Search
notch-3 (Drosophila) homolog protein (NOTCH3)
Function:
- 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) & a N-terminal fragment N(EC) which are probably linked by disulfide bonds
- interacts with MAML1, MAML2 & MAML3 which act as transcriptional coactivators for NOTCH3
Structure:
- belongs to the NOTCH family
- contains 5 ANK repeats
- contains 34 EGF-like domains
- contains 3 LNR (lin/notch) repeats
Compartment:
- cell membrane; single-pass type 1 membrane protein
- notch 3 intracellular domain (NICD): nucleus
- following proteolytical processing NICD is translocated to the nucleus
Expression:
- ubiquitously expressed in fetal & adult tissues
Pathology:
- defects in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
- mutations affect highly conserved Cys within EGF domains
General
ankyrin repeat domain protein (ANKRD)
glycoprotein
notch (Drosophila) homolog protein
Properties
SIZE: MW = 244 kD
entity length = 2321 aa
COMPARTMENT: plasma membrane
MOTIF: signal sequence {1-39}
ligand-binding site
EGF domain (34)
glycosylation site
Notch/Lin12 repeat {1387-1505} (3)
transmembrane domain {1644-1664}
proteolysis
ankyrin repeat
NAME: ankyrin repeat
SITE: 1838-1867
ankyrin repeat
NAME: ankyrin repeat
SITE: 1871-1901
ankyrin repeat
NAME: ankyrin repeat
SITE: 1905-1934
ankyrin repeat
NAME: ankyrin repeat
SITE: 1938-1967
ankyrin repeat
NAME: ankyrin repeat
SITE: 1971-2000
Database Correlations
OMIM correlations
MORBIDMAP 600276
UniProt Q9UM47
PFAM correlations
Entrez Gene 4854
Kegg hsa:4854
References
- UniProt :accession Q9UM47
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org//genes/NOTCH3ID41557ch19p13.html
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NOTCH3