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

Notch homolog 2 N-terminal-like protein B (NOTCH2NLB) is a human-specific protein that plays a key role in the development and evolutionary expansion of the human neocortex through its positive regulation of the Notch signaling pathway. NOTCH2NLB is primarily involved in promoting the proliferation and self-renewal of cortical apical progenitors, thereby delaying their differentiation into neurons and expanding the pool of neural progenitors during development. Mechanistically, NOTCH2NLB acts by enhancing Notch signaling via direct binding to NOTCH2, and by inhibiting interactions between NOTCH2 and DLL1 in a cell-autonomous manner. The expansion of the neural progenitor pool is thought to underlie increased neuronal numbers and larger cortex size in humans; accordingly, alterations in NOTCH2NL family gene dosage are linked to neurodevelopmental and neuropsychiatric disorders, although NOTCH2NLB itself is not currently considered a direct therapeutic target or druggable receptor. The NOTCH2NL family (including NOTCH2NLB, NOTCH2NLA, NOTCH2NLC) is a set of recent gene duplications unique to humans, sharing high sequence similarity and functional overlap in modulating neurogenesis during cortical development. NOTCH2NLB protein preferentially localizes to the extracellular space and regulates downstream signaling by interacting with canonical Notch pathway components, but does not fit into major classic therapeutic target classes like "receptor," "ion channel," or "enzyme." No current drugs are known to directly target NOTCH2NLB.

Other names

Notch homolog 2 N-terminal-like protein BNOTCH2NLBN2NNOTCH2NLNOTCH2NLANotch homolog 2 N-terminal-like protein ANotch homolog 2 N-terminal-like protein