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| - | ==Crystal sturcture of human bromodomain protein== | + | |
| - | <StructureSection load='2yyn' size='340' side='right' caption='[[2yyn]], [[Resolution|resolution]] 2.50Å' scene=''> | + | ==Crystal structure of human bromodomain protein== |
| | + | <StructureSection load='2yyn' size='340' side='right'caption='[[2yyn]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2yyn]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YYN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2yyn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YYN FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIM24, RNF82, TIF1, TIF1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=2yyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yyn OCA], [https://pdbe.org/2yyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yyn RCSB], [https://www.ebi.ac.uk/pdbsum/2yyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yyn ProSAT], [https://www.topsan.org/Proteins/RSGI/2yyn TOPSAN]</span></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=2yyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yyn OCA], [http://pdbe.org/2yyn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yyn RCSB], [http://www.ebi.ac.uk/pdbsum/2yyn PDBsum], [http://www.topsan.org/Proteins/RSGI/2yyn TOPSAN]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN]] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:[http://omim.org/entry/188550 188550]]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene. | + | [https://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN]] Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).<ref>PMID:16322096</ref> <ref>PMID:19556538</ref> <ref>PMID:21164480</ref> | + | [https://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN] Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).<ref>PMID:16322096</ref> <ref>PMID:19556538</ref> <ref>PMID:21164480</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yy/2yyn_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yy/2yyn_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| Line 24: |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kishishita, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Murayama, K]] | + | [[Category: Kishishita S]] |
| - | [[Category: Structural genomic]] | + | [[Category: Murayama K]] |
| - | [[Category: Shirouzu, M]] | + | [[Category: Shirouzu M]] |
| - | [[Category: Terada, T]] | + | [[Category: Terada T]] |
| - | [[Category: Uchikubo-Kamo, T]] | + | [[Category: Uchikubo-Kamo T]] |
| - | [[Category: Yokoyama, S]] | + | [[Category: Yokoyama S]] |
| - | [[Category: Bromo domain]]
| + | |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Disease
TIF1A_HUMAN Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:188550. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.
Function
TIF1A_HUMAN Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Teyssier C, Ou CY, Khetchoumian K, Losson R, Stallcup MR. Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators. Mol Endocrinol. 2006 Jun;20(6):1276-86. Epub 2005 Dec 1. PMID:16322096 doi:10.1210/me.2005-0393
- ↑ Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, Bergmann A, Johnson RL, Barton MC. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11612-6. doi:, 10.1073/pnas.0813177106. Epub 2009 Jun 25. PMID:19556538 doi:10.1073/pnas.0813177106
- ↑ Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC. TRIM24 links a non-canonical histone signature to breast cancer. Nature. 2010 Dec 16;468(7326):927-32. PMID:21164480 doi:10.1038/nature09542
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