Affinage

TAF5

Transcription initiation factor TFIID subunit 5 · UniProt Q15542

Length
800 aa
Mass
86.8 kDa
Annotated
2026-06-10
36 papers in source corpus 21 papers cited in narrative 21 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

TAF5 is an essential WD-40 repeat-containing subunit of the general transcription factor TFIID that functions principally as a structural scaffold for complex assembly and integrity (PMID:9045704, PMID:16895980). It nucleates a two-fold symmetric core subcomplex with the histone-fold TAFs TAF4, TAF6, TAF9, and TAF12, and RNAi depletion of TAF5 destabilizes TFIID in vivo, defining it as a stability determinant of the complex (PMID:16895980, PMID:23292512). The N-terminal half of TAF5 forms a flexible, extended dimer, and its two copies span the trilobed TFIID architecture, with TAF5 and TAF6 forming a topologically closed tetramer that stabilizes the compact lobed structure and contributes the linker domains connecting lobes (PMID:14765106, PMID:17227857, PMID:30405110). TAF5 regulates assembly of the TAF6-TAF9 submodule, and its incorporation is gated by the chaperonin CCT, which captures nascent cytoplasmic TAF5 before handing it over to TAF6-TAF9 for holo-TFIID formation (PMID:22696218, PMID:30510221). Beyond its scaffolding role, TAF5 serves as a direct target of transcriptional activators and coactivators: the SAYP coactivator binds TAF5 to couple SWI/SNF chromatin remodeling and TFIID into a supercomplex, and the yeast ortholog contains a Rap1-binding domain required for ribosomal protein gene transcription (PMID:19541607, PMID:20189987, PMID:28196871). The shared subunit also resides in the SAGA coactivator core, where it adopts a distinct conformation from TFIID (PMID:31969703). Functionally, TAF5 is required for the bulk of embryonic mRNA transcription and conveys locus specificity to TFIID during early development, with its loss causing failed implantation in mouse and craniofacial and cardiac defects in zebrafish; inclusion of its alternative exon-8 is required for TFIID assembly and global gene expression in human cells (PMID:11566890, PMID:38917794, PMID:37746814, PMID:38593904).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Established TAF5 as an integral TFIID subunit with selective interactions among the histone-fold TAFs and a core-promoter-specific function, distinguishing TATA-less from TATA-containing promoter requirements.

    Evidence Co-IP and antibody inhibition of in vitro transcription on defined promoters

    PMID:9045704

    Open questions at the time
    • Did not resolve TAF5 architecture within TFIID
    • Mechanism of promoter selectivity not defined structurally
  2. 2004 High

    Mapped TAF5 within the trilobed TFIID, showing two copies span separate lobes and contribute the inter-lobe linker, establishing its scaffolding geometry.

    Evidence EM, immunomapping, and reconstitution of a recombinant TAF5/histone-fold TAF subcomplex in yeast

    PMID:14765106

    Open questions at the time
    • Low resolution precluded atomic interactions
    • Did not define assembly order
  3. 2007 High

    Resolved the TAF5 N-terminal domain structure and demonstrated it forms a flexible extended dimer, identifying a biochemical property required for TFIID assembly.

    Evidence X-ray crystallography of NTD2 (2.2 Å) plus biochemical dimerization assays

    PMID:17227857

    Open questions at the time
    • Functional consequence of dimerization in cells not tested
    • Partner contacts of NTD2 clefts unidentified
  4. 2006 High

    Showed TAF5 is a stability determinant of TFIID, contributing to a stable core subcomplex, while having limited direct effect on transcription of tested promoters.

    Evidence RNAi knockdown in Drosophila cells with complex-stability and in vitro transcription readouts

    PMID:16895980

    Open questions at the time
    • Genome-wide transcriptional impact not assessed
    • Distinction between scaffolding and direct transcriptional roles unresolved
  5. 2010 High

    Identified a Rap1-binding domain in yeast Taf5 required for ribosomal protein gene transcription but dispensable for TFIID integrity, separating an activator-recruitment function from the scaffolding role.

    Evidence Domain mutagenesis, in vitro binding, yeast genetics, and gene-specific transcription assays

    PMID:20189987

    Open questions at the time
    • Whether human TAF5 carries an equivalent activator-binding surface unknown
    • Structural basis of Rap1 contact undefined
  6. 2009 Medium

    Demonstrated TAF5 is a direct docking target for the SAYP coactivator, coupling SWI/SNF chromatin remodeling to TFIID in an activation-required supercomplex.

    Evidence Direct binding, Co-IP, and functional transcription assays in Drosophila

    PMID:19541607

    Open questions at the time
    • Binding interface on TAF5 not mapped
    • Conservation in mammals not shown
  7. 2012 High

    Defined TAF5 as a regulator of TAF6-TAF9 submodule assembly and refined the human core-TFIID architecture, showing TAF5 within a two-fold symmetric core whose symmetry is broken by TAF8-TAF10 binding.

    Evidence TAF6C crystal structure, mutagenesis, Co-IP (idx 7) and cryo-EM of core-TFIID with reconstitution (idx 9)

    PMID:22696218 PMID:23292512

    Open questions at the time
    • Order of TAF5 entry into the assembly pathway not yet established
    • ChIP-based snRNA-gene and p21 recruitment claims (idx 4, 8) were single-method
  8. 2018 High

    Placed TAF5 at the center of a chaperoned, ordered cytoplasmic assembly pathway, with CCT capturing nascent TAF5 as a checkpoint before handover to TAF6-TAF9, and resolved a TAF5-TAF6 tetramer stabilizing the trilobed TFIID.

    Evidence Quantitative proteomics, structural and mutational analysis of the TAF5-TAF6-TAF9 submodule (idx 11), cryo-EM of promoter-bound yeast TFIID with cross-linking MS (idx 12), and yeast genetic suppression (idx 13)

    PMID:29485702 PMID:30405110 PMID:30510221

    Open questions at the time
    • Trigger that releases TAF5 from CCT not defined
    • How TAF9 is partitioned between TFIID and SAGA mechanistically unresolved
  9. 2020 High

    Showed the same Taf5 subunit adopts distinct conformations in SAGA versus TFIID, providing a structural basis for functional specialization of a shared subunit between two coactivator complexes.

    Evidence Cryo-EM of yeast SAGA core module (3.3 Å)

    PMID:31969703

    Open questions at the time
    • Determinants directing TAF5 to SAGA versus TFIID not identified
    • Human SAGA-specific paralog relationships addressed only later (idx 20, preprint)
  10. 2024 Medium

    Connected TAF5 to organismal phenotypes and locus-specific transcription, showing it is required for early embryonic transcription, conveys locus specificity in mammalian development, and that its alternative exon-8 is required for TFIID assembly and global expression.

    Evidence C. elegans/mouse RNAi and conditional knockout with RNA-seq (idx 16, 19), zebrafish forward-genetic knockout with metabolomics (idx 18), and CRISPR exon-deletion screens with mechanistic validation in human cells (idx 17)

    PMID:11566890 PMID:37746814 PMID:38593904 PMID:38917794

    Open questions at the time
    • Molecular basis of locus specificity conferred by TAF5 not defined
    • Whether developmental phenotypes reflect TFIID assembly defects versus selective gene targets unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAF5 mechanistically directs promoter and locus selectivity within TFIID, and what governs its release from CCT and partitioning between TFIID and SAGA, remain unresolved.
  • No structural model linking TAF5 conformation to gene-specific output
  • CCT-release trigger unknown
  • Human activator-binding surface analogous to yeast Rap1-binding domain not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2
Partners
CCTRAP1SAYPTAF12TAF4TAF6TAF9TBP
Complex memberships
BTFly supercomplexSAGATFIIDcore-TFIID (TAF5-TAF6-TAF9-TAF4-TAF12)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Human TAF5 (hTAFII100) is an integral subunit of TFIID that interacts strongly with histone H4-related hTAFII80 and histone H3-related hTAFII31 (both separately and as a stable complex), and shows weaker interactions with TBP, hTAFII250, hTAFII28, and hTAFII20, but not hTAFII55. Anti-hTAFII100 antibodies selectively inhibit basal transcription from a TATA-less initiator-containing promoter but not a TATA-containing promoter, suggesting a core promoter-specific function. Immunoprecipitation (in vivo and in vitro binding assays), antibody inhibition of in vitro transcription The Journal of biological chemistry High 9045704
2004 Yeast TFIID contains two copies of WD-40 repeat-containing TAF5, with its C- and N-termini located in different lobes of the trilobed TFIID structure. A recombinant complex containing TAF5 complexed with six histone fold-containing TAFs can form a trilobed structure. TAF5 contributes to the linker domains connecting the lobes. Electron microscopy, digital image analysis, immunomapping, reconstitution of recombinant subcomplex The EMBO journal High 14765106
2006 In Drosophila, RNAi knockdown of TAF5 (along with TAF4, TAF6, TAF9, TAF12) destabilizes the TFIID complex in vivo, indicating TAF5 plays a key role in TFIID stability. TAF5 contributes to a stable core subcomplex (with TAF4, TAF6, TAF9, TAF12). In contrast to TAF1 and TAF4, RNAi knockdown of TAF5 had little effect on transcription from either TATA-containing or TATA-less DPE-containing promoters. RNAi knockdown in Drosophila tissue culture cells, in vitro transcription assays Proceedings of the National Academy of Sciences of the United States of America High 16895980
2007 Crystal structure of the human TAF5-NTD2 domain at 2.2 Å resolution reveals an alpha-helical domain with distant structural similarity to RNA polymerase II CTD-interacting factors, containing several conserved clefts likely critical for TFIID assembly. Biochemical analysis shows the N-terminal half of TAF5 forms a flexible, extended dimer, a key property for TFIID complex assembly. X-ray crystallography (2.2 Å), biochemical dimerization assays Proceedings of the National Academy of Sciences of the United States of America High 17227857
2007 TFIID subunits TAF4, TAF5, and TBP are detected on the p21 core promoter prior to TAF1 upon UV-induced DNA damage in cells, suggesting that distinct TFIID subunits can be recruited separately to the promoter, with TAF5 being part of the initial promoter-bound TFIID scaffold. Chromatin immunoprecipitation (ChIP) at the p21 promoter in UV-irradiated cells Molecular cell Medium 17996705
2009 The SAYP transcription coactivator directly binds the TAF5 subunit of TFIID through its evolutionarily conserved SAY activation domain, thereby coupling the chromatin-remodeling factor Brahma (SWI/SNF) and TFIID into a stable supercomplex called BTFly. This interaction is required for transcription activation. Protein interaction assays (direct binding of SAY domain to TAF5), co-immunoprecipitation, functional transcription assays in Drosophila Proceedings of the National Academy of Sciences of the United States of America Medium 19541607
2010 Yeast Taf5 contains a Rap1-binding domain (RBD) that is essential for viability and required for transcription of ribosomal protein genes. The Taf5 RBD is dispensable for Taf-Taf interactions and TFIID stability. Cells with altered Taf5 RBD show reduced Rap1-binding affinity and selective defects in ribosomal protein gene transcription. Mutagenesis of Rap1-binding domain, in vitro binding assays, yeast genetics, gene-specific transcription assays The Journal of biological chemistry High 20189987
2012 TAF5 modulates the formation of the TAF6-TAF9 complex: mutations in the HEAT repeat domain of TAF6 that disrupt TAF6-TAF9 interaction have an even stronger effect in the context of a TAF5-TAF6-TAF9 trimeric complex, indicating TAF5 plays a regulatory role in TAF6-TAF9 submodule assembly within TFIID. Crystal structure of TAF6C domain (1.9 Å), mutagenesis, co-immunoprecipitation in HeLa cells, in vitro protein interaction assays The Journal of biological chemistry High 22696218
2012 TAF5 is associated with RNA polymerase II-transcribed snRNA genes by ChIP, but the full complement of TAFs at these genes differs from protein-coding gene promoters; TAF5 is present on snRNA genes whereas TAF1, TAF10, and TAF4 are not detected, indicating TAF5 is part of a distinct, snRNA gene-specific TBP/TAF complex. ChIP and siRNA-mediated knockdown Transcription Medium 22441827
2013 Cryo-EM structure of human core-TFIID at 11.6 Å resolution reveals a two-fold symmetric, interlaced architecture accommodating TAF4, TAF5, TAF6, TAF9, and TAF12 with their histone folds. TAF5 contributes to this symmetric core. Binding of one TAF8-TAF10 complex breaks the original symmetry, producing an asymmetric scaffold for holo-TFIID assembly. Cryo-electron microscopy (11.6 Å), biochemical reconstitution of core-TFIID subcomplex Nature High 23292512
2017 Yeast Taf5 is a direct binding target of the Rap1 transcriptional activation domain (AD). Mutation of the newly identified Rap1 AD reduces the efficiency of Rap1 binding to Taf5, confirming Taf5 as a functional coactivator target for Rap1-dependent gene transcription. Altered DNA-binding specificity variant (Rap1AS), in vitro binding assays to Taf5, transcription reporter assays The Journal of biological chemistry Medium 28196871
2018 The chaperonin CCT specifically associates with nascent TAF5 in the cytoplasm as a checkpoint for TFIID assembly, facilitating handover of TAF5 to TAF6-TAF9 for subsequent holo-TFIID formation. Structural and mutational analysis of the cytoplasmic TAF5-TAF6-TAF9 submodule identified novel interactions crucial for TFIID integrity and for allocation of TAF9 to either TFIID or the SAGA co-activator complex. Quantitative proteomics, structural analysis, mutagenesis of TAF5-TAF6-TAF9 submodule, co-immunoprecipitation in human cells Nature structural & molecular biology High 30510221
2018 Cryo-EM structure of promoter-bound yeast TFIID at better than 5 Å resolution reveals that TAF5 and TAF6 form a topologically closed tetramer that stabilizes the compact trilobed architecture of TFIID. This structural analysis confirms unique subunit stoichiometry in TFIID and reveals a hexameric arrangement of histone fold domain-containing TAFs in the Twin lobe. Cryo-electron microscopy (sub-5 Å), cross-linking mass spectrometry, crystal structure docking Nature communications High 30405110
2018 Overexpression of TAF5 (but not TAF9, TAF12, or TBP) suppresses the temperature-sensitive phenotype caused by TAF6 histone-fold domain (HFD) mutations in yeast, revealing a specific genetic and functional relationship between TAF5 and the TAF6 HFD in TFIID assembly and transcriptional activation. Yeast genetic suppression analysis, coimmunoprecipitation from yeast cell extracts The FEBS journal Medium 29485702
2020 Cryo-EM structure of yeast SAGA reveals that the core module contains Taf5 (ortholog of human TAF5) along with Sgf73, Spt20, and a histone octamer-like fold. Taf5 and the Taf6 HEAT domain adopt distinct conformations in SAGA compared to TFIID, explaining the functional specialization between these two complexes sharing the same subunit. Cryo-electron microscopy (3.3 Å resolution for core module) Nature High 31969703
2002 C. elegans TAF-5 (ortholog of human TAF5/TAFII100) is required for a significant fraction of embryonic mRNA transcription as shown by RNAi, but is not essential for expression of multiple developmental and metazoan-specific genes. This phenotype resembles that of TAF-9 and TAF-10 depletion, suggesting TAF-5 is part of a functional module that can be bypassed at many metazoan-specific promoters. RNA interference in C. elegans embryos, RT-PCR analysis of multiple gene targets The Journal of biological chemistry Medium 12458202
2001 C. elegans taf-5 (human TAFII130 ortholog) is required for essentially all early embryonic mRNA transcription as shown by RNAi, in contrast to taf-10 and taf-11 which have modular functions and can be bypassed at many developmental genes. This suggests a broad structural requirement for TAF-5 in either TFIID or TFTC-like complexes. RNAi in C. elegans embryos, transcriptional analysis of multiple developmental genes The EMBO journal Medium 11566890
2024 Inclusion of the TAF5 alternative exon-8 is required for assembly of the TFIID general transcription initiation complex in human cells; deletion or splice-site mutation of this exon disrupts TFIID assembly and reduces global gene expression output. Massively parallel exon deletion and splice-site mutation CRISPR screens, followed by mechanistic validation of TAF5 exon-8 effect on TFIID assembly and global gene expression Molecular cell High 38917794
2023 Loss of taf5 in zebrafish (nonsense mutation identified by forward genetic screen, confirmed by CRISPR/Cas9) causes craniofacial hypoplasia, ventricular hypoplasia, heart failure, and lethality. taf5-/- zebrafish display misregulation of metabolic gene expression, altered respiration, and metabolite changes, suggesting TAF5 contributes to cardiac and craniofacial development through regulation of metabolism. Forward genetic screen, CRISPR/Cas9 gene editing, RNA sequencing, respiration assays, metabolite studies in zebrafish Biology open Medium 37746814
2024 Mouse embryos with disrupted Taf5 fail to implant post-blastocyst formation and show aberrant lineage specification within the inner cell mass. Transcriptomic analysis reveals distinct gene targets affected by Taf5 loss compared to Taf12 or Taf13 loss, indicating TAF5 conveys locus specificity to TFIID in early mammalian development. Conditional knockout in mouse, transcriptomic analysis (RNA-seq), immunofluorescence for lineage markers Developmental biology Medium 38593904
2025 In human SAGA, TAF5L (the SAGA-specific paralog of TAF5 that arose by gene duplication in metazoans) adopts structural differences compared to canonical TAF5 that are directly implicated in accommodating the splicing-factor module (SPL). TAF6L's HEAT repeat domain provides a docking surface for SPL, with multiple differences between TAF6L/TAF5L and the canonical TFIID paralogs (TAF5/TAF6) required for this structural re-arrangement. Cryo-EM structure of endogenous human SAGA purified by affinity-ligand (high-resolution structure of SPL and TAF6L HEAT domain) bioRxivpreprint Medium bio_10.1101_2025.07.31.667873

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Human papillomavirus and the landscape of secondary genetic alterations in oral cancers. Genome research 180 30563911
2020 Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection. PeerJ 156 32547891
2006 TAF4 nucleates a core subcomplex of TFIID and mediates activated transcription from a TATA-less promoter. Proceedings of the National Academy of Sciences of the United States of America 129 16895980
2013 The architecture of human general transcription factor TFIID core complex. Nature 127 23292512
2020 Structure of the transcription coactivator SAGA. Nature 123 31969703
1997 CCAAT binding NF-Y-TBP interactions: NF-YB and NF-YC require short domains adjacent to their histone fold motifs for association with TBP basic residues. Nucleic acids research 103 9153318
2007 An acetylation switch in p53 mediates holo-TFIID recruitment. Molecular cell 82 17996705
2004 Mapping key functional sites within yeast TFIID. The EMBO journal 64 14765106
2012 Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer. Scientific reports 49 22900142
2009 Transcription coactivator SAYP combines chromatin remodeler Brahma and transcription initiation factor TFIID into a single supercomplex. Proceedings of the National Academy of Sciences of the United States of America 45 19541607
1997 Specific interactions and potential functions of human TAFII100. The Journal of biological chemistry 45 9045704
2018 Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly. Nature structural & molecular biology 43 30510221
2001 Distinct requirements for C.elegans TAF(II)s in early embryonic transcription. The EMBO journal 40 11566890
2010 Direct transactivator-transcription factor IID (TFIID) contacts drive yeast ribosomal protein gene transcription. The Journal of biological chemistry 35 20189987
2007 Nucleolar colocalization of TAF1 and testis-specific TAFs during Drosophila spermatogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 34 17823958
2018 Molecular structure of promoter-bound yeast TFIID. Nature communications 33 30405110
2004 Purification of active TFIID from Saccharomyces cerevisiae. Extensive promoter contacts and co-activator function. The Journal of biological chemistry 32 15448131
2012 TFIID TAF6-TAF9 complex formation involves the HEAT repeat-containing C-terminal domain of TAF6 and is modulated by TAF5 protein. The Journal of biological chemistry 24 22696218
2007 Structural analysis and dimerization potential of the human TAF5 subunit of TFIID. Proceedings of the National Academy of Sciences of the United States of America 24 17227857
2003 Novel subunits of the TATA binding protein free TAFII-containing transcription complex identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry following one-dimensional gel electrophoresis. Proteomics 23 12601814
2008 Expression analysis of TFIID in single human oocytes: new potential molecular markers of oocyte quality. Reproductive biomedicine online 22 18765004
2012 A novel TBP-TAF complex on RNA polymerase II-transcribed snRNA genes. Transcription 21 22441827
2004 An extensive requirement for transcription factor IID-specific TAF-1 in Caenorhabditis elegans embryonic transcription. The Journal of biological chemistry 19 14726532
2024 Genome-scale exon perturbation screens uncover exons critical for cell fitness. Molecular cell 17 38917794
2020 Fine mapping of QTL conferring Cercospora leaf spot disease resistance in mungbean revealed TAF5 as candidate gene for the resistance. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 12 33188437
2024 TATA-binding associated factors have distinct roles during early mammalian development. Developmental biology 9 38593904
2019 TAF5L functions as transcriptional coactivator of MITF involved in the immune response of the clam Meretrix petechialis. Fish & shellfish immunology 8 31743760
2002 A broad but restricted requirement for TAF-5 (human TAFII100) for embryonic transcription in Caenorhabditis elegans. The Journal of biological chemistry 8 12458202
2024 Novel insights into the mechanisms of seasonal cyclicity of testicles by proteomics and transcriptomics analyses in goose breeder lines. Poultry science 5 39190991
2017 Identification of a transcriptional activation domain in yeast repressor activator protein 1 (Rap1) using an altered DNA-binding specificity variant. The Journal of biological chemistry 5 28196871
2015 Indenes and tetralenes analogues attenuates lipopolysaccharide-induced inflammation: An in-vitro and in-vivo study. Chemico-biological interactions 5 26731479
2023 Deletion of taf1 and taf5 in zebrafish capitulate cardiac and craniofacial abnormalities associated with TAFopathies through perturbations in metabolism. Biology open 4 37746814
2018 Mutational analysis of TAF6 revealed the essential requirement of the histone-fold domain and the HEAT repeat domain for transcriptional activation. The FEBS journal 3 29485702
1981 Race-specific interactions between wheat genotypes and Indian cultures of stem rust. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 1 24276688
2025 Research on the diagnosis model of osteoarthritis based on methylation-related genes using machine learning algorithms. Frontiers in genetics 0 40822282
2023 Recessive embryonic lethal mutations uncovered in heterozygous condition in silkworm semiconsomic strains. Insect biochemistry and molecular biology 0 36931352

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