Jagged-2 (JAG2)

Jagged-2 (JAG2) is a single-pass transmembrane protein that serves as a canonical ligand for Notch receptors (Notch1–4) and is encoded by the JAG2 gene in humans[1][4]. Structurally, it features multiple EGF-like repeats in its extracellular domain, enabling it to interact with Notch receptors on adjacent cells and thereby trigger the canonical Notch signaling cascade[4]. JAG2, together with Jagged-1 (JAG1), constitutes one of two major Serrate-like ligands in mammals, distinguished from the Delta-like ligand family (DLL1, DLL3, DLL4)[3][4]. JAG2 is expressed in multiple tissues, notably high in both cortical and medullary thymic epithelial cells, and plays a key role in hematopoietic lineage commitment by promoting T-cell and inhibiting B-cell differentiation[3]. Dysregulation or aberrant expression of JAG2 is associated with cancer progression and developmental disorders[2][4]. Therapeutic manipulation of the Notch pathway—including indirectly targeting JAG2 interactions—has been explored but is limited by safety and specificity concerns due to the pathway’s broad biological importance[4].

Other names

JAG2jagged canonical Notch ligand 2Protein jagged-2HJ2SER2jagged 2hJ2LGMDR27

Notch pathway modulation (drugs such as γ-secretase inhibitors block downstream signaling after ligand-receptor interaction); Antisense oligonucleotides or siRNAs targeting JAG2 mRNA (e.g., miR-1280 has been reported to inhibit JAG2 expression)