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| | ==Solution structures of the WHEP-TRS domain of human histidyl-tRNA synthetase== | | ==Solution structures of the WHEP-TRS domain of human histidyl-tRNA synthetase== |
| - | <StructureSection load='1x59' size='340' side='right'caption='[[1x59]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1x59' size='340' side='right'caption='[[1x59]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1x59]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X59 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1x59]] 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=1X59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X59 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HARS ([https://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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histidine--tRNA_ligase Histidine--tRNA ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.21 6.1.1.21] </span></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1x59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x59 OCA], [https://pdbe.org/1x59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x59 RCSB], [https://www.ebi.ac.uk/pdbsum/1x59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x59 ProSAT], [https://www.topsan.org/Proteins/RSGI/1x59 TOPSAN]</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=1x59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x59 OCA], [https://pdbe.org/1x59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x59 RCSB], [https://www.ebi.ac.uk/pdbsum/1x59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x59 ProSAT], [https://www.topsan.org/Proteins/RSGI/1x59 TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/SYHC_HUMAN SYHC_HUMAN]] Defects in HARS are a cause of Usher syndrome type 3B (USH3B) [MIM:[https://omim.org/entry/614504 614504]]. USH3B is a syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life.<ref>PMID:22279524</ref> Note=HARS mutations may be involved in peripheral neuropathy, a disease mainly characterized by distal motor and sensory dysfunction. Inherited peripheral neuropathies are clinically and genetically heterogeneous with variable age of onset and reduced penetrance associated with specific loci. HARS mutations may directly predispose patients to peripheral neuropathy or may modify a peripheral neuropathy phenotype by contributing to the genetic and environmental load in a given patient (PubMed:22930593).
| + | [https://www.uniprot.org/uniprot/HARS1_HUMAN HARS1_HUMAN] Autosomal dominant Charcot-Marie-Tooth disease type 2W;Usher syndrome type 3. The disease may be caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HARS1_HUMAN HARS1_HUMAN] Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP) (PubMed:29235198). Plays a role in axon guidance (PubMed:26072516).<ref>PMID:26072516</ref> <ref>PMID:29235198</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: Histidine--tRNA ligase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Inoue, M]] | + | [[Category: Inoue M]] |
| - | [[Category: Kigawa, T]] | + | [[Category: Kigawa T]] |
| - | [[Category: Koshiba, S]] | + | [[Category: Koshiba S]] |
| - | [[Category: Nameki, N]] | + | [[Category: Nameki N]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sasagawa A]] |
| - | [[Category: Sasagawa, A]] | + | [[Category: Tomizawa T]] |
| - | [[Category: Tomizawa, T]] | + | [[Category: Yokoyama S]] |
| - | [[Category: Yokoyama, S]] | + | |
| - | [[Category: Hisr]]
| + | |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| Structural highlights
Disease
HARS1_HUMAN Autosomal dominant Charcot-Marie-Tooth disease type 2W;Usher syndrome type 3. The disease may be caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
HARS1_HUMAN Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP) (PubMed:29235198). Plays a role in axon guidance (PubMed:26072516).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Safka Brozkova D, Deconinck T, Griffin LB, Ferbert A, Haberlova J, Mazanec R, Lassuthova P, Roth C, Pilunthanakul T, Rautenstrauss B, Janecke AR, Zavadakova P, Chrast R, Rivolta C, Zuchner S, Antonellis A, Beg AA, De Jonghe P, Senderek J, Seeman P, Baets J. Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. Brain. 2015 Aug;138(Pt 8):2161-72. doi: 10.1093/brain/awv158. Epub 2015 Jun 13. PMID:26072516 doi:http://dx.doi.org/10.1093/brain/awv158
- ↑ Abbott JA, Meyer-Schuman R, Lupo V, Feely S, Mademan I, Oprescu SN, Griffin LB, Alberti MA, Casasnovas C, Aharoni S, Basel-Vanagaite L, Zuchner S, De Jonghe P, Baets J, Shy ME, Espinos C, Demeler B, Antonellis A, Francklyn C. Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. Hum Mutat. 2018 Mar;39(3):415-432. doi: 10.1002/humu.23380. Epub 2017 Dec 26. PMID:29235198 doi:http://dx.doi.org/10.1002/humu.23380
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