Vacuolar protein sorting-associated protein 41 homolog
Function
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act in part as a core component of the putative HOPS endosomal tethering complex is 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 (PubMed:23351085, PubMed:33851776). Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes implicated in degradation of endocytosed cargo (PubMed:23167963, PubMed:25445562, PubMed:25908847, PubMed:9159129). Required for fusion of autophagosomes with lysosomes (PubMed:25783203). Links the HOPS complex to endosomal Rab7 via its association with RILP and to lysosomal membranes via its association with ARL8B, suggesting that these interactions may bring the compartments to close proximity for fusion (PubMed:21802320, PubMed:25445562, PubMed:25908847). Involved in the direct trans-Golgi network to late endosomes transport of lysosomal membrane proteins independently of HOPS (PubMed:23322049). Involved in sorting to the regulated secretory pathway presumably implicating the AP-3 adapter complex (By similarity). May play a role in HOPS-independent function in the regulated secretory pathway (PubMed:24210660).
Involvement in disease
Spinocerebellar ataxia, autosomal recessive, 29
SCAR29
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR29 is a progressive disease characterized by delayed motor development in early infancy followed by difficulty walking due to an ataxic gait or inability to walk, hypotonia, and variably impaired intellectual development.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the VPS41 family.
Tissue Specificity
Expressed in cerebral cortex and cerebellum. Highly expressed in Purkinje cells.
Cellular localization
- Endosome membrane
- Peripheral membrane protein
- Late endosome membrane
- Peripheral membrane protein
- Early endosome membrane
- Peripheral membrane protein
- Lysosome membrane
- Peripheral membrane protein
- Golgi apparatus
- trans-Golgi network
- Cytoplasmic vesicle
- Clathrin-coated vesicle
- Cytoplasm
- Cytosol
- (Microbial infection) Sequestrated at the late endosome by SARS coronavirus-2/SARS-CoV-2 ORF3A protein.
Alternative names
Vacuolar protein sorting-associated protein 41 homolog, S53, VPS41