- Length
- 584 aa
- Mass
- 65.0 kDa
- Annotated
- 2026-04-28
68 papers in source corpus
10 papers cited in narrative
10 extracted findings
Mechanistic narrative
Synthesis pass · prose summary of the discoveries below
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Mechanism profile
Synthesis pass · controlled-vocabulary classification · explore literature graph →
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Evidence
Reading pass · 10 per-paper findings extracted from the source corpus
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2001 | BTN3A3 is part of a cluster of seven BTN genes in the extended MHC region at 6p22.1, organized in two subfamilies (BTN2 and BTN3) in alternating pairs. BTN3A3 encodes a predicted type I transmembrane protein with IgV/IgC ectodomains and a transmembrane domain but lacks the B30.2 domain found in BTN2 subfamily members. Surface expression of BTN3A3-GFP fusion proteins was demonstrated in mammalian cell transfectants by immunofluorescence. | Genomic sequencing, structural analysis, immunofluorescence of GFP fusion proteins in transfected mammalian cells | Genomics | Medium | 11170752 |
| 2018 | BTN3A2 regulates the subcellular localization of BTN3A1, including its association with the endoplasmic reticulum (ER), and is specifically required for optimal BTN3A1-mediated Vγ9Vδ2 T cell activation. Domain-shuffling and knockdown experiments demonstrated that BTN3A subfamily members function through heteromeric interactions; BTN3A3 is part of this subfamily context but BTN3A2 was the functionally essential partner for BTN3A1 in this study. | Domain-shuffling, siRNA knockdown, subcellular fractionation, immunofluorescence, Vγ9Vδ2 T cell activation assays | Proceedings of the National Academy of Sciences of the United States of America | Medium | 29339503 |
| 2019 | BTN3A3 was identified as the receptor for LSECtin on breast cancer cells, mediating a juxtacrine stemness-promoting signal from tumor-associated macrophages. BTN3A3-Fc fusion protein and anti-BTN3A3 monoclonal antibody disrupted the LSECtin-BTN3A3 interaction and had therapeutic effects in xenograft models. Macrophage-specific ablation of LSECtin or silencing of BTN3A3 in breast cancer cells decreased cancer stem cell frequency and tumor growth. | Co-immunoprecipitation, BTN3A3-Fc fusion protein binding assays, anti-BTN3A3 mAb blocking, siRNA knockdown, xenograft tumor models, flow cytometry for CSC frequency | Cell research | High | 30858559 |
| 2023 | Human BTN3A3 is a potent inhibitor of avian influenza A viruses (IAVs) but not human IAVs. BTN3A3 is expressed in human airways and its antiviral activity evolved in primates. BTN3A3 restriction acts primarily at early stages of the viral life cycle by inhibiting avian IAV RNA replication. Residue 313 in the viral nucleoprotein (NP) is the genetic determinant of BTN3A3 sensitivity (313F or 313L in avian viruses) or evasion (313Y or 313V in human viruses). Avian IAV serotypes H7 and H9 that have spilled over into humans evade BTN3A3 via substitutions (N, H, or Q) at NP residue 52, which is adjacent to residue 313 in the NP structure. | RNA replication assays, NP mutagenesis, viral growth assays, overexpression and knockdown of BTN3A3 in human airway cells, structural analysis of NP, phylogenetic analysis | Nature | High | 37380775 |
| 2022 | BTN3A3 inhibits proliferation, migration, and invasion of ovarian cancer cells. Immunoprecipitation followed by mass spectrometry identified FGF2 as a BTN3A3-binding partner. BTN3A3 overexpression reduced FGF2 protein levels, leading to decreased ERK1/2 phosphorylation. The tumor-suppressive effect of BTN3A3 knockdown could be rescued by ERK1/2 inhibitor SCH772984, placing BTN3A3 upstream of the FGF2/ERK1/2 axis. | Co-immunoprecipitation, mass spectrometry, siRNA knockdown, overexpression, ERK1/2 inhibitor rescue experiments, proliferation/migration/invasion assays | Frontiers in oncology | Medium | 36059652 |
| 2023 | Loss-of-function variants in BTN3A3 are associated with generalized pustular psoriasis (GPP). Functional analysis showed that BTN3A3 regulates cell proliferation and inflammatory balance; loss of BTN3A3 function activated NF-κB and promoted inflammatory cytokine production by inhibiting IL-36Ra expression, thereby disturbing the IL-1/IL-36 inflammatory axis and enhancing the TNF-α-mediated pathway. | Whole-exome sequencing, gene burden testing, functional loss-of-function assays, NF-κB reporter assays, cytokine measurements, IL-36Ra expression analysis | The Journal of investigative dermatology | Medium | 36804966 |
| 2023 | BTN3A3 inhibits proliferation, migration, and invasion of clear cell renal cell carcinoma (ccRCC) cells. Immunoprecipitation followed by mass spectrometry identified RPS3A as a direct BTN3A3 binding partner. Simultaneous overexpression of RPS3A reversed the pro-tumorigenic effects of BTN3A3 knockdown. BTN3A3 and RPS3A together increase cellular oxygen consumption rate (OCR) and reactive oxygen species (ROS) levels, and BTN3A3 negatively regulates the MAPK signaling pathway, suggesting the BTN3A3/RPS3A complex suppresses ccRCC via modulation of ROS and MAPK signaling. | Co-immunoprecipitation, mass spectrometry, siRNA knockdown, overexpression rescue experiments, OCR measurement, ROS measurement, H2O2 rescue, RNA-Seq, immunoblotting | Cellular signalling | Medium | 37806541 |
| 2025 | Mevalonate diphosphate (MPP) functions as a natural endogenous ligand of BTN3A3. A single point mutation in BTN3A3 enabled it to detect HMBPP (normally a BTN3A1 ligand), suggesting BTN3A3 has its own distinct ligand-binding capacity. 31P NMR confirmed MPP binding to both BTN3A1 and BTN3A3 internal (intracellular) domains. BTN2A1 can form a complex with BTN3A3-MPP. Transfection of CHO-K1 cells with BTN2A1 + BTN3A3 (without BTN3A1) enabled γ9δ2 T cell activation in response to 6-fluoromevalonate (6-FM), and BTN3A1-knockout K562 cells could also detect 6-FM, establishing a BTN3A1-independent BTN3A3 pathway. | 31P NMR ligand binding, molecular docking, point mutagenesis, γ9δ2 T cell activation assays, LC-MS metabolite measurement, CHO-K1 transfection/coculture, BTN3A1 knockout K562 cells | Cellular and molecular life sciences : CMLS | High | 41236636 |
| 2023 | NP residue 313 (F/L in avian viruses vs. Y/V in human-adapted viruses) and residue 52 (N/H/Q in H7/H9 serotypes that spilled into humans) are the key determinants of BTN3A3 sensitivity or evasion in influenza A viruses, consistent with the primary Nature report. | Review/commentary integrating findings from the primary BTN3A3 restriction paper | MedComm | Low | 38045831 |
| 2025 | BTN3A3 overexpression in cells reduced polymerase activity of avian H5N1 influenza in human cells (minigenome assay), confirming BTN3A3 as a host restriction factor for avian IAV polymerase. Novel mammalian-adaptive NP mutations were identified using BTN3A3-overexpressing cells as a screening tool. | Minigenome assay in human cells overexpressing BTN3A3, phylogenetic analysis, polymerase activity measurement | bioRxivpreprint | Medium | bio_10.1101_2025.10.27.684835 |
Source papers
Stage 0 corpus · 68 papers · ranked by NIH iCite citations
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2002 | Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. | Proceedings of the National Academy of Sciences of the United States of America | 1479 | 12477932 |
| 2015 | The BioPlex Network: A Systematic Exploration of the Human Interactome. | Cell | 1118 | 26186194 |
| 2017 | Architecture of the human interactome defines protein communities and disease networks. | Nature | 1085 | 28514442 |
| 2021 | Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. | Cell | 705 | 33961781 |
| 2011 | Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. | Briefings in bioinformatics | 656 | 21873635 |
| 1994 | Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. | Gene | 492 | 8125298 |
| 2012 | Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset. | Blood | 482 | 22767497 |
| 2004 | The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Genome research | 438 | 15489334 |
| 2005 | Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. | Genome research | 409 | 16344560 |
| 2021 | A proximity-dependent biotinylation map of a human cell. | Nature | 339 | 34079125 |
| 2003 | The DNA sequence and analysis of human chromosome 6. | Nature | 242 | 14574404 |
| 2011 | Toward an understanding of the protein interaction network of the human liver. | Molecular systems biology | 207 | 21988832 |
| 2018 | Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules governing γδ T cell biology. | Proceedings of the National Academy of Sciences of the United States of America | 145 | 29339503 |
| 2001 | The cluster of BTN genes in the extended major histocompatibility complex. | Genomics | 116 | 11170752 |
| 2010 | BTN1A1, the mammary gland butyrophilin, and BTN2A2 are both inhibitors of T cell activation. | Journal of immunology (Baltimore, Md. : 1950) | 107 | 20208008 |
| 1990 | Sequencing and expression of complementary DNA for the general transcription factor BTF3. | Nature | 106 | 2320128 |
| 2017 | The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion. | Oncogene | 96 | 28692057 |
| 2004 | Signal peptide prediction based on analysis of experimentally verified cleavage sites. | Protein science : a publication of the Protein Society | 92 | 15340161 |
| 1999 | Structure and evolution of the extended B7 family. | Immunology today | 88 | 10354554 |
| 1995 | An insertional mutation in the BTF3 transcription factor gene leads to an early postimplantation lethality in mice. | Transgenic research | 88 | 7655515 |
| 1997 | A 1.1-Mb transcript map of the hereditary hemochromatosis locus. | Genome research | 79 | 9149941 |
| 2014 | Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia. | Bipolar disorders | 77 | 25243493 |
| 2023 | BTN3A3 evasion promotes the zoonotic potential of influenza A viruses. | Nature | 74 | 37380775 |
| 2019 | LSECtin on tumor-associated macrophages enhances breast cancer stemness via interaction with its receptor BTN3A3. | Cell research | 59 | 30858559 |
| 2007 | Basic transcription factor 3 (BTF3) regulates transcription of tumor-associated genes in pancreatic cancer cells. | Cancer biology & therapy | 51 | 17312387 |
| 2013 | Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue. | PloS one | 44 | 24386364 |
| 1992 | The EGD1 product, a yeast homolog of human BTF3, may be involved in GAL4 DNA binding. | Molecular and cellular biology | 43 | 1448098 |
| 2005 | Translation initiation factor (iso) 4E interacts with BTF3, the beta subunit of the nascent polypeptide-associated complex. | Gene | 41 | 15716105 |
| 1994 | Yeast BTF3 protein is encoded by duplicated genes and inhibits the expression of some genes in vivo. | Nucleic acids research | 41 | 8052529 |
| 2019 | BTF3 sustains cancer stem-like phenotype of prostate cancer via stabilization of BMI1. | Journal of experimental & clinical cancer research : CR | 33 | 31138311 |
| 2023 | Matrine Targets BTF3 to Inhibit the Growth of Canine Mammary Tumor Cells. | International journal of molecular sciences | 32 | 38203709 |
| 1992 | Genomic structure of the putative BTF3 transcription factor. | Gene | 31 | 1386332 |
| 2018 | Inhibition of BTF3 sensitizes luminal breast cancer cells to PI3Kα inhibition through the transcriptional regulation of ERα. | Cancer letters | 26 | 30315845 |
| 2013 | Clinicopathological significance of BTF3 expression in colorectal cancer. | Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | 23 | 23532689 |
| 2021 | BTF3 confers oncogenic activity in prostate cancer through transcriptional upregulation of Replication Factor C. | Cell death & disease | 21 | 33414468 |
| 2021 | BTF3-mediated regulation of BMI1 promotes colorectal cancer through influencing epithelial-mesenchymal transition and stem cell-like traits. | International journal of biological macromolecules | 21 | 34293363 |
| 2016 | Kahweol induces apoptosis by suppressing BTF3 expression through the ERK signaling pathway in non-small cell lung cancer cells. | International journal of oncology | 21 | 27748804 |
| 2010 | Defining the membrane proteome of NK cells. | Journal of mass spectrometry : JMS | 21 | 19946888 |
| 2021 | MiR-27a-5p regulates acrylamide-induced mitochondrial dysfunction and intrinsic apoptosis via targeting Btf3 in rats. | Food chemistry | 20 | 34416489 |
| 2020 | Quantitative Proteomics Links the LRRC59 Interactome to mRNA Translation on the ER Membrane. | Molecular & cellular proteomics : MCP | 20 | 32788342 |
| 2023 | BTF3 promotes proliferation and glycolysis in hepatocellular carcinoma by regulating GLUT1. | Cancer biology & therapy | 16 | 37382415 |
| 1999 | BTF3 is a potential new substrate of protein kinase CK2. | Molecular and cellular biochemistry | 16 | 10094400 |
| 2023 | A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2-Bispecific Antibody for Combination Cancer Therapy. | Clinical cancer research : an official journal of the American Association for Cancer Research | 14 | 36976175 |
| 2022 | BTN3A3 inhibits the proliferation, migration and invasion of ovarian cancer cells by regulating ERK1/2 phosphorylation. | Frontiers in oncology | 13 | 36059652 |
| 2022 | LncRNA-ZNF252P-AS1/miR-15b-5p promotes the proliferation of keloid fibroblast by regulating the BTF3-STAT3 signaling pathway. | Journal of dermatological science | 11 | 36641250 |
| 2020 | miR‑802 inhibits the epithelial‑mesenchymal transition, migration and invasion of cervical cancer by regulating BTF3. | Molecular medicine reports | 11 | 32582971 |
| 2019 | FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes to the ER Membrane. | Structure (London, England : 1993) | 11 | 31056421 |
| 2023 | Identification of the BTN3A3 Gene as a Molecule Implicated in Generalized Pustular Psoriasis in a Chinese Population. | The Journal of investigative dermatology | 10 | 36804966 |
| 2019 | Upregulation of BTF3 affects the proliferation, apoptosis, and cell cycle regulation in hypopharyngeal squamous cell carcinoma. | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | 10 | 31404775 |
| 2020 | BTF3 promotes stemness and inhibits TypeⅠInterferon signaling pathway in triple-negative breast cancer. | Biochemical and biophysical research communications | 9 | 33383560 |
| 2019 | BTF3 Silencing Inhibits the Proliferation of Osteosarcoma Cells. | Journal of Cancer | 9 | 31205542 |
| 2021 | Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer. | Frontiers in cell and developmental biology | 8 | 33644029 |
| 1997 | The visual assignment of genes by fiber-fish: BTF3 protein homologue gene (BTF3) and a novel pseudogene of human RNA helicase A (DDX9P) on 13q22. | Genomics | 8 | 9325059 |
| 2024 | ARID5B-mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3/STAT3 complex in β2GPI/anti-β2GPI-treated monocytes. | Clinical and translational medicine | 7 | 38224186 |
| 2024 | The comprehensive SARS-CoV-2 'hijackome' knowledge base. | Cell discovery | 7 | 39653747 |
| 2012 | Human beta casein fragment (54-59) modulates M. bovis BCG survival and basic transcription factor 3 (BTF3) expression in THP-1 cell line. | PloS one | 7 | 23029305 |
| 2023 | BTN3A3 inhibits clear cell renal cell carcinoma progression by regulating the ROS/MAPK pathway via interacting with RPS3A. | Cellular signalling | 6 | 37806541 |
| 2017 | Transgenic tobacco plants constitutively expressing peanut BTF3 exhibit increased growth and tolerance to abiotic stresses. | Plant biology (Stuttgart, Germany) | 6 | 27981726 |
| 1996 | BTF3 is evolutionarily conserved in fission yeast. | Biochimica et biophysica acta | 5 | 8809106 |
| 2024 | METTL3-driven m6A modification of lncRNA FAM230B suppresses ferroptosis by modulating miR-27a-5p/BTF3 axis in gastric cancer. | Biochimica et biophysica acta. General subjects | 4 | 39278369 |
| 2024 | BTF3 affects hepatocellular carcinoma progression by transcriptionally upregulating PDCD2L and inactivating p53 signaling. | Molecular medicine (Cambridge, Mass.) | 2 | 39707202 |
| 2025 | LINC00622 transcriptionally promotes RRAGD to repress mTORC1-modulated autophagic cell death by associating with BTF3 in cutaneous melanoma. | Cell death & disease | 1 | 40651979 |
| 2025 | γ9δ2 T cells detect mevalonate diphosphate via BTN3A3. | Cellular and molecular life sciences : CMLS | 1 | 41236636 |
| 2024 | Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2. | EBioMedicine | 1 | 39142074 |
| 2023 | The determinants associated with zoonotic potential of influenza A viruses: BTN3A3 evasion mediated by residue mutation in the nucleoprotein. | MedComm | 1 | 38045831 |
| 2026 | IGLC3- tumor cells drive chemoresistance in colorectal cancer by polarizing SPP1+ macrophages via the CD44-Wnt-BTF3 axis. | Frontiers in immunology | 0 | 41993204 |
| 2025 | Comparative transcriptomics of transgenic tobacco plants overexpressing Miscanthus sinensis BTF3. | BMC genomics | 0 | 40389874 |
| 2025 | RPL18 promotes melanoma progression and drug resistance via BTF3/STAT3-dependent mechanisms and immune modulation. | iScience | 0 | 41550725 |