|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3nbn' size='340' side='right'caption='[[3nbn]], [[Resolution|resolution]] 3.45Å' scene=''> | | <StructureSection load='3nbn' size='340' side='right'caption='[[3nbn]], [[Resolution|resolution]] 3.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nbn]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NBN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NBN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nbn]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NBN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NBN FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGKJRB, IGKJRB1, RBPJ, RBPJK, RBPSUH ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NOTCH1, TAN1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), KIAA0200, MAML1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.45Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nbn OCA], [https://pdbe.org/3nbn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nbn RCSB], [https://www.ebi.ac.uk/pdbsum/3nbn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nbn ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nbn OCA], [https://pdbe.org/3nbn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nbn RCSB], [https://www.ebi.ac.uk/pdbsum/3nbn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nbn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/SUH_HUMAN SUH_HUMAN]] Defects in RBPJ are the cause of Adams-Oliver syndrome 3 (AOS3) [MIM:[https://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> [[https://www.uniprot.org/uniprot/NOTC1_HUMAN NOTC1_HUMAN]] Defects in NOTCH1 are a cause of aortic valve disease 1 (AOVD1) [MIM:[https://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>
| + | [https://www.uniprot.org/uniprot/SUH_HUMAN SUH_HUMAN] Defects in RBPJ are the cause of Adams-Oliver syndrome 3 (AOS3) [MIM:[https://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> |
| | == Function == | | == Function == |
| - | [[https://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> [[https://www.uniprot.org/uniprot/MAML1_HUMAN MAML1_HUMAN]] Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions.<ref>PMID:11101851</ref> <ref>PMID:11390662</ref> <ref>PMID:12050117</ref> <ref>PMID:15546612</ref> <ref>PMID:17317671</ref> [[https://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).
| + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 24: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arnett, K L]] | + | [[Category: Arnett KL]] |
| - | [[Category: Blacklow, S C]] | + | [[Category: Blacklow SC]] |
| - | [[Category: Csl]]
| + | |
| - | [[Category: Mastermind]]
| + | |
| - | [[Category: Notch1]]
| + | |
| - | [[Category: Promoter region]]
| + | |
| - | [[Category: Rbpj]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| - | [[Category: Transcriptional activation]]
| + | |
| 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]
Publication Abstract from PubMed
Ligand-induced proteolysis of Notch produces an intracellular effector domain that transduces essential signals by regulating the transcription of target genes. This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA. These complexes form higher-order assemblies on paired, head-to-head CSL recognition sites. Here we report the X-ray structure of a dimeric human Notch1 transcription complex loaded on the paired site from the human HES1 promoter. The small interface between the Notch ankyrin domains could accommodate DNA bending and untwisting to allow a range of spacer lengths between the two sites. Cooperative dimerization occurred on the human and mouse Hes5 promoters at a sequence that diverged from the CSL-binding consensus at one of the sites. These studies reveal how promoter organizational features control cooperativity and, thus, the responsiveness of different promoters to Notch signaling.
Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes.,Arnett KL, Hass M, McArthur DG, Ilagan MX, Aster JC, Kopan R, Blacklow SC Nat Struct Mol Biol. 2010 Nov;17(11):1312-7. Epub 2010 Oct 24. PMID:20972443[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ Arnett KL, Hass M, McArthur DG, Ilagan MX, Aster JC, Kopan R, Blacklow SC. Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes. Nat Struct Mol Biol. 2010 Nov;17(11):1312-7. Epub 2010 Oct 24. PMID:20972443 doi:10.1038/nsmb.1938
|
