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| | ==Solution structure of the first two RRM domains of FIR in the complex with FBP Nbox peptide== | | ==Solution structure of the first two RRM domains of FIR in the complex with FBP Nbox peptide== |
| - | <StructureSection load='2kxh' size='340' side='right' caption='[[2kxh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kxh' size='340' side='right'caption='[[2kxh]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kxh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KXH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kxh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KXH FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kxf|2kxf]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kxh OCA], [http://pdbe.org/2kxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kxh RCSB], [http://www.ebi.ac.uk/pdbsum/2kxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kxh ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kxh OCA], [https://pdbe.org/2kxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kxh RCSB], [https://www.ebi.ac.uk/pdbsum/2kxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kxh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PUF60_HUMAN PUF60_HUMAN]] DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA.<ref>PMID:10882074</ref> <ref>PMID:10606266</ref> <ref>PMID:11239393</ref> <ref>PMID:16452196</ref> <ref>PMID:16628215</ref> <ref>PMID:17579712</ref> [[http://www.uniprot.org/uniprot/FUBP1_HUMAN FUBP1_HUMAN]] Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription.<ref>PMID:8125259</ref> | + | [https://www.uniprot.org/uniprot/PUF60_HUMAN PUF60_HUMAN] DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA.<ref>PMID:10882074</ref> <ref>PMID:10606266</ref> <ref>PMID:11239393</ref> <ref>PMID:16452196</ref> <ref>PMID:16628215</ref> <ref>PMID:17579712</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cukier, C D]] | + | [[Category: Large Structures]] |
| - | [[Category: Diaz-Moreno, I]] | + | [[Category: Cukier CD]] |
| - | [[Category: Hollingworth, D]] | + | [[Category: Diaz-Moreno I]] |
| - | [[Category: Kelly, G]] | + | [[Category: Hollingworth D]] |
| - | [[Category: Ramos, A]] | + | [[Category: Kelly G]] |
| - | [[Category: Fbp]]
| + | [[Category: Ramos A]] |
| - | [[Category: Fir]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein-protein complex]]
| + | |
| - | [[Category: Rrm]]
| + | |
| Structural highlights
Function
PUF60_HUMAN DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Liu J, He L, Collins I, Ge H, Libutti D, Li J, Egly JM, Levens D. The FBP interacting repressor targets TFIIH to inhibit activated transcription. Mol Cell. 2000 Feb;5(2):331-41. PMID:10882074
- ↑ Page-McCaw PS, Amonlirdviman K, Sharp PA. PUF60: a novel U2AF65-related splicing activity. RNA. 1999 Dec;5(12):1548-60. PMID:10606266
- ↑ Liu J, Akoulitchev S, Weber A, Ge H, Chuikov S, Libutti D, Wang XW, Conaway JW, Harris CC, Conaway RC, Reinberg D, Levens D. Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum. Cell. 2001 Feb 9;104(3):353-63. PMID:11239393
- ↑ Matsushita K, Tomonaga T, Shimada H, Shioya A, Higashi M, Matsubara H, Harigaya K, Nomura F, Libutti D, Levens D, Ochiai T. An essential role of alternative splicing of c-myc suppressor FUSE-binding protein-interacting repressor in carcinogenesis. Cancer Res. 2006 Feb 1;66(3):1409-17. PMID:16452196 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-4459
- ↑ Liu J, Kouzine F, Nie Z, Chung HJ, Elisha-Feil Z, Weber A, Zhao K, Levens D. The FUSE/FBP/FIR/TFIIH system is a molecular machine programming a pulse of c-myc expression. EMBO J. 2006 May 17;25(10):2119-30. Epub 2006 Apr 20. PMID:16628215 doi:http://dx.doi.org/7601101
- ↑ Hastings ML, Allemand E, Duelli DM, Myers MP, Krainer AR. Control of pre-mRNA splicing by the general splicing factors PUF60 and U2AF65. PLoS One. 2007 Jun 20;2(6):e538. PMID:17579712 doi:http://dx.doi.org/10.1371/journal.pone.0000538
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