VPS16
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 recruitment of VPS33A to the HOPS complex (PubMed:23901104). Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS33A but not VPS33B (PubMed:25783203). The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG (PubMed:24554770).
Involvement in disease
Dystonia 30
DYT30
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT30 is characterized by early onset and predominantly cervical, bulbar, orofacial, and upper limb involvement. Some patients have a more complex phenotype with neurocognitive impairment, including mild intellectual disability or psychiatric manifestations. Loss of ambulation is observed in some cases. DYT30 inheritance is autosomal dominant with incomplete penetrance.
None
The disease is caused by variants affecting the gene represented in this entry. The transmission pattern of DYT30 in most families is consistent with autosomal dominant inheritance. However, a homozygous VPS16 variant has been found in a multigenerational consanguineous family with autosomal recessive inheritance of DYT30.
Sequence Similarities
Belongs to the VPS16 family.
Tissue Specificity
Ubiquitous.
Cellular localization
- Late endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Lysosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Early endosome
- Cytoplasmic vesicle
- Clathrin-coated vesicle
- Cytoplasmic vesicle
- Autophagosome
- Colocalizes with AP-3, clathrin, Rab5 and Rab7b (By similarity). Cytoplasmic, peripheral membrane protein associated with early endosomes and late endosomes/lysosomes.
Alternative names
Vacuolar protein sorting-associated protein 16 homolog, hVPS16, VPS16