notch-2 (Drosophila) homolog protein (NOTCH2)
Jump to navigation
Jump to search
Function
- functions as a receptor for membrane-bound ligands Jagged1, Jagged2 & delta1 to regulate cell-fate determination
- upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBP-J kappa & activates genes of the enhancer of split locus
- affects implementation of differentiation, proliferation & apoptotic programs (putative)
- 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) & 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 (putative)
- phosphorylated (putative)
- heterodimer of a C-terminal fragment N(TM) & an N-terminal fragment N(EC) which are probably linked by disulfide bonds (putative)
- interacts with MAML1, MAML2 & MAML3 which act as transcriptional coactivators for NOTCH2
Structure
- belongs to the NOTCH family
- contains 6 ANK repeats
- contains 35 EGF-like domains
- contains 3 LNR (lin/notch) repeats
Compartment
- cell membrane; single-pass type 1 membrane protein
- notch 2 intracellular domain: nucleus
- following proteolytical processing NICD is translocated to the nucleus
Expression
- expressed in the brain, heart, kidney, lung, skeletal muscle & liver
Pathology
- defects in NOTCH2 are the cause of Alagille syndrome type 2
More general terms
- notch (Drosophila) homolog protein
- glycoprotein
- ankyrin repeat domain protein (ANKRD)
- phosphoprotein
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q04721.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/NOTCH2ID41556ch1p12.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=NOTCH2