Numb contains an amino-terminal phosphotyrosine-binding (PTB) domain and carboxy-terminal endocytic binding motifs for α-adaptin and EH (Eps15 homology) domain-containing proteins, indicating a role in endocytosis. Mammalian NUMB homologs play a role in the determination of cell fates during development and bind with EPS15, LNX1, and NOTCH1. Conditional mouse mutants with deletion of NUMB in developing sensory ganglia show a reduction in axonal arborization in afferent fibers. Alternative splicing results in multiple transcript variants.
