Transactivation domain
The transactivation domain or trans-activating domain (TAD) is a transcription factor scaffold domain which contains binding sites for other proteins such as transcription coregulators. These binding sites are frequently referred to as activation functions (AFs).[1] 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 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.[2][3][4][5][6][7][8][9]
In general we can distinguish four classes of TADs:[10]
- acidic domains (called also “acid blobs” or “negative noodles", rich in D and E amino acids, present in Gal4, Gcn4 and VP16).[11]
- glutamine-rich domains (contains multiple repetitions like "QQQXXXQQQ", present in SP1)[12]
- proline-rich domains (contains repetitions like "PPPXXXPPP" present in
- isoleucine-rich domains (repetitions "IIXXII", present in NTF-1)[14]
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.[15]
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, Gln3, Gcn4 in yeast, and by p53, NFAT, NF-κB and VP16 in mammals. The definition largely overlaps with an "acidic" family definition. A 9aaTAD prediction tool is available.[16] 9aaTADs tend to have an associated 3-aa hydrophobic (usually Leu-rich) region immediately to its N-terminal.[17]
9aaTAD transcription factors
The KIX domain of general coactivators Med15(Gal11) interacts with 9aaTAD transcription factors
Source | 9aaTAD | Peptide-KIX interaction (NMR) |
---|---|---|
p53 TAD1 | E TFSD LWKL | LSPEETFSDLWKLPE |
p53 TAD2 | D DIEQ WFTE | QAMDDLMLSPDDIEQWFTEDPGPD |
MLL | S DIMD FVLK | DCGNILPSDIMDFVLKNTP |
E2A | D LLDF SMMF | PVGTDKELSDLLDFSMMFPLPVT |
Rtg3 | E TLDF SLVT | E2A homolog |
CREB | R KILN DLSS | RREILSRRPSYRKILNDLSSDAP |
CREBaB6 | E AILA ELKK | CREB-mutant binding to KIX |
Gli3 | D DVVQ YLNS | TAD homology to CREB/KIX |
Gal4 | D DVYN YLFD | Pdr1 and Oaf1 homolog |
Oaf1 | D LFDY DFLV | DLFDYDFLV |
Pip2 | D FFDY DLLF | Oafl homolog |
Pdr1 | E DLYS ILWS | EDLYSILWSDWY |
Pdr3 | T DLYH TLWN | Pdr1 homolog |
Glutamine-rich
Glutamine (Q)-rich TADs are found in
See also
References
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