Neurogenic locus notch homolog protein 3 (NOTCH3)

The protein contains 2321 amino acids for an estimated molecular weight of 243631 Da.

 

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). (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
dbSNP:rs147373451
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1; no effect on ligand-binding; no effect on cell membrane localization; reduced proteolytic processing
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1; requires 2 nucleotide substitutions
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
dbSNP:rs11670799
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
CADASIL1
dbSNP:rs35769976
CADASIL1
CADASIL1
CADASIL1; requires 2 nucleotide substitutions
dbSNP:rs112197217
dbSNP:rs10408676
CADASIL1
CADASIL1
CADASIL1
brain small-vessel-disease; exhibits increased NOTCH3 signaling in a ligand-independent fashion
IMF2
dbSNP:rs1044009

The reference OMIM entry for this protein is 125310

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy; cadasil
Dementia, hereditary multi-infarct type
Casil

A number sign (#) is used with this entry because of evidence that autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by heterozygous mutation in the NOTCH3 gene (600276) on chromosome 19p13.

DESCRIPTION

Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a progressive disorder of the small arterial vessels of the brain manifest by migraine, strokes, and white matter lesions, with resultant cognitive impairment in some patients (review by Kalimo et al., 1999).

CLINICAL FEATURES

Hereditary multi-infarct dementia in multiple members of families in a pattern consistent with autosomal dominant inheritance was reported by Sourander and Walinder (1977) and Sonninen and Savontaus (1987). The disorder is characterized by relapsing strokes with neuropsychiatric symptoms and affects relatively young adults of both sexes. CT scans have demonstrated occlusive cerebrovascular infarcts in the white matter, which was usually reduced. Sonninen and Savontaus (1987) thought that cerebrovascular amyloidosis (105150) is a separate disorder because the course of that disease was much more rapid and death occurred at an earlier age than in the family they reported. This may be the same disorder as that called chronic familial vascular encephalopathy by Stevens et al. (1977) and that called familial subcortical dementia with arteriopathic leukoencephalopathy by Davous and Fallet-Bianco (1991). In a family originating from northern France, Mas et al. (1992) described a genetic disorder characterized by recurrent attacks of focal brain dysfunction starting in midadulthood and leading in some to severe motor disability with pseudobulbar palsy and dementia of the subcortical type. Neuroimaging evidence of leukoencephalopathy and well-circumscribed lesions consistent with small deep infarcts were found in clinically affected individuals as well as in some asymptomatic members of the family. Although there was an instance of first-cousin marriage in the family, Mas et al. (1992) thought that the pedigree pattern suggested autosomal dominant inheritance. Members of 4 successive generations were thought to be affected. The only instance of male-to-male transmission was from a deceased father who was probably affected and an asymptomatic son who was affected by evidence on neuroimaging. Although Mas et al. (1992) thought their family represented a distinct disorder, it is quite possible that all of these reports related to the same condition. See also the large family reported by Tournier-Lasserve et al. (1991) in which of 45 subjects studied, 9 were clinically affected and 8 others, although clinically asymptomatic, had MRI signs of leukoencephalopathy. Baudrimont et al. (1993) reported the pathologic findings in 1 of the affected members of the family reported by Tournier-Lasserve et al. (1991). A previously healthy woman was 40 years old when she first experienced a grand mal seizure. Twelve years later she suffered 2 other grand mal seizures and thereafter had recurrent strokes as well as psychiatric disturbances (depression, manic episodes, and dementia). After a stroke at the age of 57, she became tetraplegic with severe pseudobulbar palsy and died 2 years later. Pathologic examination demonstrated a recent capsulolenticular hematoma, multiple small deep infarcts, diffuse myelin loss and pallor of the hemispheric white matter, and ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 125310 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).