Affinage

BDP1

Transcription factor TFIIIB component B'' homolog · UniProt A6H8Y1

Length
2624 aa
Mass
293.9 kDa
Annotated
2026-04-28
21 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BDP1 is an essential subunit of the RNA polymerase III transcription factor TFIIIB that, together with TBP and Brf1/Brf2, assembles on Pol III promoters to drive transcription initiation of tRNAs, 5S rRNA, U6 snRNA, and other small non-coding RNAs. Its SANT domain anchors the Brf1 interaction interface, while a distinct essential N-terminal region inserts into the Pol III active site cleft—contacting the C128 catalytic subunit and the C37 subunit—to promote the closed-to-open pre-initiation complex transition required for transcription initiation (PMID:26055328, PMID:28743884). At U6 snRNA promoters, Bdp1 is selectively recruited through direct interaction with SNAPc bound to the proximal sequence element, and it participates in subsequent TBP loading onto the TATA box (PMID:29932462, PMID:32253345). BDP1 activity is cell-cycle regulated: CK2 phosphorylates Bdp1 during mitosis, causing its dissociation from chromatin and repression of Pol III transcription (PMID:15469824).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    Identification of TFC5/B" as the gene encoding the third TFIIIB subunit resolved a longstanding gap in understanding how this minimal factor reconstitutes Pol III transcription together with TBP and Brf1.

    Evidence Recombinant protein reconstitution with DNase I footprinting and in vitro transcription in yeast

    PMID:7568218

    Open questions at the time
    • No structural information on how Bdp1 integrates into the TFIIIB complex
    • Mammalian ortholog not yet characterized
  2. 2002 High

    Systematic deletion analysis defined three essential segments within Bdp1 and revealed functional interactions with both TBP and Brf1, establishing that Bdp1 makes multiple contacts within TFIIIB rather than acting through a single interaction surface.

    Evidence Deletion analysis, genetic suppression with SPT15/BRF1 overexpression, co-immunoprecipitation in yeast

    PMID:11971960

    Open questions at the time
    • Residue-level mapping of Bdp1-TBP and Bdp1-Brf1 interfaces not achieved
    • Functional significance of the Bdp1-RNase P interaction unclear
  3. 2003 High

    Discovery that CK2 phosphorylates Bdp1 during mitosis, causing its release from chromatin and Pol III transcription repression, established the first mechanism for cell-cycle regulation of TFIIIB activity.

    Evidence In vitro kinase assay, ChIP, cell cycle fractionation, CK2 inhibitor rescue in human cells

    PMID:15469824

    Open questions at the time
    • Specific phosphorylation sites on Bdp1 not fully mapped
    • Whether other kinases or phosphatases reverse this regulation in G1
  4. 2003 Medium

    Mapping the Bdp1-Tfc4 (TFIIIC subunit) interaction via TPR repeats and showing overlap with the Brf1 binding site clarified how TFIIIC hands off promoter-bound DNA to TFIIIB during complex assembly.

    Evidence Genetic suppression and in vitro binding/complex reconstitution assays in yeast

    PMID:12930823

    Open questions at the time
    • Sequential order of Brf1 vs Bdp1 entry into the TFIIIC-DNA complex not resolved
    • No structural detail of the TFIIIC-TFIIIB handoff
  5. 2006 High

    Residue-level mapping revealed that the SANT domain of Bdp1 (helices 1 and 3) provides the principal docking surface for a 66-amino acid segment of the Brf1 C-terminal domain, establishing the structural basis of the core Brf1-Bdp1 interaction.

    Evidence Site-directed mutagenesis, photochemical cross-linking, and NMR spectroscopy in yeast

    PMID:16551611 PMID:19086269

    Open questions at the time
    • Full atomic structure of the Brf1-Bdp1-TBP-DNA complex not yet available
    • Whether SANT domain contacts DNA directly was unclear
  6. 2006 Medium

    Demonstration that Brf1-Bdp1 entry into the TBP-DNA complex imposes strict TATA-box sequence selectivity revealed that TFIIIB subunits actively reshape the promoter DNA contact, not merely passively bind it.

    Evidence SELEX with altered-specificity TBP mutant in yeast

    PMID:17028095

    Open questions at the time
    • Structural mechanism by which Bdp1 alters TBP-DNA contacts not determined
  7. 2011 High

    Photo-cross-linking placed Bdp1 at the Rpc37/53 (TFIIF-like) dimer within the Pol III pre-initiation complex, revealing for the first time that Bdp1 bridges TFIIIB to the polymerase active center.

    Evidence BPA incorporation photo-cross-linking and hydroxyl radical probing in yeast Pol III PIC

    PMID:21536656

    Open questions at the time
    • Functional consequence of disrupting the Bdp1-Rpc37 contact not fully tested
  8. 2015 High

    An essential N-terminal region of Bdp1 was shown to insert into the Pol III active site cleft by cross-linking to the C128 catalytic subunit, establishing a direct mechanism by which Bdp1 participates in transcription initiation beyond promoter recognition.

    Evidence BPA photo-cross-linking combined with functional mutagenesis in yeast

    PMID:26055328

    Open questions at the time
    • Whether this N-terminal insertion triggers DNA melting or stabilizes the open complex was not distinguished
  9. 2017 High

    The 2.7 Å crystal structure of Brf2-TBP-Bdp1 on DNA, validated by single-molecule FRET, revealed that Bdp1 makes essential DNA contacts, structurally resembles TFIIA/TFIIF, and drives the closed-to-open PIC transition, providing the definitive structural framework for TFIIIB function.

    Evidence X-ray crystallography, single-molecule FRET, in vitro biochemistry on human TFIIIB

    PMID:28743884

    Open questions at the time
    • Full Pol III PIC structure with Bdp1 at atomic resolution not yet achieved
    • How Bdp1 structural changes couple to DNA strand separation remains incompletely resolved
  10. 2018 Medium

    Selective recruitment of Bdp1 to U6 promoters by SNAPc bound to the PSE (but not U1 PSE) established the molecular basis for how a single promoter-recognition factor discriminates Pol III from Pol II transcription at snRNA genes.

    Evidence In vitro binding and promoter specificity assays with domain mapping in Drosophila

    PMID:29932462

    Open questions at the time
    • Whether the same SNAPc-Bdp1 recruitment logic operates in mammalian cells with distinct SNAPc architecture
  11. 2020 Medium

    Cross-linking mass spectrometry and functional mapping showed that the SNAPc-Bdp1 complex recruits TBP to U6 promoters, defining Bdp1 as an active participant in TFIIIB assembly at type III promoters rather than a passively recruited subunit.

    Evidence UV cross-linking, cross-linking mass spectrometry, functional domain mapping in Drosophila

    PMID:32253345

    Open questions at the time
    • Order and kinetics of TBP vs Bdp1 loading on type III promoters in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete atomic-resolution structure of the full Pol III pre-initiation complex incorporating Bdp1 is still lacking, and the mechanism by which Bdp1's N-terminal insertion into the active site cleft couples to promoter DNA melting remains unresolved.
  • No full Pol III PIC structure with Bdp1 at atomic resolution
  • Mechanism coupling Bdp1 cleft insertion to DNA strand separation unknown
  • Role of Bdp1 phosphorylation sites in fine-tuning gene-specific Pol III transcription not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0005198 structural molecule activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 1
Partners
BRF1BRF2POLR3BRPC37SNAPCTBPTFC4
Complex memberships
TFIIIB

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TFC5 (yeast BDP1/B") encodes a 594-amino acid subunit of TFIIIB; recombinant B" reconstitutes fully functional TFIIIB with Brf1 and TBP, supporting both TFIIIC-directed and TATA box-dependent DNA binding and transcription in vitro. Recombinant protein reconstitution, DNase I footprinting, in vitro transcription assay Proceedings of the National Academy of Sciences of the United States of America High 7568218
2002 Yeast Bdp1 contains three essential segments; functional interactions with TBP and Brf1 were mapped to specific Bdp1 regions by suppression genetics; a physical interaction between Bdp1 and RNase P was demonstrated, linking Bdp1 to tRNA processing. Deletion analysis, genetic suppression (SPT15/BRF1 overexpression), in vitro transcription, co-immunoprecipitation, pull-down assay Molecular and cellular biology High 11971960
2003 CK2 phosphorylates the Bdp1 subunit of TFIIIB during mitosis, causing Bdp1 dissociation from the U6 promoter and chromatin, thereby repressing RNA polymerase III transcription in a cell cycle-specific manner. In vitro kinase assay, chromatin immunoprecipitation, cell cycle fractionation, CK2 inhibitor rescue experiments Molecular cell High 15469824
2003 The Bdp1 subunit of TFIIIB interacts with the Tfc4 (tau131) subunit of TFIIIC via TPR repeats 1–9, with Bdp1 and Brf1 sharing overlapping binding sites on Tfc4; the Tfc4 L469K mutation impairs both Brf1 and Bdp1 incorporation into TFIIIB-TFIIIC-DNA complexes. Genetic suppression, in vitro binding assays, TFIIIC-DNA complex reconstitution The Journal of biological chemistry Medium 12930823
2003 Negative regulation of HER2 (ErbB2) receptor tyrosine kinase signaling by the PEST-type protein-tyrosine phosphatase BDP1: BDP1 overexpression inhibits ligand-induced HER2 phosphorylation and downstream Gab1/MAPK signaling, while BDP1 knockdown increases HER2 phosphorylation. Overexpression, siRNA knockdown, immunoprecipitation/western blot of phosphorylation The Journal of biological chemistry Medium 14660651
2003 A specific internal deletion (aa 253–269) in Bdp1 selectively impairs TFIIIC-dependent assembly of TFIIIB on the RPR1 promoter (but not other Pol III genes), leading to gene-specific transcription defects in vitro. In vitro transcription assay, TFIIIB-TFIIIC-DNA complex assembly analysis FEBS letters Medium 12885403
2006 The principal interaction site between Brf1 and Bdp1 was mapped: a 66-amino acid segment of Brf1's C-terminal domain provides a two-sided adhesive surface for Bdp1, while the interacting Bdp1 domain spans 66 amino acids encompassing the SANT domain, the most phylogenetically conserved region of Bdp1. Site-directed mutagenesis, photochemical protein-DNA cross-linking, deletion analysis The Journal of biological chemistry High 16551611
2006 Human BDP1 (aa 1–299 N-terminal region) interacts with the zinc finger protein ZNF297B (via ZNF297B BTB/POZ domain, aa 1–127), identified by yeast two-hybrid and confirmed by co-immunoprecipitation. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence Biological chemistry Low 16542149
2006 Entry of Brf1 and Bdp1 into the TBP-DNA complex imposes a strict sequence preference for the downstream half of the TATA box (selecting TGTAAATA, matching the U6 snRNA gene TATA box), suggesting that the Brf1-Bdp1 proteins alter TBP-DNA complex structure or dynamics. Altered-specificity TBP mutant (TBPm3), iterative in vitro selection (SELEX) Nucleic acids research Medium 17028095
2008 NMR mapping of the Brf1-Bdp1 interaction interface showed that Bdp1 SANT domain helices 1 and 3 form the principal anchorage surface for a Brf1 segment (residues 470–495). NMR spectroscopy, structural modeling Biochemistry Medium 19086269
2011 The C-terminal domain of Rpc37 (within the TFIIF-like Rpc37/53 dimer of Pol III) contains binding sites for Bdp1; photo-cross-linking localized these interactions, revealing Bdp1's position within the Pol III preinitiation complex and its connection to the active center. Unnatural amino acid photo-cross-linking (BPA incorporation), site-directed hydroxyl radical probing Molecular and cellular biology High 21536656
2015 An essential N-terminal region of yeast Bdp1 (distinct from the SANT domain) cross-links to the Pol III catalytic subunit C128 (N-terminal region) and the C-terminal domain of C37 subunit, positioning this Bdp1 region within the Pol III active site cleft and showing it is necessary for transcription initiation. Photoreactive unnatural amino acid (BPA) incorporation, photo-cross-linking, functional mutagenesis Molecular and cellular biology High 26055328
2017 Crystal structure of the Brf2-TBP-Bdp1 complex bound to DNA at 2.7 Å resolution, combined with single-molecule FRET and in vitro biochemical assays, reveals how Bdp1 assembles into TFIIIB, its structural and functional similarities to Pol II factors TFIIA and TFIIF, essential DNA contacts, interactions with SNAPc, and its role in driving the closed-to-open pre-initiation complex transition. X-ray crystallography (2.7 Å), single-molecule FRET, in vitro biochemical assays Nature communications High 28743884
2018 In Drosophila, DmSNAPc bound to the U6 PSE (but not U1 PSE) directly recruits Bdp1 to the U6 promoter via a specific 87-residue region of Bdp1, establishing that SNAPc conformation dictates selective Bdp1 recruitment for Pol III (versus Pol II) gene transcription. In vitro binding assays, promoter specificity assays (U6 vs. U1 PSE), deletion mapping FEBS letters Medium 29932462
2020 In Drosophila, DmSNAPc-Bdp1 recruits TBP to the U6 promoter; a specific region of Bdp1 is sufficient for TBP recruitment and cross-links to nucleotides within the U6 PSE; cross-linking mass spectrometry identified interactions of specific DmSNAPc subunits with Bdp1 and TBP. Functional domain mapping, UV cross-linking, cross-linking mass spectrometry Molecular and cellular biology Medium 32253345

Source papers

Stage 0 corpus · 21 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Cloning, expression, and function of TFC5, the gene encoding the B" component of the Saccharomyces cerevisiae RNA polymerase III transcription factor TFIIIB. Proceedings of the National Academy of Sciences of the United States of America 93 7568218
2011 The TFIIF-like Rpc37/53 dimer lies at the center of a protein network to connect TFIIIC, Bdp1, and the RNA polymerase III active center. Molecular and cellular biology 62 21536656
2004 CK2 phosphorylation of Bdp1 executes cell cycle-specific RNA polymerase III transcription repression. Molecular cell 53 15469824
2017 Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation. Nature communications 46 28743884
2013 Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. PloS one 46 24312468
2003 Negative regulation of HER2 signaling by the PEST-type protein-tyrosine phosphatase BDP1. The Journal of biological chemistry 46 14660651
2002 Essential roles of Bdp1, a subunit of RNA polymerase III initiation factor TFIIIB, in transcription and tRNA processing. Molecular and cellular biology 41 11971960
1996 Characterization of the PEST family protein tyrosine phosphatase BDP1. Oncogene 23 8950995
2006 Mapping the principal interaction site of the Brf1 and Bdp1 subunits of Saccharomyces cerevisiae TFIIIB. The Journal of biological chemistry 20 16551611
2003 The Brf1 and Bdp1 subunits of transcription factor TFIIIB bind to overlapping sites in the tetratricopeptide repeats of Tfc4. The Journal of biological chemistry 17 12930823
2015 A Region of Bdp1 Necessary for Transcription Initiation That Is Located within the RNA Polymerase III Active Site Cleft. Molecular and cellular biology 15 26055328
2022 Structural insights into acetylated histone ligand recognition by the BDP1 bromodomain of Plasmodium falciparum. International journal of biological macromolecules 9 36328269
2008 Structural characterization of the interaction between TFIIIB components Bdp1 and Brf1. Biochemistry 8 19086269
2018 Bdp1 interacts with SNAPc bound to a U6, but not U1, snRNA gene promoter element to establish a stable protein-DNA complex. FEBS letters 7 29932462
2022 BDP1 Alterations Correlate with Clinical Outcomes in Breast Cancer. Cancers 6 35406430
2019 TFIIIB Subunit Bdp1 Participates in RNA Polymerase III Transcription in the Protozoan Parasite Leishmania major. BioMed research international 6 31058184
2022 BDP1 as a biomarker in serous ovarian cancer. Cancer medicine 5 36305848
2020 Assembly of SNAPc, Bdp1, and TBP on the U6 snRNA Gene Promoter in Drosophila melanogaster. Molecular and cellular biology 5 32253345
2006 The zinc finger protein ZNF297B interacts with BDP1, a subunit of TFIIIB. Biological chemistry 4 16542149
2006 The Saccharomyces cerevisiae RNA polymerase III recruitment factor subunits Brf1 and Bdp1 impose a strict sequence preference for the downstream half of the TATA box. Nucleic acids research 3 17028095
2003 A gene-specific effect of an internal deletion in the Bdp1 subunit of the RNA polymerase III transcription initiation factor TFIIIB. FEBS letters 3 12885403