| Structural highlights
5wnm 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: | 5wni, 5wnj, 5wnk, 5wnl |
| Gene: | Ripk4, Ankrd3, Pkk (LK3 transgenic mice) |
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RIPK4_MOUSE] Involved in stratified epithelial development (By similarity). It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation.[1] [2]
Publication Abstract from PubMed
Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease.
Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.,Huang CS, Oberbeck N, Hsiao YC, Liu P, Johnson AR, Dixit VM, Hymowitz SG Structure. 2018 May 1;26(5):767-777.e5. doi: 10.1016/j.str.2018.04.002. Epub 2018, Apr 26. PMID:29706531[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Meylan E, Martinon F, Thome M, Gschwendt M, Tschopp J. RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-kappa B and is processed during apoptosis. EMBO Rep. 2002 Dec;3(12):1201-8. doi: 10.1093/embo-reports/kvf236. Epub 2002 Nov , 21. PMID:12446564 doi:http://dx.doi.org/10.1093/embo-reports/kvf236
- ↑ Mitchell K, O'Sullivan J, Missero C, Blair E, Richardson R, Anderson B, Antonini D, Murray JC, Shanske AL, Schutte BC, Romano RA, Sinha S, Bhaskar SS, Black GC, Dixon J, Dixon MJ. Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus. Am J Hum Genet. 2012 Jan 13;90(1):69-75. doi: 10.1016/j.ajhg.2011.11.013. Epub, 2011 Dec 22. PMID:22197488 doi:10.1016/j.ajhg.2011.11.013
- ↑ Huang CS, Oberbeck N, Hsiao YC, Liu P, Johnson AR, Dixit VM, Hymowitz SG. Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity. Structure. 2018 May 1;26(5):767-777.e5. doi: 10.1016/j.str.2018.04.002. Epub 2018, Apr 26. PMID:29706531 doi:http://dx.doi.org/10.1016/j.str.2018.04.002
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