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 gene family TBP is a member of a small gene family of TBP-related factors. The first TBP-related factor (TRF/TRF1) was identified in the fruit fly Drosophila, but appears to be fly or insect-specific. Subsequently TBPL1/TRF2 was found in the genomes of many metazoans, whereas vertebrate genomes encode a third vertebrate family member, TBPL2/TRF3. In specific cell types or on specific promoters TBP can be replaced by one of these TBP-related factors, some of which interact with the TATA box similarly to TBP. Role as transcription factor TBP is a subunit of the eukaryotic general transcription factor TFIID. TFIID is the first protein to bind to DNA during the formation of the transcription preinitiation complex of RNA polymerase II (RNA Pol II). 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. Majority of human promoters are TATA-less housekeeping gene promoters. The binding of TBP to these promoters is facilitated by housekeeping gene regulators. Interestingly, transcription initiates within a narrow region at around 30 bp downstream of TATA box on TATA-containing promoters, while transcription start sites of TATA-less promoters are dispersed within a 200 bp region. 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 contains several protein subunits. TBP is also important for transcription by RNA polymerase I and RNA polymerase III, and is therefore involved in transcription initiation by all three RNA polymerases. 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