4y5o

Structural highlights

Disease

[CCM2_HUMAN] Hereditary cerebral cavernous malformation. The disease is caused by mutations affecting the gene represented in this entry.

Function

[CCM2_HUMAN] Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions (By similarity). May function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity). [M3K3_HUMAN] Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.^{[1] [2] [3] [4]}

References

1. ↑ Ellinger-Ziegelbauer H, Brown K, Kelly K, Siebenlist U. Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative. J Biol Chem. 1997 Jan 31;272(5):2668-74. PMID:9006902
2. ↑ Nakamura K, Johnson GL. PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway. J Biol Chem. 2003 Sep 26;278(39):36989-92. Epub 2003 Aug 11. PMID:12912994 doi:http://dx.doi.org/10.1074/jbc.C300313200
3. ↑ Huang Q, Yang J, Lin Y, Walker C, Cheng J, Liu ZG, Su B. Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Nat Immunol. 2004 Jan;5(1):98-103. Epub 2003 Dec 7. PMID:14661019 doi:http://dx.doi.org/10.1038/ni1014
4. ↑ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol. 2004 Feb;6(2):97-105. Epub 2004 Jan 25. PMID:14743216 doi:http://dx.doi.org/10.1038/ncb1086