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FLASH GENE
Symbol TBP contributors: mct - updated : 17-06-2020
HGNC name TATA box binding protein
HGNC id 11588
Corresponding disease
SCA17 spinocerebellar ataxia 17
Location 6q27      Physical location : 170.863.420 - 170.881.957
Synonym name transcription initiation factor TFIID TBP subunit
Synonym symbol(s) GTF2D, TF2D, GTF2D1, MGC117320, MGC126054, MGC126055, TFIID, SCA17
DNA
TYPE functioning gene
STRUCTURE 18.48 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
motif repetitive sequence   triplet
text structure
  • triplet CAG (<42 repeats) in the third exon, a methylation free CpG island spanning their promoter region
  • presence of a TATA-box motif in the promoter that has been strongly linked with noise
  • MAPPING cloned Y linked N status confirmed
    regionally located closely linked to PDCD2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1867 - 339 - 2009 19285969
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Endocrineneuroendocrinepituitary  highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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