NOTCH3 Antibody – Goat Polyclonal

This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, 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. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]

Function: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs

By similarity.

Subunit structure: Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds

By similarity. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN. Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location: Cell membrane; Single-pass type I membrane protein. Notch 3 intracellular domain: Nucleus. Note: Following proteolytical processing NICD is translocated to the nucleus.

Tissue specificity: Ubiquitously expressed in fetal and adult tissues.

Post-translational modification: Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane

By similarity.Phosphorylated

By similarity.Hydroxylated by HIF1AN.

Involvement in disease: Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL) [MIM:125310]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy, dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30Myofibromatosis, infantile 2 (IMF2) [MIM:615293]: A rare mesenchymal disorder characterized by the development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with high morbidity and mortality.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30 Ref.31

Sequence similarities: Belongs to the NOTCH family.Contains 5 ANK repeats.Contains 34 EGF-like domains.Contains 3 LNR (Lin/Notch) repeats.