Description: Homo sapiens notch 3 (NOTCH3), mRNA. RefSeq Summary (NM_000435): This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data because transcript sequence consistent with the reference genome assembly was not available for all regions of the RefSeq transcript. The extent of this transcript is supported by transcript alignments. Transcript (Including UTRs) Position: hg19 chr19:15,270,444-15,311,792 Size: 41,349 Total Exon Count: 33 Strand: - Coding Region Position: hg19 chr19:15,271,473-15,311,716 Size: 40,244 Coding Exon Count: 33
ID:NOTC3_HUMAN DESCRIPTION: RecName: Full=Neurogenic locus notch homolog protein 3; Short=Notch 3; Contains: RecName: Full=Notch 3 extracellular truncation; Contains: RecName: Full=Notch 3 intracellular domain; Flags: Precursor; FUNCTION: 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 (By similarity). SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and a N- terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN. INTERACTION: Q9R1P4:Psma1 (xeno); NbExp=2; IntAct=EBI-1236377, EBI-991653; SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Notch 3 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus. TISSUE SPECIFICITY: Ubiquitously expressed in fetal and adult tissues. PTM: Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C- terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity). PTM: Phosphorylated (By similarity). PTM: Hydroxylated by HIF1AN. DISEASE: Defects in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [MIM:125310]. CADASIL causes a type of stroke and dementia of which key features include recurrent subcortical ischemic events and vascular dementia. The disorder affects relatively young adults of both sexes. Mutations affect highly conserved cysteine residues within epidermal growth factor (EGF)-like repeat domains in the extracellular part of the receptor. SIMILARITY: Belongs to the NOTCH family. SIMILARITY: Contains 5 ANK repeats. SIMILARITY: Contains 34 EGF-like domains. SIMILARITY: Contains 3 LNR (Lin/Notch) repeats. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/NOTCH3ID41557ch19p13.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NOTCH3";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UM47
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
