InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NOTCH3

Summary

InnateDB Protein

IDBP-34311.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NOTCH3

Protein Name

notch 3

Synonyms

CADASIL; CASIL; IMF2;

Species

Homo sapiens

Ensembl Protein

ENSP00000263388

InnateDB Gene

IDBG-34309 (NOTCH3)

Protein Structure

UniProt Annotation

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}.

Subcellular Localization

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

Disease Associations

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:0000269PubMed:10227618, ECO:0000269PubMed:10371548, ECO:0000269PubMed:10802807, ECO:0000269PubMed:10854111, ECO:0000269PubMed:11058919, ECO:0000269PubMed:11102981, ECO:0000269PubMed:11559313, ECO:0000269PubMed:11755616, ECO:0000269PubMed:11810186, ECO:0000269PubMed:12136071, ECO:0000269PubMed:12146805, ECO:0000269PubMed:12589106, ECO:0000269PubMed:12810003, ECO:0000269PubMed:15229130, ECO:0000269PubMed:15300988, ECO:0000269PubMed:15364702, ECO:0000269PubMed:15378071, ECO:0000269PubMed:15818833, ECO:0000269PubMed:16009764, ECO:0000269PubMed:9388399}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:23731542}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitously expressed in fetal and adult tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 25 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	25 [view]
Protein-Protein	22 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0019899	enzyme binding

Biological Process

GO:0006355	regulation of transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0007219	Notch signaling pathway
GO:0007220	Notch receptor processing
GO:0007275	multicellular organismal development
GO:0010467	gene expression
GO:0030154	cell differentiation
GO:0030900	forebrain development
GO:0045596	negative regulation of cell differentiation
GO:0045665	negative regulation of neuron differentiation
GO:0048661	positive regulation of smooth muscle cell proliferation
GO:0048663	neuron fate commitment
GO:0050793	regulation of developmental process
GO:0072104	glomerular capillary formation

Cellular Component

GO:0000139	Golgi membrane
GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005789	endoplasmic reticulum membrane
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0015629	actin cytoskeleton
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

InterPro

IPR000742 Epidermal growth factor-like domain
IPR000800 Notch domain
IPR001881 EGF-like calcium-binding domain
IPR002110 Ankyrin repeat
IPR008297 Notch
IPR010660 Notch, NOD domain
IPR011656 Notch, NODP domain
IPR013111 EGF-like domain, extracellular
IPR020683 Ankyrin repeat-containing domain
IPR022331 Neurogenic locus Notch 3
IPR024600 Domain of unknown function DUF3454, notch

PFAM