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| | <StructureSection load='1h6f' size='340' side='right'caption='[[1h6f]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='1h6f' size='340' side='right'caption='[[1h6f]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1h6f]] 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=1H6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H6F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1h6f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H6F FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</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=1h6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h6f OCA], [http://pdbe.org/1h6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1h6f RCSB], [http://www.ebi.ac.uk/pdbsum/1h6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1h6f ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=1h6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h6f OCA], [https://pdbe.org/1h6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h6f RCSB], [https://www.ebi.ac.uk/pdbsum/1h6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h6f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/TBX3_HUMAN TBX3_HUMAN] Ulnar-mammary syndrome. The disease is caused by variants affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TBX3_HUMAN TBX3_HUMAN] Transcriptional repressor involved in developmental processes (PubMed:10468588). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence, or a half-site, which are present in the regulatory region of several genes (PubMed:12000749). Probably plays a role in limb pattern formation (PubMed:10468588). Required for mammary placode induction, and maintenance of the mammary buds during development (By similarity). Involved in branching morphogenesis in both developing lungs and adult mammary glands, via negative modulation of target genes; acting redundantly with TBX2 (By similarity). Required, together with TBX2, to maintain cell proliferation in the embryonic lung mesenchyme; perhaps acting downstream of SHH, BMP and TGFbeta signaling (By similarity). Involved in modulating early inner ear development, acting independently of, and also redundantly with, TBX2 in different subregions of the developing ear (By similarity). Acts as a negative regulator of PML function in cellular senescence (PubMed:22002537).[UniProtKB:P70324]<ref>PMID:10468588</ref> <ref>PMID:12000749</ref> <ref>PMID:22002537</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | *[[Brachyury|Brachyury]] | | *[[Brachyury|Brachyury]] |
| | *[[T-box proteins|T-box proteins]] | | *[[T-box proteins|T-box proteins]] |
| - | *[[TBX3|TBX3]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Coll, M]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Muller, C W]] | + | [[Category: Coll M]] |
| - | [[Category: Developmental protein]] | + | [[Category: Muller CW]] |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Holt-oram-syndrome]]
| + | |
| - | [[Category: Ig-fold]]
| + | |
| - | [[Category: Nuclear protein]]
| + | |
| - | [[Category: Repressor]]
| + | |
| - | [[Category: T-box transcription factor]]
| + | |
| - | [[Category: Tbx3]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Ulnar-mammary syndrome]]
| + | |
| Structural highlights
Disease
TBX3_HUMAN Ulnar-mammary syndrome. The disease is caused by variants affecting the gene represented in this entry.
Function
TBX3_HUMAN Transcriptional repressor involved in developmental processes (PubMed:10468588). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence, or a half-site, which are present in the regulatory region of several genes (PubMed:12000749). Probably plays a role in limb pattern formation (PubMed:10468588). Required for mammary placode induction, and maintenance of the mammary buds during development (By similarity). Involved in branching morphogenesis in both developing lungs and adult mammary glands, via negative modulation of target genes; acting redundantly with TBX2 (By similarity). Required, together with TBX2, to maintain cell proliferation in the embryonic lung mesenchyme; perhaps acting downstream of SHH, BMP and TGFbeta signaling (By similarity). Involved in modulating early inner ear development, acting independently of, and also redundantly with, TBX2 in different subregions of the developing ear (By similarity). Acts as a negative regulator of PML function in cellular senescence (PubMed:22002537).[UniProtKB:P70324][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.
Publication Abstract from PubMed
T-box genes encode transcription factors involved in morphogenesis and organogenesis of vertebrates and invertebrates. Mutations in human T-box genes TBX3, TBX5, and TBX1 cause severe genetic disorders known as Ulnar-Mammary syndrome (UMS), Holt-Oram syndrome (HOS), and DiGeorge syndrome, respectively. The crystal structure of the T-box domain of the first human T-box transcription factor, TBX3, in complex with DNA at 1.7 A resolution explains structural consequences of T-box domain point mutations observed in UMS and HOS patients. Comparison with the structure of the T-box domain from Xenopus laevis (Xbra) bound to DNA shows differences in several secondary structure elements and in the quaternary structure of the two complexes. TBX3 independently recognizes the two binding sites present in the palindromic DNA duplex, whereas in Xbra, binding to the palindrome is stabilized through interactions between the two monomers. The different quaternary structures suggest different DNA binding modes for T-box transcription factors.
Structure of the DNA-bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome.,Coll M, Seidman JG, Muller CW Structure. 2002 Mar;10(3):343-56. PMID:12005433[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ He Ml, Wen L, Campbell CE, Wu JY, Rao Y. Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10212-7. PMID:10468588 doi:10.1073/pnas.96.18.10212
- ↑ Lingbeek ME, Jacobs JJ, van Lohuizen M. The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. J Biol Chem. 2002 Jul 19;277(29):26120-7. PMID:12000749 doi:10.1074/jbc.M200403200
- ↑ Martin N, Benhamed M, Nacerddine K, Demarque MD, van Lohuizen M, Dejean A, Bischof O. Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence. EMBO J. 2012 Jan 4;31(1):95-109. PMID:22002537 doi:10.1038/emboj.2011.370
- ↑ Coll M, Seidman JG, Muller CW. Structure of the DNA-bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome. Structure. 2002 Mar;10(3):343-56. PMID:12005433
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