2f8x

Structural highlights

Disease

SUH_HUMAN Defects in RBPJ are the cause of Adams-Oliver syndrome 3 (AOS3) [MIM:614814. An autosomal dominant form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. AOS3 patients manifest characteristic vertex scalp defects and terminal limb defects, but without congenital heart defects, other associated defects, or immune defects.^[1]

Function

SUH_HUMAN Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes. Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively. Specifically binds to the immunoglobulin kappa-type J segment recombination signal sequence. Binds specifically to methylated DNA.^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Hassed SJ, Wiley GB, Wang S, Lee JY, Li S, Xu W, Zhao ZJ, Mulvihill JJ, Robertson J, Warner J, Gaffney PM. RBPJ mutations identified in two families affected by Adams-Oliver syndrome. Am J Hum Genet. 2012 Aug 10;91(2):391-5. doi: 10.1016/j.ajhg.2012.07.005. PMID:22883147 doi:10.1016/j.ajhg.2012.07.005
2. ↑ Bartels SJ, Spruijt CG, Brinkman AB, Jansen PW, Vermeulen M, Stunnenberg HG. A SILAC-based screen for Methyl-CpG binding proteins identifies RBP-J as a DNA methylation and sequence-specific binding protein. PLoS One. 2011;6(10):e25884. doi: 10.1371/journal.pone.0025884. Epub 2011 Oct 3. PMID:21991380 doi:10.1371/journal.pone.0025884
3. ↑ Nam Y, Sliz P, Song L, Aster JC, Blacklow SC. Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell. 2006 Mar 10;124(5):973-83. PMID:16530044 doi:10.1016/j.cell.2005.12.037