notch homolog 2 N-terminal-like protein C (NOTCH2NLC)

Function

• human-specific protein
• promotes neural progenitor proliferation & evolutionary expansion of the brain neocortex by regulating the notch signaling pathway
• able to promote neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thud delaying the differentiation of neuronal progenitors leading to an overall increase in neuronal production
• acts by enhancing the notch signaling pathway via two different mechanisms that probably work in parallel to reach thesame effect
  • enhances notch signaling pathway in a non-cell-autonomous manner via direct interaction with NOTCH2
  • promotes notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, which promotes neuronal differentiation (putative)

Structure

belongs to the NOTCH family,

Compartment

secreted

Expression

• expressed in radial glia neural stem cells during cortical development
• expressed at very low level during corticogenesis

Pathology

• a CGG repeat expansion in the 5-prime untranslated region of the gene is responsible for neuronal intranuclear inclusion disease
• defects in NOTCH2NLC may be a cause of chromosome 1q21.1 deletion syndrome

Genetics

• NOTCH2NLA, NOTCH2NLB & NOTCH2NLC paralogs arose between 4 & 3 million years ago after the separation of hominids from the chimpanzee & during the early stages of the expansion of the human cortex

More general terms

• notch (Drosophila) homolog protein
• secreted protein
• evolutionary divergent human protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=388677
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:388677
• OMIM: https://mirror.omim.org/entry/603472
• OMIM: https://mirror.omim.org/entry/618025
• UniProt: http://www.uniprot.org/uniprot/P0DPK4.html