Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0043066 negative regulation of apoptotic process	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0019900 kinase binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0035591 signaling adaptor activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: The automated adaptor term is a valid high-level description of TAX1BP1, but it is less informative than the selective-autophagy cargo-adaptor role curated separately below. Reason: Keep the broad adaptor label as non-core context. A more specific selective-autophagy cargo-adaptor annotation is added separately for the PN-focused biology. Supporting Evidence: PMID:26451915 Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy. PMID:29940186 TAX1BP1 may not only function as an autophagy receptor to recruit ubiquitylated substrates for autophagic degradation, but also serve as a Myosin VI cargo adaptor protein for mediating the maturation of autophagosome. PMID:30459273 NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy.
GO:0043066 negative regulation of apoptotic process	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0043124 negative regulation of canonical NF-kappaB signal transduction	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:2000660 negative regulation of interleukin-1-mediated signaling pathway	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:10920205 T6BP, a TRAF6-interacting protein involved in IL-1 signaling...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:14697242 TODO: Fetch title	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:15231748 Functional proteomics mapping of a human signaling pathway.	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:17703191 Essential role for TAX1BP1 in the termination of TNF-alpha-,...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:19131965 The ubiquitin-editing enzyme A20 requires RNF11 to downregul...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:21765415 TODO: Fetch title	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-κB s...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	PENDING	Summary: TODO: Review this GOA annotation
GO:0000407 phagophore assembly site	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: TAX1BP1 supports cargo-proximal autophagosome initiation, but this localization is supporting context rather than the best statement of core function. Reason: Literature supports recruitment of upstream autophagy-initiation machinery around TAX1BP1-bound cargo. The more informative core curation is the selective-autophagy cargo adaptor activity itself. Supporting Evidence: PMID:33226137 TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3.
GO:0005737 cytoplasm	IEA GO_REF:0000044	PENDING	Summary: TODO: Review this GOA annotation
GO:0005739 mitochondrion	IEA GO_REF:0000044	PENDING	Summary: TODO: Review this GOA annotation
GO:0005776 autophagosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: TAX1BP1 associates with autophagic membranes during selective autophagy, but this cellular component annotation is supporting context rather than the core activity. Reason: Valid localization that fits receptor function on autophagic membranes, yet it should not eclipse the more informative cargo-adaptor role. Supporting Evidence: PMID:26451915 This mutually exclusive binding and the association of TAX1BP1 with LC3 on the outer limiting membrane of autophagosomes may suggest a molecular mechanism for recruitment of this motor to autophagosomes.
GO:0000407 phagophore assembly site	EXP PMID:33226137 Receptor-mediated clustering of FIP200 bypasses the role of ...	KEEP AS NON CORE	Summary: The experimental paper supports TAX1BP1-driven local autophagosome initiation around cargo, which is compatible with phagophore assembly site localization. Reason: Useful mechanistic localization in selective autophagy, but not the main evolved function statement for the gene. Supporting Evidence: PMID:33226137 TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3.
GO:0000407 phagophore assembly site	EXP PMID:34471133 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005737 cytoplasm	EXP PMID:30909570 Autophagy Promotes Infectious Particle Production of Mopeia ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway	IDA PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th...	KEEP AS NON CORE	Summary: TAX1BP1 negatively regulates TNF-induced NF-kappaB signaling through the A20/TNFAIP3 axis, but this immune-signaling role is contextual relative to the gene's selective-autophagy core. Reason: Biologically sound and experimentally supported, yet it captures a signaling consequence/context rather than the PN-relevant cargo-adaptor activity emphasized in this review. Supporting Evidence: PMID:18239685 Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets. PMID:17703191 Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20.
GO:0035591 signaling adaptor activity	IDA PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th...	KEEP AS NON CORE	Summary: Early immune-signaling work supports TAX1BP1 as an A20-linked signaling adaptor, but that role is broader and more contextual than the selective-autophagy cargo-adaptor function. Reason: Accurate experimentally, yet not the most informative core annotation once the selective-autophagy receptor/adaptor biology is considered. Supporting Evidence: PMID:18239685 Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets. PMID:17703191 Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20.
GO:0043124 negative regulation of canonical NF-kappaB signal transduction	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:2000660 negative regulation of interleukin-1-mediated signaling pathway	IDA PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice th...	KEEP AS NON CORE	Summary: TAX1BP1 dampens IL-1 signaling through the A20 axis, but this is a context-specific immune-signaling role rather than the core PN function. Reason: Retain as experimentally supported context while keeping the selective-autophagy cargo-adaptor role as the primary functional summary. Supporting Evidence: PMID:17703191 The NF-kappaB transcription factor is normally transiently activated by proinflammatory cytokines and bacterial lipopolysaccharide (LPS); however, persistent NF-kappaB activation is commonly observed in inflammatory disease and malignancy. PMID:18239685 Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation
GO:0005737 cytoplasm	IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005739 mitochondrion	IDA PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating It...	KEEP AS NON CORE	Summary: TAX1BP1 can relocalize to mitochondria during virus infection through MAVS, but the accessible evidence here supports a context-dependent localization rather than a standalone core mitochondrial or mitophagy annotation. Reason: Keep the experimentally observed localization, but do not treat it as evidence that mitophagy is a core established TAX1BP1 function in this local review. Supporting Evidence: PMID:27736772 Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating It...	KEEP AS NON CORE	Summary: This paper supports adaptor activity in antiviral signaling via the MAVS/ITCH axis, but not the more specific selective-autophagy cargo-adaptor claim. Reason: Valid context-specific adaptor function. It should be retained separately from the autophagy cargo-adaptor curation rather than folded into the core PN call. Supporting Evidence: PMID:27736772 TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of...	KEEP AS NON CORE	Summary: In the TRIF study, TAX1BP1 clearly behaves as a selective-autophagy receptor/adaptor, but the broad adaptor term can be retained as non-core context alongside a more specific new cargo-adaptor annotation. Reason: Keep the generic adaptor term as a contextual statement while adding the more specific autophagy cargo adaptor activity call separately. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-notes.md TRIM32-mediated as well as poly(I:C)- and LPS-induced degradation of TRIF is inhibited by deficiency of TAX1BP1, a receptor for selective autophagy. file:human/TAX1BP1/TAX1BP1-notes.md TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation.
GO:0034144 negative regulation of toll-like receptor 4 signaling pathway	IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of...	KEEP AS NON CORE	Summary: The TRIF paper supports negative regulation of TLR3/4 signaling via selective autophagic degradation of TRIF, but this immune pathway role is contextual rather than core PN biology. Reason: Keep as a context-specific innate immune consequence of TAX1BP1-mediated selective autophagy; do not elevate it to the main conserved function. Supporting Evidence: file:human/TAX1BP1/TAX1BP1-notes.md TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation.
GO:0039532 negative regulation of cytoplasmic pattern recognition receptor signaling pathway	IDA PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating It...	KEEP AS NON CORE	Summary: TAX1BP1 negatively modulates MAVS-dependent antiviral signaling, but this pathway annotation is context-specific. Reason: The experimental work supports antiviral signaling restraint via MAVS turnover, yet the autophagy cargo-adaptor role is the more informative core curation for PN purposes. Supporting Evidence: PMID:27736772 MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; PMID:27736772 TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression.
GO:1905161 protein localization to phagocytic vesicle	IDA PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of...	UNDECIDED	Summary: The accessible abstract supports TAX1BP1-mediated selective autophagic degradation of TRIF, but it does not clearly justify this more specific vesicle-localization process term. Reason: I cannot confidently connect the currently accessible evidence to protein localization to phagocytic vesicle without fuller paper context. The more defensible local update is the autophagy cargo-adaptor reading instead.
GO:0160247 autophagy cargo adaptor activity	IDA PMID:26451915 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosi...	NEW	Summary: TAX1BP1 acts as a selective-autophagy cargo adaptor/receptor that links ubiquitylated cargo to the autophagy machinery. Reason: This specific molecular function is central to the PN-focused biology and is better supported than the currently seeded broad adaptor terms. The literature directly describes TAX1BP1 as an autophagy receptor/cargo adaptor in xenophagy and related selective-autophagy settings. Supporting Evidence: PMID:26451915 In summary, this work highlights the importance of TAX1BP1 as a novel autophagy receptor in myosin VI-mediated xenophagy. PMID:29940186 TAX1BP1 may not only function as an autophagy receptor to recruit ubiquitylated substrates for autophagic degradation, but also serve as a Myosin VI cargo adaptor protein for mediating the maturation of autophagosome. PMID:30459273 NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy. file:human/TAX1BP1/TAX1BP1-deep-research-openai.md the strongest evidence supports it as a selective-autophagy cargo adaptor / autophagy receptor. file:human/TAX1BP1/TAX1BP1-deep-research-manual.md TAX1BP1 is best supported as a ubiquitin-binding selective-autophagy cargo adaptor/receptor rather than as a general signaling adaptor or a dedicated mitophagy/fusion factor.
GO:0016236 macroautophagy	IDA PMID:33226137 Receptor-mediated clustering of FIP200 bypasses the role of ...	NEW	Summary: TAX1BP1 directly promotes cargo-coupled autophagosome formation and FIP200 recruitment during selective macroautophagy. Reason: The available literature supports direct involvement in macroautophagy via local autophagosome initiation around TAX1BP1-bound cargo, while more specific xenophagy is captured separately below. Supporting Evidence: PMID:33226137 TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3. file:human/TAX1BP1/TAX1BP1-notes.md TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62-ubiquitin condensates.
GO:0098792 xenophagy	IDA PMID:26451915 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosi...	NEW	Summary: TAX1BP1 is directly recruited to ubiquitylated Salmonella and is required for autophagic clearance of the pathogen. Reason: This specific selective-autophagy process annotation is missing from the seeded GOA set but is directly supported by the Salmonella study and fits the PN xenophagy context cleanly. Supporting Evidence: PMID:26451915 Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy. PMID:26451915 In summary, this work highlights the importance of TAX1BP1 as a novel autophagy receptor in myosin VI-mediated xenophagy.
GO:0070062 extracellular exosome	HDA PMID:18570454 Proteomic analysis of exosomes from human neural stem cells ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:15474016 A20 is a potent inhibitor of TLR3- and Sendai virus-induced ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0019900 kinase binding	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-5693055	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-5693108	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-937337	PENDING	Summary: TODO: Review this GOA annotation
GO:0043066 negative regulation of apoptotic process	TAS PMID:10435631 TODO: Fetch title	PENDING	Summary: TODO: Review this GOA annotation

Core Functions

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:

autophagy cargo adaptor activity

Directly Involved In:

macroautophagy xenophagy

Supporting Evidence:

PMID:26451915
Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy.
PMID:29940186
TAX1BP1 may not only function as an autophagy receptor to recruit ubiquitylated substrates for autophagic degradation, but also serve as a Myosin VI cargo adaptor protein for mediating the maturation of autophagosome.
PMID:30459273
NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy.
PMID:33226137
TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3.

References

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

PMID:10435631

TODO: Fetch title

PMID:10920205

T6BP, a TRAF6-interacting protein involved in IL-1 signaling.

PMID:14697242

TODO: Fetch title

PMID:15231748

Functional proteomics mapping of a human signaling pathway.

PMID:15474016

A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF-kappaB and ISRE and IFN-beta promoter.

PMID:17703191

Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling.

PMID:18239685

Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation.

PMID:18570454

Proteomic analysis of exosomes from human neural stem cells by flow field-flow fractionation and nanoflow liquid chromatography-tandem mass spectrometry.

PMID:26451915

The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy.

PMID:29940186

Mechanistic Insights into Recognitions of Ubiquitin and Myosin VI by Autophagy Receptor TAX1BP1.

PMID:30459273

Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1.

PMID:19131965

The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling.

PMID:21765415

TODO: Fetch title

PMID:21988832

Toward an understanding of the protein interaction network of the human liver.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:26871637

Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PMID:27736772

TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS.

PMID:28898289

TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses.

PMID:29892012

An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.

PMID:30561431

A protein-protein interaction map of the TNF-induced NF-κB signal transduction pathway.

PMID:30909570

Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33226137

Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34471133

Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation.

Reactome:R-HSA-5693055

TAX1BP1:TNFAIP3(A20) binds RIPK1-containing complexes

Reactome:R-HSA-5693108

TNFAIP3 (A20) ubiquitinates RIPK1 with K48-linked Ub chains

Reactome:R-HSA-937337

TAX1BP1:A20 inhibit TBK1/IKKi K63-polyubiquitination

file:human/TAX1BP1/TAX1BP1-notes.md

Manual literature notes for TAX1BP1 PN/autophagy review

file:human/TAX1BP1/TAX1BP1-deep-research-openai.md

OpenAI focused deep research for TAX1BP1 proteostasis review

file:human/TAX1BP1/TAX1BP1-deep-research-manual.md

Manual deep research fallback for TAX1BP1 PN review

Suggested Experiments

Experiment: Compare TAX1BP1 knockout/rescue with separation-of-function mutants that disrupt ubiquitin binding, FIP200 recruitment, or Myosin VI binding across xenophagy, ubiquitin-condensate autophagy, and PINK1/Parkin mitophagy assays to resolve which TAX1BP1 activities are core versus context-specific.

📚 Additional Documentation

Deep Research Manual

(TAX1BP1-deep-research-manual.md)

TAX1BP1 manual deep research

Generated on 2026-04-24 as a manual fallback after provider-based deep research did not produce a usable report in this worktree.

Update on 2026-04-25: a provider-generated focused OpenAI report was subsequently created at
TAX1BP1-deep-research-openai.md. This manual memo is retained as a fallback synthesis and
local provenance record for the earlier provider failures.

Provenance

Attempted just deep-research-falcon human TAX1BP1; the Edison/Falcon job remained active for several minutes without producing an output file.
Attempted just deep-research-openai human TAX1BP1; the OpenAI deep-research job likewise remained long-running without producing an output file in a usable window.
Attempted just deep-research-perplexity-lite human TAX1BP1; this failed immediately with 401 insufficient_quota.
This fallback memo synthesizes the locally cached publications already used for the PN-focused review.

PN-focused conclusion

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.

Xenophagy/selective-autophagy receptor function is directly supported by Salmonella and structural/autophagy-receptor studies PMID:26451915 PMID:29940186 PMID:30459273.
Cargo-coupled macroautophagy initiation is supported by FIP200 recruitment around ubiquitin-positive cargo PMID:33226137 PMID:34471133.
Innate immune pathway effects are real but are best interpreted as contextual consequences of selective autophagic cargo handling in the PN frame PMID:28898289 PMID:28898289.
Older A20/NF-kappaB pathway papers support a broader adaptor role, but not one that should displace the autophagy-centered core call PMID:17703191 PMID:18239685.

Conservative boundaries

Mitophagy should remain non-core here. The local evidence shows mitochondrial localization in a MAVS setting PMID:27736772, but this does not by itself justify a standalone core mitophagy annotation.
Autophagosome-lysosome fusion should also remain below the threshold for direct promotion. PMID:26451915 supports a Myosin VI-linked maturation connection PMID:26451915, but the available TAX1BP1-specific evidence is still indirect for a direct fusion term.
Broad signaling-adaptor annotations are acceptable as contextual/non-core descriptions, but the GO-facing core remains better captured by autophagy cargo adaptor activity plus the selective-autophagy process calls.

Impact on the local review

The current PN-focused YAML remains appropriately conservative. This manual fallback does not justify promoting additional core terms beyond:

autophagy cargo adaptor activity
macroautophagy
xenophagy

It also does not justify promoting standalone core annotations for:

mitophagy
autophagosome-lysosome fusion
broad inflammatory-signaling adaptor terms

Deep Research Openai

(TAX1BP1-deep-research-openai.md)

provider: openai
model: gpt-5.4-mini
cached: false
start_time: '2026-04-25T18:52:42.590618'
end_time: '2026-04-25T18:53:09.196558'
duration_seconds: 26.61
provider_config:
timeout: 600
max_retries: 3
parameters:
allowed_domains: []
temperature: 0.1
top_p: 1.0
citation_count: 10

Question

Research human TAX1BP1 (UniProt Q86VP1) with a narrow proteostasis focus. Determine whether the strongest evidence supports selective-autophagy cargo adaptor activity, macroautophagy, xenophagy, mitophagy, or autophagosome-lysosome fusion. Keep core roles distinct from contextual innate-immune signaling functions and cite each substantive claim.

Output

Bottom line

For human TAX1BP1 (UniProt Q86VP1), the strongest evidence supports it as a selective-autophagy cargo adaptor / autophagy receptor. Within that broad class, the best-supported proteostasis-related roles are aggrephagy and lysophagy. It also has well-supported roles in xenophagy and mitophagy, but these appear more context-specific than its core identity as a cargo adaptor. I found no strong evidence that TAX1BP1’s primary proteostasis function is autophagosome-lysosome fusion itself; rather, it helps recruit/organize upstream autophagy machinery and cargo. (pmc.ncbi.nlm.nih.gov)

Classification, from strongest to weakest support

1) Selective-autophagy cargo adaptor activity — strongest support

TAX1BP1 is consistently described as a selective autophagy receptor / cargo adaptor that binds ubiquitinated cargo and LC3/GABARAP-family proteins via its ubiquitin-binding and LIR-containing regions. Reviews and mechanistic studies describe SLRs as adaptor-like proteins that tether cargo to the phagophore, and TAX1BP1 is repeatedly placed in that group. A 2024 mechanistic paper further emphasizes TAX1BP1’s interactions with RB1CC1/FIP200 and ATG8-family proteins, reinforcing its receptor/adaptor identity rather than a late fusion factor. (pmc.ncbi.nlm.nih.gov)

2) Macroautophagy — supported, but as a broader pathway context

TAX1BP1 participates in selective macroautophagy, especially in cargo-specific autophagic sequestration. Studies show TAX1BP1 can trigger LC3 lipidation in reconstituted systems and can recruit the autophagy initiation machinery to cargo, which is macroautophagy-related but still in the selective-autophagy subclass. So “macroautophagy” is true in a broad sense, but it is less precise than “selective-autophagy cargo adaptor.” (pmc.ncbi.nlm.nih.gov)

3) Lysophagy — strong proteostasis-relevant evidence

Among specific cargo contexts, TAX1BP1 has strong evidence for lysophagy. Quantitative proteomics studies found TAX1BP1 recruited to damaged lysosomes, and functional work showed TAX1BP1 is required for efficient lysophagic flux. The mechanism involves TAX1BP1’s SKICH domain and interactions with TBK1 and RB1CC1/FIP200, which places it firmly in autophagy initiation around damaged lysosomes. This is one of the cleanest proteostasis phenotypes for TAX1BP1. (pubmed.ncbi.nlm.nih.gov)

4) Aggrephagy — strong and arguably the most proteostasis-specific substrate class

For misfolded-protein handling, TAX1BP1 has strong support in aggrephagy. Reviews summarize that TAX1BP1 contributes to clearance of protein aggregates, and 2024 work specifically describes TAX1BP1 as an autophagy initiator that advances aggrephagy from cargo collection to sequestration. Another recent study shows TAX1BP1 recruits FIP200 in p62-aggregate aggrephagy. If your focus is narrow proteostasis, this is likely the most relevant substrate-specific function besides lysophagy. (pmc.ncbi.nlm.nih.gov)

5) Xenophagy — real and well supported, but more context-dependent

TAX1BP1 was shown to be required for clearance of Salmonella Typhimurium by autophagy, i.e. xenophagy, and is recruited to cytosolic bacteria. However, this function is one branch of its selective-autophagy repertoire rather than the dominant proteostasis role. It is meaningful, but not the most convincing “core” function if you are choosing one label for TAX1BP1 overall. (pmc.ncbi.nlm.nih.gov)

6) Mitophagy — supported, but not the strongest overall identity

TAX1BP1 is repeatedly implicated in Parkin/PINK1-dependent mitophagy. Reconstitution experiments used TAX1BP1 as one of the mitophagy cargo receptors capable of driving cargo-induced LC3 lipidation, and proteogenetic analyses of PARK2-dependent mitophagy identified TAX1BP1 as a receptor recruited to ubiquitinated mitochondria. That said, the mitophagy literature generally places TAX1BP1 alongside other receptors such as OPTN and NDP52, rather than uniquely emphasizing TAX1BP1. (pmc.ncbi.nlm.nih.gov)

7) Autophagosome-lysosome fusion — weakest / not primary

I did not find strong evidence that TAX1BP1 is a core autophagosome-lysosome fusion factor. Some papers mention roles in amphisome formation or recruitment of motor/adaptor machinery, but that is distinct from directly mediating autophagosome-lysosome fusion. The current evidence supports TAX1BP1 more as an upstream cargo adaptor and autophagy initiator than as a fusion executor. (pmc.ncbi.nlm.nih.gov)

Distinguishing core proteostasis roles from innate-immune signaling

TAX1BP1 is also involved in innate-immune and inflammatory signaling pathways, including regulation of NF-κB-, TNF-, TLR-, RIG-I-, and antiviral pathways. Those functions are real, but they are separable from its core proteostasis role as an autophagy receptor/cargo adaptor. Reactome and reviews explicitly list TAX1BP1 as participating in inflammatory and antiviral processes as well as selective autophagy regulation. (reactome.org)

Overall conclusion

If you need one best label for human TAX1BP1 in a proteostasis-focused analysis, choose:

Selective-autophagy cargo adaptor / autophagy receptor
with strongest substrate-context evidence in aggrephagy and lysophagy, and additional evidence for xenophagy and mitophagy.
It is not best classified primarily as an autophagosome-lysosome fusion factor. (pmc.ncbi.nlm.nih.gov)

If you want, I can turn this into a ranked evidence table with columns for mechanism, substrate, assay type, and strength of evidence.

Notes

(TAX1BP1-notes.md)

TAX1BP1 notes

PN-relevant synthesis

TAX1BP1 is well supported as a selective-autophagy receptor/cargo adaptor, especially in xenophagy and ubiquitin-condensate-directed autophagy [PMID:26451915 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy., "Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy."] [PMID:29940186 Mechanistic Insights into Recognitions of Ubiquitin and Myosin VI by Autophagy Receptor TAX1BP1., "TAX1BP1 may not only function as an autophagy receptor to recruit ubiquitylated substrates for autophagic degradation, but also serve as a Myosin VI cargo adaptor protein for mediating the maturation of autophagosome."] [PMID:30459273 Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1., "NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy."].
Cargo-coupled macroautophagy initiation is directly supported by FIP200 recruitment and local autophagosome formation [PMID:33226137 Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy., "TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3."] [PMID:34471133 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation., "TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62-ubiquitin condensates."].
The TRIF paper supports a selective-autophagy receptor/adaptor interpretation and places the innate immune pathway effects in context [PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses., "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."] [PMID:28898289 TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses., "TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation."].
Older immune-signaling work supports a valid but contextual A20-linked adaptor role [PMID:17703191 Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling., "Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20."] [PMID:18239685 Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation., "Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets."].

Conservative boundaries

Mitochondrial localization is experimentally observed in virus infection [PMID:27736772 TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS., "Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS."], but the accessible local evidence here does not justify treating mitophagy as a standalone core TAX1BP1 annotation.
TAX1BP1 is linked to late autophagy maturation through Myosin VI [PMID:26451915 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy., "Our previous work demonstrated that myosin VI mediates the delivery of endocytic membranes to autophagosomes, a process that is required for autophagosome maturation and its fusion with the lysosome."], but the accessible TAX1BP1-specific evidence in this review is still indirect for a direct GO:0061909 autophagosome-lysosome fusion annotation.

📄 View Raw YAML

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
  PN-relevant 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.
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: 'TODO: Review this GOA annotation'
    action: PENDING
- 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: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- 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: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000660
    label: negative regulation of interleukin-1-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10920205
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14697242
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15231748
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17703191
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18239685
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19131965
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21765415
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30561431
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- 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: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- 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.
- 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: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:30909570
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- 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: 'TODO: Review this GOA annotation'
    action: PENDING
- 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: 'TODO: Review this GOA annotation'
    action: PENDING
- 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.
- 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.
- 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.
- 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.
- 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: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15474016
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693055
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-937337
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: TAS
  original_reference_id: PMID:10435631
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
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: 'TODO: Fetch title'
  findings: []
- id: PMID:10920205
  title: T6BP, a TRAF6-interacting protein involved in IL-1 signaling.
  findings: []
- id: PMID:14697242
  title: 'TODO: Fetch title'
  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: 'TODO: Fetch title'
  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: []
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?
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.

TAX1BP1

Gene Description

Existing Annotations Review

Core Functions

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.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Deep Research Manual

TAX1BP1 manual deep research

Provenance

PN-focused conclusion

Conservative boundaries

Impact on the local review

Deep Research Openai

Question

Output

Bottom line

Classification, from strongest to weakest support

1) Selective-autophagy cargo adaptor activity — strongest support

2) Macroautophagy — supported, but as a broader pathway context

3) Lysophagy — strong proteostasis-relevant evidence

4) Aggrephagy — strong and arguably the most proteostasis-specific substrate class

5) Xenophagy — real and well supported, but more context-dependent

6) Mitophagy — supported, but not the strongest overall identity

7) Autophagosome-lysosome fusion — weakest / not primary

Distinguishing core proteostasis roles from innate-immune signaling

Overall conclusion

Notes

TAX1BP1 notes

PN-relevant synthesis

Conservative boundaries

📄 View Raw YAML