Affinage

SNAPC3

snRNA-activating protein complex subunit 3 · UniProt Q92966

Length
411 aa
Mass
46.8 kDa
Annotated
2026-04-28
26 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNAPC3 (SNAP43) is a core subunit of the five-subunit small nuclear RNA-activating protein complex (SNAPc), which binds the proximal sequence element (PSE) of snRNA gene promoters and is essential for transcription initiation by both RNA polymerase II and RNA polymerase III (PMID:7715707, PMID:9732265). Within SNAPc, SNAPC3 directly contacts SNAP50 and SNAP190 to form a minimal PSE-binding subcomplex, and it additionally interacts with the DNA-binding domain of TBP to recruit TBP to the TATA box of RNA polymerase III-dependent promoters such as U6 (PMID:11056176, PMID:12621023). A 3.49 Å cryo-EM structure of the mini-SNAPc (SNAP190 N-terminus, SNAP50, and SNAPC3) bound to the U6-1 PSE reveals a wrap-around DNA-binding architecture in which SNAPC3 is an integral structural component (PMID:36369505). SNAPC3 occupies a position in SNAPc assembly that is distinct from SNAPC4 (SNAP45) and is connected to SNAPC1 (SNAP19) through an interaction whose broader complex integrity is regulated by SNAPC1 SUMOylation (PMID:40956881).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1995 High

    Identification of SNAPC3 as a subunit of a novel TBP-TAF complex (SNAPc) that binds the PSE established the first molecular framework for how snRNA genes are transcribed by both RNA Pol II and Pol III.

    Evidence Biochemical purification and in vitro transcription assays from human cell extracts

    PMID:7715707

    Open questions at the time
    • Individual contributions of each subunit to PSE binding were unknown
    • No information on subunit–subunit contacts within the complex
  2. 1996 Medium

    Mapping pairwise interactions showed SNAPC3 directly contacts SNAP50 but not SNAP45 or TBP, beginning to define the internal architecture of SNAPc.

    Evidence Co-immunoprecipitation and UV cross-linking in HeLa extracts

    PMID:9003788

    Open questions at the time
    • Only pairwise interactions tested; higher-order contacts could be missed
    • No domain-resolution mapping of the SNAPC3–SNAP50 interface
  3. 1998 High

    Reconstitution of the complete five-subunit SNAPc from recombinant proteins demonstrated that SNAPC3 is essential for a functional complex capable of PSE binding and dual-polymerase transcription.

    Evidence Recombinant co-expression and in vitro transcription of both Pol II and Pol III snRNA templates

    PMID:9732265

    Open questions at the time
    • No structure available to explain how five subunits cooperate for PSE recognition
    • Mechanism by which SNAPc discriminates Pol II versus Pol III promoters remained unclear
  4. 2000 High

    Systematic domain mapping identified specific regions of SNAPC3, SNAP50, and SNAP190 required for mutual association and PSE binding, showing the minimal determinants of complex assembly.

    Evidence Co-immunoprecipitation with deletion mutants and PSE EMSA

    PMID:11056176

    Open questions at the time
    • Atomic-resolution contacts between domains remained undetermined
    • Functional contribution of individual domains to transcription not tested
  5. 2002 High

    Discovery that a mini-SNAPc containing SNAPC3, SNAP50, and the SNAP190 N-terminus directly recruits TBP to the U6 TATA box resolved how SNAPc nucleates the Pol III preinitiation complex, with SNAPC3 making direct contact with TBP's DNA-binding domain.

    Evidence TBP recruitment assays, direct protein interaction mapping, and in vitro Pol III transcription with truncation mutants

    PMID:12391172 PMID:12621023

    Open questions at the time
    • Structural basis of the SNAPC3–TBP interaction unknown
    • Whether SNAPC3–TBP contact is also relevant for Pol II snRNA transcription was not resolved
  6. 2006 High

    Co-expression of a four-subunit partial SNAPc in E. coli confirmed that SNAPC3 is part of the minimal assembly sufficient for PSE binding, TBP recruitment, and both Pol II and Pol III transcription, validating the mini-SNAPc paradigm.

    Evidence Recombinant co-expression in E. coli with in vitro transcription of U1 and U6 templates

    PMID:16603380

    Open questions at the time
    • Role of SNAP45 in the full complex assembly pathway remained structurally unresolved
    • Post-translational regulation of the complex was unexplored
  7. 2022 High

    A 3.49 Å cryo-EM structure of mini-SNAPc bound to U6-1 PSE revealed a wrap-around DNA-binding mode, providing the first atomic-level view of SNAPC3 within the complex and explaining how it contributes to the structural scaffold for PSE recognition.

    Evidence Cryo-EM structure determination of the human mini-SNAPc–PSE complex

    PMID:36369505

    Open questions at the time
    • Structure of full five-subunit SNAPc with SNAP19 and SNAP45 not determined
    • SNAPC3–TBP interface not visualized structurally
  8. 2025 Medium

    Endogenous tagging and deSUMOylation experiments showed that SNAPC3 and SNAPC4 occupy distinct assembly positions connected through SNAPC1, and that SNAPC1 SUMOylation regulates the SNAPC1–SNAPC4 but not the SNAPC1–SNAPC3 interaction, revealing a post-translational switch governing SNAPc integrity.

    Evidence Endogenous tagging, co-immunoprecipitation, CRISPR/dCas9-SENP1 targeting, and inducible degron system in human cells

    PMID:40956881

    Open questions at the time
    • Functional consequence of disrupted SNAPC1–SNAPC4 interaction for snRNA transcription not directly measured
    • Whether SUMOylation regulates SNAPc in different cell types or developmental contexts is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of the SNAPC3–TBP interaction, the full five-subunit SNAPc structure including SNAP45 and SNAP19, and the mechanism by which SNAPc switches between Pol II and Pol III transcription modes remain unresolved.
  • No structure of SNAPC3–TBP interface
  • No complete five-subunit SNAPc structure
  • Mechanism of Pol II versus Pol III promoter discrimination by SNAPc is not defined at the molecular level

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0005198 structural molecule activity 2 GO:0044183 protein folding chaperone 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4
Partners
SNAPC1SNAPC2SNAPC4SNAPC5TBP
Complex memberships
SNAPc (snRNA-activating protein complex)

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 SNAPc (containing SNAP43/SNAPC3, SNAP45, SNAP50, and TBP) was identified as a TBP-TAF complex that binds specifically to the proximal sequence element (PSE) and is required for transcription of both RNA polymerase II and III snRNA genes. Biochemical purification, in vitro transcription assays, DNA binding assays Nature High 7715707
1996 SNAP43 (SNAPC3) interacts with SNAP50 in co-immunoprecipitation experiments but not with SNAP45 or TBP, defining initial subunit-subunit contacts within SNAPc. Co-immunoprecipitation, antibody depletion, UV cross-linking The EMBO journal Medium 9003788
1998 SNAPc was reconstituted from five recombinant subunits — SNAP43 (SNAPC3), SNAP45, SNAP50, SNAP190, and the newly identified SNAP19 — and this recombinant complex binds specifically to the PSE and directs both RNA polymerase II and III snRNA gene transcription. Recombinant protein reconstitution, PSE binding assays, in vitro transcription Genes & development High 9732265
2000 A detailed map of SNAPc subunit-subunit contacts was established, identifying specific domains within SNAP43 (SNAPC3), SNAP45, SNAP50, SNAP190, and SNAP19 required for subunit-subunit association; complexes containing little more than these mapped domains bind specifically to the PSE. Co-immunoprecipitation with deletion mutants, PSE binding assays The Journal of biological chemistry High 11056176
2002 A mini-SNAPc containing SNAP43 (SNAPC3), SNAP50, and the N-terminal third of SNAP190 binds cooperatively with TBP to the core U6 promoter and supports RNA polymerase III transcription; SNAP43 directly interacts with the TBP DNA binding domain. TBP recruitment assays, in vitro transcription, protein interaction assays with truncation mutants Molecular and cellular biology High 12391172
2003 SNAP43 (SNAPC3) directly interacts with the TBP DNA binding domain and is one of two SNAPc subunits (along with SNAP190) that recruit TBP to the U6 TATA box, facilitating assembly of a RNA polymerase III-specific preinitiation complex. TBP recruitment assays, direct protein interaction assays, in vitro transcription The Journal of biological chemistry High 12621023
2006 A partial SNAPc containing SNAP190(1-505), SNAP50, SNAP43 (SNAPC3), and SNAP19 co-expressed in E. coli binds PSE DNA specifically, recruits TBP to U6 promoter DNA, and supports transcription of both U1 and U6 snRNA genes by RNA polymerases II and III. Recombinant co-expression in E. coli, DNA binding assays, TBP recruitment assays, in vitro transcription Protein expression and purification High 16603380
2022 Cryo-EM structure of human SNAPc (N-terminal domain of SNAP190, SNAP50, and SNAP43/SNAPC3) in complex with U6-1 PSE at 3.49 Å resolution reveals a 'wrap-around' mode of PSE binding; SNAP43 is part of the stable mini-SNAPc assembly with defined three-dimensional organization. Cryo-electron microscopy structure determination at 3.49 Å resolution Nature communications High 36369505
2025 SNAPC3 (endogenously tagged) was shown to interact with SNAPC1 in the SNAPc complex; a SUMOylation-deficient SNAPC1 mutant retains interaction with SNAPC3 but shows impaired interaction with SNAPC4, indicating SNAPC3 and SNAPC4 occupy distinct positions in the SNAPc assembly that depend on SNAPC1 SUMOylation. Endogenous tagging, co-immunoprecipitation, CRISPR/dCas9-SENP1 targeting, inducible degron system Proceedings of the National Academy of Sciences of the United States of America Medium 40956881

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 A TBP-TAF complex required for transcription of human snRNA genes by RNA polymerase II and III. Nature 128 7715707
2009 Histone acetylations mark origins of polycistronic transcription in Leishmania major. BMC genomics 115 19356248
1998 The large subunit of basal transcription factor SNAPc is a Myb domain protein that interacts with Oct-1. Molecular and cellular biology 82 9418884
1998 SNAP19 mediates the assembly of a functional core promoter complex (SNAPc) shared by RNA polymerases II and III. Genes & development 73 9732265
1996 Cloning and characterization of SNAP50, a subunit of the snRNA-activating protein complex SNAPc. The EMBO journal 51 9003788
2005 Involvement of SRD2-mediated activation of snRNA transcription in the control of cell proliferation competence in Arabidopsis. The Plant journal : for cell and molecular biology 46 16098103
2002 RNA polymerase II-dependent transcription in trypanosomes is associated with a SNAP complex-like transcription factor. Proceedings of the National Academy of Sciences of the United States of America 46 12486231
2019 Expression of MHC class I, HLA-A and HLA-B identifies immune-activated breast tumors with favorable outcome. Oncoimmunology 44 31646075
2000 A map of protein-protein contacts within the small nuclear RNA-activating protein complex SNAPc. The Journal of biological chemistry 41 11056176
2021 Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma cancer. BMC cancer 38 34922489
2021 DNA methylation mediates the association between breastfeeding and early-life growth trajectories. Clinical epigenetics 37 34937578
2004 The Trypanosoma brucei spliced leader RNA and rRNA gene promoters have interchangeable TbSNAP50-binding elements. Nucleic acids research 36 14757834
2002 Redundant cooperative interactions for assembly of a human U6 transcription initiation complex. Molecular and cellular biology 34 12391172
2014 Dual-trait selection for ethanol consumption and withdrawal: genetic and transcriptional network effects. Alcoholism, clinical and experimental research 28 25581648
2004 Molecular hierarchy in neurons differentiated from mouse ES cells containing a single human chromosome 21. Biochemical and biophysical research communications 22 14733910
2003 The small nuclear RNA-activating protein 190 Myb DNA binding domain stimulates TATA box-binding protein-TATA box recognition. The Journal of biological chemistry 22 12621023
2006 The unorthodox SNAP50 zinc finger domain contributes to cooperative promoter recognition by human SNAPC. The Journal of biological chemistry 16 16901896
2022 Structural basis of human SNAPc recognizing proximal sequence element of snRNA promoter. Nature communications 11 36369505
2013 Genomic analysis of sequence-dependent DNA curvature in Leishmania. PloS one 8 23646176
2006 Co-expression of multiple subunits enables recombinant SNAPC assembly and function for transcription by human RNA polymerases II and III. Protein expression and purification 6 16603380
2004 Failure to detect binding of Trypanosoma brucei SNAPc to U2 and U6 snRNA gene sequences by in vitro transcription competition and pull-down assays. Molecular and biochemical parasitology 5 15383299
2024 Integrating Genetic and Transcriptomic Data to Identify Genes Underlying Obesity Risk Loci. medRxiv : the preprint server for health sciences 2 38903089
2021 TBP and SNAP50 transcription factors bind specifically to the Pr77 promoter sequence from trypanosomatid non-LTR retrotransposons. Parasites & vectors 1 34108018
2025 A Systematic, Evidence-Based Workflow for Classifying KMT2A Fusions in Acute Myeloid Leukemia. The Journal of molecular diagnostics : JMD 0 40706988
2025 SUMO conjugation to promoter-proximal sequence elements-associated proteins impacts on snRNA transcription. Proceedings of the National Academy of Sciences of the United States of America 0 40956881
2025 Integrating genetic and transcriptomic data to identify genes underlying obesity risk loci. International journal of obesity (2005) 0 41006818