Neurogenic locus notch homolog protein 2 (Notch 2) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''NOTCH2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
NOTCH2 is associated with
Alagille syndrome and
Hajdu–Cheney syndrome.
Function
Notch 2 is a member of the
notch family. Members of this
type 1 transmembrane protein
A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the org ...
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 that regulates interactions between physically adjacent cells. In ''
Drosophila
''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
'', 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.
Mutations within the last coding exon of Notch2 that remove the
PEST domain and escape the
nonsense-mediated mRNA decay have been shown to be the main cause of the
Hajdu–Cheney syndrome.
Interactions
NOTCH2 has been shown to
interact with:
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Delta-like 1
Delta-like protein 1 is a protein that in humans is encoded by the ''DLL1'' gene.
Function
DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions ...
GSK3B
Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the ''GSK3B'' gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased susce ...
,[
]
References
Further reading
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External links
GeneReviews/NCBI/UW/NIH entry on Alagille syndrome
OMIM entries on Alagille syndrome
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{{Notch signaling pathway