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FLASH GENE
Symbol TBP contributors: mct - updated : 17-06-2020
HGNC name TATA box binding protein
HGNC id 11588
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a polymorphic polyglutamine (polyQ) domain in its N terminus
  • a DNA-binding domain in its highly conserved C terminus
    • mono polymer monomer
    HOMOLOGY
    interspecies homolog to murine Tbp
    Homologene
    FAMILY
  • transcription factor (architectural) TF2D family
  • TBP family
    • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • large multiprotein complex, composed of the TATA box-binding protein (TBP) and 14 TBP-associated factors (TAFs), which plays a key role in the regulation of gene expression by RNA polymerase II
  • TBP, BTAF1, and DR1 establish a regulatory circuit that controls downstream core promoter element-dependent versus TATA-dependent transcription b
  • gene transcription in mammalian cells is a dynamic process involving regulated assembly of transcription complexes on chromatin in which TBP plays a central role (PMIS: 20627952)
  • is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery
  • is an essential factor that is required at virtually every eukaryotic promoter to initiate transcription
  • plays a central role in eukaryotic gene transcription
  • eukaryotic TBP initially acquired multiple Eukarya-specific interactors through asymmetric evolution of the two repeats
  • TBP is likely required for re-establishing the transcription program following mitosis
  • plays a central role in regulating gene expression and is the first step in the process of pre-initiation complex (PIC) formation on promoter DNA
    • CELLULAR PROCESS nucleotide, transcription, initiation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the multisubunit complex TFIID, general transcription factor IID DNA binding subunit
  • s1 also component of TFIIIB and general transcription factor SL1
  • component of the transcription factor
    • SL1/TIFIB complex, composed of TBP and at least TAF1A, TAF1B and TAF1C
  • TBP/GTF2B/Pol II complexes were linked to the production of non-polyadenylated RNA rather than polyadenylated transcripts
    • INTERACTION
    DNA
  • binds DNA as monomer
  • binds to TATA boxes in core promoters and bends the TATA DNA
    • RNA
    small molecule
    protein
  • MYC binding, RUVBL1
  • TATA-box binding
  • DNA binding by TAF4/TAF4B-TAF12 facilitates the association of TBP with the core promoter of a subset of genes
  • BTAF1 negatively regulates TBP and DR1 binding to active promoters
  • interacting with BTAF1 (BTAF1 thus acts as a TBP chaperone to control its interaction with other macromolecules)
  • TBP interacts with NFY subunit A (NFYA), which could be a target of mutant TBP in SCA17
  • H3K4me3, through interactions with TAF3, directs global TBP recruitment
  • H3K4me3 facilitates global TBP recruitment to the core promoters of active genes
  • TAF4 having coactivator function for E proteins that involves enhanced TBP binding
  • may be predominantly crosslinking to GTF2B, rather than directly to the TATA element
  • action of BTAF1 is required to clear TBP from intrinsically preferred (TATA-containing) binding sites, ensuring sufficient soluble TBP to bind intrinsically disfavored (TATA-less) sites
  • TAF9 is required for FAM48A and TBP promoter occupancy to promote transcriptional activation
  • salt-dependent changes in the nucleosome conformation regulate TBP access to the TATA box, where access is highly constrained under physiological conditions
  • GATA2, SP1 and TATA-binding protein (TBP)interacting with the proximal promoter region of MAOA
  • upregulation of HUWE1 expression during myogenesis induces TBP degradation and myotube differentiation
  • interplay between an E3 ligase and a deubiquitinating enzyme regulating TBP levels during cellular differentiation
  • TBP-DNA affinity as well as other aspects of promoter sequence influence BTAF1 function
  • TBP loading by AFF1 through TAF1A, TAF1B, TAF1C is the major rate-limiting step in MLL fusion-dependent transcription
  • key checkpoint function for the chaperonin TCP1, which specifically associates with nascent TAF5 for subsequent handover to TAF6-TAF9 and ultimate holo-TBP formation
  • lifetime of TBP at the promoter site is controlled by several cofactors including the Modifier of transcription 1 (BTAF1)
  • O-GlcNAcylation at T114 of TBP blocks its interaction with BTAF1, hence the formation of the B-TFIID complex, and its dynamic cycling on and off of DNA
    • cell & other
    REGULATION
    Other TBP protein levels are tightly regulated by the ubiquitin-proteasome system
    ASSOCIATED DISORDERS
    corresponding disease(s) SCA17
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    of an N-terminal fragment of the TATA-box binding protein (TBP) in Alzheimer's disease brain tissue
    tumoral     --over  
    contribute to enhanced VEGFA transcription early in colorectal cancer development to drive tumorigenesis
    Susceptibility to type I diabetes( see IDDM8)
    Variant & Polymorphism other CAG/CAA polymorphism in exon 3 associated with diabetes susceptibility
    Candidate gene for mental retardation in the 6q subtelomeric deletion phenotype (DEL6QD)
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • polyQ expansion causes abnormal interaction of TBP with the general transcription factor TFIIB and induces neurodegeneration in transgenic SCA17 mice
  • chronic alcohol administration in mice leads to enhanced expression of Tbp, Brf1, tRNA, and 5S rRNA gene transcription in the liver