Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the ''NOTCH1''
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 ...
.
Notch 1 is a single-pass transmembrane
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
.
Function
This gene encodes 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
In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...
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 humans, 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 insi ...
, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play multiple roles during development.
A deficiency can be associated with
bicuspid aortic valve
Bicuspid aortic valve (BAV) is a form of heart disease in which two of the leaflets of the aortic valve fuse during development in the womb resulting in a two-leaflet (bicuspid) valve instead of the normal three-leaflet (tricuspid) valve. BAV is ...
.
There is evidence that activated Notch 1 and
Notch 3
Neurogenic locus notch homolog protein 3 (Notch 3) is a protein that in humans is encoded by the ''NOTCH3'' gene.
Function
This gene encodes the third discovered human homologue of the ''Drosophila melanogaster'' type I membrane protein Notch ...
promote differentiation of progenitor cells into
astroglia
Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of end ...
.
Notch 1, when activated before birth, induces
radial glia
Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and ol ...
differentiation,
but postnatally induces the differentiation into
astrocyte
Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of en ...
s.
One study shows that Notch-1 cascade is activated by
Reelin
Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this importa ...
in an unidentified way.
Reelin and Notch1 cooperate in the development of the
dentate gyrus
The dentate gyrus (DG) is one of the subfields of the hippocampus, in the hippocampal formation. The hippocampal formation is located in the temporal lobe of the brain, and includes the hippocampus (including CA1 to CA4) subfields, and other su ...
, according to another.
Interactions
NOTCH1 has been shown to
interact with:
*
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 ...
,
*
Lck,
*
MAML1,
*
Mothers against decapentaplegic homolog 3
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.
SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by ...
*
NFKB1
Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the ''NFKB1'' gene.
This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD pro ...
,
*
NOV,
*
RBPJ
Recombination signal binding protein for immunoglobulin kappa J region is a protein that in humans is encoded by the ''RBPJ'' gene.
RBPJ also known as CBF1, is the human homolog for the Drosophila gene Su(H), Suppressor of Hairless. Its promoter ...
,
*
SNW1,
*
Ubiquitin C
Polyubiquitin-C is a protein encoded by the ''UBC'' gene in humans. Polyubiquitin-C is one of the sources of ubiquitin, along with UBB, UBA52, and RPS27A.
''UBC'' gene is one of the two stress-regulated polyubiquitin genes (''UBB'' and ''UBC' ...
,
and
*
YY1.
*
USP10.
References
Further reading
*
*
*
*
External links
*
NOTCH1
{{Notch signaling pathway