| Structural highlights
4g3g is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 4g3c, 4g3d, 4g3e, 4g3f |
| Gene: | Map3k14, NF-kappaB inducing kinase (NIK), Nik (LK3 transgenic mice) |
| Activity: | Mitogen-activated protein kinase kinase kinase, with EC number 2.7.11.25 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[M3K14_MOUSE] 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
- ↑ Xiao G, Harhaj EW, Sun SC. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell. 2001 Feb;7(2):401-9. PMID:11239468
- ↑ 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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