NOTCH3

Neurogenic locus notch homolog protein 3 (Notch 3) is a protein that in humans is encoded by the NOTCH3 gene.^[5][6]

NOTCH3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZLP, 5CZX, 5CZV
Identifiers
Aliases	NOTCH3, CADASIL, CASIL, IMF2, LMNS, CADASIL1, notch 3, notch receptor 3
External IDs	OMIM: 600276; MGI: 99460; HomoloGene: 376; GeneCards: NOTCH3; OMA:NOTCH3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.12 Start 15,159,038 bp[1] End 15,200,995 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 B1|17 17.37 cM Start 32,339,794 bp[2] End 32,385,826 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in popliteal artery tibial arteries right coronary artery ventricular zone Descending thoracic aorta ascending aorta left coronary artery saphenous vein skin of leg stromal cell of endometrium Top expressed in external carotid artery corneal stroma internal carotid artery ankle joint molar vas deferens Gonadal ridge left lung lobe lactiferous gland carotid body More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding protein binding enzyme binding cadherin binding identical protein binding signaling receptor activity Cellular component integral component of membrane endoplasmic reticulum membrane membrane Golgi membrane receptor complex plasma membrane nucleoplasm extracellular region actin cytoskeleton nucleus cytosol cell surface Biological process Notch signaling pathway cell differentiation regulation of transcription, DNA-templated negative regulation of neuron differentiation negative regulation of cell differentiation glomerular capillary formation negative regulation of transcription by RNA polymerase II transcription, DNA-templated multicellular organism development artery morphogenesis forebrain development neuron fate commitment transcription initiation from RNA polymerase II promoter positive regulation of transcription by RNA polymerase II positive regulation of smooth muscle cell proliferation regulation of developmental process positive regulation of transcription of Notch receptor target Notch receptor processing, ligand-dependent negative regulation of Notch signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4854 18131 Ensembl ENSG00000074181 ENSMUSG00000038146 UniProt Q9UM47 Q61982 RefSeq (mRNA) NM_000435 NM_008716 RefSeq (protein) NP_000426 NP_032742 Location (UCSC) Chr 19: 15.16 – 15.2 Mb Chr 17: 32.34 – 32.39 Mb PubMed search [3] [4]
Wikidata
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Function

This gene encodes the third discovered human homologue of the Drosophila melanogaster type I membrane protein notch. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined.

Pathology

Micrograph showing CADASIL with a Notch 3 immunostain

Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).^[6] Mutations in NOTCH3 have also been identified in families with Alzheimer's disease.^[7] Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.^[8] Mutations in NOTCH3 are associated to lateral meningocele syndrome.^[9]

Pharmaceutical target

Notch3 is being investigated as a target for anti-cancer drugs, as it is overexpressed in several types of cancers.^[10] Early clinical trials of Pfizer's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors.^[11]