{"gene":"TAF11","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2017,"finding":"TAF11 and TAF13 form a ternary complex with TBP via their histone fold (HF) domains. TAF11/TAF13 competes with TATA-box DNA for binding to the DNA-binding surface of TBP, and also competes with the N-terminal domain of TAF1 (previously implicated in TATA-box mimicry). Cross-linking mass spectrometry and crystal coordinates defined the architecture of the TAF11/TAF13/TBP complex. A highly conserved C-terminal TBP-interaction domain (CTID) in TAF13 was identified as essential for supporting cell growth.","method":"Crystal structure, cross-linking mass spectrometry (CLMS), biochemical competition assays, mutagenesis","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal coordinates, CLMS, biochemical competition assays with mutagenesis, multiple orthogonal methods in one rigorous study","pmids":["29111974"],"is_preprint":false},{"year":2005,"finding":"The TAF11–TFIIA interaction involves two distinct regions of TAF11: the conserved histone fold domain and the N-terminal region. TAF11 imparts changes to both TFIIA-DNA and TBP-DNA contacts at promoter DNA, enhancing formation and stabilization of the TFIIA-TBP-DNA complex. A TAF11 allele defective for interaction with TFIIA causes conditional growth phenotypes and transcription defects in yeast.","method":"Genetic suppressor screen (compensatory mutant isolation), in vivo transcription assay, DNA footprinting/binding assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with compensatory mutations, transcription assays, DNA binding analyses; single lab but multiple orthogonal methods","pmids":["15657423"],"is_preprint":false},{"year":2003,"finding":"In yeast, TAF11 and TAF13 provide critical functional contacts with TBP during preinitiation complex (PIC) assembly. Depletion of TAF11 (via temperature-sensitive mutation) impairs TBP recruitment and PIC assembly at dependent promoters.","method":"Temperature-sensitive yeast mutants, genome-wide expression profiling, chromatin immunoprecipitation (TBP recruitment/PIC assembly assays)","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — temperature-sensitive alleles with genome-wide expression profiling plus ChIP for PIC assembly; replicated across all 13 essential TAFs in same study","pmids":["12840001"],"is_preprint":false},{"year":1996,"finding":"Human TAF(II)28 (TAF11) promotes transcriptional stimulation by the activation function 2 (AF-2) of retinoid X receptors (RXR) in mammalian cells. TAF(II)28 is selectively depleted in COS cell TFIID, explaining the lack of RXR AF-2 activity in these cells. The potentiation effect correlated with the ability of TAF(II)28 to interact with TBP, but did not appear to require direct TAF(II)28–RXR interactions.","method":"Transient transfection/coexpression in COS and HeLa cells, transcriptional reporter assays","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — transcription reporter assays in cells, correlation of TBP interaction with function, single lab with multiple receptor types tested","pmids":["8670810"],"is_preprint":false},{"year":1997,"finding":"Human TAF(II)28 (TAF11) directly interacts with the HTLV-I Tax transactivator protein both in transfected HeLa cells (co-immunoprecipitation) and in vitro with purified proteins. Overexpression of hTAF(II)28 significantly increases transactivation by Tax, and this potentiation requires both Tax–TAF(II)28 interaction and TAF(II)28–TBP interaction.","method":"Co-immunoprecipitation in transfected HeLa cells, in vitro binding with purified proteins, transient transcription reporter assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and in vitro pulldown with purified proteins plus functional reporter assay; single lab","pmids":["9108034"],"is_preprint":false},{"year":2000,"finding":"hTAF(II)28 (TAF11) interacts with the ligand-binding domains (LBDs) of the vitamin D3 receptor (VDR) and thyroid hormone receptor alpha (TRalpha) in a ligand-reversible manner when coexpressed in COS cells. Fine mapping showed that the determinants for TAF(II)28 interaction map to alpha-helix H3 of VDR and are distinct from those for hTAF(II)55 interaction.","method":"Coexpression and co-immunoprecipitation in COS cells, deletion and point mutagenesis mapping","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP with mutagenesis mapping in cells, single lab; ligand-reversibility tested with multiple receptors","pmids":["10744685"],"is_preprint":false},{"year":1998,"finding":"TIF1alpha selectively phosphorylates TAF(II)28 (TAF11) in vitro, along with TFIIEalpha and TAF(II)55. Purified recombinant TIF1alpha possesses intrinsic kinase activity and undergoes autophosphorylation.","method":"In vitro kinase assay with purified recombinant proteins","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro kinase assay with purified proteins is Tier 1, but single lab, single method for this specific finding on TAF11","pmids":["9632676"],"is_preprint":false},{"year":2002,"finding":"TAF(II)28 (TAF11) does not contribute to STAT2-mediated IFN-stimulated transcription; overexpression of TAF(II)28 did not potentiate STAT2 function, in contrast to TAF(II)130.","method":"Transient transfection/coexpression in cells, transcriptional reporter assays","journal":"Nature cell biology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single method; this is a negative result establishing that TAF11 is not required for this specific pathway","pmids":["11802163"],"is_preprint":false},{"year":2006,"finding":"In Drosophila TFIID, TAF11 is a peripheral subunit that contributes very little to overall TFIID complex stability, in contrast to core subunits TAF4, TAF5, TAF6, TAF9, and TAF12. RNAi knockdown of TAF11 does not substantially destabilize the TFIID complex.","method":"RNAi knockdown in Drosophila tissue culture cells, western blot analysis of TFIID subunit levels","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic RNAi of all TFIID subunits with protein-level readouts; single lab but comprehensive comparative study","pmids":["16895980"],"is_preprint":false},{"year":2017,"finding":"Rapid degron-dependent depletion of yeast TAF11 causes strong decreases in nascent transcription at nearly all mRNA-coding genes, demonstrating that TAF11 is required for expression of essentially all yeast mRNAs, irrespective of TATA vs. TATA-less promoter class.","method":"Degron-mediated rapid protein depletion, nascent transcription measurement (NET-seq or equivalent)","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — rapid degron depletion (acute loss-of-function) with genome-wide nascent transcription readout; replicated with multiple TAF subunits in same study","pmids":["28918900"],"is_preprint":false},{"year":2015,"finding":"Drosophila TAF11 is a component of the RISC Loading Complex (RLC) in addition to its nuclear role in TFIID. TAF11 associates with Dcr-2/R2D2 in the cytoplasm and localizes to D2 bodies. TAF11 forms a tetramer that facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading. The RLC was reconstituted in vitro using recombinant Dcr-2-R2D2 complex, TAF11, and duplex siRNA.","method":"Genetic screen (taf11 null mutant), co-immunoprecipitation, in vitro RLC reconstitution, siRNA binding and RISC loading assays, cytoplasmic localization imaging","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of RLC plus genetic screen plus Co-IP and localization; multiple orthogonal methods establishing cytoplasmic RNAi function of TAF11","pmids":["26257286"],"is_preprint":false},{"year":2017,"finding":"TAF13 variants (p.Met40Lys and p.Leu31His) associated with intellectual disability and microcephaly impair formation of the TAF13-TAF11 heterodimer, as demonstrated by co-immunoprecipitation in HeLa cells. The TAF11-TAF13 heterodimer is required for their recruitment into the TFIID complex.","method":"Co-immunoprecipitation in transfected HeLa cells, molecular modeling","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP in human cells with disease-associated mutants; single lab but supported by structural modeling","pmids":["28257693"],"is_preprint":false},{"year":2019,"finding":"TAF11 is essential for EBV super-enhancer (ESE) activity and MYC transcription in lymphoblastoid cell lines (LCLs). CRISPR knockout of TAF11 significantly decreased 525ESE reporter activity and MYC expression.","method":"Genome-wide CRISPR screen, CRISPR knockout, luciferase reporter assay, RT-qPCR","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO with defined transcriptional phenotype, single lab, multiple readouts","pmids":["31167905"],"is_preprint":false},{"year":2025,"finding":"TAF11 overexpression (driven by a variant that recruits more STAT1/STAT3 to the TAF11 promoter) downregulates CDH1 and CTNND1 by binding to their promoter regions and inhibiting transcriptional activity, thereby disrupting cranial neural crest cell migration and causing craniofacial defects in zebrafish.","method":"ChIP, EMSA/supershift, dual-luciferase reporter assay, RNA-seq, zebrafish overexpression model with alcian blue staining, time-lapse imaging, WISH, immunofluorescence, TUNEL assay","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (ChIP, EMSA, reporter assay, in vivo zebrafish model); single lab","pmids":["39727181"],"is_preprint":false},{"year":2025,"finding":"In Taf13-null mouse embryos and ESCs, loss of the Taf11-Taf13 heterodimer had little effect on TFIID integrity and caused only a mild reduction of TBP promoter recruitment, but led to altered PIC formation and globally reduced RNA Pol II recruitment. This indicates that the Taf11-Taf13 heterodimer is not essential for TBP/TFIID recruitment, revealing plasticity in PIC formation pathways.","method":"Gene knockout in mice and ESCs, cryo-EM (referenced), ChIP for TBP and Pol II recruitment, embryoid body formation assay","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic knockout with genome-wide ChIP readouts; single lab; contradicts the strong predicted role for TAF11-TAF13 in TBP deposition from structural studies","pmids":["40491483"],"is_preprint":false}],"current_model":"TAF11 (TAFII28) is a peripheral subunit of the TFIID general transcription factor complex that, together with TAF13, forms a histone fold domain-containing heterodimer that binds the DNA-binding surface of TBP and competes with both TATA-box DNA and the TAF1 N-terminal domain for TBP association, thereby contributing to TBP regulation, PIC assembly, and near-universal RNA Pol II transcription; it also mediates transcriptional coactivation by directly interacting with nuclear receptors (VDR, TRα), viral transactivators (Tax), and can be phosphorylated by TIF1α, while in Drosophila it unexpectedly functions in the cytoplasm as a structural component of the RISC Loading Complex, facilitating Dcr-2/R2D2 tetramerization and RNAi efficiency."},"narrative":{"mechanistic_narrative":"TAF11 is a peripheral subunit of the general transcription factor TFIID that contributes to RNA Polymerase II preinitiation complex (PIC) assembly across essentially the entire mRNA-coding genome [PMID:28918900]. It functions as a histone-fold heterodimer with TAF13, and this TAF11/TAF13 pairing engages the DNA-binding surface of TBP, competing with both TATA-box DNA and the TATA-mimicking N-terminal domain of TAF1 for TBP association [PMID:29111974]; heterodimer formation is in turn required for recruitment of both TAFs into TFIID [PMID:28257693]. Within the assembling complex TAF11 makes functional contacts that support TBP recruitment and stabilizes the TFIIA-TBP-DNA complex through its histone fold and N-terminal regions [PMID:15657423, PMID:12840001]. Despite this, TAF11 contributes little to overall TFIID structural stability, marking it as a regulatory rather than scaffolding subunit [PMID:16895980], and genetic loss of the TAF11-TAF13 heterodimer perturbs PIC formation and Pol II recruitment more than TFIID integrity or TBP deposition, indicating plasticity in how PICs assemble [PMID:40491483]. Beyond core transcription, TAF11 acts as a coactivator surface that potentiates activation by nuclear receptors and viral transactivators: it relays RXR AF-2 activity in a manner correlating with its TBP interaction [PMID:8670810], binds the ligand-binding domains of VDR and TRalpha in a ligand-reversible manner [PMID:10744685], and directly binds the HTLV-I Tax protein to enhance Tax-dependent transactivation [PMID:9108034]. In Drosophila, TAF11 has an unexpected cytoplasmic function distinct from transcription, serving as a structural component of the RISC Loading Complex where its tetramerization promotes Dcr-2/R2D2 assembly and efficient siRNA loading [PMID:26257286]. TAF11 has been linked to disease contexts including TAF13-associated intellectual disability and microcephaly through impaired heterodimer formation [PMID:28257693] and craniofacial defects arising from TAF11 overexpression and aberrant repression of CDH1 and CTNND1 [PMID:39727181].","teleology":[{"year":1996,"claim":"Established that TAF11 is not merely a passive TFIID subunit but a functional relay for activator signals, linking it to nuclear receptor coactivation.","evidence":"Transient coexpression and reporter assays in COS and HeLa cells testing RXR AF-2 stimulation","pmids":["8670810"],"confidence":"Medium","gaps":["Effect correlated with TBP interaction rather than direct TAF11-RXR contact, leaving the mechanistic bridge undefined","Reporter-based readout without endogenous gene analysis"]},{"year":1997,"claim":"Demonstrated a direct physical and functional link between TAF11 and a viral transactivator, showing the coactivator role extends to Tax-driven transcription.","evidence":"Reciprocal Co-IP in HeLa cells and in vitro binding with purified proteins plus reporter assays","pmids":["9108034"],"confidence":"Medium","gaps":["Single lab; structural basis of the Tax-TAF11 interface not resolved","Endogenous viral target genes not assayed"]},{"year":1998,"claim":"Identified TAF11 as a substrate of TIF1alpha kinase, raising the possibility of post-translational regulation of TFIID coactivator function.","evidence":"In vitro kinase assay with purified recombinant TIF1alpha and TFIID components","pmids":["9632676"],"confidence":"Medium","gaps":["Phosphosite on TAF11 not mapped","Functional consequence of phosphorylation in cells not established","Single in vitro method"]},{"year":2000,"claim":"Refined the nuclear receptor coactivation model by mapping ligand-reversible TAF11 contacts to a defined receptor surface distinct from other TAF interactions.","evidence":"Co-IP with deletion/point mutagenesis mapping of VDR and TRalpha LBDs in COS cells","pmids":["10744685"],"confidence":"Medium","gaps":["Interaction shown by Co-IP without structural confirmation","Physiological consequence on target gene expression untested"]},{"year":2002,"claim":"Delimited the coactivator specificity of TAF11 by showing it is dispensable for STAT2-mediated interferon transcription, distinguishing it from TAF130.","evidence":"Transient coexpression and reporter assays in cells","pmids":["11802163"],"confidence":"Medium","gaps":["Negative result from a single reporter system","Does not exclude roles in other STAT pathways"]},{"year":2003,"claim":"Established that TAF11, with TAF13, provides critical TBP contacts during PIC assembly, defining its core mechanistic role in transcription initiation.","evidence":"Temperature-sensitive yeast mutants with genome-wide expression profiling and ChIP for TBP recruitment","pmids":["12840001"],"confidence":"High","gaps":["ts-mutant depletion is slow and may permit secondary effects","Direct biochemical mechanism of TBP contact not resolved here"]},{"year":2005,"claim":"Resolved how TAF11 stabilizes the early initiation complex by defining two TAF11 regions that contact TFIIA and remodel TBP-DNA and TFIIA-DNA interactions.","evidence":"Genetic suppressor screen, in vivo transcription assays, and DNA footprinting in yeast","pmids":["15657423"],"confidence":"High","gaps":["Structural detail of the TAF11-TFIIA interface not solved","Generality to all promoter classes not tested"]},{"year":2006,"claim":"Classified TAF11 as a peripheral, non-scaffolding TFIID subunit, distinguishing its regulatory function from structural core TAFs.","evidence":"Systematic RNAi of all TFIID subunits with western blot readouts in Drosophila cells","pmids":["16895980"],"confidence":"Medium","gaps":["Stability readout does not address functional contribution to transcription","Single comparative study"]},{"year":2015,"claim":"Revealed a transcription-independent cytoplasmic function: TAF11 acts as a structural tetramerizing component of the RISC Loading Complex to drive RNAi.","evidence":"Drosophila genetic screen, Co-IP, in vitro RLC reconstitution, siRNA binding/RISC loading assays, and localization imaging","pmids":["26257286"],"confidence":"High","gaps":["Whether this RNAi role is conserved beyond Drosophila is unaddressed","Structural basis of the TAF11 tetramer not solved"]},{"year":2017,"claim":"Provided the structural mechanism by which TAF11/TAF13 regulates TBP, showing the heterodimer occupies TBP's DNA-binding surface and competes with both TATA DNA and TAF1.","evidence":"Crystal structure, cross-linking mass spectrometry, biochemical competition assays, and mutagenesis","pmids":["29111974"],"confidence":"High","gaps":["How the inhibitory heterodimer is displaced to permit promoter DNA binding in vivo is not defined","Static structure does not capture assembly dynamics"]},{"year":2017,"claim":"Demonstrated by acute depletion that TAF11 is required for near-universal mRNA transcription, settling its role as a general rather than promoter-class-specific factor.","evidence":"Degron-mediated rapid depletion with genome-wide nascent transcription measurement in yeast","pmids":["28918900"],"confidence":"High","gaps":["Does not separate direct TFIID requirement from indirect effects","Mammalian generality not tested in this system"]},{"year":2017,"claim":"Connected TAF11 heterodimer formation to human disease, showing TAF13 mutations that disrupt the TAF11-TAF13 interface underlie intellectual disability and microcephaly.","evidence":"Reciprocal Co-IP of disease-associated TAF13 mutants in HeLa cells with molecular modeling","pmids":["28257693"],"confidence":"Medium","gaps":["Co-IP-based; downstream transcriptional consequences of heterodimer loss not measured","Causality demonstrated for TAF13 variants rather than TAF11 itself"]},{"year":2019,"claim":"Linked TAF11 to oncogenic enhancer function, showing it is required for EBV super-enhancer activity and MYC expression.","evidence":"Genome-wide CRISPR screen, CRISPR knockout, luciferase reporter, and RT-qPCR in lymphoblastoid cell lines","pmids":["31167905"],"confidence":"Medium","gaps":["Whether the effect is direct via TFIID at the super-enhancer is not resolved","Single cell-line context"]},{"year":2025,"claim":"Showed TAF11 can act as a transcriptional repressor in development, with overexpression downregulating adhesion genes and disrupting neural crest migration.","evidence":"ChIP, EMSA, dual-luciferase reporter, RNA-seq, and zebrafish overexpression model","pmids":["39727181"],"confidence":"Medium","gaps":["Mechanism of promoter-specific repression by a general TFIID subunit unclear","Single in vivo model"]},{"year":2025,"claim":"Challenged the structural model by showing in vivo loss of the Taf11-Taf13 heterodimer minimally affects TFIID integrity and TBP recruitment yet impairs PIC formation and Pol II loading, revealing plasticity in assembly pathways.","evidence":"Taf13 knockout in mice and ESCs with ChIP for TBP and Pol II recruitment and embryoid body assays","pmids":["40491483"],"confidence":"Medium","gaps":["Apparent tension with crystallographic TBP-regulation model unresolved","Mechanism of the residual PIC-formation defect not defined"]},{"year":null,"claim":"How TAF11/TAF13's TBP-occluding configuration is regulated and displaced in vivo to permit promoter engagement, and how a general TFIID subunit achieves the gene-specific activating versus repressing outcomes seen in development and disease, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No mechanism connecting the inhibitory structural state to in vivo PIC assembly dynamics","No model reconciling general transcription requirement with promoter-selective regulatory outcomes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[3,4,13]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,11]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[13]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[10]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,2,8]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[10]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,2,9]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[10]}],"complexes":["TFIID","RISC Loading Complex"],"partners":["TAF13","TBP","TFIIA","TAF1","DCR-2","R2D2","VDR","TRALPHA"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15544","full_name":"Transcription initiation factor TFIID subunit 11","aliases":["TFIID subunit p30-beta","Transcription initiation factor TFIID 28 kDa subunit","TAF(II)28","TAFII-28","TAFII28"],"length_aa":211,"mass_kda":23.3,"function":"The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). TAF11, together with TAF13 and TBP, play key roles during promoter binding by the TFIID and TFIIA transcription factor complexes (PubMed:33795473)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q15544/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TAF11","classification":"Not Classified","n_dependent_lines":104,"n_total_lines":1208,"dependency_fraction":0.08609271523178808},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TAF11","total_profiled":1310},"omim":[{"mim_id":"617432","title":"INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 60; MRT60","url":"https://www.omim.org/entry/617432"},{"mim_id":"609514","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 8; TAF8","url":"https://www.omim.org/entry/609514"},{"mim_id":"600774","title":"TAF13 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 18-KD; TAF13","url":"https://www.omim.org/entry/600774"},{"mim_id":"600772","title":"TAF11 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 28-KD; TAF11","url":"https://www.omim.org/entry/600772"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAF11"},"hgnc":{"alias_symbol":["TAFII28"],"prev_symbol":["TAF2I"]},"alphafold":{"accession":"Q15544","domains":[{"cath_id":"1.20.5","chopping":"86-128","consensus_level":"medium","plddt":84.5065,"start":86,"end":128}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15544","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15544-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15544-F1-predicted_aligned_error_v6.png","plddt_mean":72.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAF11","jax_strain_url":"https://www.jax.org/strain/search?query=TAF11"},"sequence":{"accession":"Q15544","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15544.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15544/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15544"}},"corpus_meta":[{"pmid":"16895980","id":"PMC_16895980","title":"TAF4 nucleates a core subcomplex of TFIID and mediates activated transcription from a TATA-less promoter.","date":"2006","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/16895980","citation_count":129,"is_preprint":false},{"pmid":"28918900","id":"PMC_28918900","title":"Transcription of Nearly All Yeast RNA Polymerase II-Transcribed Genes Is Dependent on Transcription Factor TFIID.","date":"2017","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/28918900","citation_count":129,"is_preprint":false},{"pmid":"11802163","id":"PMC_11802163","title":"IFN-Stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff.","date":"2002","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11802163","citation_count":105,"is_preprint":false},{"pmid":"12840001","id":"PMC_12840001","title":"Systematic analysis of essential yeast TAFs in genome-wide transcription and preinitiation complex assembly.","date":"2003","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/12840001","citation_count":88,"is_preprint":false},{"pmid":"8670810","id":"PMC_8670810","title":"Human TAF(II28) promotes transcriptional stimulation by activation function 2 of the retinoid X receptors.","date":"1996","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/8670810","citation_count":73,"is_preprint":false},{"pmid":"17030624","id":"PMC_17030624","title":"ATM and ATR pathways signal alternative splicing of Drosophila TAF1 pre-mRNA in response to DNA damage.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17030624","citation_count":61,"is_preprint":false},{"pmid":"9632676","id":"PMC_9632676","title":"The putative cofactor TIF1alpha is a protein kinase that is hyperphosphorylated upon interaction with liganded nuclear receptors.","date":"1998","source":"The Journal of biological 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interacts with the human T cell leukemia virus type I Tax transactivator and promotes its transcriptional activity.","date":"1997","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/9108034","citation_count":33,"is_preprint":false},{"pmid":"35681201","id":"PMC_35681201","title":"Enhancer-promoter interaction maps provide insights into skeletal muscle-related traits in pig genome.","date":"2022","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/35681201","citation_count":30,"is_preprint":false},{"pmid":"10336414","id":"PMC_10336414","title":"The TATA-binding protein and its associated factors are differentially expressed in adult mouse tissues.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10336414","citation_count":30,"is_preprint":false},{"pmid":"28257693","id":"PMC_28257693","title":"Hypomorphic Pathogenic Variants in TAF13 Are Associated with Autosomal-Recessive Intellectual Disability and Microcephaly.","date":"2017","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28257693","citation_count":29,"is_preprint":false},{"pmid":"27752147","id":"PMC_27752147","title":"Identification of reliable reference genes for qRT-PCR studies of the developing mouse mammary gland.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27752147","citation_count":21,"is_preprint":false},{"pmid":"9569032","id":"PMC_9569032","title":"Genomics and transcription analysis of human TFIID.","date":"1998","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/9569032","citation_count":21,"is_preprint":false},{"pmid":"15657423","id":"PMC_15657423","title":"Mapping and functional characterization of the TAF11 interaction with TFIIA.","date":"2005","source":"Molecular and cellular 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cell","url":"https://pubmed.ncbi.nlm.nih.gov/26257286","citation_count":13,"is_preprint":false},{"pmid":"31620231","id":"PMC_31620231","title":"Dual Inhibition of TAF1 and BET Bromodomains from the BI-2536 Kinase Inhibitor Scaffold.","date":"2019","source":"ACS medicinal chemistry letters","url":"https://pubmed.ncbi.nlm.nih.gov/31620231","citation_count":13,"is_preprint":false},{"pmid":"21811308","id":"PMC_21811308","title":"Epigenetic regulation of the X-chromosomal macrosatellite repeat encoding for the cancer/testis gene CT47.","date":"2011","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/21811308","citation_count":12,"is_preprint":false},{"pmid":"38254370","id":"PMC_38254370","title":"Detection of Runs of Homozygosity and Identification of Candidate Genes in the Whole Genome of Tunchang Pigs.","date":"2024","source":"Animals : an open access journal from 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Genetic Association Analysis of Skin Traits and the TAF11 Gene in Shenxian Pigs. Animals 2026, 16, 593.","date":"2026","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/42072047","citation_count":0,"is_preprint":false},{"pmid":"41131451","id":"PMC_41131451","title":"The impact of haplotypes derived from Chinese pigs on genetic variation and economic traits in the Duroc breed.","date":"2025","source":"Genetics, selection, evolution : GSE","url":"https://pubmed.ncbi.nlm.nih.gov/41131451","citation_count":0,"is_preprint":false},{"pmid":"40666909","id":"PMC_40666909","title":"Cotranslational assembly confers specificity for in vivo target heterodimerization of paralogous H2B-like TAF12 proteins in the human fungal pathogen Candida albicans.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40666909","citation_count":0,"is_preprint":false},{"pmid":"41651412","id":"PMC_41651412","title":"Histone fold domain positioning dictates cotranslational heterodimeric assembly of paralogous TAF12/TAF12L in Candida albicans.","date":"2026","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41651412","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.23.660276","title":"Cotranslational assembly confers specificity for in vivo target heterodimerization of paralogous H2B-like TAF12 proteins in the human fungal pathogen  <i>Candida albicans</i>","date":"2025-06-26","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.23.660276","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17655,"output_tokens":3865,"usd":0.05547,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11552,"output_tokens":4485,"usd":0.084943,"stage2_stop_reason":"end_turn"},"total_usd":0.140413,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"TAF11 and TAF13 form a ternary complex with TBP via their histone fold (HF) domains. TAF11/TAF13 competes with TATA-box DNA for binding to the DNA-binding surface of TBP, and also competes with the N-terminal domain of TAF1 (previously implicated in TATA-box mimicry). Cross-linking mass spectrometry and crystal coordinates defined the architecture of the TAF11/TAF13/TBP complex. A highly conserved C-terminal TBP-interaction domain (CTID) in TAF13 was identified as essential for supporting cell growth.\",\n      \"method\": \"Crystal structure, cross-linking mass spectrometry (CLMS), biochemical competition assays, mutagenesis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal coordinates, CLMS, biochemical competition assays with mutagenesis, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"29111974\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The TAF11–TFIIA interaction involves two distinct regions of TAF11: the conserved histone fold domain and the N-terminal region. TAF11 imparts changes to both TFIIA-DNA and TBP-DNA contacts at promoter DNA, enhancing formation and stabilization of the TFIIA-TBP-DNA complex. A TAF11 allele defective for interaction with TFIIA causes conditional growth phenotypes and transcription defects in yeast.\",\n      \"method\": \"Genetic suppressor screen (compensatory mutant isolation), in vivo transcription assay, DNA footprinting/binding assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with compensatory mutations, transcription assays, DNA binding analyses; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"15657423\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"In yeast, TAF11 and TAF13 provide critical functional contacts with TBP during preinitiation complex (PIC) assembly. Depletion of TAF11 (via temperature-sensitive mutation) impairs TBP recruitment and PIC assembly at dependent promoters.\",\n      \"method\": \"Temperature-sensitive yeast mutants, genome-wide expression profiling, chromatin immunoprecipitation (TBP recruitment/PIC assembly assays)\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — temperature-sensitive alleles with genome-wide expression profiling plus ChIP for PIC assembly; replicated across all 13 essential TAFs in same study\",\n      \"pmids\": [\"12840001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"Human TAF(II)28 (TAF11) promotes transcriptional stimulation by the activation function 2 (AF-2) of retinoid X receptors (RXR) in mammalian cells. TAF(II)28 is selectively depleted in COS cell TFIID, explaining the lack of RXR AF-2 activity in these cells. The potentiation effect correlated with the ability of TAF(II)28 to interact with TBP, but did not appear to require direct TAF(II)28–RXR interactions.\",\n      \"method\": \"Transient transfection/coexpression in COS and HeLa cells, transcriptional reporter assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — transcription reporter assays in cells, correlation of TBP interaction with function, single lab with multiple receptor types tested\",\n      \"pmids\": [\"8670810\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"Human TAF(II)28 (TAF11) directly interacts with the HTLV-I Tax transactivator protein both in transfected HeLa cells (co-immunoprecipitation) and in vitro with purified proteins. Overexpression of hTAF(II)28 significantly increases transactivation by Tax, and this potentiation requires both Tax–TAF(II)28 interaction and TAF(II)28–TBP interaction.\",\n      \"method\": \"Co-immunoprecipitation in transfected HeLa cells, in vitro binding with purified proteins, transient transcription reporter assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and in vitro pulldown with purified proteins plus functional reporter assay; single lab\",\n      \"pmids\": [\"9108034\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"hTAF(II)28 (TAF11) interacts with the ligand-binding domains (LBDs) of the vitamin D3 receptor (VDR) and thyroid hormone receptor alpha (TRalpha) in a ligand-reversible manner when coexpressed in COS cells. Fine mapping showed that the determinants for TAF(II)28 interaction map to alpha-helix H3 of VDR and are distinct from those for hTAF(II)55 interaction.\",\n      \"method\": \"Coexpression and co-immunoprecipitation in COS cells, deletion and point mutagenesis mapping\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP with mutagenesis mapping in cells, single lab; ligand-reversibility tested with multiple receptors\",\n      \"pmids\": [\"10744685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"TIF1alpha selectively phosphorylates TAF(II)28 (TAF11) in vitro, along with TFIIEalpha and TAF(II)55. Purified recombinant TIF1alpha possesses intrinsic kinase activity and undergoes autophosphorylation.\",\n      \"method\": \"In vitro kinase assay with purified recombinant proteins\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro kinase assay with purified proteins is Tier 1, but single lab, single method for this specific finding on TAF11\",\n      \"pmids\": [\"9632676\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"TAF(II)28 (TAF11) does not contribute to STAT2-mediated IFN-stimulated transcription; overexpression of TAF(II)28 did not potentiate STAT2 function, in contrast to TAF(II)130.\",\n      \"method\": \"Transient transfection/coexpression in cells, transcriptional reporter assays\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method; this is a negative result establishing that TAF11 is not required for this specific pathway\",\n      \"pmids\": [\"11802163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"In Drosophila TFIID, TAF11 is a peripheral subunit that contributes very little to overall TFIID complex stability, in contrast to core subunits TAF4, TAF5, TAF6, TAF9, and TAF12. RNAi knockdown of TAF11 does not substantially destabilize the TFIID complex.\",\n      \"method\": \"RNAi knockdown in Drosophila tissue culture cells, western blot analysis of TFIID subunit levels\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic RNAi of all TFIID subunits with protein-level readouts; single lab but comprehensive comparative study\",\n      \"pmids\": [\"16895980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Rapid degron-dependent depletion of yeast TAF11 causes strong decreases in nascent transcription at nearly all mRNA-coding genes, demonstrating that TAF11 is required for expression of essentially all yeast mRNAs, irrespective of TATA vs. TATA-less promoter class.\",\n      \"method\": \"Degron-mediated rapid protein depletion, nascent transcription measurement (NET-seq or equivalent)\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — rapid degron depletion (acute loss-of-function) with genome-wide nascent transcription readout; replicated with multiple TAF subunits in same study\",\n      \"pmids\": [\"28918900\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Drosophila TAF11 is a component of the RISC Loading Complex (RLC) in addition to its nuclear role in TFIID. TAF11 associates with Dcr-2/R2D2 in the cytoplasm and localizes to D2 bodies. TAF11 forms a tetramer that facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading. The RLC was reconstituted in vitro using recombinant Dcr-2-R2D2 complex, TAF11, and duplex siRNA.\",\n      \"method\": \"Genetic screen (taf11 null mutant), co-immunoprecipitation, in vitro RLC reconstitution, siRNA binding and RISC loading assays, cytoplasmic localization imaging\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of RLC plus genetic screen plus Co-IP and localization; multiple orthogonal methods establishing cytoplasmic RNAi function of TAF11\",\n      \"pmids\": [\"26257286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TAF13 variants (p.Met40Lys and p.Leu31His) associated with intellectual disability and microcephaly impair formation of the TAF13-TAF11 heterodimer, as demonstrated by co-immunoprecipitation in HeLa cells. The TAF11-TAF13 heterodimer is required for their recruitment into the TFIID complex.\",\n      \"method\": \"Co-immunoprecipitation in transfected HeLa cells, molecular modeling\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP in human cells with disease-associated mutants; single lab but supported by structural modeling\",\n      \"pmids\": [\"28257693\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TAF11 is essential for EBV super-enhancer (ESE) activity and MYC transcription in lymphoblastoid cell lines (LCLs). CRISPR knockout of TAF11 significantly decreased 525ESE reporter activity and MYC expression.\",\n      \"method\": \"Genome-wide CRISPR screen, CRISPR knockout, luciferase reporter assay, RT-qPCR\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO with defined transcriptional phenotype, single lab, multiple readouts\",\n      \"pmids\": [\"31167905\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TAF11 overexpression (driven by a variant that recruits more STAT1/STAT3 to the TAF11 promoter) downregulates CDH1 and CTNND1 by binding to their promoter regions and inhibiting transcriptional activity, thereby disrupting cranial neural crest cell migration and causing craniofacial defects in zebrafish.\",\n      \"method\": \"ChIP, EMSA/supershift, dual-luciferase reporter assay, RNA-seq, zebrafish overexpression model with alcian blue staining, time-lapse imaging, WISH, immunofluorescence, TUNEL assay\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (ChIP, EMSA, reporter assay, in vivo zebrafish model); single lab\",\n      \"pmids\": [\"39727181\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In Taf13-null mouse embryos and ESCs, loss of the Taf11-Taf13 heterodimer had little effect on TFIID integrity and caused only a mild reduction of TBP promoter recruitment, but led to altered PIC formation and globally reduced RNA Pol II recruitment. This indicates that the Taf11-Taf13 heterodimer is not essential for TBP/TFIID recruitment, revealing plasticity in PIC formation pathways.\",\n      \"method\": \"Gene knockout in mice and ESCs, cryo-EM (referenced), ChIP for TBP and Pol II recruitment, embryoid body formation assay\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockout with genome-wide ChIP readouts; single lab; contradicts the strong predicted role for TAF11-TAF13 in TBP deposition from structural studies\",\n      \"pmids\": [\"40491483\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAF11 (TAFII28) is a peripheral subunit of the TFIID general transcription factor complex that, together with TAF13, forms a histone fold domain-containing heterodimer that binds the DNA-binding surface of TBP and competes with both TATA-box DNA and the TAF1 N-terminal domain for TBP association, thereby contributing to TBP regulation, PIC assembly, and near-universal RNA Pol II transcription; it also mediates transcriptional coactivation by directly interacting with nuclear receptors (VDR, TRα), viral transactivators (Tax), and can be phosphorylated by TIF1α, while in Drosophila it unexpectedly functions in the cytoplasm as a structural component of the RISC Loading Complex, facilitating Dcr-2/R2D2 tetramerization and RNAi efficiency.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TAF11 is a peripheral subunit of the general transcription factor TFIID that contributes to RNA Polymerase II preinitiation complex (PIC) assembly across essentially the entire mRNA-coding genome [#9]. It functions as a histone-fold heterodimer with TAF13, and this TAF11/TAF13 pairing engages the DNA-binding surface of TBP, competing with both TATA-box DNA and the TATA-mimicking N-terminal domain of TAF1 for TBP association [#0]; heterodimer formation is in turn required for recruitment of both TAFs into TFIID [#11]. Within the assembling complex TAF11 makes functional contacts that support TBP recruitment and stabilizes the TFIIA-TBP-DNA complex through its histone fold and N-terminal regions [#1, #2]. Despite this, TAF11 contributes little to overall TFIID structural stability, marking it as a regulatory rather than scaffolding subunit [#8], and genetic loss of the TAF11-TAF13 heterodimer perturbs PIC formation and Pol II recruitment more than TFIID integrity or TBP deposition, indicating plasticity in how PICs assemble [#14]. Beyond core transcription, TAF11 acts as a coactivator surface that potentiates activation by nuclear receptors and viral transactivators: it relays RXR AF-2 activity in a manner correlating with its TBP interaction [#3], binds the ligand-binding domains of VDR and TRalpha in a ligand-reversible manner [#5], and directly binds the HTLV-I Tax protein to enhance Tax-dependent transactivation [#4]. In Drosophila, TAF11 has an unexpected cytoplasmic function distinct from transcription, serving as a structural component of the RISC Loading Complex where its tetramerization promotes Dcr-2/R2D2 assembly and efficient siRNA loading [#10]. TAF11 has been linked to disease contexts including TAF13-associated intellectual disability and microcephaly through impaired heterodimer formation [#11] and craniofacial defects arising from TAF11 overexpression and aberrant repression of CDH1 and CTNND1 [#13].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Established that TAF11 is not merely a passive TFIID subunit but a functional relay for activator signals, linking it to nuclear receptor coactivation.\",\n      \"evidence\": \"Transient coexpression and reporter assays in COS and HeLa cells testing RXR AF-2 stimulation\",\n      \"pmids\": [\"8670810\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Effect correlated with TBP interaction rather than direct TAF11-RXR contact, leaving the mechanistic bridge undefined\", \"Reporter-based readout without endogenous gene analysis\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Demonstrated a direct physical and functional link between TAF11 and a viral transactivator, showing the coactivator role extends to Tax-driven transcription.\",\n      \"evidence\": \"Reciprocal Co-IP in HeLa cells and in vitro binding with purified proteins plus reporter assays\",\n      \"pmids\": [\"9108034\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; structural basis of the Tax-TAF11 interface not resolved\", \"Endogenous viral target genes not assayed\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Identified TAF11 as a substrate of TIF1alpha kinase, raising the possibility of post-translational regulation of TFIID coactivator function.\",\n      \"evidence\": \"In vitro kinase assay with purified recombinant TIF1alpha and TFIID components\",\n      \"pmids\": [\"9632676\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphosite on TAF11 not mapped\", \"Functional consequence of phosphorylation in cells not established\", \"Single in vitro method\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Refined the nuclear receptor coactivation model by mapping ligand-reversible TAF11 contacts to a defined receptor surface distinct from other TAF interactions.\",\n      \"evidence\": \"Co-IP with deletion/point mutagenesis mapping of VDR and TRalpha LBDs in COS cells\",\n      \"pmids\": [\"10744685\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction shown by Co-IP without structural confirmation\", \"Physiological consequence on target gene expression untested\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Delimited the coactivator specificity of TAF11 by showing it is dispensable for STAT2-mediated interferon transcription, distinguishing it from TAF130.\",\n      \"evidence\": \"Transient coexpression and reporter assays in cells\",\n      \"pmids\": [\"11802163\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Negative result from a single reporter system\", \"Does not exclude roles in other STAT pathways\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Established that TAF11, with TAF13, provides critical TBP contacts during PIC assembly, defining its core mechanistic role in transcription initiation.\",\n      \"evidence\": \"Temperature-sensitive yeast mutants with genome-wide expression profiling and ChIP for TBP recruitment\",\n      \"pmids\": [\"12840001\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"ts-mutant depletion is slow and may permit secondary effects\", \"Direct biochemical mechanism of TBP contact not resolved here\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Resolved how TAF11 stabilizes the early initiation complex by defining two TAF11 regions that contact TFIIA and remodel TBP-DNA and TFIIA-DNA interactions.\",\n      \"evidence\": \"Genetic suppressor screen, in vivo transcription assays, and DNA footprinting in yeast\",\n      \"pmids\": [\"15657423\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural detail of the TAF11-TFIIA interface not solved\", \"Generality to all promoter classes not tested\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Classified TAF11 as a peripheral, non-scaffolding TFIID subunit, distinguishing its regulatory function from structural core TAFs.\",\n      \"evidence\": \"Systematic RNAi of all TFIID subunits with western blot readouts in Drosophila cells\",\n      \"pmids\": [\"16895980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stability readout does not address functional contribution to transcription\", \"Single comparative study\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed a transcription-independent cytoplasmic function: TAF11 acts as a structural tetramerizing component of the RISC Loading Complex to drive RNAi.\",\n      \"evidence\": \"Drosophila genetic screen, Co-IP, in vitro RLC reconstitution, siRNA binding/RISC loading assays, and localization imaging\",\n      \"pmids\": [\"26257286\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether this RNAi role is conserved beyond Drosophila is unaddressed\", \"Structural basis of the TAF11 tetramer not solved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Provided the structural mechanism by which TAF11/TAF13 regulates TBP, showing the heterodimer occupies TBP's DNA-binding surface and competes with both TATA DNA and TAF1.\",\n      \"evidence\": \"Crystal structure, cross-linking mass spectrometry, biochemical competition assays, and mutagenesis\",\n      \"pmids\": [\"29111974\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the inhibitory heterodimer is displaced to permit promoter DNA binding in vivo is not defined\", \"Static structure does not capture assembly dynamics\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrated by acute depletion that TAF11 is required for near-universal mRNA transcription, settling its role as a general rather than promoter-class-specific factor.\",\n      \"evidence\": \"Degron-mediated rapid depletion with genome-wide nascent transcription measurement in yeast\",\n      \"pmids\": [\"28918900\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not separate direct TFIID requirement from indirect effects\", \"Mammalian generality not tested in this system\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected TAF11 heterodimer formation to human disease, showing TAF13 mutations that disrupt the TAF11-TAF13 interface underlie intellectual disability and microcephaly.\",\n      \"evidence\": \"Reciprocal Co-IP of disease-associated TAF13 mutants in HeLa cells with molecular modeling\",\n      \"pmids\": [\"28257693\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-IP-based; downstream transcriptional consequences of heterodimer loss not measured\", \"Causality demonstrated for TAF13 variants rather than TAF11 itself\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Linked TAF11 to oncogenic enhancer function, showing it is required for EBV super-enhancer activity and MYC expression.\",\n      \"evidence\": \"Genome-wide CRISPR screen, CRISPR knockout, luciferase reporter, and RT-qPCR in lymphoblastoid cell lines\",\n      \"pmids\": [\"31167905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the effect is direct via TFIID at the super-enhancer is not resolved\", \"Single cell-line context\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed TAF11 can act as a transcriptional repressor in development, with overexpression downregulating adhesion genes and disrupting neural crest migration.\",\n      \"evidence\": \"ChIP, EMSA, dual-luciferase reporter, RNA-seq, and zebrafish overexpression model\",\n      \"pmids\": [\"39727181\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of promoter-specific repression by a general TFIID subunit unclear\", \"Single in vivo model\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Challenged the structural model by showing in vivo loss of the Taf11-Taf13 heterodimer minimally affects TFIID integrity and TBP recruitment yet impairs PIC formation and Pol II loading, revealing plasticity in assembly pathways.\",\n      \"evidence\": \"Taf13 knockout in mice and ESCs with ChIP for TBP and Pol II recruitment and embryoid body assays\",\n      \"pmids\": [\"40491483\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Apparent tension with crystallographic TBP-regulation model unresolved\", \"Mechanism of the residual PIC-formation defect not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TAF11/TAF13's TBP-occluding configuration is regulated and displaced in vivo to permit promoter engagement, and how a general TFIID subunit achieves the gene-specific activating versus repressing outcomes seen in development and disease, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mechanism connecting the inhibitory structural state to in vivo PIC assembly dynamics\", \"No model reconciling general transcription requirement with promoter-selective regulatory outcomes\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [3, 4, 13]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 11]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2, 8]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 2, 9]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\"TFIID\", \"RISC Loading Complex\"],\n    \"partners\": [\"TAF13\", \"TBP\", \"TFIIA\", \"TAF1\", \"Dcr-2\", \"R2D2\", \"VDR\", \"TRalpha\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}