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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.
| Aspect | Summary for AZI2/NAP1 | Key evidence / mechanistic detail | Citations |
|---|---|---|---|
| Verified identity | Human AZI2 encodes 5-azacytidine-induced protein 2, also called NAK-associated protein 1 (NAP1), a TBK1 adaptor protein. | Recent literature explicitly equates AZI2 with NAP1 and studies it in human cell systems in innate immunity, autophagy, mitosis, and TNF signaling. | (paul2023nakassociatedprotein1nap1 pages 1-2, yeo2024azi2mediatestbk1 pages 1-2, ujevic2024tbk1associatedadapterstank pages 1-2) |
| Primary molecular function | Scaffold/adaptor for TBK1 rather than an enzyme or transporter. | AZI2 binds TBK1 and promotes its activation by adaptor-driven assembly/oligomerization and TBK1 Ser172 autophosphorylation; it links TBK1 to different signaling platforms and cargo receptor complexes. | (paul2023nakassociatedprotein1nap1 pages 1-2, zhou2020tbk1acentral pages 1-2, zhou2020tbk1acentral pages 2-3) |
| TBK1-binding role | AZI2 directly engages the TBK1 adaptor-binding region through its own TBK1-binding domain (TBD). | Reviews and mechanistic studies describe a central TBD in NAP1/AZI2 that associates with the C-terminal adaptor-binding domain of TBK1; adaptor competition with TANK/SINTBAD helps specify pathway usage. | (glon2025nap1switchesfrom pages 1-5, zhou2020tbk1acentral pages 2-3) |
| Structural features / domains | Modular coiled-coil adaptor with homodimerization region, central TBD, intrinsically disordered regions, and a FIP200-binding region (FIR) used in selective autophagy. | NAP1/AZI2 is described as one of three homologous TBK1 adaptors; structural work resolved NAP1 FIR interaction with RB1CC1/FIP200 and places NAP1 in NDP52–TBK1–FIP200 assemblies. | (glon2025nap1switchesfrom pages 1-5, fu2021structuralandbiochemical pages 1-2) |
| Type I IFN pathway | AZI2 is a positive regulator of TBK1–IRF3/IRF7 signaling for type I interferon induction. | TBK1 is the central kinase downstream of RLR-MAVS, cGAS-STING, and TLR3/TRIF; AZI2/NAP1 is one of the key TBK1 adaptors that helps activate this axis. In some contexts, AZI2 also promotes DDX3X–IRF3 signaling and pro-inflammatory chemokine transcription. | (yeo2024azi2mediatestbk1 pages 1-2, zhou2020tbk1acentral pages 1-2, yeo2024azi2mediatestbk1 pages 2-4) |
| TNF signaling pathway | AZI2 helps recruit TBK1 to the TNF receptor signaling complex to restrain inflammatory cell death. | In 2024 work, AZI2 and TANK cooperatively sustained TBK1 activation in TNF signaling; AZI2 was recruited later via A20, enabling TBK1-dependent suppression of RIPK1-driven apoptosis/necroptosis and limiting excessive NF-κB pathway activation. | (ujevic2024tbk1associatedadapterstank pages 1-2, ujevic2024tbk1associatedadapterstank pages 2-3) |
| Selective autophagy pathway | AZI2 bridges cargo receptors to TBK1 and promotes selective autophagy execution. | NDP52 binds NAP1/SINTBAD, which recruit TBK1; NAP1 also engages FIP200/RB1CC1, integrating TBK1 and ULK/FIP200 modules at cargo. Structural work shows competitive interactions among NAP1, RB1CC1, and ATG8-family proteins. | (fu2021structuralandbiochemical pages 1-2, adriaenssens2024controlofmitophagy pages 2-3) |
| Mitophagy control | AZI2 acts as a context-dependent rheostat in mitophagy. | Under PINK1/Parkin mitophagy, NAP1/SINTBAD can inhibit OPTN-driven initiation by competing for TBK1, yet support NDP52-driven progression by recruiting TBK1 and stabilizing NDP52–FIP200 interactions. Artificial mitochondrial tethering of NAP1 was sufficient to induce mitophagy-like responses. | (adriaenssens2024controlofmitophagy pages 1-2, adriaenssens2024controlofmitophagy pages 2-3, adriaenssens2024controlofmitophagy pages 3-4) |
| Mitosis and cytokinesis | AZI2 is required for TBK1 activation during cell division and supports accurate mitosis/cytokinesis. | NAP1/AZI2 localizes with TBK1 at centrosomes; loss of NAP1 reduces mitotic p-TBK1 and causes slower growth, binucleation/multinucleation, spindle defects, lagging chromosomes, and cytokinetic abnormalities. | (paul2023nakassociatedprotein1nap1 pages 1-2, paul2023nakassociatedprotein1nap1 pages 2-5) |
| Cell-death control | AZI2 contributes to a cell-death checkpoint by supporting TBK1 anti-death signaling. | In TNF signaling, AZI2 enables TBK1-mediated inhibition of RIPK1 activation; in AML-related work, NAP1 also interacted with PTPN23 to facilitate endosomal sorting of TNFR1 and influence sensitivity to TNFα-induced cytotoxicity. | (ujevic2024tbk1associatedadapterstank pages 1-2, song2024ptpn23dependentescrtmachinery pages 1-2, ujevic2024tbk1associatedadapterstank pages 2-3) |
| Cancer-related implementation | AZI2-TBK1 signaling can be exploited to increase tumor immunogenicity and CD8 T-cell infiltration. | In breast cancer models, RB1CC1/FIP200 loss caused AZI2 puncta, TBK1 activation, DDX3X–IRF3 signaling, chemokine induction, and increased CD8+ T-cell infiltration; Lys05 was identified as a pharmacologic inducer of this pathway. | (yeo2024azi2mediatestbk1 pages 1-2, okamoto2020fip200suppressesimmune pages 1-3, yeo2024azi2mediatestbk1 pages 2-4) |
| Basal subcellular localization | Predominantly diffuse cytosolic under unstimulated conditions. | Mitophagy and condensate studies report NAP1/SINTBAD dispersed through the cytosol before pathway induction. | (adriaenssens2024controlofmitophagy pages 2-3) |
| Localization in mitosis | Centrosomes and associated spindle structures. | NAP1 is described as a centrosomal protein required for local TBK1 activation during mitosis; activated TBK1 signal extends across centrosome/spindle regions. | (paul2023nakassociatedprotein1nap1 pages 1-2, paul2023nakassociatedprotein pages 9-12) |
| Localization in mitophagy | Recruited to depolarized mitochondria and early autophagosome initiation sites. | Upon oligomycin/antimycin treatment, HA-NAP1 accumulated on damaged mitochondria and colocalized with WIPI2, indicating function at phagophore initiation sites. | (adriaenssens2024controlofmitophagy pages 2-3) |
| Localization in selective-autophagy blockade | Forms cytoplasmic AZI2 puncta with active TBK1, ubiquitin, and cargo receptors. | RB1CC1 depletion caused AZI2 puncta that colocalized with p-TBK1, SQSTM1/p62, TAX1BP1, NBR1, OPTN, and ubiquitin, supporting a role at unresolved cargo receptor complexes rather than generic bulk autophagy structures. | (yeo2024azi2mediatestbk1 pages 1-2, yeo2024azi2mediatestbk1 pages 2-4) |
| Localization in innate immune signaling | Present in cytoplasmic liquid-like condensates after danger signaling. | Endogenous NAP1, SINTBAD, TANK, and TBK1 accumulate in cytoplasmic condensates after viral infection or 5'ppp-dsRNA stimulation; NAP1 condensates concentrate TBK1 and later PP2A. | (glon2025nap1switchesfrom pages 1-5, glon2025nap1switchesfrom pages 5-9) |
| Regulation by condensate formation | AZI2 can first activate and then limit TBK1 signaling through condensate dynamics. | NAP1 initially enhances TBK1 activity; subsequent TBK1-dependent phosphorylation favors NAP1 condensate formation that concentrates TBK1 with PP2A phosphatase, promoting TBK1 dephosphorylation and dampening IFN output. | (glon2025nap1switchesfrom pages 1-5, glon2025nap1switchesfrom pages 5-9) |
| Regulation by competing adaptors / cargo receptors | AZI2 function is tuned by competition with OPTN, NDP52, TANK, and SINTBAD for TBK1 or pathway assembly. | In mitophagy, NAP1/SINTBAD compete with OPTN for TBK1 but support NDP52-driven progression; in innate signaling, the homologous adaptors compete for TBK1 binding and create pathway-specific assemblies. | (adriaenssens2024controlofmitophagy pages 1-2, adriaenssens2024controlofmitophagy pages 2-3, zhou2020tbk1acentral pages 2-3) |
| Regulation by FIP200/RB1CC1 | RB1CC1/FIP200 restrains AZI2-TBK1 signaling in some settings but also physically interfaces with NAP1 in selective autophagy. | Structural and cancer studies show NAP1 binds FIP200/RB1CC1; loss of RB1CC1 causes AZI2 accumulation in puncta and TBK1 hyperactivation, indicating a regulatory brake on AZI2-TBK1 signaling. | (fu2021structuralandbiochemical pages 1-2, okamoto2020fip200suppressesimmune pages 1-3, yeo2024azi2mediatestbk1 pages 2-4) |
| Regulation by proteostasis | AZI2 abundance is controlled by TBK1-dependent phosphorylation and ubiquitin-proteasome degradation in mitosis. | Phosphoproteomic and cell-cycle studies identified NAP1 Ser318 as a TBK1-regulated site associated with mitotic degradation, supporting negative feedback on NAP1 levels during cell division. | (paul2023nakassociatedprotein1nap1 pages 1-2, paul2023nakassociatedprotein pages 9-12) |
Table: This table compiles the main experimentally supported functions of human AZI2/NAP1, emphasizing its role as a TBK1 adaptor across innate immune signaling, selective autophagy, TNF signaling, and mitosis. It also summarizes context-specific localization, structural features, and regulatory mechanisms with direct citations to the available evidence.
This report synthesizes recent, high-quality evidence on AZI2/NAP1, organizing its functional annotation in human with quantitative and mechanistic depth. For details, see embedded artifact and referenced literature.
References
(paul2023nakassociatedprotein1nap1 pages 1-2): Swagatika Paul, Shireen A. Sarraf, Ki Hong Nam, Leila Zavar, Nicole DeFoor, Sahitya Ranjan Biswas, Lauren E. Fritsch, Tomer M. Yaron, Jared L. Johnson, Emily M. Huntsman, Lewis C. Cantley, Alban Ordureau, and Alicia M. Pickrell. Nak-associated protein 1/nap1 activates tbk1 to ensure accurate mitosis and cytokinesis. The Journal of Cell Biology, Dec 2023. URL: https://doi.org/10.1083/jcb.202303082, doi:10.1083/jcb.202303082. This article has 9 citations.
(yeo2024azi2mediatestbk1 pages 1-2): Syn Kok Yeo, Michael Haas, Kanakaraju Manupati, Mingang Hao, Fuchun Yang, Song Chen, and Jun-Lin Guan. Azi2 mediates tbk1 activation at unresolved selective autophagy cargo receptor complexes with implications for cd8 t-cell infiltration in breast cancer. Autophagy, 20:525-540, Sep 2024. URL: https://doi.org/10.1080/15548627.2023.2259775, doi:10.1080/15548627.2023.2259775. This article has 9 citations and is from a domain leading peer-reviewed journal.
(ujevic2024tbk1associatedadapterstank pages 1-2): Andrea Ujevic, Daniela Knizkova, Alzbeta Synackova, Michaela Pribikova, Tijana Trivic, Anna Dalinskaya, Ales Drobek, Veronika Niederlova, Darina Paprckova, Roldan De Guia, Petr Kasparek, Jan Prochazka, Juraj Labaj, Olha Fedosieieva, Bernhard Florian Roeck, Ondrej Mihola, Zdenek Trachtulec, Radislav Sedlacek, Ondrej Stepanek, and Peter Draber. Tbk1-associated adapters tank and azi2 protect mice against tnf-induced cell death and severe autoinflammatory diseases. Nature Communications, Nov 2024. URL: https://doi.org/10.1038/s41467-024-54399-4, doi:10.1038/s41467-024-54399-4. This article has 7 citations and is from a highest quality peer-reviewed journal.
(fu2021structuralandbiochemical pages 1-2): Tao Fu, Mingfang Zhang, Zixuan Zhou, Ping Wu, Chao Peng, Yingli Wang, Xinyu Gong, Ying Li, Yaru Wang, Xiaolong Xu, Miao Li, Liqiang Shen, and Lifeng Pan. Structural and biochemical advances on the recruitment of the autophagy-initiating ulk and tbk1 complexes by autophagy receptor ndp52. Aug 2021. URL: https://doi.org/10.1126/sciadv.abi6582, doi:10.1126/sciadv.abi6582. This article has 53 citations and is from a highest quality peer-reviewed journal.
(glon2025nap1switchesfrom pages 1-5): Damien Glon, Quentin Riller, Frédéric Rivière, Benjamin Léonardon, Ariane Guillemot, Laïla Sago, Olivier Pellé, Duong Ho-Nhat, Karine Brochard, Brigitte Bader-Meunier, Marie-Louise Frémond, Alice Lepelley, Yanick Crow, Maud Tusseau, Alexandre Belot, Cécile Lagaudrière-Gesbert, Frédéric Rieux-Laucat, and Yves Gaudin. Nap1 switches from an activator to a limiter of interferon induction by trapping tbk1 in condensates. bioRxiv, May 2025. URL: https://doi.org/10.1101/2025.05.21.655319, doi:10.1101/2025.05.21.655319. This article has 0 citations.
(zhou2020tbk1acentral pages 2-3): Ruyuan Zhou, Qian Zhang, and Pinglong Xu. Tbk1, a central kinase in innate immune sensing of nucleic acids and beyond. Acta biochimica et biophysica Sinica, 52:757-767, May 2020. URL: https://doi.org/10.1093/abbs/gmaa051, doi:10.1093/abbs/gmaa051. This article has 105 citations and is from a peer-reviewed journal.
(yeo2024azi2mediatestbk1 pages 2-4): Syn Kok Yeo, Michael Haas, Kanakaraju Manupati, Mingang Hao, Fuchun Yang, Song Chen, and Jun-Lin Guan. Azi2 mediates tbk1 activation at unresolved selective autophagy cargo receptor complexes with implications for cd8 t-cell infiltration in breast cancer. Autophagy, 20:525-540, Sep 2024. URL: https://doi.org/10.1080/15548627.2023.2259775, doi:10.1080/15548627.2023.2259775. This article has 9 citations and is from a domain leading peer-reviewed journal.
(adriaenssens2024controlofmitophagy pages 1-2): Elias Adriaenssens, Thanh Ngọc Nguyen, Justyna Sawa-Makarska, Grace Khuu, Martina Schuschnig, Stephen Shoebridge, Emily Maria Watts, Kitti Dora Csalyi, Benjamin Scott Padman, Michael Lazarou, and Sascha Martens. Control of mitophagy initiation and progression by the tbk1 adaptors nap1 and sintbad. Feb 2024. URL: https://doi.org/10.5281/zenodo.10637352, doi:10.5281/zenodo.10637352. This article has 45 citations.
(adriaenssens2024controlofmitophagy pages 2-3): Elias Adriaenssens, Thanh Ngọc Nguyen, Justyna Sawa-Makarska, Grace Khuu, Martina Schuschnig, Stephen Shoebridge, Emily Maria Watts, Kitti Dora Csalyi, Benjamin Scott Padman, Michael Lazarou, and Sascha Martens. Control of mitophagy initiation and progression by the tbk1 adaptors nap1 and sintbad. Feb 2024. URL: https://doi.org/10.5281/zenodo.10637352, doi:10.5281/zenodo.10637352. This article has 45 citations.
(ujevic2024tbk1associatedadapterstank pages 2-3): Andrea Ujevic, Daniela Knizkova, Alzbeta Synackova, Michaela Pribikova, Tijana Trivic, Anna Dalinskaya, Ales Drobek, Veronika Niederlova, Darina Paprckova, Roldan De Guia, Petr Kasparek, Jan Prochazka, Juraj Labaj, Olha Fedosieieva, Bernhard Florian Roeck, Ondrej Mihola, Zdenek Trachtulec, Radislav Sedlacek, Ondrej Stepanek, and Peter Draber. Tbk1-associated adapters tank and azi2 protect mice against tnf-induced cell death and severe autoinflammatory diseases. Nature Communications, Nov 2024. URL: https://doi.org/10.1038/s41467-024-54399-4, doi:10.1038/s41467-024-54399-4. This article has 7 citations and is from a highest quality peer-reviewed journal.
(glon2025nap1switchesfrom pages 5-9): Damien Glon, Quentin Riller, Frédéric Rivière, Benjamin Léonardon, Ariane Guillemot, Laïla Sago, Olivier Pellé, Duong Ho-Nhat, Karine Brochard, Brigitte Bader-Meunier, Marie-Louise Frémond, Alice Lepelley, Yanick Crow, Maud Tusseau, Alexandre Belot, Cécile Lagaudrière-Gesbert, Frédéric Rieux-Laucat, and Yves Gaudin. Nap1 switches from an activator to a limiter of interferon induction by trapping tbk1 in condensates. bioRxiv, May 2025. URL: https://doi.org/10.1101/2025.05.21.655319, doi:10.1101/2025.05.21.655319. This article has 0 citations.
(adriaenssens2024controlofmitophagy pages 3-4): Elias Adriaenssens, Thanh Ngọc Nguyen, Justyna Sawa-Makarska, Grace Khuu, Martina Schuschnig, Stephen Shoebridge, Emily Maria Watts, Kitti Dora Csalyi, Benjamin Scott Padman, Michael Lazarou, and Sascha Martens. Control of mitophagy initiation and progression by the tbk1 adaptors nap1 and sintbad. Feb 2024. URL: https://doi.org/10.5281/zenodo.10637352, doi:10.5281/zenodo.10637352. This article has 45 citations.
(paul2023nakassociatedprotein pages 9-12): Swagatika Paul, Shireen A. Sarraf, Ki Hong Nam, Leila Zavar, Sahitya Ranjan Biswas, Lauren E. Fritsch, Nicole DeFoor, Tomer M. Yaron, Jared L. Johnson, Emily M. Huntsman, Lewis C. Cantley, Alban Ordureau, and Alicia M. Pickrell. Nak associated protein 1/nap1 is required for mitosis and cytokinesis by activating tbk1. bioRxiv, Jan 2023. URL: https://doi.org/10.1101/2022.03.09.483647, doi:10.1101/2022.03.09.483647. This article has 0 citations.
(zhou2020tbk1acentral pages 1-2): Ruyuan Zhou, Qian Zhang, and Pinglong Xu. Tbk1, a central kinase in innate immune sensing of nucleic acids and beyond. Acta biochimica et biophysica Sinica, 52:757-767, May 2020. URL: https://doi.org/10.1093/abbs/gmaa051, doi:10.1093/abbs/gmaa051. This article has 105 citations and is from a peer-reviewed journal.
(paul2023nakassociatedprotein1nap1 pages 2-5): Swagatika Paul, Shireen A. Sarraf, Ki Hong Nam, Leila Zavar, Nicole DeFoor, Sahitya Ranjan Biswas, Lauren E. Fritsch, Tomer M. Yaron, Jared L. Johnson, Emily M. Huntsman, Lewis C. Cantley, Alban Ordureau, and Alicia M. Pickrell. Nak-associated protein 1/nap1 activates tbk1 to ensure accurate mitosis and cytokinesis. The Journal of Cell Biology, Dec 2023. URL: https://doi.org/10.1083/jcb.202303082, doi:10.1083/jcb.202303082. This article has 9 citations.
(song2024ptpn23dependentescrtmachinery pages 1-2): Dongyan Song, Yuxin Cen, Zhe Qian, Xiaoli S. Wu, Keith Rivera, Tse-Luen Wee, Osama E. Demerdash, Kenneth Chang, Darryl Pappin, Christopher R. Vakoc, and Nicholas K. Tonks. Ptpn23-dependent escrt machinery functions as a cell death checkpoint. Nature Communications, Nov 2024. URL: https://doi.org/10.1038/s41467-024-54749-2, doi:10.1038/s41467-024-54749-2. This article has 6 citations and is from a highest quality peer-reviewed journal.
(okamoto2020fip200suppressesimmune pages 1-3): Takako Okamoto, Syn Kok Yeo, Mingang Hao, Mary Rose Copley, Michael A. Haas, Song Chen, and Jun-Lin Guan. Fip200 suppresses immune checkpoint therapy responses in breast cancers by limiting azi2/tbk1/irf signaling independent of its canonical autophagy function. Cancer Research, 80:3580-3592, Sep 2020. URL: https://doi.org/10.1158/0008-5472.can-20-0519, doi:10.1158/0008-5472.can-20-0519. This article has 35 citations and is from a highest quality peer-reviewed journal.