AF-2 domain binding
Definition
Target type: molecularfunction
Binding to an AF-2 protein domain, a highly conserved ligand-dependent transactivation domain which is essential for receptor-mediated transcriptional activation. [PMID:9682036]
The AF-2 domain, also known as the activation function 2 domain, is a highly conserved protein domain found in nuclear receptors. These receptors are a superfamily of ligand-dependent transcription factors that play crucial roles in regulating gene expression in response to diverse stimuli, including hormones, vitamins, and environmental signals. The AF-2 domain is responsible for mediating the interaction with coactivator proteins, which are essential for the recruitment of the transcriptional machinery to DNA and the subsequent activation of gene transcription. The binding of ligands, such as hormones, to the nuclear receptor results in a conformational change within the receptor, leading to the exposure of the AF-2 domain. This exposed AF-2 domain can then interact with coactivator proteins, which typically contain LXXLL motifs (where L is leucine and X is any amino acid). The interaction between the AF-2 domain and coactivators is mediated by a complex interplay of hydrophobic interactions and electrostatic forces. Once the coactivator protein is bound to the AF-2 domain, it recruits other components of the transcriptional machinery, including histone acetyltransferases (HATs) and mediator proteins, to the promoter region of the target gene. HATs modify histones by adding acetyl groups, leading to chromatin relaxation and increased accessibility for transcription factors. Mediator proteins act as bridging molecules that facilitate the interaction between the transcription factors and the basal transcription machinery. Together, these interactions result in the activation of gene transcription, leading to the production of specific proteins that mediate the physiological effects of the ligand. Therefore, the molecular function of AF-2 domain binding is essential for the regulation of gene expression in response to diverse stimuli by facilitating the recruitment of coactivator proteins, HATs, and mediator proteins, ultimately leading to the activation of gene transcription.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Estrogen-related receptor gamma | An estrogen-related receptor gamma that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62508] | Homo sapiens (human) |
Compounds (10)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| bisphenol a | 4,4'-isopropylidene diphenol: stimulates proliferative responses and cytokine productions of murine spleen cells and thymus cells in vitro bisphenol : By usage, the methylenediphenols, HOC6H4CH2C6H4OH, commonly p,p-methylenediphenol, and their substitution products (generally derived from condensation of two equivalent amounts of a phenol with an aldehyde or ketone). The term also includes analogues in the the methylene (or substituted methylene) group has been replaced by a heteroatom. bisphenol A : A bisphenol that is 4,4'-methanediyldiphenol in which the methylene hydrogens are replaced by two methyl groups. | bisphenol | endocrine disruptor; environmental contaminant; xenobiotic; xenoestrogen |
| 4-cumylphenol | diarylmethane | ||
| 4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol | stilbenoid | ||
| diethylstilbestrol | diethylstilbestrol : An olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups. Diethylstilbestrol: A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed) | olefinic compound; polyphenol | antifungal agent; antineoplastic agent; autophagy inducer; calcium channel blocker; carcinogenic agent; EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor; endocrine disruptor; xenoestrogen |
| afimoxifene | afimoxifene : A tertiary amino compound that is tamoxifen in which the phenyl group which is in a Z- relationship to the ethyl substituent is hydroxylated at the para- position. It is the active metabolite of tamoxifen. | phenols; tertiary amino compound | antineoplastic agent; estrogen receptor antagonist; metabolite |
| tamoxifen | stilbenoid; tertiary amino compound | angiogenesis inhibitor; antineoplastic agent; bone density conservation agent; EC 1.2.3.1 (aldehyde oxidase) inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; estrogen antagonist; estrogen receptor antagonist; estrogen receptor modulator | |
| 4-hydroxytoremifene | 4-hydroxytoremifene: metabolite of toremifene; RN refers to (Z)-isomer; structure in first source | ||
| gsk 4716 | GSK 4716: structure in first source | monoterpenoid | |
| n'-((1e)-(4-(diethylamino)phenyl)methylene)-4-hydroxybenzohydrazide | N'-((1E)-(4-(diethylamino)phenyl)methylene)-4-hydroxybenzohydrazide: structure in first source | ||
| gsk5182 | GSK5182: an estrogen-related receptor gamma inverse agonist |