This gene encodes a protein containing multiple ankyrin repeats and RING finger domains that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1). [provided by RefSeq, Jun 2013],function:E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis.,miscellaneous:In epilepsy brain tissue, levels of expression are increased in the cytoplasm and microsomal fractions (endoplasmic reticulum).,pathway:Protein modification, protein ubiquitination.,PTM:Ubiquitinated. Possibly via autoubiquitination.,similarity:Contains 1 ZZ-type zinc finger.,similarity:Contains 2 MIB/HERC2 domains.,similarity:Contains 3 RING-type zinc fingers.,similarity:Contains 9 ANK repeats.,subcellular location:Localizes to the plasma membrane (By similarity). According to PubMed:15048887, it is mitochondrial, however such localization remains unclear.,tissue specificity:Widely expressed at low level. Expressed at higher level in spinal cord, ovary, whole brain, and all specific brain regions examined.,
