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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''NOTCH2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
NOTCH2 is associated with
Alagille syndrome
Alagille syndrome is a genetic disorder that affects primarily the liver and the heart. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and t ...
and
Hajdu–Cheney syndrome
Hajdu–Cheney syndrome, also called acroosteolysis with osteoporosis and changes in skull and mandible, arthrodentoosteodysplasia and Cheney syndrome, is an extremely rare autosomal dominant congenital disorder of the connective tissue character ...
.
Function
Notch 2 is 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 that regulates interactions between physically adjacent cells. In ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'', 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
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
, 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
Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that exists in all eukaryotes. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons. Translation of these aberran ...
have been shown to be the main cause of the
Hajdu-Cheney syndrome.
Interactions
NOTCH2 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
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 d ...
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 suscept ...
,JAG1
Jagged1 (''JAG1'') is one of five cell surface proteins (ligands) that interact with four receptors in the mammalian Notch signaling pathway. The Notch Signaling Pathway is a highly conserved pathway that functions to establish and regulate cell fa ...
,JAG2
Jagged-2 is a protein that in humans is encoded by the ''JAG2'' gene.
Function
The Notch signaling pathway is an intercellular signaling mechanism that is essential for proper embryonic development. Members of the Notch gene family encode tran ...
.[
]
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