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==The crystal structure of the human Bub1 TPR domain in complex with the KI motif of Knl1==
==The crystal structure of the human Bub1 TPR domain in complex with the KI motif of Knl1==
<StructureSection load='4a1g' size='340' side='right' caption='[[4a1g]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='4a1g' size='340' side='right'caption='[[4a1g]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4a1g]] is a 8 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=4A1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A1G FirstGlance]. <br>
<table><tr><td colspan='2'>[[4a1g]] is a 8 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=4A1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A1G FirstGlance]. <br>
</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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]] 2.6&#8491;</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=4a1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a1g OCA], [http://pdbe.org/4a1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a1g RCSB], [http://www.ebi.ac.uk/pdbsum/4a1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a1g ProSAT]</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=4a1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a1g OCA], [https://pdbe.org/4a1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a1g RCSB], [https://www.ebi.ac.uk/pdbsum/4a1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a1g ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/CASC5_HUMAN CASC5_HUMAN]] Autosomal recessive primary microcephaly. A chromosomal aberration involving CASC5 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A/MLL1. May give rise to a KMT2A/MLL1-CASC5 fusion protein. The disease is caused by mutations affecting the gene represented in this entry.  
[https://www.uniprot.org/uniprot/KNL1_HUMAN KNL1_HUMAN] Autosomal recessive primary microcephaly. A chromosomal aberration involving KNL1 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A. May give rise to a KMT2A-KNL1 fusion protein.<ref>PMID:12618766</ref>  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/BUB1_HUMAN BUB1_HUMAN]] Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.<ref>PMID:10198256</ref> <ref>PMID:15020684</ref> <ref>PMID:15525512</ref> <ref>PMID:15723797</ref> <ref>PMID:16760428</ref> <ref>PMID:17158872</ref> <ref>PMID:19487456</ref>  [[http://www.uniprot.org/uniprot/CASC5_HUMAN CASC5_HUMAN]] Performs two crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Required for attachment of the kinetochores to the spindle microtubules. Directly links BUB1 and BUB1B to kinetochores. Part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore.<ref>PMID:15502821</ref> <ref>PMID:17981135</ref> <ref>PMID:18045986</ref>
[https://www.uniprot.org/uniprot/KNL1_HUMAN KNL1_HUMAN] Performs two crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Required for attachment of the kinetochores to the spindle microtubules. Directly links BUB1 and BUB1B to kinetochores. Part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore.<ref>PMID:15502821</ref> <ref>PMID:17981135</ref> <ref>PMID:18045986</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
==See Also==
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Krenn, V]]
[[Category: Krenn V]]
[[Category: Li, X]]
[[Category: Li X]]
[[Category: Musacchio, A]]
[[Category: Musacchio A]]
[[Category: Santaguida, S]]
[[Category: Santaguida S]]
[[Category: Wehenkel, A]]
[[Category: Wehenkel A]]
[[Category: Cell cycle]]
[[Category: Kmn network]]
[[Category: Knl1]]
[[Category: Mitosis]]
[[Category: Spindle assembly checkpoint]]
[[Category: Tpr repeat]]
[[Category: Transferase]]
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