NOTCH2NLA
Developmental stage
Expressed at low levels at 7-9 gestational weeks and then increases at later stages, including in the non-cortical plate region at gestational week 21, containing the outer-subventricular zone (PubMed:29856955). Expressed at lower level than NOTCH2NLB (PubMed:29856955).
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).
Involvement in disease
Defects in NOTCH2NLA 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).
Post-translational modifications
Cleaved by ELANE.
Sequence Similarities
Belongs to the NOTCH family.
Tissue Specificity
Widely expressed with higher levels in leukocytes and lymph nodes (PubMed:14673143). Expressed in radial glia neural stem cells during cortical development (PubMed:29856954).
Cellular localization
- Secreted
- Cytoplasm
Alternative names
N2N, NOTCH2NL, NOTCH2NLA, Notch homolog 2 N-terminal-like protein A, Notch homolog 2 N-terminal-like protein