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MGP002119

UniProt Annotations

Entry Information

Gene Name	notch 3
Protein Entry	NOTC3_HUMAN
UniProt ID	Q9UM47
Species	Human

Comments

Comment type	Description
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. {ECO:0000269\|PubMed:10227618, ECO:0000269\|PubMed:10371548, ECO:0000269\|PubMed:10802807, ECO:0000269\|PubMed:10854111, ECO:0000269\|PubMed:11058919, ECO:0000269\|PubMed:11102981, ECO:0000269\|PubMed:11559313, ECO:0000269\|PubMed:11755616, ECO:0000269\|PubMed:11810186, ECO:0000269\|PubMed:12136071, ECO:0000269\|PubMed:12146805, ECO:0000269\|PubMed:12589106, ECO:0000269\|PubMed:12810003, ECO:0000269\|PubMed:15229130, ECO:0000269\|PubMed:15300988, ECO:0000269\|PubMed:15364702, ECO:0000269\|PubMed:15378071, ECO:0000269\|PubMed:15818833, ECO:0000269\|PubMed:16009764, ECO:0000269\|PubMed:24000151, ECO:0000269\|PubMed:9388399}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Myofibromatosis, 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. {ECO:0000269\|PubMed:23731542}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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). {ECO:0000250}.
Interaction	Q9R1P4:Psma1 (xeno); NbExp=2; IntAct=EBI-1236377, EBI-991653;
Ptm	Hydroxylated by HIF1AN. {ECO:0000269\|PubMed:18299578}.
Ptm	Phosphorylated. {ECO:0000250}.
Ptm	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). {ECO:0000250}.
Similarity	Belongs to the NOTCH family. {ECO:0000305}.
Similarity	Contains 34 EGF-like domains. {ECO:0000255\|PROSITE- ProRule:PRU00076}.
Similarity	Contains 3 LNR (Lin/Notch) repeats. {ECO:0000255\|PROSITE-ProRule:PRU00525}.
Similarity	Contains 5 ANK repeats. {ECO:0000255\|PROSITE- ProRule:PRU00023}.
Subcellular Location	Cell membrane; Single-pass type I membrane protein.
Subcellular Location	Notch 3 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.
Subunit	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. {ECO:0000250, ECO:0000269\|PubMed:11101851, ECO:0000269\|PubMed:12370315, ECO:0000269\|PubMed:17292860, ECO:0000269\|PubMed:17573339}.
Tissue Specificity	Ubiquitously expressed in fetal and adult tissues.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NOTCH3ID41557ch19p13.html";