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Structural highlights

Disease

[TAF2_HUMAN] Microcephaly-thin corpus callosum-intellectual disability syndrome. The disease is caused by mutations affecting the gene represented in this entry. [TBP_HUMAN] Defects in TBP are the cause of spinocerebellar ataxia type 17 (SCA17) [MIM:607136]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA17 is an autosomal dominant cerebellar ataxia (ADCA) characterized by widespread cerebral and cerebellar atrophy, dementia and extrapyramidal signs. The molecular defect in SCA17 is the expansion of a CAG repeat in the coding region of TBP. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.^{[1] [2] [3]}

Function

[TAF12_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TAFs components-TIIFD are essential for mediating regulation of RNA polymerase transcription. [TAF7_HUMAN] Functions as a component of the DNA-binding general transcription factor complex TFIID, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Present in both of the previously described TFIID species which either lack or contain TAFII30 (TFIID alpha and TFIID beta respectively). [TAF2_HUMAN] Transcription factor TFIID is one of the general factors required for accurate and regulated initiation by RNA polymerase II. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. It requires core promoter-specific cofactors for productive transcription stimulation. TAF2 stabilizes TFIID binding to core promoter.^{[4] [5]} [T2AG_HUMAN] TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity.^[6] [TAF6_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. [TAF4_HUMAN] Makes part of TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone. [TAF9_HUMAN] Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription.^[7] [TBP_HUMAN] General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.^[8] [TAF8_HUMAN] Transcription factor TFIID is one of the general factors required for accurate and regulated initiation by RNA polymerase II. Mediates both basal and activator-dependent transcription. Plays a role in the differentiation of preadipocyte fibroblasts to adipocytes, however, does not seem to play a role in differentiation of myoblasts. Required for the integration of TAF10 in the TAF complex. May be important for survival of cells of the inner cell mass which constitute the pluripotent cell population of the early embryo (By similarity). [TAF5_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TAFs components-TIIFD are essential for mediating regulation of RNA polymerase transcription. TAF5/TAFII100 interacts strongly with the histone H4-related TAF6/TAFII80 and the histone H3-related TAF9/TAFII31, as well as a stable complex comprised of both TAF5/TAFII80 and TAF6/TAFII31. Apparently weaker interactions of TAF5/TAFII100 with TBP, TAF1/TAFII250, TAF11/TAFII28, and TAF12/TAFII20, but not TAF7/TAFII55, also have been observed. [TAF10_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors.

References

1. ↑ Zuhlke C, Hellenbroich Y, Dalski A, Kononowa N, Hagenah J, Vieregge P, Riess O, Klein C, Schwinger E. Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia. Eur J Hum Genet. 2001 Mar;9(3):160-4. PMID:11313753 doi:10.1038/sj.ejhg.5200617
2. ↑ Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet. 2001 Jul 1;10(14):1441-8. PMID:11448935
3. ↑ Silveira I, Miranda C, Guimaraes L, Moreira MC, Alonso I, Mendonca P, Ferro A, Pinto-Basto J, Coelho J, Ferreirinha F, Poirier J, Parreira E, Vale J, Januario C, Barbot C, Tuna A, Barros J, Koide R, Tsuji S, Holmes SE, Margolis RL, Jardim L, Pandolfo M, Coutinho P, Sequeiros J. Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. Arch Neurol. 2002 Apr;59(4):623-9. PMID:11939898
4. ↑ Kaufmann J, Ahrens K, Koop R, Smale ST, Muller R. CIF150, a human cofactor for transcription factor IID-dependent initiator function. Mol Cell Biol. 1998 Jan;18(1):233-9. PMID:9418870
5. ↑ Martinez E, Ge H, Tao Y, Yuan CX, Palhan V, Roeder RG. Novel cofactors and TFIIA mediate functional core promoter selectivity by the human TAFII150-containing TFIID complex. Mol Cell Biol. 1998 Nov;18(11):6571-83. PMID:9774672
6. ↑ Mitsiou DJ, Stunnenberg HG. TAC, a TBP-sans-TAFs complex containing the unprocessed TFIIAalphabeta precursor and the TFIIAgamma subunit. Mol Cell. 2000 Sep;6(3):527-37. PMID:11030333
7. ↑ Frontini M, Soutoglou E, Argentini M, Bole-Feysot C, Jost B, Scheer E, Tora L. TAF9b (formerly TAF9L) is a bona fide TAF that has unique and overlapping roles with TAF9. Mol Cell Biol. 2005 Jun;25(11):4638-49. PMID:15899866 doi:http://dx.doi.org/25/11/4638
8. ↑ Friedrich JK, Panov KI, Cabart P, Russell J, Zomerdijk JC. TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter. J Biol Chem. 2005 Aug 19;280(33):29551-8. Epub 2005 Jun 21. PMID:15970593 doi:10.1074/jbc.M501595200
9. ↑ Patel AB, Louder RK, Greber BJ, Grunberg S, Luo J, Fang J, Liu Y, Ranish J, Hahn S, Nogales E. Structure of human TFIID and mechanism of TBP loading onto promoter DNA. Science. 2018 Nov 15. pii: science.aau8872. doi: 10.1126/science.aau8872. PMID:30442764 doi:http://dx.doi.org/10.1126/science.aau8872