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| | ==NMR structure of HESX-1 homeodomain double mutant R31L/E42L== | | ==NMR structure of HESX-1 homeodomain double mutant R31L/E42L== |
| - | <StructureSection load='2k40' size='340' side='right' caption='[[2k40]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2k40' size='340' side='right'caption='[[2k40]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k40]] is a 1 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=2K40 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K40 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k40]] is a 1 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=2K40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K40 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HESX1, HANF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2k40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k40 OCA], [http://pdbe.org/2k40 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k40 RCSB], [http://www.ebi.ac.uk/pdbsum/2k40 PDBsum]</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=2k40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k40 OCA], [https://pdbe.org/2k40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k40 RCSB], [https://www.ebi.ac.uk/pdbsum/2k40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k40 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/HESX1_HUMAN HESX1_HUMAN]] Hypothyroidism due to deficient transcription factors involved in pituitary development or function;Combined pituitary hormone deficiencies, genetic forms;Pituitary stalk interruption syndrome;Septo-optic dysplasia;Kallmann syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9620767</ref> <ref>PMID:11136712</ref> The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:11136712</ref> <ref>PMID:17148560</ref> The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:11136712</ref> <ref>PMID:14561704</ref> | + | [https://www.uniprot.org/uniprot/HESX1_HUMAN HESX1_HUMAN] Hypothyroidism due to deficient transcription factors involved in pituitary development or function;Combined pituitary hormone deficiencies, genetic forms;Pituitary stalk interruption syndrome;Septo-optic dysplasia;Kallmann syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9620767</ref> <ref>PMID:11136712</ref> The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:11136712</ref> <ref>PMID:17148560</ref> The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:11136712</ref> <ref>PMID:14561704</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HESX1_HUMAN HESX1_HUMAN]] Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation (By similarity). | + | [https://www.uniprot.org/uniprot/HESX1_HUMAN HESX1_HUMAN] Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation (By similarity). |
| | == 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/k4/2k40_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k4/2k40_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> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2k40 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Asensio, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Bastida, A]] | + | [[Category: Asensio J]] |
| - | [[Category: Gonzalez, C]] | + | [[Category: Bastida A]] |
| - | [[Category: Torrado, M]] | + | [[Category: Gonzalez C]] |
| - | [[Category: Developmental protein]]
| + | [[Category: Torrado M]] |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Dwarfism]]
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| - | [[Category: Homeobox]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Thermostable homeodomain variant]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
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| Structural highlights
Disease
HESX1_HUMAN Hypothyroidism due to deficient transcription factors involved in pituitary development or function;Combined pituitary hormone deficiencies, genetic forms;Pituitary stalk interruption syndrome;Septo-optic dysplasia;Kallmann syndrome. The disease is caused by mutations affecting the gene represented in this entry.[1] [2] The disease is caused by mutations affecting the gene represented in this entry.[3] [4] The disease is caused by mutations affecting the gene represented in this entry.[5] [6]
Function
HESX1_HUMAN Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Martensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet. 1998 Jun;19(2):125-33. PMID:9620767 doi:http://dx.doi.org/10.1038/477
- ↑ Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS. Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Genet. 2001 Jan 1;10(1):39-45. PMID:11136712
- ↑ Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS. Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Genet. 2001 Jan 1;10(1):39-45. PMID:11136712
- ↑ McNay DE, Turton JP, Kelberman D, Woods KS, Brauner R, Papadimitriou A, Keller E, Keller A, Haufs N, Krude H, Shalet SM, Dattani MT. HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. J Clin Endocrinol Metab. 2007 Feb;92(2):691-7. Epub 2006 Dec 5. PMID:17148560 doi:http://dx.doi.org/10.1210/jc.2006-1609
- ↑ Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS. Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Genet. 2001 Jan 1;10(1):39-45. PMID:11136712
- ↑ Carvalho LR, Woods KS, Mendonca BB, Marcal N, Zamparini AL, Stifani S, Brickman JM, Arnhold IJ, Dattani MT. A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction. J Clin Invest. 2003 Oct;112(8):1192-201. PMID:14561704 doi:http://dx.doi.org/10.1172/JCI18589
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