MIB1

mib1 is 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).

Full Name

mindbomb homolog 1 (Drosophila)

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 (By similarity).

Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation.

Biological Process

Blood vessel development Source: Ensembl
Endocytosis Source: GO_Central
Heart looping Source: Ensembl
In utero embryonic development Source: Ensembl
Negative regulation of neuron differentiation Source: Ensembl
Neural tube formation Source: Ensembl
Notch signaling pathway Source: GO_Central
Positive regulation of endocytosis Source: Ensembl
Protein ubiquitination Source: GO_Central
Somitogenesis Source: Ensembl
Ubiquitin-dependent protein catabolic process Source: CACAO

Cellular Location

Cytoskeleton
centriolar satellite
Plasma membrane
Cell membrane
Cytoplasm
Note: Localizes to the plasma membrane (By similarity). According to PubMed:15048887, it is mitochondrial, however such localization remains unclear. Displaced from centriolar satellites in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock.

Involvement in disease

Left ventricular non-compaction 7 (LVNC7):
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC7 is an autosomal dominant condition.

PTM

Ubiquitinated; possibly via autoubiquitination (By similarity). Ubiquitinated; this modification is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock.