Human Gene NOTCH2 (ENST00000256646.7) from GENCODE V44
Description: Homo sapiens notch receptor 2 (NOTCH2), transcript variant 1, mRNA. (from RefSeq NM_024408) RefSeq Summary (NM_024408): This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway which regulates interactions between physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]. Gencode Transcript: ENST00000256646.7 Gencode Gene: ENSG00000134250.21 Transcript (Including UTRs) Position: hg38 chr1:119,911,553-120,069,662 Size: 158,110 Total Exon Count: 34 Strand: - Coding Region Position: hg38 chr1:119,915,306-120,069,406 Size: 154,101 Coding Exon Count: 34
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.