-binding site mapping, ubiquitin condensate assays The EMBO journal High 39448883
2024 Tau fibrils from Alzheimer's disease brains are recognized by p62 but fail to recruit TAX1BP1 due to masking of ubiquitin moieties by excessive p62 coating. Monomeric Tau recruits both p62 and TAX1BP1. This irreversible, nonproductive p62-fibril interaction (due to fibril resistance to deubiquitylation) explains autophagy evasion by Tau aggregates. In vitro reconstitution with purified proteins and patient-derived Tau fibrils, ubiquitination assays, deubiquitylation resistance assays Science advances High 38865459
2025 TAX1BP1 acts as an autophagic receptor for STING1 degradation through its coiled-coil domain interacting with the cyclic dinucleotide binding domain of STING1. K63-ubiquitination of STING1 at K224 is required for TAX1BP1-dependent STING1 autophagic degradation. TAX1BP1 thus negatively regulates cGAS-STING-dependent antitumor immunity. Proteomic lysosomal analysis, co-immunoprecipitation, systematic K-to-R STING1 mutagenesis, ubiquitination assays, TAX1BP1 KO cells Autophagy Medium 40000606
2026 TAX1BP1 negatively regulates cGAS-STING signaling by promoting STING degradation through microautophagy via facilitating STING interaction with the ESCRT-0 protein HGS. TAX1BP1 also mediates autophagic degradation of fragmented Golgi (Golgiphagy) upon STING activation. TAX1BP1-deficient macrophages accumulate higher-order STING aggregates at the trans-Golgi network and show heightened type I IFN and proinflammatory cytokine production. TAX1BP1-KO macrophages, co-immunoprecipitation (STING-HGS interaction), ESCRT-pathway assays, Golgi morphology imaging, cytokine measurement, cGAS/STING agonist treatment Nature communications Medium 41673009
2025 Parkin-dependent K63-ubiquitination of TAX1BP1 at K549 within its third coiled-coil domain (CC3) regulates TAX1BP1's mitophagy function. This modification is not required for proteasomal degradation of TAX1BP1 but is a regulatory modification; ubiquitination-deficient TAX1BP1 (lacking CC3) reroutes mitochondria degradation to a less efficient endolysosomal pathway engaging VPS35. Mass spectrometry-based phosphoproteomics/ubiquitinomics, parkin WT vs catalytically inactive mutant, lysosomal inhibitor (bafilomycin A), TAX1BP1 ubiquitination-deficient mutant, mitophagy flux assays bioRxivpreprint Medium 40475537
2008 Tax1BP1 functions as a transcriptional coactivator for nuclear receptors (glucocorticoid receptor). It forms a complex with p300 and synergistically enhances E2-dependent viral transcription. Tax1BP1 prevents proteasomal degradation of HPV E2 protein, regulating E2 steady-state levels. The C-terminal region of Tax1BP1 interacts with the N-terminal transactivation domain of BPV1 E2. Yeast two-hybrid, co-immunoprecipitation, chromatin immunoprecipitation, transcriptional reporter assays, proteasome inhibitor experiments Journal of virology Medium 19109394
2007 TAX1BP1 is a nuclear receptor coactivator that forms a complex with the glucocorticoid receptor. HTLV-1 Tax protein binds TAX1BP1 directly, induces dissociation of TAX1BP1 from the glucocorticoid receptor complex, and represses TAX1BP1's coactivator function. Genetic knockout of Tax1bp1 in mice abrogates Tax's influence on nuclear receptor activation. Co-immunoprecipitation, immunofluorescence colocalization, TAX1BP1 KO mice, nuclear receptor transcriptional assays Cancer research Medium 17283140
2009 NRP/Optineurin interacts with TAX1BP1 in a cooperative manner to modulate Tax1 ubiquitination and NF-κB activation. NRP requires Tax1's ubiquitination sites and its own ubiquitin-binding activity for interaction with Tax1. NRP, TAX1BP1, and Tax1 colocalize in Golgi-associated structures. Co-immunoprecipitation, immunofluorescence, ubiquitin-binding domain mutagenesis, NF-κB reporter assays PLoS pathogens Medium 19609363
2024 TAX1BP1 and FIP200 mediate non-canonical autophagic degradation of p62 aggregates in neural stem cells (NSCs). Conditional deletion of Tax1bp1 in fip200 cKI mice (which have blocked canonical autophagy) leads to NSC deficiency and p62 aggregate accumulation phenocopying fip200 cKO mice. A TAX1BP1 mutant unable to bind FIP200 or NBR1/p62 fails to restore NSC maintenance. Conditional KO mouse models, TAX1BP1 domain mutants (FIP200-binding and NBR1/p62-binding deficient), NSC maintenance assays, p62 aggregate quantification Zoological research Medium 39021082
2025 ASFV p22 promotes the association of TAX1BP1 with IFNAR1 via p22's transmembrane region, facilitating autophagic degradation of IFNAR1 and impairing JAK-STAT signaling. TAX1BP1 acts as the autophagy receptor mediating IFNAR1 degradation in this context. Co-immunoprecipitation, p22 domain mutagenesis (transmembrane region), IFNAR1 degradation assays, JAK-STAT signaling assays, TAX1BP1 interaction assays PLoS pathogens Medium 40668839
2025 The TBK1-SCFFBXO3-TMEM192-TAX1BP1 regulatory axis orchestrates lysophagic flux. TBK1-dependent phosphorylation of FBXO3 facilitates FBXO3 interaction with TMEM192, promoting its ubiquitination, which is then recognized by TAX1BP1. Disruption of this pathway reduces lysophagic flux and causes accumulation of damaged lysosomes. TBK1 inhibition/KO, co-immunoprecipitation (FBXO3-TMEM192), ubiquitination assays, TAX1BP1 interaction assays, lysophagy flux assays Autophagy Low 40083080
2022 TAX1BP1 (T6BP) influences both autophagy-dependent and -independent endogenous MHC-II presentation of viral antigens. T6BP silencing induces mislocalization of MHC-II loading compartments and rapid degradation of the invariant chain (CD74) without altering MHC-II expression or internalization. T6BP interacts with calnexin via calnexin's cytosolic tail, and calnexin silencing replicates the functional consequences of T6BP silencing. siRNA silencing, immunopeptidome analysis (MHC-II ligandome), co-immunoprecipitation (TAX1BP1-calnexin), confocal microscopy, T cell activation assays EMBO reports Medium 36215666
2025 TAX1BP1 interacts with the SKICH domain-binding SINTBAD adaptor to recruit TBK1 kinase to ubiquitin condensates for autophagosome biogenesis initiation. TAX1BP1 is not a constitutive component of p62/NBR1-driven condensates but is recruited upon autophagy induction. In vitro reconstitution, SINTBAD co-IP, TAX1BP1 localization assays at condensates, ubiquitin load modulation The EMBO journal High 39448883

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. Nature communications 185 34471133
2015 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy. PLoS pathogens 171 26451915
2007 Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling. The EMBO journal 164 17703191
2010 TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases. The Journal of biological chemistry 146 20304918
2008 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation. The EMBO journal 135 18239685
2020 Loss of TAX1BP1-Directed Autophagy Results in Protein Aggregate Accumulation in the Brain. Molecular cell 120 33207181
2012 TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical NF-κB signalling. PloS one 113 23209807
2017 TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses. PLoS pathogens 106 28898289
2011 The kinase IKKα inhibits activation of the transcription factor NF-κB by phosphorylating the regulatory molecule TAX1BP1. Nature immunology 100 21765415
2011 ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling. The Journal of biological chemistry 73 21885437
2021 Galectin-8 Senses Phagosomal Damage and Recruits Selective Autophagy Adapter TAX1BP1 To Control Mycobacterium tuberculosis Infection in Macrophages. mBio 71 34225486
2009 NRP/Optineurin Cooperates with TAX1BP1 to potentiate the activation of NF-kappaB by human T-lymphotropic virus type 1 tax protein. PLoS pathogens 71 19609363
2017 The Ubiquitin Binding Protein TAX1BP1 Mediates Autophagasome Induction and the Metabolic Transition of Activated T Cells. Immunity 61 28314591
2011 TAX1BP1, a ubiquitin-binding adaptor protein in innate immunity and beyond. Trends in biochemical sciences 56 21546252
2022 PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles. Journal of nanobiotechnology 53 35305662
2018 TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy. Biochimica et biophysica acta. Molecular basis of disease 53 29476905
2018 Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1. Proceedings of the National Academy of Sciences of the United States of America 53 30459273
2016 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS. Molecular and cellular biology 53 27736772
2022 Multifaceted roles of TAX1BP1 in autophagy. Autophagy 43 35470757
2008 Tax1BP1 interacts with papillomavirus E2 and regulates E2-dependent transcription and stability. Journal of virology 40 19109394
2021 TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner. Science bulletin 38 36654301
2021 TRIM11 suppresses ferritinophagy and gemcitabine sensitivity through UBE2N/TAX1BP1 signaling in pancreatic ductal adenocarcinoma. Journal of cellular physiology 35 33629745
2016 TAX1BP1 downregulation by EBV-miR-BART15-3p enhances chemosensitivity of gastric cancer cells to 5-FU. Archives of virology 35 27757686
2023 TNIP1 inhibits selective autophagy via bipartite interaction with LC3/GABARAP and TAX1BP1. Molecular cell 31 36898370
2007 Human T-cell leukemia virus oncoprotein tax represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1. Cancer research 29 17283140
2024 Tau fibrils evade autophagy by excessive p62 coating and TAX1BP1 exclusion. Science advances 22 38865459
2019 LAMTOR2/LAMTOR1 complex is required for TAX1BP1-mediated xenophagy. Cellular microbiology 21 30428163
2020 Sesamin attenuates carrageenan-induced lung inflammation through upregulation of A20 and TAX1BP1 in rats. International immunopharmacology 19 33182047
2018 Mechanistic Insights into Recognitions of Ubiquitin and Myosin VI by Autophagy Receptor TAX1BP1. Journal of molecular biology 19 29940186
2020 A novel target TAX1BP1 and P38/Nrf2 pathway independently involved in the anti-neuroinflammatory effect of isobavachalcone. Free radical biology & medicine 18 32311491
2024 Phosphorylation of the selective autophagy receptor TAX1BP1 by TBK1 and IKBKE/IKKi promotes ATG8-family protein-dependent clearance of MAVS aggregates. Autophagy 16 39193925
2013 The structure of TAX1BP1 UBZ1+2 provides insight into target specificity and adaptability. Journal of molecular biology 16 24239949
2024 Recruitment of autophagy initiator TAX1BP1 advances aggrephagy from cargo collection to sequestration. The EMBO journal 15 39448883
2023 TAX1BP1 contributes to deoxypodophyllotoxin-induced glioma cell parthanatos via inducing nuclear translocation of AIF by activation of mitochondrial respiratory chain complex I. Acta pharmacologica Sinica 15 37186123
2020 Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis. Scientific reports 15 33004985
2024 Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins. Proceedings of the National Academy of Sciences of the United States of America 14 38437556
2016 Regulation of B cell differentiation by the ubiquitin-binding protein TAX1BP1. Scientific reports 13 27515252
2022 The Autophagy Receptor TAX1BP1 (T6BP) improves antigen presentation by MHC-II molecules. EMBO reports 12 36215666
2023 Upregulation of A20 and TAX1BP1 contributes to the anti-neuroinflammatory and antidepressant effects of bavachalcone. International immunopharmacology 11 37393841
2021 Depletion of TAX1BP1 Amplifies Innate Immune Responses during Respiratory Syncytial Virus Infection. Journal of virology 11 34431698
2016 Correction: The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy. PLoS pathogens 11 26820152
2013 Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice. PloS one 11 24086273
2025 TAX1BP1-dependent autophagic degradation of STING1 impairs anti-tumor immunity. Autophagy 9 40000606
2022 Chicken TAX1BP1 suppresses type I interferon production via degrading chicken MAVS and facilitates infectious bursal diseases virus replication. Developmental and comparative immunology 9 35793720
2014 Expression, purification and crystallization of the SKICH domain of human TAX1BP1. Acta crystallographica. Section F, Structural biology communications 7 24817723
2024 TAX1BP1/A20 inhibited TLR2-NF-κB activation to induce tolerant expression of IL-6 in endothelial cells. International immunopharmacology 6 39079200
2023 TAX1BP1 downregulation by STAT3 in cardiac fibroblasts contributes to diabetes-induced heart failure with preserved ejection fraction. Biochimica et biophysica acta. Molecular basis of disease 6 38065272
2015 Immunization of mice with a peptide derived from the HTLV-1 TAX1BP1 protein induces cross-reactive antibodies against aquaporin 4. Autoimmunity 5 26287441
2010 Analysis of the TAX1BP1 gene in head and neck cancer patients. Brazilian journal of otorhinolaryngology 5 20549079
2025 The African swine fever virus p22 inhibits the JAK-STAT signaling pathway by promoting the TAX1BP1-mediated degradation of the type I interferon receptor. PLoS pathogens 4 40668839
2024 Astragalus membranaceus-Carthamus tinctorius herb pair antagonizes parthanatos in cerebral ischemia/reperfusion injury via regulating PARP-1/TAX1BP1-mediated mitochondrial respiratory chain complex I. Journal of ethnopharmacology 4 39701216
2023 Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function. International immunology 4 37465957
2025 EPIC-1042 alleviates cerebral ischemic/reperfusion injury through TAX1BP1-induced mitophagy. Free radical biology & medicine 3 40107570
2025 Mycobacterium tuberculosis triggers reduced inflammatory cytokine responses and virulence in mice lacking Tax1bp1. PLoS pathogens 3 41171885
2025 KLHL8-mediated ubiquitination and TAX1BP1-dependent autophagic degradation of GPX4 drive neuronal ferroptosis. Free radical biology & medicine 2 41478420
2024 TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance. Zoological research 2 39021082
2024 Tax1bp1 enhances bacterial virulence and promotes inflammatory responses during Mycobacterium tuberculosis infection of alveolar macrophages. bioRxiv : the preprint server for biology 2 39763950
2026 Negative feedback regulation of STING signaling by TAX1BP1-directed Golgiphagy. Nature communications 1 41673009
2025 TAX1BP1 regulates the apoptosis of renal tubular epithelial cells in ischemia/reperfusion injury via the NF-kB/PMAIP1 signaling pathway. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 1 39762558
2025 The TBK1-SCFFBXO3-TMEM192-TAX1BP1 axis: a novel regulatory mechanism for lysophagy. Autophagy 1 40083080
2025 Nomilin Alleviates Neuroinflammation and Depressive-like Behaviors in Mice through the Upregulation of TAX1BP1-Mediated Modulation of Microglia Polarization. ACS chemical neuroscience 1 40701838
2026 TAX1BP1 protects against doxorubicin-induced cardiotoxicity via maintaining mitochondrial function in a mTORC2-SGK1-VDAC1 manner. Molecular medicine (Cambridge, Mass.) 0 41731367
2026 TAX1BP1 targets STING1 via microautophagy and Golgiphagy to limit inflammatory signaling. Autophagy 0 41968678
2025 Parkin-dependent ubiquitination of TAX1BP1 directs efficient autophagic removal of defective mitochondria. bioRxiv : the preprint server for biology 0 40475537
2024 TRIM11 Prevents Ferroptosis in model of asthma by UBE2N-TAX1BP1 signaling. BMC pulmonary medicine 0 39472837

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