id: Q86VP1
gene_symbol: TAX1BP1
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q86VP1-1
- name: 2 (TXBP151-L)
  id: Q86VP1-2
  sequence_note: VSP_018355
- name: 3 (TXBP151-S)
  id: Q86VP1-3
  sequence_note: VSP_018354, VSP_018355
- name: '4'
  id: Q86VP1-4
  sequence_note: VSP_045921, VSP_018355
existing_annotations:
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: 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
    - reference_id: PMID:27736772
      supporting_text: TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS
- term:
    id: GO:0010804
    label: negative regulation of tumor necrosis factor-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:18239685
      supporting_text: Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation
    - reference_id: PMID:17703191
      supporting_text: TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        A prominent regulatory principle supported by mechanistic evidence is phosphorylation-dependent modulation of TAX1BP1 trafficking/function by antiviral kinases (...TBK1 and IKBKE/IKKi...).
- term:
    id: GO:0035591
    label: signaling adaptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:26451915
      supporting_text: Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy.
    - reference_id: PMID:29940186
      supporting_text: 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.
    - reference_id: PMID:30459273
      supporting_text: NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biologically supported but an indirect outcome of TAX1BP1's adaptor and
      cargo-receptor activities. Retain as non-core, consistent with the IBA row.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: 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
    - reference_id: PMID:27736772
      supporting_text: TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Well supported experimentally but represents a context-specific
      immune-signaling function rather than the core selective-autophagy
      cargo-adaptor role.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation.
    - reference_id: PMID:18239685
      supporting_text: Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation
- term:
    id: GO:2000660
    label: negative regulation of interleukin-1-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported context-specific immune-signaling role rather
      than the core cargo-adaptor function.
    supported_by:
    - reference_id: PMID:18239685
      supporting_text: Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation
    - reference_id: PMID:17703191
      supporting_text: TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10920205
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:10920205
      supporting_text: 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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14697242
  review:
    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.
    action: UNDECIDED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15231748
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interaction supporting only the generic GO:0005515 term;
      it adds no specific molecular-function information for TAX1BP1.
    supported_by:
    - reference_id: PMID:15231748
      supporting_text: We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17703191
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18239685
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:18239685
      supporting_text: Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19131965
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:19131965
      supporting_text: Here, we demonstrate a novel function of RNF11 as a negative regulator of
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21765415
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:21988832
      supporting_text: 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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Systematic interactome mapping supporting only the uninformative GO:0005515
      term. It adds no specific molecular-function content for TAX1BP1.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Systematic interactome screen supporting only the uninformative GO:0005515
      term; no specific molecular-function information for TAX1BP1.
    supported_by:
    - reference_id: PMID:26871637
      supporting_text: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput screen supporting only the uninformative GO:0005515 term;
      no TAX1BP1-specific functional information.
    supported_by:
    - reference_id: PMID:29892012
      supporting_text: An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30561431
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:30561431
      supporting_text: Here, we present a protein-protein interaction dataset of the TNFR1-induced signaling pathway.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interaction screen supporting only the uninformative
      GO:0005515 term; no specific molecular-function information for TAX1BP1.
    supported_by:
    - reference_id: PMID:31515488
      supporting_text: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Reference interactome mapping supporting only the uninformative GO:0005515
      term; no specific molecular-function information for TAX1BP1.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome screen supporting only the uninformative
      GO:0005515 term; no specific molecular-function information for TAX1BP1.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Proteome-scale AP-MS interactome supporting only the uninformative
      GO:0005515 term; no specific molecular-function information for TAX1BP1.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      TAX1BP1 supports cargo-proximal autophagosome initiation, but this
      localization is supporting context rather than the best statement of core
      function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:33226137
      supporting_text: TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    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.
    action: ACCEPT
    reason: >-
      Accurate and uncontroversial broad localization consistent with TAX1BP1's
      cytosolic function. A correct, if general, cellular-component annotation.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:27736772
      supporting_text: Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS.
- term:
    id: GO:0005776
    label: autophagosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      TAX1BP1 associates with autophagic membranes during selective autophagy,
      but this cellular component annotation is supporting context rather than
      the core activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Valid localization that fits receptor function on autophagic membranes,
      yet it should not eclipse the more informative cargo-adaptor role.
    supported_by:
    - reference_id: PMID:26451915
      supporting_text: 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.
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        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.
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: EXP
  original_reference_id: PMID:33226137
  review:
    summary: >-
      The experimental paper supports TAX1BP1-driven local autophagosome
      initiation around cargo, which is compatible with phagophore assembly site
      localization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Useful mechanistic localization in selective autophagy, but not the main
      evolved function statement for the gene.
    supported_by:
    - reference_id: PMID:33226137
      supporting_text: TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3.
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: EXP
  original_reference_id: PMID:34471133
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:34471133
      supporting_text: While all three receptors interact with FIP200, TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62-ubiquitin condensates.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:30909570
  review:
    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.
    action: ACCEPT
    reason: >-
      Correct, well-supported broad cytoplasmic localization consistent with
      TAX1BP1's role as a cytosolic autophagy receptor. Duplicates the cytoplasm
      annotations from other sources.
    supported_by:
    - reference_id: PMID:30909570
      supporting_text: 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.
- term:
    id: GO:0010804
    label: negative regulation of tumor necrosis factor-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:18239685
  review:
    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.
    action: KEEP_AS_NON_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.
    supported_by:
    - reference_id: PMID:18239685
      supporting_text: Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets.
    - reference_id: PMID:17703191
      supporting_text: Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20.
- term:
    id: GO:0035591
    label: signaling adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:18239685
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate experimentally, yet not the most informative core annotation once
      the selective-autophagy receptor/adaptor biology is considered.
    supported_by:
    - reference_id: PMID:18239685
      supporting_text: Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets.
    - reference_id: PMID:17703191
      supporting_text: Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20.
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Well supported experimentally but represents a context-specific
      immune-signaling function rather than the core selective-autophagy
      cargo-adaptor role.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: TAX1BP1 is essential for the termination of NF-kappaB and JNK activation in response to TNF-alpha, IL-1 and LPS stimulation.
    - reference_id: PMID:18239685
      supporting_text: Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation
- term:
    id: GO:2000660
    label: negative regulation of interleukin-1-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:18239685
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retain as experimentally supported context while keeping the
      selective-autophagy cargo-adaptor role as the primary functional summary.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: 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.
    - reference_id: PMID:18239685
      supporting_text: Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:28898289
  review:
    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.
    action: ACCEPT
    reason: >-
      Correct, well-supported broad cytoplasmic localization consistent with
      TAX1BP1's cytosolic autophagy-receptor function; duplicates other cytoplasm
      annotations.
    supported_by:
    - reference_id: PMID:28898289
      supporting_text: 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.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:27736772
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:27736772
      supporting_text: Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS.
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        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.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:27736772
  review:
    summary: >-
      This paper supports adaptor activity in antiviral signaling via the
      MAVS/ITCH axis, but not the more specific selective-autophagy
      cargo-adaptor claim.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:27736772
      supporting_text: 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.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:28898289
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Keep the generic adaptor term as a contextual statement while adding the
      more specific autophagy cargo adaptor activity call separately.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-notes.md
      supporting_text: 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.
    - reference_id: file:human/TAX1BP1/TAX1BP1-notes.md
      supporting_text: TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation.
- term:
    id: GO:0034144
    label: negative regulation of toll-like receptor 4 signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:28898289
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Keep as a context-specific innate immune consequence of TAX1BP1-mediated
      selective autophagy; do not elevate it to the main conserved function.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-notes.md
      supporting_text: TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation.
- term:
    id: GO:0039532
    label: negative regulation of cytoplasmic pattern recognition receptor signaling
      pathway
  evidence_type: IDA
  original_reference_id: PMID:27736772
  review:
    summary: >-
      TAX1BP1 negatively modulates MAVS-dependent antiviral signaling, but this
      pathway annotation is context-specific.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:27736772
      supporting_text: MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis;
    - reference_id: PMID:27736772
      supporting_text: 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.
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        A concrete mechanistic example is ...MAVS aggrephagy...: TAX1BP1 functions as an aggrephagy receptor promoting ...MAVS aggregate clearance..., which directly reduces downstream innate immune signaling.
- term:
    id: GO:1905161
    label: protein localization to phagocytic vesicle
  evidence_type: IDA
  original_reference_id: PMID:28898289
  review:
    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.
    action: UNDECIDED
    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.
- term:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:26451915
  review:
    summary: >-
      TAX1BP1 acts as a selective-autophagy cargo adaptor/receptor that links
      ubiquitylated cargo to the autophagy machinery.
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:26451915
      supporting_text: In summary, this work highlights the importance of TAX1BP1 as a novel autophagy receptor in myosin VI-mediated xenophagy.
    - reference_id: PMID:29940186
      supporting_text: 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.
    - reference_id: PMID:30459273
      supporting_text: NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy.
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-openai.md
      supporting_text: the strongest evidence supports it as a selective-autophagy cargo adaptor / autophagy receptor.
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-manual.md
      supporting_text: 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.
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        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).
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IDA
  original_reference_id: PMID:33226137
  review:
    summary: >-
      TAX1BP1 directly promotes cargo-coupled autophagosome formation and FIP200
      recruitment during selective macroautophagy.
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:33226137
      supporting_text: TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3.
    - reference_id: file:human/TAX1BP1/TAX1BP1-notes.md
      supporting_text: TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62-ubiquitin condensates.
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        infection conditions can also route TAX1BP1 to lysosomes through an ATG8-family-independent mechanism requiring ...RB1CC1/FIP200....
- term:
    id: GO:0098792
    label: xenophagy
  evidence_type: IDA
  original_reference_id: PMID:26451915
  review:
    summary: >-
      TAX1BP1 is directly recruited to ubiquitylated Salmonella and is required
      for autophagic clearance of the pathogen.
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:26451915
      supporting_text: Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy.
    - reference_id: PMID:26451915
      supporting_text: In summary, this work highlights the importance of TAX1BP1 as a novel autophagy receptor in myosin VI-mediated xenophagy.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:18570454
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:18570454
      supporting_text: Exosomal lysates of each fraction were digested and analyzed using nanoflow LC-ESI-MS-MS for protein identification.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15474016
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:15474016
      supporting_text: 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.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Kinase association is supported, but it is an upstream regulatory input to
      the selective-autophagy receptor function rather than the core activity.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        A prominent regulatory principle supported by mechanistic evidence is phosphorylation-dependent modulation of TAX1BP1 trafficking/function by antiviral kinases (...TBK1 and IKBKE/IKKi...).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693055
  review:
    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.
    action: ACCEPT
    reason: >-
      Accurate broad localization consistent with TAX1BP1's cytosolic
      adaptor/autophagy-receptor function. Duplicates the cytoplasm annotations.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693108
  review:
    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.
    action: ACCEPT
    reason: >-
      Accurate broad cytosolic localization consistent with TAX1BP1's function;
      duplicates the other cytosol/cytoplasm annotations.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-937337
  review:
    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.
    action: ACCEPT
    reason: >-
      Accurate broad cytosolic localization consistent with TAX1BP1's
      adaptor/autophagy-receptor function; duplicates other cytosol/cytoplasm
      annotations.
    supported_by:
    - reference_id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
      supporting_text: |-
        TAX1BP1 acts mainly in the ...cytosol... and at sites of selective autophagy cargo capture
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: TAS
  original_reference_id: PMID:10435631
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:17703191
      supporting_text: 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
    - reference_id: PMID:27736772
      supporting_text: TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied
    by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
  findings: []
- id: PMID:10435631
  title: 'The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases.'
  findings: []
- id: PMID:10920205
  title: T6BP, a TRAF6-interacting protein involved in IL-1 signaling.
  findings: []
- id: PMID:14697242
  title: 'Chromosome 13q12 encoded Rho GTPase activating protein suppresses growth of breast carcinoma cells, and yeast two-hybrid screen shows its interaction with several proteins.'
  findings: []
- id: PMID:15231748
  title: Functional proteomics mapping of a human signaling pathway.
  findings: []
- id: PMID:15474016
  title: A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of
    NF-kappaB and ISRE and IFN-beta promoter.
  findings: []
- id: PMID:17703191
  title: Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated
    NF-kappaB and JNK signaling.
  findings: []
- id: PMID:18239685
  title: Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective
    NF-kappaB activation.
  findings: []
- id: PMID:18570454
  title: Proteomic analysis of exosomes from human neural stem cells by flow field-flow
    fractionation and nanoflow liquid chromatography-tandem mass spectrometry.
  findings: []
- id: PMID:26451915
  title: The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required
    for Clearance of Salmonella Typhimurium by Autophagy.
  findings: []
- id: PMID:29940186
  title: Mechanistic Insights into Recognitions of Ubiquitin and Myosin VI by Autophagy
    Receptor TAX1BP1.
  findings: []
- id: PMID:30459273
  title: Mechanistic insights into the interactions of NAP1 with the SKICH domains
    of NDP52 and TAX1BP1.
  findings: []
- id: PMID:19131965
  title: The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB
    signalling.
  findings: []
- id: PMID:21765415
  title: 'The kinase IKKα inhibits activation of the transcription factor NF-κB by phosphorylating the regulatory molecule TAX1BP1.'
  findings: []
- id: PMID:21988832
  title: Toward an understanding of the protein interaction network of the human liver.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
- id: PMID:27736772
  title: TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation
    of the Mitochondrial Adaptor MAVS.
  findings: []
- id: PMID:28898289
  title: TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively
    regulates TLR3/4-mediated innate immune responses.
  findings: []
- id: PMID:29892012
  title: An interactome perturbation framework prioritizes damaging missense mutations
    for developmental disorders.
  findings: []
- id: PMID:30561431
  title: A protein-protein interaction map of the TNF-induced NF-κB signal transduction
    pathway.
  findings: []
- id: PMID:30909570
  title: Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33226137
  title: Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation
    in autophagy.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:34471133
  title: Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin
    condensate formation and autophagy initiation.
  findings: []
- id: Reactome:R-HSA-5693055
  title: 'TAX1BP1:TNFAIP3(A20) binds RIPK1-containing complexes'
  findings: []
- id: Reactome:R-HSA-5693108
  title: 'TNFAIP3 (A20) ubiquitinates RIPK1 with K48-linked Ub chains '
  findings: []
- id: Reactome:R-HSA-937337
  title: 'TAX1BP1:A20 inhibit TBK1/IKKi K63-polyubiquitination'
  findings: []
- id: file:human/TAX1BP1/TAX1BP1-notes.md
  title: Manual literature notes for TAX1BP1 PN/autophagy review
  findings: []
- id: file:human/TAX1BP1/TAX1BP1-deep-research-openai.md
  title: OpenAI focused deep research for TAX1BP1 proteostasis review
  findings: []
- id: file:human/TAX1BP1/TAX1BP1-deep-research-manual.md
  title: Manual deep research fallback for TAX1BP1 PN review
  findings: []
- id: file:human/TAX1BP1/TAX1BP1-deep-research-falcon.md
  title: Falcon (Edison) deep research for TAX1BP1 functional annotation
  findings:
  - statement: >-
      TAX1BP1 is a ubiquitin-directed selective-autophagy cargo receptor that
      uses two C-terminal UBZ (ubiquitin-binding zinc finger) domains, the
      SKICH domain, and LC3-interacting regions to route ubiquitylated cargo to
      lysosomal degradation; the second UBZ is essential for ubiquitin binding
      and prefers K63-linked chains while also binding linear tetra-ubiquitin
      and K48-linked chains.
    reference_section_type: RESULTS
    supporting_text: |-
      ...Two C-terminal UBZ (ubiquitin-binding zinc finger) domains... in TAX1BP1; the cited discussion emphasizes that the ...second UBZ... is essential for ubiquitin binding and shows preference for ...K63-linked ubiquitin chains..., can bind ...linear tetra-ubiquitin..., and (unlike OPTN/NDP52 in that discussion) TAX1BP1 can also bind ...K48-linked... chains.
  - statement: >-
      TAX1BP1 functions as an aggrephagy receptor that promotes clearance of
      MAVS aggregates via an ATG8-family-protein-dependent pathway, thereby
      attenuating downstream innate immune (IFN/NF-kappaB) signaling.
    reference_section_type: RESULTS
    supporting_text: |-
      A concrete mechanistic example is ...MAVS aggrephagy...: TAX1BP1 functions as an aggrephagy receptor promoting ...MAVS aggregate clearance..., which directly reduces downstream innate immune signaling.
  - statement: >-
      Phosphorylation of TAX1BP1 by the antiviral kinases TBK1 and IKBKE/IKKi
      promotes its lysosomal localization and receptor function; infection can
      also route TAX1BP1 to lysosomes through an ATG8-family-independent
      mechanism requiring RB1CC1/FIP200.
    reference_section_type: RESULTS
    supporting_text: |-
      ...TBK1 and IKBKE/IKKi... redundantly phosphorylate TAX1BP1...Phosphorylation promotes TAX1BP1 ...lysosomal localization... and influences its receptor function...TAX1BP1 is required for clearance of MAVS aggregates via an ...ATG8-family protein-dependent... pathway; infection conditions can also route TAX1BP1 to lysosomes through an ATG8-family-independent mechanism requiring ...RB1CC1/FIP200....
  - statement: >-
      TAX1BP1 is reported to be sufficient to promote lysophagy (selective
      autophagy of damaged lysosomes).
    reference_section_type: RESULTS
    supporting_text: |-
      In lysophagy-focused discussion, TAX1BP1 is specifically reported as ...sufficient to promote lysophagy... (selective autophagy of damaged lysosomes).
  - statement: >-
      A 2024 cryo-EM study of myosin VI lists TAX1BP1 among myosin VI cargo
      adapter proteins, with myosin VI binding the autophagy receptors NDP52,
      TAX1BP1, and Optineurin via its cargo-binding domains.
    reference_section_type: RESULTS
    supporting_text: |-
      A 2024 Nature Communications cryo-EM study of ...myosin VI... explicitly lists TAX1BP1 among myosin VI cargo adapter proteins and notes myosin VI binding to autophagy receptors including ...NDP52, TAX1BP1, and Optineurin... via myosin VI cargo-binding domains.
  - statement: >-
      Later work implicates TAX1BP1 in negative-feedback regulation of STING
      signaling via TAX1BP1-directed golgiphagy, extending its role in
      restraining innate immune signaling to the Golgi compartment.
    reference_section_type: RESULTS
    supporting_text: |-
      Later work also implicates TAX1BP1 in ...Golgi-associated autophagic regulation...
  - statement: >-
      TAX1BP1 acts mainly in the cytosol and at selective-autophagy
      compartments, including autophagosomes/autophagic vacuoles, the outer
      autophagosome membrane, and lysosomes (increased LAMP1 colocalization
      when phosphorylated).
    reference_section_type: RESULTS
    supporting_text: |-
      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.
core_functions:
- description: >-
    TAX1BP1 is a ubiquitin-binding selective-autophagy cargo adaptor that links
    ubiquitylated pathogens and ubiquitin-rich cargo condensates to upstream
    autophagy machinery, especially TBK1/FIP200-driven local autophagosome
    formation.
  molecular_function:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  directly_involved_in:
  - id: GO:0016236
    label: macroautophagy
  - id: GO:0098792
    label: xenophagy
  supported_by:
  - reference_id: PMID:26451915
    supporting_text: Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy.
  - reference_id: PMID:29940186
    supporting_text: 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.
  - reference_id: PMID:30459273
    supporting_text: NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy.
  - reference_id: PMID:33226137
    supporting_text: TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3.
proposed_new_terms: []
suggested_questions:
- question: >-
    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?
- question: >-
    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?
- question: >-
    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?
suggested_experiments:
- description: >-
    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.