Affinage

BDP1

Transcription factor TFIIIB component B'' homolog · UniProt A6H8Y1

Length
2624 aa
Mass
293.9 kDa
Annotated
2026-06-09
21 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BDP1 is the third subunit of the RNA polymerase III general transcription initiation factor TFIIIB, where it assembles with TBP and a Brf-family subunit (Brf1/Brf2) to form the complex that directs Pol III preinitiation (PMID:7568218, PMID:28743884). In yeast, recombinant B''/Bdp1 reconstitutes fully functional TFIIIB capable of TFIIIC-directed, TATA-dependent DNA binding and transcription, and discrete internal segments mediate functional interactions with TBP and Brf1 (PMID:7568218, PMID:11971960). BDP1 is recruited to promoters by the TFIIIC subunit Tfc4 through its TPR array, overlapping the Brf1-binding region (PMID:12930823), and at U6 snRNA promoters it is recruited by SNAPc bound to the U6 PSE (PMID:28743884, PMID:29932462), where the SNAPc–Bdp1 module can in turn recruit TBP (PMID:32253345). Assembly into TFIIIB is driven by its phylogenetically conserved SANT domain, whose helices 1 and 3 form a convex surface that anchors a defined segment (residues ~470–495) of Brf1 (PMID:16551611, PMID:19086269); Bdp1 entry alters TBP–DNA contacts to impose sequence preference on the downstream TATA box (PMID:17028095). Within the preinitiation complex an essential N-terminal region of Bdp1 is positioned in the Pol III active-site cleft through cross-links to the catalytic subunit C128 and to the Rpc37/53 dimer, and this region is required to drive the closed-to-open transition during initiation (PMID:21536656, PMID:26055328, PMID:28743884). BDP1 is cell-cycle regulated: CK2 phosphorylates it during mitosis, causing dissociation from the U6 promoter and chromatin and repressing Pol III transcription (PMID:15469824). Beyond Pol III initiation, yeast Bdp1 physically interacts with RNase P, and a specific internal deletion impairs RPR1 transcription and tRNA processing (PMID:11971960).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1995 High

    Established that BDP1's yeast ortholog is a bona fide structural subunit of TFIIIB rather than an accessory factor, by showing it is required to reconstitute a transcription-competent complex.

    Evidence Recombinant reconstitution of TFIIIB with B''/Brf1/TBP, in vitro transcription and DNase I footprinting in S. cerevisiae

    PMID:7568218

    Open questions at the time
    • Did not resolve which domains contact TBP vs Brf1
    • No structural information on the assembled complex
    • Truncatable termini left functional roles of N/C ends undefined
  2. 2002 High

    Mapped which Bdp1 segments engage TBP and Brf1 and revealed an unexpected physical link to RNase P, broadening its role beyond Pol III initiation to RNA processing.

    Evidence Deletion analysis, genetic suppression by SPT15/BRF1, co-IP and pull-down, in vitro transcription in yeast

    PMID:11971960

    Open questions at the time
    • Functional consequence of the RNase P interaction in vivo not defined
    • Structural basis of TBP/Brf1 contacts not resolved
  3. 2003 Medium

    Defined how BDP1 is recruited to chromatin by identifying the TFIIIC subunit Tfc4 surface that delivers both Brf1 and Bdp1 onto promoter DNA.

    Evidence Mutagenesis (Tfc4 L469K), biochemical binding assays, reporter transcription; plus internal Bdp1 deletion (aa253–269) in vitro assembly assays

    PMID:12885403 PMID:12930823

    Open questions at the time
    • Recruitment shown for yeast TFIIIC; mammalian equivalent not addressed here
    • Order of Brf1 vs Bdp1 loading not fully resolved
  4. 2004 High

    Explained cell-cycle control of Pol III transcription by showing CK2 phosphorylation of human Bdp1 during mitosis drives its dissociation from chromatin.

    Evidence In vitro kinase assay, ChIP at U6 promoter, mitotic extract transcription with CK2 inhibitor rescue in human cells

    PMID:15469824

    Open questions at the time
    • Phosphosite identity and structural impact not defined
    • Whether the same applies to Brf1-TFIIIB at all gene classes not tested
  5. 2006 High

    Localized the principal Brf1–Bdp1 anchoring interaction to the conserved SANT domain and showed Bdp1 incorporation reshapes TBP–DNA sequence recognition.

    Evidence Site-directed mutagenesis, photochemical protein-DNA cross-linking, SELEX with altered-specificity TBP in vitro

    PMID:16551611 PMID:17028095

    Open questions at the time
    • Atomic interface not yet resolved at this stage
    • Generality of TATA preference shift across Pol III gene classes unclear
  6. 2008 Medium

    Resolved the Brf1–Bdp1 interface at residue level, defining the SANT helix1/helix3 convex surface as the docking site.

    Evidence NMR spectroscopy and structural modeling of the Brf1–Bdp1 interaction

    PMID:19086269

    Open questions at the time
    • Mutagenesis validation of mapped residues not reported
    • Single study, in isolation from full TFIIIB context
  7. 2015 Medium

    Positioned an essential N-terminal region of Bdp1 inside the Pol III active-site cleft, linking it directly to the catalytic machinery and the Rpc37/53 hub.

    Evidence BPA photo-cross-linking and functional mutagenesis mapping Bdp1 contacts to C128, Brf1 and Rpc37 in yeast; earlier Rpc37 hub mapping

    PMID:21536656 PMID:26055328

    Open questions at the time
    • Cross-linking does not give an atomic structure of the cleft-bound state
    • Mechanistic step driven by this region not yet defined
  8. 2017 High

    Provided the structural basis for Bdp1 assembly into TFIIIB and a mechanism for its role in initiation, showing similarity to Pol II factors TFIIA/TFIIF and a concerted closed-to-open transition.

    Evidence 2.7 Å crystal structure of human Brf2-TBP-Bdp1-DNA, single-molecule FRET, in vitro assays; Bdp1–SNAPc interaction

    PMID:28743884

    Open questions at the time
    • Structure is of Brf2-TFIIIB; full open-complex with Pol III not captured
    • Dynamics of SNAPc handoff not structurally resolved
  9. 2020 Medium

    Defined the SNAPc-dependent recruitment pathway at U6 promoters, showing Bdp1 is recruited by promoter-bound SNAPc in a PSE-specific manner and can in turn recruit TBP.

    Evidence In vitro binding, promoter-specificity and deletion mapping; cross-linking mass spectrometry and UV cross-linking in Drosophila

    PMID:29932462 PMID:32253345

    Open questions at the time
    • Mapped in Drosophila; human SNAPc–Bdp1 geometry not directly shown
    • Conformational basis of U6 vs U1 PSE discrimination inferred, not solved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CK2 phosphorylation, the active-site-cleft N-terminal region, and SNAPc/TFIIIC recruitment are integrated into a single dynamic cycle of Pol III initiation and cell-cycle regulation remains unresolved.
  • No structure of a complete Bdp1-containing open Pol III preinitiation complex
  • Functional role of the human BDP1–ZNF297B and Bdp1–RNase P interactions undefined
  • Phosphosite-level mechanism of mitotic dissociation not mapped onto structure

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 2 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2 GO:0140223 general transcription initiation factor activity 2
Localization
GO:0000228 nuclear chromosome 1 GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-1640170 Cell Cycle 1
Partners
BRF1BRF2RPC37SNAPCTBPTFC4ZNF297B
Complex memberships
TFIIIB

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TFC5/B'' (yeast ortholog of BDP1) encodes the B'' component of S. cerevisiae TFIIIB; recombinant B'' reconstitutes fully functional TFIIIB (with Brf1 and TBP) capable of TFIIIC-directed and TATA box-dependent DNA binding and transcription. A truncated form lacking 39 N-terminal and 107 C-terminal amino acids remains functional. Recombinant protein reconstitution, in vitro transcription, DNase I footprinting Proceedings of the National Academy of Sciences of the United States of America High 7568218
2002 Three segments of yeast Bdp1 are essential for viability; suppression of bdp1 conditional alleles by SPT15 (TBP) or BRF1 overexpression identifies functional interactions of specific Bdp1 segments with TBP and Brf1, respectively. Physical interaction of RNase P with Bdp1 was demonstrated by co-immunoprecipitation and pull-down assays. A specific internal deletion (aa 253–269) impairs RPR1 transcription and tRNA processing. Deletion analysis, genetic suppression, co-immunoprecipitation, pull-down assay, in vitro transcription Molecular and cellular biology High 11971960
2003 The TFIIIC subunit Tfc4 recruits both Brf1 and Bdp1 to assemble TFIIIB onto DNA; Bdp1 binding maps to the TPRs1-9 region of Tfc4 (overlapping the two Brf1 binding arrays). The L469K mutation in Tfc4 TPR7 impairs both Brf1 and Bdp1 incorporation into TFIIIB-TFIIIC-DNA complexes. Mutagenesis, biochemical binding assays, reporter gene transcription The Journal of biological chemistry Medium 12930823
2003 A specific internal deletion of Bdp1 (aa 253–269) selectively impairs TFIIIC-dependent assembly of TFIIIB on the RPR1 promoter, leading to gene-specific defective single-round and multiple-round transcription in vitro. In vitro transcription, TFIIIB assembly assay FEBS letters Medium 12885403
2004 CK2 phosphorylates the Bdp1 component of human Brf2-TFIIIB during mitosis, causing Bdp1 dissociation from the U6 promoter and from chromatin generally, resulting in repression of Pol III transcription. CK2-mediated phosphorylation of Bdp1 is the mechanism of cell cycle-specific Pol III repression. In vitro kinase assay, chromatin immunoprecipitation, mitotic extract transcription assay, CK2 inhibition Molecular cell High 15469824
2006 The principal Brf1-Bdp1 interaction site was mapped: a 66-amino acid segment of Brf1 (C-terminal half) anchors Bdp1, and the interacting Bdp1 domain is a 66-amino acid segment that includes the SANT domain, which is 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 Brf1 and Bdp1 together impose a strict sequence preference for the downstream half of the TATA box (selecting TGTAAATA), matching the TATA box of the Pol III-transcribed U6 snRNA gene, suggesting that Bdp1 entry into the TFIIIB-DNA complex alters TBP-DNA interactions. In vitro selection (SELEX) with altered-specificity TBP mutant, transcription assays Nucleic acids research Medium 17028095
2006 The zinc finger protein ZNF297B interacts with human BDP1; the interaction was confirmed by co-immunoprecipitation and mapped to the BTB/POZ domain-containing N-terminal region of ZNF297B (aa 1–127) and the N-terminal end of BDP1 (aa 1–299). Yeast two-hybrid, co-immunoprecipitation Biological chemistry Low 16542149
2008 NMR mapping of the Brf1-Bdp1 interaction interface reveals that the principal anchorage site of Brf1 on Bdp1 is located on a convex surface encompassing helix 1 and helix 3 of the SANT domain of Bdp1; the main Bdp1-binding site on Brf1 is a segment of residues 470–495. NMR spectroscopy, structural modeling Biochemistry Medium 19086269
2011 The C-terminal domain of yeast Rpc37 (within the TFIIF-like Rpc37/53 dimer of Pol III) contains binding sites for Bdp1; this positions Rpc37/53 as a hub connecting TFIIIC, Bdp1, and the Pol III active center within the preinitiation complex. BPA photo-cross-linking, site-directed hydroxyl radical probing Molecular and cellular biology Medium 21536656
2015 An essential N-terminal region of yeast Bdp1 cross-links to the Pol III catalytic subunit C128 (N-terminal region) and to the N-terminal half of Brf1 and the C-terminal domain of the Rpc37 (C37) subunit, positioning this Bdp1 region within the active site cleft of Pol III; this region is necessary for transcription initiation. BPA photo-cross-linking with photoreactive amino acids, functional mutagenesis Molecular and cellular biology Medium 26055328
2017 Crystal structure (2.7 Å) of the human Brf2-TBP-Bdp1 complex bound to DNA reveals the structural basis of Bdp1 assembly into TFIIIB; Bdp1 shows structural and functional similarities to Pol II factors TFIIA and TFIIF. Single-molecule FRET and in vitro assays support a concerted mechanism involving Bdp1 and Pol III subunits for the closed-to-open pre-initiation complex transition. Bdp1 interacts with the upstream factor SNAPc. X-ray crystallography (2.7 Å), single-molecule FRET, in vitro biochemical assays Nature communications High 28743884
2018 In Drosophila, DmSNAPc bound to a U6 PSE (but not a U1 PSE) directly recruits Bdp1 to the U6 promoter; an 87-residue region of Bdp1 was identified as responsible for this interaction, consistent with SNAPc adopting distinct conformations on U6 vs. U1 PSEs. In vitro binding assays, promoter specificity assays, deletion mapping FEBS letters Medium 29932462
2020 In Drosophila, DmSNAPc-Bdp1 can recruit TBP to the U6 promoter; a region of Bdp1 sufficient for TBP recruitment was identified, and this same region cross-links to nucleotides within the U6 PSE. Cross-linking mass spectrometry revealed specific DmSNAPc subunit interactions with Bdp1 and TBP. Cross-linking mass spectrometry, UV cross-linking assays, deletion analysis 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
2013 Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. PloS one 48 24312468
2017 Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation. Nature communications 46 28743884
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 18 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

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