View source for 6py8


==Crystal structure of the RBPJ-NOTCH1-NRARP ternary complex bound to DNA==
<StructureSection load='6py8' size='340' side='right'caption='[[6py8]], [[Resolution|resolution]] 3.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6py8]] is a 11 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PY8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PY8 FirstGlance]. <br>
</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=6py8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6py8 OCA], [http://pdbe.org/6py8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6py8 RCSB], [http://www.ebi.ac.uk/pdbsum/6py8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6py8 ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/SUH_HUMAN SUH_HUMAN]] Defects in RBPJ are the cause of Adams-Oliver syndrome 3 (AOS3) [MIM:[http://omim.org/entry/614814 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.<ref>PMID:22883147</ref>  [[http://www.uniprot.org/uniprot/NOTC1_HUMAN NOTC1_HUMAN]] Defects in NOTCH1 are a cause of aortic valve disease 1 (AOVD1) [MIM:[http://omim.org/entry/109730 109730]]. A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome.<ref>PMID:16025100</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/SUH_HUMAN 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.<ref>PMID:21991380</ref>  [[http://www.uniprot.org/uniprot/NRARP_HUMAN NRARP_HUMAN]] Downstream effector of Notch signaling. Involved in the regulation of liver cancer cells self-renewal (PubMed:25985737). Involved in angiogenesis acting downstream of Notch at branch points to regulate vascular density. Proposed to integrate endothelial Notch and Wnt signaling to control stalk cell proliferation and to stablilize new endothelial connections during angiogenesis (PubMed:19154719). During somitogenesis involved in maintenance of proper somite segmentation and proper numbers of somites and vertebrae. Required for proper anterior-posterior somite patterning. Proposed to function in a negative feedback loop to destabilize Notch 1 intracellular domain (NICD) and downregulate the Notch signal, preventing expansion of the Notch signal into the anterior somite domain (By similarity).[UniProtKB:Q91ZA8]<ref>PMID:19154719</ref> <ref>PMID:25985737</ref> <ref>PMID:25985737</ref>  [[http://www.uniprot.org/uniprot/NOTC1_HUMAN NOTC1_HUMAN]] Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May be important for normal lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. May be important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, may function as a receptor for neuronal DNER and may be involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May enhance HIF1A function by sequestering HIF1AN away from HIF1A (By similarity). 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Blacklow, S C]]
[[Category: Jarrett, S M]]
[[Category: Seegar, T C.M]]
[[Category: Dna binding protein]]
[[Category: Dna binding protein-dna complex]]
[[Category: Notch1]]
[[Category: Nrarp]]
[[Category: Rbpj]]