4a14
From Proteopedia
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| - | [[Image:4a14.jpg|left|200px]] | ||
| - | < | + | ==HUMAN KIF7, A KINESIN INVOLVED IN HEDGEHOG SIGNALLING== |
| - | + | <StructureSection load='4a14' size='340' side='right'caption='[[4a14]], [[Resolution|resolution]] 1.60Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | or the | + | <table><tr><td colspan='2'>[[4a14]] is a 1 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=4A14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A14 FirstGlance]. <br> |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | |
| - | - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <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=4a14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a14 OCA], [https://pdbe.org/4a14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a14 RCSB], [https://www.ebi.ac.uk/pdbsum/4a14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a14 ProSAT]</span></td></tr> | |
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/KIF7_HUMAN KIF7_HUMAN] Joubert syndrome;Hydrolethalus;Joubert syndrome with ocular defect;Joubert syndrome with orofaciodigital defect;Multiple epiphyseal dysplasia, Al-Gazali type;Acrocallosal syndrome. Ciliary dysfunction leads to a broad spectrum of disorders, collectively termed ciliopathies. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, and hydrolethalus syndrome among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome influence the clinical outcome. Primary ciliopathy loci can be modulated by pathogenic lesions in other ciliary genes to either exacerbate overall severity or induce specific endophenotypes. KIF7 may be causally associated with diverse ciliopathies, and also acts as a modifier gene across the ciliopathy spectrum. The gene represented in this entry may act as a disease modifier. Heterozygous missense mutations in KIF7 may genetically interact with other BBS genes and contribute to disease manifestation and severity. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KIF7_HUMAN KIF7_HUMAN] Acts as both a negative and positive regulator of sonic hedgehog (Shh) pathway, acting downstream of SMO. Negatively regulates the pathway by preventing inappropriate activation of the transcriptional activator GLI2 in the absence of ligand. Positively regulates the pathway by preventing the processing of the transcription factor GLI3 into its repressor form. Required for efficient localization of GLI3 to cilia in response to Shh. Affects microtubular dynamics and acts as a ciliary motor.<ref>PMID:21633164</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Kif7, a member of the kinesin 4 superfamily, is implicated in a variety of diseases including Joubert, hydrolethalus and acrocallosal syndromes. It is also involved in primary cilium formation and the Hedgehog signalling pathway and may play a role in cancer. Its activity is crucial for embryonic development. Kif7 and Kif27, a closely related kinesin in the same subfamily, are orthologues of the Drosophila melanogaster kinesin-like protein Costal-2 (Cos2). In vertebrates, they work together to fulfil the role of the single Cos2 gene in Drosophila. Here, the high-resolution structure of the human Kif7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. These data are a first step towards structural characterization of a kinesin-4 family member and of this interesting molecular motor of medical significance. | ||
| - | + | Structural insights into human Kif7, a kinesin involved in Hedgehog signalling.,Klejnot M, Kozielski F Acta Crystallogr D Biol Crystallogr. 2012 Feb;68(Pt 2):154-9. Epub 2012, Jan 13. PMID:22281744<ref>PMID:22281744</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4a14" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | [[ | + | *[[Kinesin 3D Structures|Kinesin 3D Structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Klejnot M]] |
| - | [[Category: | + | [[Category: Kozielski F]] |
| - | + | ||
| - | + | ||
Current revision
HUMAN KIF7, A KINESIN INVOLVED IN HEDGEHOG SIGNALLING
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