ITCH, or Atrophin-1, contains a polyglutamine repeat, the expansion of which is responsible for dentatorubral and pallidoluysian atrophy. It is a closely related member of the NEDD4-like protein family. This family of proteins are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. ITCH contains four tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. It can act as a transcriptional corepressor of p45/NFE2, and it may participate in the regulation of immune responses by modifying Notch-mediated signaling. ITCH is highly similar to the mouse ITCH protein, which has been implicated in the regulation and differentiation of erythroid and lymphoid cells.
Delta-Notch Signaling Pathway
EGFR1 Signaling Pathway
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