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| | ==Crystal structure of human NF-kappaB inducing kinase (NIK)== | | ==Crystal structure of human NF-kappaB inducing kinase (NIK)== |
| - | <StructureSection load='4g3d' size='340' side='right' caption='[[4g3d]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4g3d' size='340' side='right'caption='[[4g3d]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g3d]] is a 4 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=4G3D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G3D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g3d]] is a 4 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=4G3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G3D FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g3c|4g3c]], [[4g3e|4g3e]], [[4g3f|4g3f]], [[4g3g|4g3g]]</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=4g3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g3d OCA], [https://pdbe.org/4g3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g3d RCSB], [https://www.ebi.ac.uk/pdbsum/4g3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g3d ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAP3K14, NF-kappaB inducing kinase (NIK), NIK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></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=4g3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g3d OCA], [http://pdbe.org/4g3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g3d RCSB], [http://www.ebi.ac.uk/pdbsum/4g3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g3d ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/M3K14_HUMAN M3K14_HUMAN]] Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.<ref>PMID:15084608</ref> | + | [https://www.uniprot.org/uniprot/M3K14_HUMAN M3K14_HUMAN] Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.<ref>PMID:15084608</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: Mitogen-activated protein kinase kinase kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Hymowitz, S G]] | + | [[Category: Hymowitz SG]] |
| - | [[Category: Leon-Boenig, G de]] | + | [[Category: De Leon-Boenig G]] |
| - | [[Category: Map3k14]]
| + | |
| - | [[Category: Nf-kappab]]
| + | |
| - | [[Category: Non-rd kinase]]
| + | |
| - | [[Category: Protein serine/threonine kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
M3K14_HUMAN Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.[1]
Publication Abstract from PubMed
The NF-kappaB inducing kinase (NIK) regulates the non-canonical NF-kappaB pathway downstream of important clinical targets including BAFF, RANKL, and LTbeta. Despite numerous genetic studies associating dysregulation of this pathway with autoimmune diseases and hematological cancers, detailed molecular characterization of this central signaling node has been lacking. We undertook a systematic cloning and expression effort to generate soluble, well-behaved proteins encompassing the kinase domains of human and murine NIK. Structures of the apo NIK kinase domain from both species reveal an active-like conformation in the absence of phosphorylation. ATP consumption and peptide phosphorylation assays confirm that phosphorylation of NIK does not increase enzymatic activity. Structures of murine NIK bound to inhibitors possessing two different chemotypes reveal conformational flexibility in the gatekeeper residue controlling access to a hydrophobic pocket. Finally, a single amino acid difference affects the ability of some inhibitors to bind murine and human NIK with the same affinity.
The crystal structure of the catalytic domain of the NF-kappaB inducing kinase reveals a narrow but flexible active site.,de Leon-Boenig G, Bowman KK, Feng JA, Crawford T, Everett C, Franke Y, Oh A, Stanley M, Staben ST, Starovasnik MA, Wallweber HJ, Wu J, Wu LC, Johnson AR, Hymowitz SG Structure. 2012 Oct 10;20(10):1704-14. doi: 10.1016/j.str.2012.07.013. Epub 2012 , Aug 23. PMID:22921830[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liao G, Zhang M, Harhaj EW, Sun SC. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem. 2004 Jun 18;279(25):26243-50. Epub 2004 Apr 14. PMID:15084608 doi:10.1074/jbc.M403286200
- ↑ de Leon-Boenig G, Bowman KK, Feng JA, Crawford T, Everett C, Franke Y, Oh A, Stanley M, Staben ST, Starovasnik MA, Wallweber HJ, Wu J, Wu LC, Johnson AR, Hymowitz SG. The crystal structure of the catalytic domain of the NF-kappaB inducing kinase reveals a narrow but flexible active site. Structure. 2012 Oct 10;20(10):1704-14. doi: 10.1016/j.str.2012.07.013. Epub 2012 , Aug 23. PMID:22921830 doi:http://dx.doi.org/10.1016/j.str.2012.07.013
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