| Functional claim | Mechanism/partners/pathway | Cell/tissue/model | Key experimental evidence type | Quantitative/statistical detail (if available) | Primary source with publication date and URL/DOI | Notes (strength/limitations/species ambiguity) |
|---|---|---|---|---|---|---|
| Human AKIRIN2 (UniProt Q53H80) is the conserved nuclear Akirin-2 protein in the akirin family and functions primarily as a transcriptional cofactor rather than a DNA-binding enzyme or receptor | Lacks obvious DNA/RNA-binding motifs; contains N-terminal nuclear localization signal and conserved helical regions; acts through protein-protein interactions to couple NF-κB-responsive factors to chromatin remodeling machinery | Mammals/human ortholog context summarized from mouse and immune-cell studies | Review synthesis of KO/knockdown, promoter studies, interaction studies | Mouse Akirin2 knockout causes embryonic lethality by E9.5 | Tartey & Takeuchi, *Crit Rev Immunol* (Jan 2016), https://doi.org/10.1615/CritRevImmunol.2017019629 (pqac-00000000, pqac-00000002) | Strong mechanistic review grounded in primary studies; some evidence is from mouse rather than direct human experiments |
| AKIRIN2 is required for selective, not global, NF-κB-dependent transcription | Bridges NF-κB pathway output to SWI/SNF (BAF/Brg1) chromatin remodeling, enabling induction of specific inflammatory genes after TLR/IL-1/TNF signaling | Mouse embryonic fibroblasts, macrophages, B cells | Genetic KO/conditional deletion, promoter recruitment, transcriptional analysis | Selective defect in a subset of inducible genes rather than pan-NF-κB failure; promoters with lower CpG-island density are enriched among Akirin2-dependent genes | Tartey & Takeuchi, *Crit Rev Immunol* (Jan 2016), https://doi.org/10.1615/CritRevImmunol.2017019629 (pqac-00000000, pqac-00000003, pqac-00000005, pqac-00000007) | High-value functional annotation for human AKIRIN2 by orthology/conservation; quantitative fold changes were not provided in the retrieved excerpts |
| AKIRIN2 cooperates with IκBζ (NFKBIZ) and SWI/SNF to activate inflammatory promoters | IκBζ binds the C-terminal region of Akirin2; IκBζ-Akirin2-SWI/SNF complex interacts with NF-κB p50 and supports recruitment to Il6 and Il12b promoters after LPS/IL-1β/TLR stimulation | Macrophages | ChIP/recruitment studies, interaction mapping, stimulus-response transcription assays | No numeric recruitment values in retrieved excerpt; mechanistic link reported for Il6 and Il12b promoters | Tartey & Takeuchi, *Crit Rev Immunol* (Jan 2016), https://doi.org/10.1615/CritRevImmunol.2017019629 (pqac-00000003, pqac-00000007) | Strong pathway-specific mechanism; evidence is largely from mouse/immune-cell literature but directly relevant to conserved human AKIRIN2 function |
| AKIRIN2 supports B-cell activation and survival programs | Required for Brg1 recruitment to Myc and Ccnd2 promoters after CD40 stimulation; supports expression of Myc, Ccnd1, Ccnd2, Bcl2 and Bcl-xL | B cells | Conditional deletion, promoter recruitment, transcriptional profiling | Loss of Akirin2 severely impairs T-cell-dependent and T-cell-independent antibody responses; decreased splenic follicular and marginal zone B cells | Tartey & Takeuchi, *Crit Rev Immunol* (Jan 2016), https://doi.org/10.1615/CritRevImmunol.2017019629 (pqac-00000003, pqac-00000005) | Useful for immune-function annotation; retrieved evidence did not include exact cell-count statistics |
| Akirin proteins act as molecular selectors that confer NF-κB target-gene specificity through chromatin remodeling, a mechanism conserved to mammals | In Drosophila, Akirin binds Relish and BAP60 (SWI/SNF/BAP), forming a bridge to remodel chromatin at selected promoters; authors note conservation with mouse Akirin-2 binding BAF60 homologs | Drosophila innate immune system with mammalian conservation inference | Genome-wide expression analysis, proteomics, interaction studies, infection phenotyping | Akirin required for 9 of 41 Relish-dependent immune-related genes; Akirin alone required for 31 genes independently of Relish; loss caused derepression/overexpression of 205 genes | Bonnay et al., *EMBO Journal* (Sep 2014), https://doi.org/10.15252/embj.201488456 (pqac-00000004, pqac-00000006) | Not human-specific, but highly informative for conserved Akirin biology; should be used as evolutionary/mechanistic support, not as sole human evidence |
| AKIRIN2 contains a newly observed ligandable cysteine near a proteasome-related motif, suggesting potential chemical tractability | Chemoproteomics identified AKIRIN2 Cys3 as a uniquely liganded cysteine; text notes proximity to the 20S proteasome binding motif | Human proteome-scale chemoproteomics dataset | Chemoproteomics (sCIP-TMT), Figure 5C | 29 uniquely liganded cysteines identified in study; 760/789 liganded cysteines had prior CysDB support, placing AKIRIN2 Cys3 among newly observed sites | Burton & Backus, *Communications Chemistry* (Apr 2024), https://doi.org/10.1038/s42004-024-01162-x (pqac-00000009, pqac-00000015, pqac-00000016) | Important recent finding, but it does not establish AKIRIN2 biochemical function or therapeutic efficacy; ligandability ≠ validated drug target |
| AKIRIN2 can behave as a conditional NRF2-responsive gene in some pharmacologic activation contexts | AKIRIN2 was induced mainly in drug-mediated NRF2 activation datasets, but not consistently in TCGA LUAD or NSCLC cell-line analyses; thus not part of the most universal core NRF2 output | Multiple transcriptomic datasets including pharmacologic CDDO-2P-Im treatment and genetic KEAP1-knockout models | RNA-seq / transcriptomic meta-analysis | Seven transcriptomic databases used to derive a 15-gene candidate NRF2 core set; AKIRIN2 highlighted as conditionally induced rather than universally upregulated | Luo et al., *Antioxidants & Redox Signaling* (Dec 2024), https://doi.org/10.1089/ars.2023.0409 (pqac-00000008) | Recent and useful for regulatory context; this is association/expression evidence, not proof of direct NRF2 binding to AKIRIN2 regulatory DNA |
| 2024 IκBζ review reinforces the SWI/SNF-dependent selective NF-κB transcription mechanism relevant to AKIRIN2, but the retrieved excerpt does not explicitly mention Akirin2 | IκBζ promotes BRG1/SWI/SNF recruitment and chromatin remodeling at secondary NF-κB target genes such as IL6/LCN2, with p50 preference and promoter motif selectivity | Inflammatory gene regulation context | Review synthesis of ChIP/ATAC/structural studies | BRG1 recruitment to Lcn2 promoter is abolished without IκBζ; no AKIRIN2-specific quantitative measure in excerpt | Yamazaki, *Cells* (Aug 2024), https://doi.org/10.3390/cells13171467 (pqac-00000010) | Useful contextual support for the IκBζ arm of the pathway; limitation: excerpt did not directly mention AKIRIN2, so it supports pathway context more than direct annotation |
| FBI1/Akirin2 has tumor-related functions in liver-cancer models, but this evidence is not specific to human AKIRIN2 and should be interpreted cautiously | Reported as a 14-3-3β-binding protein that sustains ERK1/2 activation by suppressing MKP-1; silencing FBI1/Akirin2 increases Lu/BCAM expression, consistent with Lu/BCAM as a possible downstream target | Rat hepatoma / rat liver cancer cells | Review citing functional silencing/overexpression studies | No exact effect sizes in retrieved excerpt; claim is qualitative (increased Lu/BCAM on Akirin2 silencing; reduced colony formation/migration/invasion with Lu/BCAM overexpression) | Jin et al., *Int J Mol Sci* (Jul 2024), https://doi.org/10.3390/ijms25137268 (pqac-00000011, pqac-00000012) | Important caveat: these findings concern rat cells/ortholog context and FBI1 alias usage; not sufficient alone for direct human AKIRIN2 functional annotation |
| AKIRIN2 has been implicated in cancer-associated phenotypes and nuclear accumulation in resistance states | Conserved nuclear NF-κB cofactor; increased nuclear AKIRIN2 reported in imatinib-resistant CML cells; related literature links AKIRIN2/FBI1 to tumorigenicity/metastasis and glioblastoma chemosensitivity | Human CML cells; broader tumor-cell literature summarized | Expression analysis, nuclear protein localization, literature synthesis | Increased nuclear accumulation in resistant cells reported, but no exact fold-change in retrieved excerpt | Karabay et al., *Hematology* (Jun 2018), https://doi.org/10.1080/10245332.2018.1488795 (pqac-00000001, pqac-00000014) | Human disease relevance is suggestive, but this is downstream/association-heavy and not the strongest source for core molecular function |


*Table: This table summarizes experimentally supported and recent literature-based functional annotation evidence for human AKIRIN2 (UniProt Q53H80), including core mechanism, pathway context, localization/function in immune transcription, and recent 2024 omics/chemoproteomics findings. It also flags species and evidence-strength limitations where the literature is indirect or ortholog-based.*