TATA-binding protein

TBP
crystal structure of a yeast brf1-tbp-dna ternary complex
Identifiers
Symbol	TBP
Pfam	PF00352
Pfam clan	CL0407
InterPro	IPR000814
PROSITE	PDOC00303
SCOP	1tbp
SUPERFAMILY	1tbp
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

TATA box binding protein
PDB rendering based on 1c9b.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1C9B, 1CDW, 1JFI, 1NVP, 1TGH
Identifiers
Symbols	TBP ; GTF2D; GTF2D1; HDL4; SCA17; TFIID
External IDs	OMIM: 600075 MGI: 101838 HomoloGene: 2404 GeneCards: TBP Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II repressing transcription factor binding • sequence-specific DNA binding transcription factor activity • protein binding • transcription factor binding • enzyme binding • transcription regulatory region DNA binding • repressing transcription factor binding Cellular component • female pronucleus • male pronucleus • nucleoplasm • transcription factor TFIID complex • transcription factor TFIIA complex • nuclear euchromatin • cytoplasm Biological process • chromatin silencing at rDNA • transcription from RNA polymerase I promoter • transcription initiation from RNA polymerase I promoter • transcription elongation from RNA polymerase I promoter • termination of RNA polymerase I transcription • transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • transcription elongation from RNA polymerase II promoter • transcription from RNA polymerase III promoter • spermatogenesis • gene expression • viral process • regulation of gene expression, epigenetic • negative regulation of gene expression, epigenetic • positive regulation of transcription, DNA-templated Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6908	21374
Ensembl	ENSG00000112592	ENSMUSG00000014767
UniProt	P20226	P29037
RefSeq (mRNA)	NM_001172085	NM_013684
RefSeq (protein)	NP_001165556	NP_038712
Location (UCSC)	Chr 6: 170.55 – 170.57 Mb	Chr 17: 15.5 – 15.53 Mb
PubMed search	[1]	[2]

The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 30 base pairs upstream of the transcription start site in some eukaryotic gene promoters. TBP, along with a variety of TBP-associated factors, make up the TFIID, a general transcription factor that in turn makes up part of the RNA polymerase II preinitiation complex. As one of the few proteins in the preinitiation complex that binds DNA in a sequence-specific manner, it helps position RNA polymerase II over the transcription start site of the gene. However, it is estimated that only 10-20% of human promoters have TATA boxes. Therefore, TBP is probably not the only protein involved in positioning RNA polymerase II.

TBP is involved in DNA melting (double strand separation) by bending the DNA by 80° (the AT-rich sequence to which it binds facilitates easy melting). The TBP is an unusual protein in that it binds the minor groove using a β sheet.

Another distinctive feature of TBP is a long string of glutamines in the N-terminus of the protein. This region modulates the DNA binding activity of the C-terminus, and modulation of DNA-binding affects the rate of transcription complex formation and initiation of transcription. Mutations that expand the number of CAG repeats encoding this polyglutamine tract, and thus increase the length of the polyglutamine string, are associated with spinocerebellar ataxia 17, a neurodegenerative disorder classified as a polyglutamine disease.

Role as transcription factor

TBP is a subunit of the eukaryotic transcription factor TFIID. TFIID is the first protein to bind to DNA during the formation of the pre-initiation transcription complex of RNA polymerase II (RNA Pol II). Binding of TFIID to the TATA box in the promoter region of the gene initiates the recruitment of other factors required for RNA Pol II to begin transcription. Some of the other recruited transcription factors include TFIIA, TFIIB, and TFIIF. Each of these transcription factors is formed from the interaction of many protein subunits, indicating that transcription is a heavily regulated process.

TBP is also a necessary component of RNA polymerase I and RNA polymerase III, and is, it is thought, the only common subunit required by all three of the RNA polymerases.

DNA-Protein Interactions

When TBP binds to a TATA box within the DNA, it distorts the DNA by inserting amino acid side-chains between base pairs, partially unwinding the helix, and doubly kinking it. The distortion is accomplished through a great amount of surface contact between the protein and DNA. TBP binds with the negatively charged phosphates in the DNA backbone through positively charged lysine and arginine amino acid residues. The sharp bend in the DNA is produced through projection of four bulky phenylalanine residues into the minor groove. As the DNA bends, its contact with TBP increases, thus enhancing the DNA-protein interaction.

The strain imposed on the DNA through this interaction initiates melting, or separation, of the strands. Because this region of DNA is rich in adenine and thymine residues, which base-pair through only two hydrogen bonds, the DNA strands are more easily separated. Separation of the two strands exposes the bases and allows RNA polymerase II to begin transcription of the gene.

TBP's C-terminus composes of a helicoidal shape that (incompletely) complements the T-A-T-A region of DNA. It is interesting to note that this incompleteness allows DNA to be passively bent on binding.

For information on the use of TBP in cells see: RNA polymerase I, RNA polymerase II, and RNA polymerase III.

Protein-Protein interactions

TATA-binding protein has been shown to interact with:

• BRF1,
• BTAF1,
• C-Fos,
• C-jun,
• EDF1,
• GTF2B (TFIIB),
• GTF2A1 (TFIIA subunit 1),
• GTF2F1 (TFIIF subunit 1)
• GTF2H4 (TFIIH subunit 4),
• Mdm2,
• MSX1,
• NFYB,
• P53,
• PAX6,
• POLR2A,
• POU2F1,
• RELA,
• NR2B1,
• TAF1,
• TAF4,
• TAF5,
• TAF6,
• TAF7,
• TAF9.
• TAF10,
• TAF11,
• TAF13, and
• TAF15.

Complex Assembly

The TATA-box binding protein (TBP) is required for the initiation of transcription by RNA polymerases I, II and III, from promoters with or without a TATA box. TBP associates with a host of factors, including the general transcription factors TFIIA, -B, -D, -E, and -H, to form huge multi-subunit pre-initiation complexes on the core promoter. Through its association with different transcription factors, TBP can initiate transcription from different RNA polymerases. There are several related TBPs, including TBP-like (TBPL) proteins.

Structure

The C-terminal core of TBP (~180 residues) is highly conserved and contains two 88-amino acid repeats that produce a saddle-shaped structure that straddles the DNA; this region binds to the TATA box and interacts with transcription factors and regulatory proteins . By contrast, the N-terminal region varies in both length and sequence.

External links

• GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 17
• Interactive TBP Structure at massey.ac.nz
• PDB Molecule of the Month TATA-binding protein
• TATA-Box Binding Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook TBP