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| | ==Structure of the C-terminal doamin of Knl1== | | ==Structure of the C-terminal doamin of Knl1== |
| - | <StructureSection load='4nfa' size='340' side='right' caption='[[4nfa]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4nfa' size='340' side='right'caption='[[4nfa]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nfa]] is a 1 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=4NFA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NFA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nfa]] 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=4NFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NFA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nf9|4nf9]]</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=4nfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nfa OCA], [https://pdbe.org/4nfa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nfa RCSB], [https://www.ebi.ac.uk/pdbsum/4nfa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nfa ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASC5, KIAA1570, KNL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4nfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nfa OCA], [http://pdbe.org/4nfa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nfa RCSB], [http://www.ebi.ac.uk/pdbsum/4nfa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nfa 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/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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Keller, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Mattiuzzo, M]] | + | [[Category: Keller J]] |
| - | [[Category: Mosalaganti, S]] | + | [[Category: Mattiuzzo M]] |
| - | [[Category: Musacchio, A]] | + | [[Category: Mosalaganti S]] |
| - | [[Category: Overlack, K]] | + | [[Category: Musacchio A]] |
| - | [[Category: Pasqualato, S]] | + | [[Category: Overlack K]] |
| - | [[Category: Petrovic, A]] | + | [[Category: Pasqualato S]] |
| - | [[Category: Raunser, S]] | + | [[Category: Petrovic A]] |
| - | [[Category: Wohlgemuth, S]] | + | [[Category: Raunser S]] |
| - | [[Category: Cell cycle]]
| + | [[Category: Wohlgemuth S]] |
| - | [[Category: Rwd domain]]
| + | |
| Structural highlights
Disease
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.[1] The disease is caused by variants affecting the gene represented in this entry.
Function
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.[2] [3] [4]
Publication Abstract from PubMed
Faithful chromosome segregation is mandatory for cell and organismal viability. Kinetochores, large protein assemblies embedded in centromeric chromatin, establish a mechanical link between chromosomes and spindle microtubules. The KMN network, a conserved 10-subunit kinetochore complex, harbors the microtubule-binding interface. RWD domains in the KMN subunits Spc24 and Spc25 mediate kinetochore targeting of the microtubule-binding subunits by interacting with the Mis12 complex, a KMN subcomplex that tethers directly onto the underlying chromatin layer. Here, we show that Knl1, a KMN subunit involved in mitotic checkpoint signaling, also contains RWD domains that bind the Mis12 complex and that mediate kinetochore targeting of Knl1. By reporting the first 3D electron microscopy structure of the KMN network, we provide a comprehensive framework to interpret how interactions of RWD-containing proteins with the Mis12 complex shape KMN network topology. Our observations unveil a regular pattern in the construction of the outer kinetochore.
Modular Assembly of RWD Domains on the Mis12 Complex Underlies Outer Kinetochore Organization.,Petrovic A, Mosalaganti S, Keller J, Mattiuzzo M, Overlack K, Krenn V, De Antoni A, Wohlgemuth S, Cecatiello V, Pasqualato S, Raunser S, Musacchio A Mol Cell. 2014 Feb 20;53(4):591-605. doi: 10.1016/j.molcel.2014.01.019. Epub 2014, Feb 13. PMID:24530301[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chinwalla V, Chien A, Odero M, Neilly MB, Zeleznik-Le NJ, Rowley JD. A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15. Oncogene. 2003 Mar 6;22(9):1400-10. PMID:12618766 doi:http://dx.doi.org/10.1038/sj.onc.1206273
- ↑ Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat Cell Biol. 2004 Nov;6(11):1135-41. Epub 2004 Oct 24. PMID:15502821 doi:http://dx.doi.org/10.1038/ncb1187
- ↑ Kiyomitsu T, Obuse C, Yanagida M. Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1. Dev Cell. 2007 Nov;13(5):663-76. PMID:17981135 doi:http://dx.doi.org/10.1016/j.devcel.2007.09.005
- ↑ Cheeseman IM, Hori T, Fukagawa T, Desai A. KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates. Mol Biol Cell. 2008 Feb;19(2):587-94. Epub 2007 Nov 28. PMID:18045986 doi:http://dx.doi.org/10.1091/mbc.E07-10-1051
- ↑ Petrovic A, Mosalaganti S, Keller J, Mattiuzzo M, Overlack K, Krenn V, De Antoni A, Wohlgemuth S, Cecatiello V, Pasqualato S, Raunser S, Musacchio A. Modular Assembly of RWD Domains on the Mis12 Complex Underlies Outer Kinetochore Organization. Mol Cell. 2014 Feb 20;53(4):591-605. doi: 10.1016/j.molcel.2014.01.019. Epub 2014, Feb 13. PMID:24530301 doi:http://dx.doi.org/10.1016/j.molcel.2014.01.019
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