Neurogenic locus notch homolog 4 (Notch 4) 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 ''NOTCH4''
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 ...
located on
chromosome 6
Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total ...
.
Gene
An
alternative splice variant of the NOTCH4 gene has been described, but its biological significance has not been determined.
Structure
The neurogenic locus notch homolog 4 protein is a member of the
Notch family. Members of this type 1
transmembrane
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
protein family share structural characteristics. These include an extracellular domain consisting of multiple
epidermal growth factor-like (EGF)
repeats, and an intracellular domain that consists of multiple, but different, domain types.
Function
Notch protein family members play a role in a variety of developmental processes by controlling cell fate decisions. The
Notch signaling pathway
The Notch signaling pathway is a highly Conserved sequence, conserved cell signaling system present in most animals. Mammals possess four different Notch proteins, notch receptors, referred to as NOTCH1, NOTCH2, Notch 3, NOTCH3, and NOTCH4. The ...
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'' interacts with its cell-bound ligands (delta and serrate), and establishes an intercellular signaling pathway that then plays a key role in development. Homologues of the ''notch''-ligands have also been identified in humans, but precise interactions between these ligands and the human ''notch'' homologues remain to be determined. The ''notch'' 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 then presented on the cell surface as a
heterodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
. The protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal, and hepatic development.
Clinical significance
Mutations in the ''notch4'' gene may be associated with susceptibility to
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
in a small portion of cases.
References
Further reading
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{{Notch signaling pathway