MIB1 is a 1006 amino acid E3 ubiquitin ligase that activates the Notch ligand, Delta. MIB1 ubiquinates Delta by binding to its intracellular domain, leading to the endocytosis and eventual degradation of the Delta receptor, which, paradoxically, results in the up-regulation of receptor activity and enhances Notch signaling. MIB1 also interacts with DAPK, a protein that plays an important role in the regulation of apoptosis. Ubiquination of DAPK leads to inhibition of caspase-dependent apoptosis, therefore it is likely that overexpression of MIB1 can lead to tumor growth. Although it seems to be widely expressed at low levels, MIB1 is expressed at highest concentrations in the CNS and ovary. Both DAPK and MIB1 are overexpressed in epileptic brain tissue, suggesting that they probably cooperate as regulators of neuronal death in epilepsy.
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.
Subcellular Location:
Cytoplasm. Cell membrane. 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.
Post-translational modifications:
Ubiquitinated. Possibly via autoubiquitination.
Similarity:
Contains 9 ANK repeats.
Contains 2 MIB/HERC2 domains.
Contains 3 RING-type zinc fingers.
Contains 1 ZZ-type zinc finger.
SWISS:
Q86YT6
Gene ID:
57534
Database links:
Entrez Gene: 57534 Human
Entrez Gene: 225164 Mouse
Omim: 608677 Human
SwissProt: Q86YT6 Human
SwissProt: Q80SY4 Mouse
Unigene: 140903 Human
Unigene: 651768 Human
Unigene: 2300 Mouse
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