notch homolog 2 N-terminal-like protein B (NOTCH2NLB)

Function

• human-specific protein
• promotes neural progenitor proliferation & evolutionary expansion of the brain neocortex by regulating the notch signaling pathway
• promotes neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thus delaying differentiation of neuronal progenitors leading to an increase in neuronal production
• acts by enhancing the notch signaling pathway via two different mechanisms that probably work in parallel to reach the same 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

Structure

belongs to the NOTCH family,

Compartment

secreted

Alternative splicing

named isoforms=2

Expression

• expressed in radial glia neural stem cells during cortical development
• expressed at low levels at 7-9 gestational weeks & then increases at later stages, including in the non-cortical plate region at gestational week 21, containing the outer-subventricular zone

Pathology

• defects in NOTCH2NLB may be a cause of chromosome 1q21.1 deletion/duplication syndrome
• deletions of NOTCH2NL (NOTCH2NLA, NOTCH2NLB &/or NOTCH2NLC) are present in patients affected by microcephaly, whereas macrocephaly is observed in patients with NOTCH2NL duplications

Evolution

• NOTCH2NLA, NOTCH2NLB & NOTCH2NLC paralogs arosebetween 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

• UniProt: http://www.uniprot.org/uniprot/P0DPK3.html