RING finger, H2 subclass, found in vacuolar protein sorting-associated protein 18 (Vps18) and similar proteins
Vps18 is an ubiquitin ligase E3 that is highly expressed in heart. It induces the ubiquitylation and degradation of serum-inducible kinase (SNK). Vps18 associates with Vps11, Vps16, and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport) protein complexes. CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form. Vps18 deficiency inhibits dendritogenesis in Purkinje cells by blocking the lysosomal degradation of lysyl oxidase. Vps18 contains a clathrin heavy chain repeat, a coiled-coil domain, and a C3H2C3-type RING-H2 finger domain close to its C-terminus. This subfamily also includes Vps18 homologs found in insects and fungi, such as Drosophila melanogaster protein deep orange (dor) gene encoding protein Dor, and Saccharomyces cerevisiae vacuolar membrane protein Pep3p, also known as carboxypeptidase Y-deficient protein 3, or vacuolar morphogenesis protein 8. Drosophila Dor is part of a protein complex, which also includes the Sep1p homolog carnation (car), which localizes to endosomal compartments and is required not only for the biogenesis of pigment granules but also for the normal delivery of proteins to lysosomes. Pep3p is a vacuolar peripheral membrane protein that is required for vacuolar biogenesis in Saccharomyces cerevisiae. Pep3p associates with Pep5p to form a core Pep3p/Pep5p complex that promotes vesicular docking/fusion reactions in conjunction with SNARE proteins at multiple steps in transport routes to the vacuole.