juxtamembrane and transmembrane (JMTM) domain found in neurogenic locus notch homolog protein 2 (Notch2) and similar proteins
Neurogenic locus notch homolog protein 2 (Notch2) functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Notch2 is involved in bone remodeling and homeostasis. In collaboration with RELA/p65, it enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. Notch2 positively regulates self-renewal of liver cancer cells. This model corresponds to the juxtamembrane and transmembrane (JMTM) domain of Notch2, which comprises an extended coil, a transmembrane helix (TM), and a beta-strand.
Feature 1:putative polypeptide substrate binding site [polypeptide binding site]
Evidence:
Comment:Following an initial cleavage by alpha-secretase, the resulting transmembrane domain of Notch is cleaved by gamma-secretase to release the intracellular transcription factor.
Comment:Based on the structure evidence that Homo sapiens Notch1 interacts with nicastrin and presenilin-1.
Jiyao W et al.(2023). "The conserved domain database in 2023.",