Human Notch Homolog 2 (NOTCH2) Protein

Background

NOTCH2 is a key receptor in the Notch signaling pathway that regulates cell proliferation, differentiation, and tissue patterning during development. Ligand binding induces proteolytic cleavage, releasing the NOTCH2 intracellular domain (NICD), which activates transcription of target genes to control cell fate decisions. NOTCH2 is particularly critical for organogenesis, including kidney development, where it regulates nephron formation and podocyte differentiation. Dysregulation of NOTCH2 is linked to various pathologies, including Alagille syndrome, where mutations impair liver, heart, and kidney development. NOTCH2 also plays a role in cancer, where aberrant signaling promotes tumorigenesis, particularly in breast, pancreatic, and biliary tract cancers. Knockout models demonstrate defects in kidney morphogenesis, osteoclast development, and hematopoiesis, highlighting NOTCH2’s essential role in organ development, cellular differentiation, and disease progression.