View source for 4apc


==Crystal Structure of Human NIMA-related Kinase 1 (NEK1)==
<StructureSection load='4apc' size='340' side='right'caption='[[4apc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4apc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4APC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4APC FirstGlance]. <br>
</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></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=4apc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4apc OCA], [https://pdbe.org/4apc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4apc RCSB], [https://www.ebi.ac.uk/pdbsum/4apc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4apc ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/NEK1_HUMAN NEK1_HUMAN]] Short rib-polydactyly syndrome, Majewski type. The disease is caused by mutations affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617).<ref>PMID:21211617</ref>  
== Function ==
[[https://www.uniprot.org/uniprot/NEK1_HUMAN NEK1_HUMAN]] Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity. Implicated in the control of meiosis (By similarity). Involved in cilium assembly. In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death.<ref>PMID:20230784</ref> <ref>PMID:21211617</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation. Here we report on the structure of the kinase domain of human NEK1 in its apo- and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow the design of NEK specific chemo-sensitizing agents to act in conjunction with chemo- or radiation therapy of cancer cells. Furthermore, we characterized the dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin. Our data suggest that NEK1 and its interaction partners trigger the DNA damage pathways responsible for correcting DNA crosslinks.

NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin.,Melo-Hanchuk TD, Slepicka PF, Meirelles GV, Basei FL, Lovato DV, Granato DC, Pauletti BA, Domingues RR, Leme AFP, Pelegrini AL, Lenz G, Knapp S, Elkins JM, Kobarg J Sci Rep. 2017 Jul 14;7(1):5445. doi: 10.1038/s41598-017-05325-w. PMID:28710492<ref>PMID:28710492</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4apc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Arrowsmith, C]]
[[Category: Basei, F L]]
[[Category: Bountra, C]]
[[Category: Edwards, A]]
[[Category: Elkins, J M]]
[[Category: Hanchuk, T D.M]]
[[Category: Knapp, S]]
[[Category: Kobarg, J]]
[[Category: Krojer, T]]
[[Category: Lovato, D V]]
[[Category: Mahajan, P]]
[[Category: Meirelles, G V]]
[[Category: Pike, A C.W]]
[[Category: Rellos, P]]
[[Category: Szklarz, M]]
[[Category: Vollmar, M]]
[[Category: Zhang, Y]]
[[Category: Transferase]]