NOTCH2NLC
entrez
100996717
canonical
uniprot
P0DPK4
canonical
ensembl
ENSG00000264343
resolver
ensembl
ENSG00000286219
resolver
ensp
ENSP00000498514
resolver
ensp
ENSP00000499085
resolver
genesymbol
NOTCH2NLC
resolver
hgnc
HGNC:53924
resolver
uniprot
A0A494C1K9
resolver
uniprot_entry
NT2NC_HUMAN
resolver
uniprot_sec
A0A494C1K9
resolver
amino_acid_sequence
MWICPGGGGGGGGGGGGGDREDARPAPLCCGRCWRSGCAARPPRMCRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGEYCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYSTSHPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWTDACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCETDVNECDIPGHCQHGGTCLNLPGSYQCQCLQGFTGQYCDSLYVPCAPSPCVNGGTCRQTGDFTFECNCLPETVRRGTELWERDREVWNGKEHDEN
uniprot
proteins
disease_involvement
DISEASE: Neuronal intranuclear inclusion disease (NIID) [MIM:603472]: An autosomal dominant, slowly progressive, neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. Clinical manifestations are variable and include pyramidal and extrapyramidal symptoms, cerebellar ataxia, cognitive decline and dementia, peripheral neuropathy, and autonomic dysfunction. {ECO:0000269|PubMed:31178126, ECO:0000269|PubMed:31332380, ECO:0000269|PubMed:31332381}. Note=The disease is caused by variants affecting the gene represented in this entry. The molecular defect in NOTCH2NLC is a CGG repeat expansion in the 5-prime untranslated region of the gene. The expansion can be greater than one hundred repeat units in patients, while healthy individuals have 5 to 43 repeats. {ECO:0000269|PubMed:31178126, ECO:0000269|PubMed:31332380, ECO:0000269|PubMed:31332381}.; DISEASE: Note=Defects in NOTCH2NLC may be a cause of chromosome 1q21.1 deletion/duplication syndrome (PubMed:29856954). Deletions of NOTCH2NL (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC) are present in patients affected by microcephaly, whereas macrocephaly is observed in patients with NOTCH2NL duplications (PubMed:29856954). {ECO:0000269|PubMed:29856954}.; DISEASE: Tremor, hereditary essential 6 (ETM6) [MIM:618866]: A form of essential tremor, a common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles may also be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. ETM6 inheritance is autosomal dominant. {ECO:0000269|PubMed:32333675}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Oculopharyngodistal myopathy 3 (OPDM3) [MIM:619473]: A form of oculopharyngodistal myopathy, a rare hereditary muscle disease characterized by progressive distal limb weakness, ptosis, ophthalmoplegia, bulbar muscle weakness and rimmed vacuoles on muscle biopsy. In addition to muscular features, OPDM3 patients may develop pigmentary retinopathy, peripheral neuropathy, or hearing loss. Cognition is usually not affected, but there may be deficits or psychiatric manifestations. Brain imaging tends to show a leukoencephalopathy, often with a characteristic linear signal along the corticomedullary junction on brain imaging. OPDM3 is a slowly progressive form with an autosomal dominant transmission pattern, and variable age at onset ranging from childhood to late adulthood. {ECO:0000269|PubMed:33239111, ECO:0000269|PubMed:33693509}. Note=The disease is caused by variants affecting the gene represented in this entry. The causative mutation is a heterozygous trinucleotide repeat expansion (CGG) that results in expanded polyglycine (polyG) tract in isoform 1. Mutant proteins may form aggregates that contribute to toxicity and induce cell death. {ECO:0000269|PubMed:33693509}.
uniprot
proteins
function
FUNCTION: Human-specific protein that promotes neural progenitor proliferation and evolutionary expansion of the brain neocortex by regulating the Notch signaling pathway (PubMed:29561261, PubMed:29856954, PubMed:29856955). Able to promote neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thereby delaying the differentiation of neuronal progenitors and leading to an overall final increase in neuronal production (PubMed:29856954). Acts by enhancing the Notch signaling pathway via two different mechanisms that probably work in parallel to reach the same effect (PubMed:29856954). Enhances Notch signaling pathway in a non-cell-autonomous manner via direct interaction with NOTCH2 (PubMed:29856954). Also promotes Notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, which promotes neuronal differentiation (By similarity). {ECO:0000250|UniProtKB:P0DPK3, ECO:0000269|PubMed:29561261, ECO:0000269|PubMed:29856954, ECO:0000269|PubMed:29856955}.
uniprot
proteins
mass_dalton
31544
uniprot
proteins
protein_family
NOTCH family
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
29561261
uniprot
proteins
pubmed
29856954
uniprot
proteins
pubmed
29856955
uniprot
proteins
pubmed
31178126
uniprot
proteins
pubmed
31332380
uniprot
proteins
pubmed
31332381
uniprot
proteins
pubmed
31819945
uniprot
proteins
pubmed
32333675
uniprot
proteins
pubmed
33239111
uniprot
proteins
pubmed
33693509
uniprot
proteins
pubmed
34435201
uniprot
proteins
sequence_length
293
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29856954, ECO:0000269|PubMed:33693509}.
uniprot
proteins