TATA Binding Protein
Encyclopedia
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 35 base pair
s 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.
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.
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) compliments 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
.
with:
General transcription factor
General transcription factors or basal transcription factors are protein transcription factors that have been shown to be important in the transcription of class II genes to mRNA templates...
that binds specifically to a DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
sequence called the TATA box
TATA box
The TATA box is a DNA sequence found in the promoter region of genes in archaea and eukaryotes; approximately 24% of human genes contain a TATA box within the core promoter....
. This DNA sequence is found about 35 base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s upstream of the transcription start site in some eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
promoters. TBP, along with a variety of TBP-associated factors, make up the TFIID, a general transcription factor
General transcription factor
General transcription factors or basal transcription factors are protein transcription factors that have been shown to be important in the transcription of class II genes to mRNA templates...
that in turn makes up part of the RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
preinitiation complex
Preinitiation complex
The preinitiation complex is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes...
. 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
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
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
Polyglutamine tract
A polyglutamine tract or polyQ tract is a portion of a protein consisting of a sequence of several glutamine units. A tract typically consists of about 10 to a few hundred such units....
, and thus increase the length of the polyglutamine string, are associated with spinocerebellar ataxia
Spinocerebellar ataxia
Spinocerebellar ataxia is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right.-Classification:...
17, a neurodegenerative disorder classified as a polyglutamine disease.
Role as Transcription Factor Subunit
TBP is a subunit of the eukaryotic transcription factorTranscription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
TFIID. TFIID is the first protein to bind to DNA during the formation of the pre-initiation transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
complex of RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
(RNA Pol II). Binding of TFIID to the TATA box
TATA box
The TATA box is a DNA sequence found in the promoter region of genes in archaea and eukaryotes; approximately 24% of human genes contain a TATA box within the core promoter....
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
RNA polymerase I
RNA polymerase I is, in eukaryotes, the enzyme that only transcribes ribosomal RNA , a type of RNA that accounts for over 50% of the total RNA synthesized in a cell....
and RNA polymerase III
RNA polymerase III
RNA polymerase III transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs. The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose expression is required in all cell types and most environmental conditions...
, 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 boxTATA box
The TATA box is a DNA sequence found in the promoter region of genes in archaea and eukaryotes; approximately 24% of human genes contain a TATA box within the core promoter....
within the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, 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
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
and arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
amino acid residues. The sharp bend in the DNA is produced through projection of four bulky phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
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
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
and thymine
Thymine
Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
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
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
to begin transcription of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
TBP's C-terminus composes of a helicoidal shape that (incompletely) compliments 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 I
RNA polymerase I is, in eukaryotes, the enzyme that only transcribes ribosomal RNA , a type of RNA that accounts for over 50% of the total RNA synthesized in a cell....
, RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
, and RNA polymerase III
RNA polymerase III
RNA polymerase III transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs. The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose expression is required in all cell types and most environmental conditions...
.
Interactions
TATA-binding protein has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- BRF1BRF1 (gene)Transcription factor IIIB 90 kDa subunit is a protein that in humans is encoded by the BRF1 gene.-Interactions:BRF1 has been shown to interact with Retinoblastoma-like protein 2, Retinoblastoma-like protein 1, TATA binding protein and Retinoblastoma protein.-External links:...
- BTAF1BTAF1TATA-binding protein-associated factor 172 is a protein that in humans is encoded by the BTAF1 gene.-Interactions:BTAF1 has been shown to interact with TATA binding protein.-Further reading:...
- C-FosC-FosIn the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.-Structure and function:c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at...
- C-junC-junc-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
- EDF1EDF1Endothelial differentiation-related factor 1 is a protein that in humans is encoded by the EDF1 gene.-Interactions:EDF1 has been shown to interact with Peroxisome proliferator-activated receptor gamma, TATA binding protein and Liver X receptor alpha....
- GTF2BTranscription Factor II BTranscription factor II B is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. It is encoded by the gene....
- GTF2A1GTF2A1Transcription initiation factor IIA subunit 1 is a protein that in humans is encoded by the GTF2A1 gene.-Interactions:GTF2A1 has been shown to interact with TATA binding protein and TBPL1.-Further reading:...
- GTF2F1GTF2F1General transcription factor IIF subunit 1 is a protein that in humans is encoded by the GTF2F1 gene.-Interactions:GTF2F1 has been shown to interact with TAF1, HNRPU, GTF2H4, CTDP1, TATA binding protein, POLR2A, MED21, TAF11, Serum response factor and Transcription Factor II B.-Further reading:...
- GTF2H4GTF2H4General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.-Interactions:GTF2H4 has been shown to interact with MED21, GTF2F1, TATA binding protein, XPB, POLR2A and Transcription Factor II B....
- Mdm2Mdm2Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...
- MSX1MSX1Msh homeobox 1, also known as MSX1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and...
- NFYBNFYBNuclear transcription factor Y subunit beta is a protein that in humans is encoded by the NFYB gene.-Interactions:NFYB has been shown to interact with CCAAT/enhancer binding protein zeta, CNTN2, TATA binding protein and Myc.-Further reading:...
- P53P53p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, - PAX6PAX6Paired box protein Pax-6 also known as aniridia type II protein or oculorhombin is a protein that in humans is encoded by the PAX6 gene.- Function :PAX6 is a member of the Pax gene family...
- POLR2APOLR2ADNA-directed RNA polymerase II subunit RPB1 is an enzyme that in humans is encoded by the POLR2A gene.-Interactions:POLR2A has been shown to interact with Transcription elongation regulator 1, CREB-binding protein, BRCA1, GTF2H4, TATA-binding protein, PCAF, GTF2F1, SUPT5H, Transcription Factor II...
, - POU2F1POU2F1POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the POU2F1 gene.-Interactions:POU2F1 has been shown to interact with SNAPC4, Ku80, Glucocorticoid receptor, Sp1 transcription factor, NPAT, POU2AF1, Host cell factor C1, TATA binding protein, RELA, Nuclear...
- RELARELATranscription factor p65 is a protein that in humans is encoded by the RELA gene.-Interactions:RELA has been shown to interact with NFKBIB, ETHE1, NFKBIE, RFC1, TRIB3, CREB binding protein, Neutrophil cytosolic factor 1, Glucocorticoid receptor, MTPN, BRCA1, C-Fos, POU2F1, BTRC, TATA-binding...
, - NR2B1Retinoid X receptor alphaRetinoid X receptor alpha , also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.- Function :...
- TAF1TAF1Transcription initiation factor TFIID subunit 1, also known as transcription initiation factor TFIID 250 kDa subunit or TBP-associated factor 250 kDa , is a protein that in humans is encoded by the TAF1 gene.-Function:...
- TAF10TAF10Transcription initiation factor TFIID subunit 10 is a protein that in humans is encoded by the TAF10 gene.-Interactions:TAF10 has been shown to interact with TAF9, Transcription initiation protein SPT3 homolog, TAF13 and TATA binding protein....
- TAF11TAF11Transcription initiation factor TFIID subunit 11 is a protein that in humans is encoded by the TAF11 gene.-Interactions:TAF11 has been shown to interact with TAF15, TAF13, TATA binding protein, GTF2F1, POLR2A and Transcription Factor II B....
- TAF13TAF13Transcription initiation factor TFIID subunit 13 is a protein that in humans is encoded by the TAF13 gene.-Interactions:TAF13 has been shown to interact with TAF15, TAF11, TAF10 and TATA binding protein.-Further reading:...
- TAF15TAF15TATA-binding protein-associated factor 2N is a protein that in humans is encoded by the TAF15 gene.-Interactions:TAF15 has been shown to interact with TAF7, POLR2C, TAF5, POLR2E, TAF13, SAFB, TAF11, TATA binding protein and POLR2G.-Further reading:...
- TAF4TAF4Transcription initiation factor TFIID subunit 4 is a protein that in humans is encoded by the TAF4 gene.-Interactions:TAF4 has been shown to interact with TATA binding protein, CBX5 and Transcription initiation protein SPT3 homolog.-Further reading:...
- TAF5TAF5Transcription initiation factor TFIID subunit 5 is a protein that in humans is encoded by the TAF5 gene.-Interactions:TAF5 has been shown to interact with TAF9, TAF15, TAF6 and TATA binding protein.-Further reading:...
- TAF6TAF6Transcription initiation factor TFIID subunit 6 is a protein that in humans is encoded by the TAF6 gene.-Interactions:TAF6 has been shown to interact with TAF5 and TATA binding protein.-Further reading:...
- TAF7TAF7Transcription initiation factor TFIID subunit 7 is a protein that in humans is encoded by the TAF7 gene.-Interactions:TAF7 has been shown to interact with TAF15, TAF1 and TATA binding protein.-External links:...
- TAF9TAF9TAF9 RNA polymerase II, TATA box binding protein -associated factor, 32kDa, also known as TAF9, is a protein which in humans is encoded by the TAF9 gene.- Function :...
.