Functions as a ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity (By similarity). Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Mainly acts as a positive regulator of Notch, but it also acts as a negative regulator, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Involved in neurogenesis, lymphogenesis and myogenesis, and may also be involved in MZB (Marginal zone B) cell differentiation. Promotes B-cell development at the expense of T-cell development, suggesting that it can antagonize NOTCH1.
Widely expressed. Strongly expressed in blood vessel. Also expressed in embryonic nervous system, pancreas, lung, adrenal gland, digestive tube and muscles. Expressed in MZB cells and developing B- and T-cells.
Protein modification; protein ubiquitination.
Belongs to the Deltex family. Contains 1 RING-type zinc finger. Contains 2 WWE domains.
The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases.
Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH.
Cytoplasm. Nucleus. Predominantly cytoplasmic. Associates with endocytic vesicles. Partially nuclear.