Neurogenic locus notch homolog protein 1(Notch 1) is a protein encoded in humans by the NOTCH1 gene. [5] Notch 1 is a single-pass transmembrane receptor.
Neurogenic locus notch homolog protein 1(Notch 1) is a protein encoded in humans by the NOTCH1 gene. [5] Notch 1 is a single-pass transmembrane receptor.
This gene encodes 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 , 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, 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. [6]
A deficiency can be associated with bicuspid aortic valve. [7]
There is evidence that activated Notch 1 and Notch 3 promote differentiation of progenitor cells into astroglia. [8] Notch 1, when activated before birth, induces radial glia differentiation, [9] but postnatally induces the differentiation into astrocytes. [10] One study shows that Notch-1 cascade is activated by Reelin in an unidentified way. [11] Reelin and Notch1 cooperate in the development of the dentate gyrus, according to another. [12]
NOTCH1 has been shown to interact with:
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL–ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.
Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.
Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the LRP8 gene. ApoER2 is a cell surface receptor that is part of the low-density lipoprotein receptor family. These receptors function in signal transduction and endocytosis of specific ligands. Through interactions with one of its ligands, reelin, ApoER2 plays an important role in embryonic neuronal migration and postnatal long-term potentiation. Another LDL family receptor, VLDLR, also interacts with reelin, and together these two receptors influence brain development and function. Decreased expression of ApoER2 is associated with certain neurological diseases.
Neurogenic locus notch homolog protein 3(Notch 3) is a protein that in humans is encoded by the NOTCH3 gene.
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 fate decisions in many organ systems. Once the JAG1-NOTCH (receptor-ligand) interactions take place, a cascade of proteolytic cleavages is triggered resulting in activation of the transcription for downstream target genes. Located on human chromosome 20, the JAG1 gene is expressed in multiple organ systems in the body and causes the autosomal dominant disorder Alagille syndrome (ALGS) resulting from loss of function mutations within the gene. JAG1 has also been designated as CD339.
Presenilin-1(PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.
Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.
Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene.
Neurogenic locus notch homolog 4(Notch 4) is a protein that in humans is encoded by the NOTCH4 gene located on chromosome 6.
Neurogenic locus notch homolog protein 2 is a protein that in humans is encoded by the NOTCH2 gene.
Protein numb homolog is a protein that in humans is encoded by the NUMB gene. The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Four transcript variants encoding different isoforms have been found for this gene.
Delta-like protein 1 is a protein that in humans is encoded by the DLL1 gene.
Recombination signal binding protein for immunoglobulin kappa J region is a protein that in humans is encoded by the RBPJ gene.
Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.
AH receptor-interacting protein (AIP) also known as aryl hydrocarbon receptor-interacting protein, immunophilin homolog ARA9, or HBV X-associated protein 2 (XAP-2) is a protein that in humans is encoded by the AIP gene. The protein is a member of the FKBP family.
Jagged-2 is a protein that in humans is encoded by the JAG2 gene.
Beta-1,3-N-acetylglucosaminyltransferase manic fringe is an enzyme that in humans is encoded by the MFNG gene, a member of the fringe gene family which also includes the radical fringe (RFNG) and lunatic fringe (LFNG).
Mastermind-like protein 1 is a protein that in humans is encoded by the MAML1 gene.
Notch proteins are a family of type 1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in metazoans. The Notch extracellular domain mediates interactions with DSL family ligands, allowing it to participate in juxtacrine signaling. The Notch intracellular domain acts as a transcriptional activator when in complex with CSL family transcription factors. Members of this type 1 transmembrane protein family share several core structures, including an extracellular domain consisting of multiple epidermal growth factor (EGF)-like repeats and an intracellular domain transcriptional activation domain (TAD). Notch family members operate in a variety of different tissues and play a role in a variety of developmental processes by controlling cell fate decisions. Much of what is known about Notch function comes from studies done in Caenorhabditis elegans (C.elegans) and Drosophila melanogaster. Human homologs have also been identified, but details of Notch function and interactions with its ligands are not well known in this context.
In molecular biology, there are a number of neurogenic proteins referred to as mastermind-like proteins (MAMLs) of which this domain is the N-terminal region. Mastermind-like proteins act as critical transcriptional co-activators for Notch signaling.
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