UniProt functional annotation for Q9UM47



	UniProt functional annotation for Q9UM47

UniProt code: Q9UM47.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). 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|UniProtKB:Q9R172, ECO:0000269|PubMed:15350543}.

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}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:15350543}; Single-pass type I membrane protein.

Subcellular location: [Notch 3 intracellular domain]: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.

Tissue specificity: Ubiquitously expressed in fetal and adult tissues.

Domain: The EGF-like domains 10 and 11 are required for binding the ligands JAG1 and DLL1. {ECO:0000269|PubMed:15350543}.

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. {ECO:0000269|PubMed:15350543}.

Ptm: Phosphorylated. {ECO:0000250}.

Ptm: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:18299578}.

Disease: Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 1 (CADASIL1) [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:15350543, 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 variants 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 variants affecting the gene represented in this entry.

Disease: Lateral meningocele syndrome (LMNS) [MIM:130720]: A very rare skeletal disorder with facial anomalies, hypotonia and neurologic dysfunction due to meningocele, a protrusion of the meninges, unaccompanied by neural tissue, through a bony defect in the skull or vertebral column. LMNS facial features include hypertelorism and telecanthus, high arched eyebrows, ptosis, mid-facial hypoplasia, micrognathia, high and narrow palate, low-set ears and a hypotonic appearance. Additional variable features are connective tissue abnormalities, aortic dilation, a high-pitched nasal voice, wormian bones and osteolysis. {ECO:0000269|PubMed:25394726}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the NOTCH family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). 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\|UniProtKB:Q9R172, ECO:0000269\|PubMed:15350543}.


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}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:15350543}; Single-pass type I membrane protein.
Subcellular location:		[Notch 3 intracellular domain]: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.
Tissue specificity:		Ubiquitously expressed in fetal and adult tissues.
Domain:		The EGF-like domains 10 and 11 are required for binding the ligands JAG1 and DLL1. {ECO:0000269\|PubMed:15350543}.
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. {ECO:0000269\|PubMed:15350543}.
Ptm:		Phosphorylated. {ECO:0000250}.
Ptm:		Hydroxylated by HIF1AN. {ECO:0000269\|PubMed:18299578}.
Disease:		Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 1 (CADASIL1) [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:15350543, 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 variants 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 variants affecting the gene represented in this entry.
Disease:		Lateral meningocele syndrome (LMNS) [MIM:130720]: A very rare skeletal disorder with facial anomalies, hypotonia and neurologic dysfunction due to meningocele, a protrusion of the meninges, unaccompanied by neural tissue, through a bony defect in the skull or vertebral column. LMNS facial features include hypertelorism and telecanthus, high arched eyebrows, ptosis, mid-facial hypoplasia, micrognathia, high and narrow palate, low-set ears and a hypotonic appearance. Additional variable features are connective tissue abnormalities, aortic dilation, a high-pitched nasal voice, wormian bones and osteolysis. {ECO:0000269\|PubMed:25394726}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the NOTCH family. {ECO:0000305}.