ID:NOTC2_HUMAN DESCRIPTION: RecName: Full=Neurogenic locus notch homolog protein 2; Short=Notch 2; Short=hN2; Contains: RecName: Full=Notch 2 extracellular truncation; Contains: RecName: Full=Notch 2 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). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and an 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 NOTCH2. Interacts with RELA/p65 (By similarity). Interacts with HIF1AN. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Notch 2 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus. TISSUE SPECIFICITY: Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Ubiquitously expressed in the embryo. 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: Hydroxylated by HIF1AN. DISEASE: Defects in NOTCH2 are the cause of Alagille syndrome type 2 (ALGS2) [MIM:610205]. Alagille syndrome is an autosomal dominant multisystem disorder defined clinically by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. DISEASE: Defects in NOTCH2 are the cause of Hajdu-Cheney syndrome (HJCYS) [MIM:102500]. A rare skeletal disorder characterized by the association of facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects, polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes. Note=NOTCH2 mutations associated with Hajdu-Cheney syndrome cluster to the last coding exon of the gene. This suggests that the mutant mRNA products may escape nonsense-mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner. SIMILARITY: Belongs to the NOTCH family. SIMILARITY: Contains 6 ANK repeats. SIMILARITY: Contains 35 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/NOTCH2ID41556ch1p12.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NOTCH2";
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 Q04721
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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.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005509 calcium ion binding GO:0005515 protein binding GO:0038023 signaling receptor activity GO:0038049 transcription factor activity, ligand-activated RNA polymerase II transcription factor binding
Biological Process: GO:0001709 cell fate determination GO:0002315 marginal zone B cell differentiation GO:0003184 pulmonary valve morphogenesis GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006915 apoptotic process GO:0007050 cell cycle arrest GO:0007219 Notch signaling pathway GO:0007275 multicellular organism development GO:0007399 nervous system development GO:0009887 animal organ morphogenesis GO:0010629 negative regulation of gene expression GO:0019827 stem cell population maintenance GO:0030097 hemopoiesis GO:0030154 cell differentiation GO:0030522 intracellular receptor signaling pathway GO:0043066 negative regulation of apoptotic process GO:0045967 negative regulation of growth rate GO:0046579 positive regulation of Ras protein signal transduction GO:0046849 bone remodeling GO:0050793 regulation of developmental process GO:0060413 atrial septum morphogenesis GO:0061314 Notch signaling involved in heart development GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:2001204 regulation of osteoclast development
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
