The transactivation domain or trans-activating domain (TAD) is a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

scaffold domain which contains binding sites for other

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

s such as

transcription coregulator In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription ar ...

s. These binding sites are frequently referred to as activation functions (AFs). TADs are named after their amino acid composition. These amino acids are either essential for the activity or simply the most abundant in the TAD. Transactivation by the

Gal4 The Gal4 transcription factor is a positive regulator of gene expression of galactose-induced genes. This protein represents a large fungal family of transcription factors, Gal4 family, which includes over 50 members in the yeast ''Saccharomyces ...

transcription factor is mediated by acidic amino acids, whereas hydrophobic residues in Gcn4 play a similar role. Hence, the TADs in Gal4 and Gcn4 are referred to as acidic or hydrophobic, respectively. In general we can distinguish four classes of TADs: * acidic domains (called also “acid blobs” or “negative noodles", rich in D and E amino acids, present in Gal4, Gcn4 and VP16). * glutamine-rich domains (contains multiple repetitions like "QQQXXXQQQ", present in SP1) * proline-rich domains (contains repetitions like "PPPXXXPPP" present in

c-jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only la ...

, AP2 and

Oct-2 Oct-2 (octamer-binding protein 2) also known as POU domain, class 2, transcription factor 2 is a protein that in humans is encoded by the POU2F2 gene. Oct-2 is an octamer transcription factor which is a member of the POU family POU or pou may r ...

) * isoleucine-rich domains (repetitions "IIXXII", present in NTF-1) Alternatively, since similar amino acid compositions does not necessary mean similar activation pathways, TADs can be grouped by the process they stimulate, either initiation or elongation.

Acidic/9aaTAD

Nine-amino-acid transactivation domain (9aaTAD) defines a domain common to a large superfamily of eukaryotic transcription factors represented by Gal4, Oaf1, Leu3, Rtg3,

Pho4 Pho4 is a protein with a basic helix-loop-helix (bHLH) transcription factor. It is found in ''S. cerevisiae'' and other yeasts. It functions as a transcription factor to regulate phosphate responsive genes located in yeast cells. The Pho4 protein ...

, Gln3, Gcn4 in yeast, and by

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

NFAT Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the developme ...

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

and

VP16 Vmw65, also known as VP16 or α-TIF (Trans Inducing Factor) is a trans-acting protein that forms a complex with the host transcription factors Oct-1 and HCF to induce immediate early gene transcription Transcription is the process of copying ...

in mammals. The definition largely overlaps with an "acidic" family definition. A 9aaTAD prediction tool is available. 9aaTADs tend to have an associated 3-aa hydrophobic (usually Leu-rich) region immediately to its N-terminal. 9aaTAD transcription factors

, MLL, E2A,

HSF1 Heat shock factor 1 (HSF1) is a protein that in humans is encoded by the ''HSF1'' gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regul ...

NF-IL6 CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the ''CEBPB'' gene. Function The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regi ...

, NFAT1 and

interact directly with the general coactivators

TAF9 TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa, also known as TAF9, is a protein that in humans is encoded by the ''TAF9'' gene. Function Initiation of transcription by RNA polymerase II requires the activities ...

and

CBP/p300 The p300-CBP coactivator family in humans is composed of two closely related transcriptional co-activating proteins (or coactivators): #p300 (also called EP300 or E1A binding protein p300) # CBP (also known as CREB-binding protein or CREBBP) ...

. p53 9aaTADs interact with TAF9, GCN5 and with multiple domains of CBP/p300 (KIX, TAZ1,TAZ2 and IBiD). The KIX domain of general coactivators Med15(Gal11) interacts with 9aaTAD transcription factors

, Pdr1, Oaf1, Gcn4, VP16,

Msn2 MSN (meaning Microsoft Network) is a web portal and related collection of Internet services and apps for Windows and mobile devices, provided by Microsoft and launched on August 24, 1995, alongside the release of Windows 95. The Microsoft N ...

Ino2 Ino or INO may refer to: Arts and music *I-No, a character in the ''Guilty Gear'' series of video games *Ino (Greek mythology), a queen of Thebes in Greek mythology * INO Records, an American Christian music label * Ino Yamanaka, a character in ...

and

P201 P, or p, is the sixteenth letter of the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is ''pee'' (pronounced ), plural ''pees''. History The ...

. Positions 1, 3-4, and 7 of the 9aaTAD are the main residues that interact with KIX. Interactions of Gal4, Pdr1 and Gcn4 with Taf9 have been observed. 9aaTAD is a common transactivation domain which recruits multiple general coactivators

MED15 Mediator of RNA polymerase II transcription subunit 15, also known as Gal11, Spt13 in yeast and PCQAP, ARC105, or TIG-1 in humans is a protein encoded by the ''MED15'' gene. Function MED15 is a general transcriptional cofactor of the mediator ...

and

GCN5 __NOTOC__ Histone acetyltransferase KAT2A is an enzyme that in humans is encoded by the ''KAT2A'' gene. Interactions GCN5L2 has been shown to interact with: * DDB1, * Ku70, * Ku80, * TADA2L, * TAF9, and * Transcription initiation protein ...

Glutamine-rich

Glutamine (Q)-rich TADs are found in

POU2F1 POU 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: * EPRS, * Glucocorticoid receptor, * Glyceraldehyde 3-phosphate dehydrogenase ...

(Oct1),

POU2F2 POU or pou may refer to: People * Pou (surname), a surname * Chu Pou (303–350), Chinese general and politician * Pou Temara (born 1948), New Zealand Māori academic Codes * POU, IATA airport code and FAA location identifier for Hudson Valley Re ...

(Oct2), and Sp1 (see also Sp/KLF family). Although such is not the case for every Q-rich TAD, Sp1 is shown to interact with

TAF4 Transcription initiation factor TFIID subunit 4 is a protein that in humans is encoded by the ''TAF4'' gene. Function Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordi ...

(TAFII 130), a part of the

TFIID Transcription factor II D (TFIID) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters o ...

assembly.

References

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External links

9aaTAD prediction tool
Transcription factors Protein domains

Acidic/9aaTAD

Glutamine-rich

See also

References

External links