The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The retrieved sources are consistent with the human protein TAX1BP1 (Tax1-binding protein 1; often discussed as a selective autophagy receptor and as a myosin VI cargo adaptor), matching the user-specified target identity (TAX1BP1/T6BP; Homo sapiens). TAX1BP1 is explicitly treated as a member of the selective autophagy receptor set alongside OPTN and NDP52, supporting correct gene/protein mapping rather than an unrelated symbol collision. (white2025phosphorylationofthe pages 1-2, kelly2023basalmitophagyas pages 65-68, niu2024autoinhibitionandactivation pages 1-2)
Selective autophagy receptors are proteins that recognize specific cargo (frequently via ubiquitin signals) and connect that cargo to the autophagy machinery via ATG8/LC3-family interactions through LC3-interacting regions (LIRs). TAX1BP1 is described within this receptor paradigm, including the general receptor features of ubiquitin binding plus LIR-mediated recruitment of autophagosome membranes. (white2025phosphorylationofthe pages 1-2, vargas2023themechanismsand pages 15-20)
In lysophagy-focused discussion, TAX1BP1 is specifically reported as sufficient to promote lysophagy (selective autophagy of damaged lysosomes). (vargas2023themechanismsand pages 15-20)
Evidence in the retrieved sources supports the following elements:
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). (white2025phosphorylationofthe pages 10-13, vargas2023themechanismsand pages 15-20)
A concrete mechanistic example is MAVS aggrephagy: TAX1BP1 functions as an aggrephagy receptor promoting MAVS aggregate clearance, which directly reduces downstream innate immune signaling. (white2025phosphorylationofthe pages 10-13, white2025phosphorylationofthe pages 1-2)
TAX1BP1 is described as constraining inflammatory signaling, including NF-κB and RLR/MAVS-associated pathways, helping prevent excessive inflammation. (white2025phosphorylationofthe pages 1-2)
A prominent regulatory principle supported by mechanistic evidence is phosphorylation-dependent modulation of TAX1BP1 trafficking/function by antiviral kinases (TBK1 and IKBKE/IKKi). (white2025phosphorylationofthe pages 1-2, white2025phosphorylationofthe pages 8-10)
A detailed mechanistic study (Autophagy; DOI indicates 2024 record, final issue 2025) reports:
- 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.
- Statistical support includes reported significant differences (e.g., p < 0.01, p < 0.001, p < 0.0001) across experiments. URL: https://doi.org/10.1080/15548627.2024.2394306. (white2025phosphorylationofthe pages 10-13, white2025phosphorylationofthe pages 8-10)
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. URL: https://doi.org/10.1038/s41467-024-45424-7 (accepted Jan 23, 2024; published 2024). (niu2024autoinhibitionandactivation pages 1-2)
The retrieved evidence supports TAX1BP1 operating in the cytosol and at selective autophagy-related compartments:
- Autophagosome context: a model places TAX1BP1 at/near the outer membrane of the autophagosome, where TAX1BP1 binds ubiquitin and then binds myosin VI, coupling cargo recognition to trafficking. (kelly2023basalmitophagyas pages 65-68)
- Lysosomes: phosphorylation-dependent localization to lysosomes (LAMP1 colocalization) and lysosomal degradation is reported, consistent with dynamic cycling through lysosomal/autolysosomal compartments. (white2025phosphorylationofthe pages 10-13, white2025phosphorylationofthe pages 8-10)
- Damaged lysosomes (lysophagy): TAX1BP1 is discussed as sufficient to promote lysophagic clearance, placing its action at damaged endolysosomal membranes. (vargas2023themechanismsand pages 15-20)
The 2024 Nature Communications cryo-EM study provides contemporary structural/biophysical reinforcement that TAX1BP1 is a recognized myosin VI cargo adaptor relevant to autophagy-linked trafficking. URL: https://doi.org/10.1038/s41467-024-45424-7. (niu2024autoinhibitionandactivation pages 1-2)
A 2024 asthma study links UBE2N–TAX1BP1 signaling to modulation of ferroptosis/inflammation in experimental asthma models and presents TAX1BP1 as part of a proposed therapeutic axis. URL: https://doi.org/10.1186/s12890-024-03351-9 (Oct 2024). This is disease-model evidence rather than a primary demonstration of TAX1BP1’s biochemical “core” function. (li2024trim11preventsferroptosis pages 1-2)
No TAX1BP1-targeted clinical trials were retrieved here. Nevertheless, the literature supports TAX1BP1 as a mechanistically attractive node for:
- tuning innate immune outputs by controlling MAVS aggregate persistence (white2025phosphorylationofthe pages 10-13)
- influencing organelle damage surveillance (lysophagy) (vargas2023themechanismsand pages 15-20)
- modulating autophagy-linked trafficking via myosin VI adapter interactions (niu2024autoinhibitionandactivation pages 1-2)
Open Targets reports association-level evidence linking TAX1BP1 to multiple diseases, including prostate carcinoma/prostate cancer and type 2 diabetes mellitus (among others). These are not proof of causality but indicate where human genetics/association evidence exists. (OpenTargets Search: -TAX1BP1)
Collectively, the retrieved literature supports the following primary functional identity for TAX1BP1:
Mechanistically, the strongest phosphorylation-centered “control knob” supported in the gathered evidence is that phosphorylation by TBK1/IKBKE alters TAX1BP1 lysosomal localization and receptor efficacy in aggregate clearance, providing a direct bridge between innate immune kinase signaling and selective autophagy execution. (white2025phosphorylationofthe pages 8-10)
| Category | Key points | Best supporting citations (pqac ids) | Source URL + pub year |
|---|---|---|---|
| Identity/domains | Verified target is human TAX1BP1 / T6BP / Tax1-binding protein 1 (UniProt Q86VP1). Current evidence supports classification as a selective autophagy receptor with a SKICH domain, LC3-interacting regions (LIRs), and two C-terminal UBZ (ubiquitin-binding zinc finger) domains; the second UBZ is essential for ubiquitin binding and shows preference for K63-linked chains, with reported binding also to linear tetra-Ub and K48-linked chains. | (kelly2023basalmitophagyas pages 65-68, suklabaidya2026negativefeedbackregulation pages 1-2, white2025phosphorylationofthe pages 1-2) | https://doi.org/10.1002/bies.202300076 (2023); https://doi.org/10.1080/15548627.2024.2394306 (2025) |
| Molecular function | TAX1BP1 functions primarily as a ubiquitin-binding adaptor/cargo receptor that links ubiquitinated cargo to autophagy machinery and suppresses excessive inflammatory signaling. Evidence supports roles in aggrephagy, lysophagy, pathogen-directed selective autophagy, and negative regulation of NF-κB and RLR/MAVS signaling. | (white2025phosphorylationofthe pages 10-13, white2025phosphorylationofthe pages 1-2, vargas2023themechanismsand pages 15-20) | https://doi.org/10.1080/15548627.2024.2394306 (2025); https://doi.org/10.1038/s41580-022-00542-2 (2023) |
| Key pathways | Best-supported pathways include: NF-κB termination via A20/TNFAIP3-associated inhibitory complexes; RLR/MAVS pathway suppression through autophagic clearance of MAVS aggregates; lysophagy where TAX1BP1 is sufficient to promote damaged-lysosome clearance; and broader roles in mitophagy/selective autophagy receptor networks. Recent work also places TAX1BP1 among receptors that can restore mitophagy when multiple SARs are removed. | (white2025phosphorylationofthe pages 10-13, white2025phosphorylationofthe pages 1-2, vargas2023themechanismsand pages 15-20, kelly2023basalmitophagyas pages 65-68) | https://doi.org/10.1080/15548627.2024.2394306 (2025); https://doi.org/10.1038/s41580-022-00542-2 (2023); https://doi.org/10.1002/bies.202300076 (2023) |
| Key binding partners | Supported partners include A20/TNFAIP3 (anti-inflammatory adaptor function), TRAF6 (historical alternate name TRAF6-binding protein), TBK1 and IKBKE/IKKi (phosphorylate TAX1BP1), RB1CC1/FIP200, ATG8-family proteins, NDP52/CALCOCO2, OPTN, p62/SQSTM1, MAVS, and myosin VI. Myosin VI is a recent structural/biophysical partner supported by 2024 cryo-EM work on the motor and by prior receptor-binding evidence. | (white2025phosphorylationofthe pages 10-13, white2025phosphorylationofthe pages 18-18, niu2024autoinhibitionandactivation pages 1-2, li2024trim11preventsferroptosis pages 1-2) | https://doi.org/10.1080/15548627.2024.2394306 (2025); https://doi.org/10.1038/s41467-024-45424-7 (2024); https://doi.org/10.1186/s12890-024-03351-9 (2024) |
| Localization | 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. Later work also implicates TAX1BP1 in Golgi-associated autophagic regulation, but strongest directly gathered support here is for cytosol-autophagosome-lysosome trafficking. | (white2025phosphorylationofthe pages 10-13, white2025phosphorylationofthe pages 8-10, kelly2023basalmitophagyas pages 65-68, niu2024autoinhibitionandactivation pages 1-2) | https://doi.org/10.1080/15548627.2024.2394306 (2025); https://doi.org/10.1038/s41467-024-45424-7 (2024) |
| Recent 2023-2024 developments | 2023 reviews place TAX1BP1 firmly within the mammalian selective autophagy receptor toolkit and note a role in mitophagy restoration relative to other SARs. A 2024 review of autophagosome-lysosome fusion lists TAX1BP1 among cargo receptors relevant to autophagy completion. A 2024 cryo-EM study of myosin VI highlights TAX1BP1 as a cargo adaptor for the motor. A 2024 asthma study links UBE2N-TAX1BP1 signaling to ferroptosis/inflammation phenotypes, though this is more disease-model evidence than core mechanistic annotation. A 2024 HTLV-1 paper provides contextual relevance to Tax/NF-κB biology but not direct TAX1BP1 mechanism. | (kelly2023basalmitophagyas pages 65-68, ke2024molecularmechanismof pages 6-7, niu2024autoinhibitionandactivation pages 1-2, li2024trim11preventsferroptosis pages 1-2, su2024pcbp1interactswith pages 1-2) | https://doi.org/10.1002/bies.202300076 (2023); https://doi.org/10.1038/s41580-022-00542-2 (2023); https://doi.org/10.3390/cells13060500 (2024); https://doi.org/10.1038/s41467-024-45424-7 (2024); https://doi.org/10.1186/s12890-024-03351-9 (2024); https://doi.org/10.3389/fimmu.2024.1375168 (2024) |
| Quantitative/statistical notes | Direct quantitative TAX1BP1 mechanistic evidence in gathered sources is limited for 2023-2024. The strongest numbers come from a later mechanistic study showing 13 putative IKBKE/IKKi-induced phosphosites, with S254, S593, S666 highlighted; phosphomimetic mutants showed stronger lysosomal colocalization and MAVS-clearance phenotypes, with reported statistics including p < 0.01, p < 0.001, and p < 0.0001 across experiments. A 2024 lysophagy review cites ~20% reduced repair in FBXO27-KO cells in a related damaged-lysosome model and notes TAX1BP1 is sufficient to promote lysophagy. | (white2025phosphorylationofthe pages 8-10, white2025phosphorylationofthe pages 10-13, vargas2023themechanismsand pages 15-20) | https://doi.org/10.1080/15548627.2024.2394306 (2025); https://doi.org/10.1038/s41580-022-00542-2 (2023) |
| Applications/disease links | TAX1BP1 is not yet an established drug target, but disease-oriented evidence connects it to inflammatory regulation, viral signaling, bacterial infection biology, ferroptosis/asthma models, and possible oncology associations. Open Targets lists associations including prostate carcinoma/prostate cancer, hypospadias, hallux valgus, and type 2 diabetes mellitus; these are association-level signals rather than definitive functional causality. The asthma study explicitly proposes the TRIM11–UBE2N–TAX1BP1 axis as a potential therapeutic avenue. | (OpenTargets Search: -TAX1BP1, li2024trim11preventsferroptosis pages 1-2) | Open Targets platform context (current); https://doi.org/10.1186/s12890-024-03351-9 (2024) |
Table: This table summarizes the best-supported functional annotation of human TAX1BP1 (UniProt Q86VP1), emphasizing domain architecture, molecular role, pathways, localization, and recent 2023-2024 developments. It is useful as a compact evidence map for building a full narrative report with source-linked claims.
References
(white2025phosphorylationofthe pages 1-2): Jesse White, Young Bong Choi, Jiawen Zhang, Mai Tram Vo, Chaoxia He, Kashif Shaikh, and Edward W. Harhaj. Phosphorylation of the selective autophagy receptor tax1bp1 by tbk1 and ikbke/ikki promotes atg8-family protein-dependent clearance of mavs aggregates. Autophagy, 21:160-177, Sep 2025. URL: https://doi.org/10.1080/15548627.2024.2394306, doi:10.1080/15548627.2024.2394306. This article has 20 citations and is from a domain leading peer-reviewed journal.
(kelly2023basalmitophagyas pages 65-68): GE Kelly. Basal mitophagy as an anti-ageing programme. Unknown journal, 2023.
(niu2024autoinhibitionandactivation pages 1-2): Fengfeng Niu, Lingxuan Li, Lei Wang, Jinman Xiao, Shun Xu, Yong Liu, Leishu Lin, Cong Yu, and Zhiyi Wei. Autoinhibition and activation of myosin vi revealed by its cryo-em structure. Nature Communications, Feb 2024. URL: https://doi.org/10.1038/s41467-024-45424-7, doi:10.1038/s41467-024-45424-7. This article has 14 citations and is from a highest quality peer-reviewed journal.
(vargas2023themechanismsand pages 15-20): Jose Norberto S. Vargas, Maho Hamasaki, Tsuyoshi Kawabata, Richard J. Youle, and Tamotsu Yoshimori. The mechanisms and roles of selective autophagy in mammals. Nature Reviews Molecular Cell Biology, 24:167-185, Oct 2023. URL: https://doi.org/10.1038/s41580-022-00542-2, doi:10.1038/s41580-022-00542-2. This article has 1059 citations and is from a domain leading peer-reviewed journal.
(white2025phosphorylationofthe pages 10-13): Jesse White, Young Bong Choi, Jiawen Zhang, Mai Tram Vo, Chaoxia He, Kashif Shaikh, and Edward W. Harhaj. Phosphorylation of the selective autophagy receptor tax1bp1 by tbk1 and ikbke/ikki promotes atg8-family protein-dependent clearance of mavs aggregates. Autophagy, 21:160-177, Sep 2025. URL: https://doi.org/10.1080/15548627.2024.2394306, doi:10.1080/15548627.2024.2394306. This article has 20 citations and is from a domain leading peer-reviewed journal.
(white2025phosphorylationofthe pages 8-10): Jesse White, Young Bong Choi, Jiawen Zhang, Mai Tram Vo, Chaoxia He, Kashif Shaikh, and Edward W. Harhaj. Phosphorylation of the selective autophagy receptor tax1bp1 by tbk1 and ikbke/ikki promotes atg8-family protein-dependent clearance of mavs aggregates. Autophagy, 21:160-177, Sep 2025. URL: https://doi.org/10.1080/15548627.2024.2394306, doi:10.1080/15548627.2024.2394306. This article has 20 citations and is from a domain leading peer-reviewed journal.
(ke2024molecularmechanismof pages 6-7): Po-Yuan Ke. Molecular mechanism of autophagosome–lysosome fusion in mammalian cells. Cells, 13:500, Mar 2024. URL: https://doi.org/10.3390/cells13060500, doi:10.3390/cells13060500. This article has 67 citations.
(li2024trim11preventsferroptosis pages 1-2): Na Li, Guoqing Qiu, Xiangqin Xu, Yan Shen, and Yuming Chen. Trim11 prevents ferroptosis in model of asthma by ube2n-tax1bp1 signaling. BMC Pulmonary Medicine, Oct 2024. URL: https://doi.org/10.1186/s12890-024-03351-9, doi:10.1186/s12890-024-03351-9. This article has 0 citations and is from a peer-reviewed journal.
(OpenTargets Search: -TAX1BP1): Open Targets Query (-TAX1BP1, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(su2024pcbp1interactswith pages 1-2): Rui Su, Xue Kang, Yifan Niu, Tiesuo Zhao, and Hui Wang. Pcbp1 interacts with the htlv-1 tax oncoprotein to potentiate nf-κb activation. Frontiers in immunology, 15:1375168, Apr 2024. URL: https://doi.org/10.3389/fimmu.2024.1375168, doi:10.3389/fimmu.2024.1375168. This article has 9 citations and is from a peer-reviewed journal.
(suklabaidya2026negativefeedbackregulation pages 1-2): Sujit Suklabaidya, Suchitra Mohanty, Irene E. Reider, Jesse White, Dominic Colter, Sarah M. McCormick, Noula Shembade, Young Bong Choi, Christopher C. Norbury, and Edward W. Harhaj. Negative feedback regulation of sting signaling by tax1bp1-directed golgiphagy. Nature Communications, Feb 2026. URL: https://doi.org/10.1038/s41467-026-69422-z, doi:10.1038/s41467-026-69422-z. This article has 1 citations and is from a highest quality peer-reviewed journal.
(white2025phosphorylationofthe pages 18-18): Jesse White, Young Bong Choi, Jiawen Zhang, Mai Tram Vo, Chaoxia He, Kashif Shaikh, and Edward W. Harhaj. Phosphorylation of the selective autophagy receptor tax1bp1 by tbk1 and ikbke/ikki promotes atg8-family protein-dependent clearance of mavs aggregates. Autophagy, 21:160-177, Sep 2025. URL: https://doi.org/10.1080/15548627.2024.2394306, doi:10.1080/15548627.2024.2394306. This article has 20 citations and is from a domain leading peer-reviewed journal.