VPS11
Function
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). Involved in cargo transport from early to late endosomes and required for the transition from early to late endosomes (PubMed:21148287). Involved in the retrograde Shiga toxin transport (PubMed:23593995).
Involvement in disease
Leukodystrophy, hypomyelinating, 12
HLD12
An autosomal recessive neurologic disorder characterized by developmental delay, spasticity, truncal hypotonia, acquired microcephaly, intellectual disability with variable seizure disorder, accompanied by thin corpus callosum, paucity of white matter and delayed myelination.
None
The disease is caused by variants affecting the gene represented in this entry.
Dystonia 32
DYT32
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT32 is an autosomal recessive, slowly progressive form with onset in adulthood and generalized involvement of the limbs, trunk, neck, and larynx, resulting in dysarthria and dysphagia. Brain imaging may show abnormalities in the basal ganglia.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the VPS11 family.
Tissue Specificity
Ubiquitous. Expression was highest in heart and low in lung.
Cellular localization
- Endosome
- Late endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Lysosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Early endosome
- Cytoplasmic vesicle
- Cytoplasmic vesicle
- Autophagosome
- Cytoplasmic vesicle
- Clathrin-coated vesicle
Alternative names
RNF108, PP3476, VPS11, Vacuolar protein sorting-associated protein 11 homolog, hVPS11, RING finger protein 108