InterPro domain: IPR043155

Vacuolar protein sorting-associated protein 33 (Vps33) is essential for vacuolar biogenesis, maturation and function. It is involved in the sorting of vacuolar proteins from the Golgi apparatus and their targeting to the vacuole [ 1 ]. In worm, fly, zebrafish and mammals two homologues of yeast Vps33p have been detected (termed VPS33A and VPS33B in humans). These homologues may reflect the evolution of organelle/tissue-specific functions in multicellular organisms. It is thought that VPS33B may be required for transport to conventional lysosomes, while VPS33A is mainly involved in biogenesis of melanosomes and related lysosomal compartments [ 2 , 3 ].

The nSec1 polypeptide chain can be divided into three domains. The first domain, consists of a five-stranded parallel beta-sheet flanked by five alpha-helices. The second domain, like the first one, has an alpha-beta-alpha fold, however the beta-sheet of domain 2 features five parallel strands with an additional antiparallel strand on one edge. The third domain is a large insertion between the third and fourth parallel strands of domain 2, and can be subdivided in two [ 4 ].

Members of the Sec1 family include Sec1, Sly1, Slp1/Vps33, Vps45/Stt10 (yeast), Unc-18 (nematode), Munc-18b/muSec1, Munc-18c (mouse), Rop (Drosophila), Munc-18/n-Sec1/rbSec1A and rbSec1B (rat) [ 5 ].

This superfamily entry represents the C-terminal region of domain 3 (called domain 3b) found in VPS33.

1. Characterization of vps33+, a gene required for vacuolar biogenesis and protein sorting in Schizosaccharomyces pombe. Yeast 20, 845-55
2. The mouse organellar biogenesis mutant buff results from a mutation in Vps33a, a homologue of yeast vps33 and Drosophila carnation. Proc. Natl. Acad. Sci. U.S.A. 100, 1146-50
3. Comparative evolutionary analysis of VPS33 homologues: genetic and functional insights. Hum. Mol. Genet. 14, 1261-70
4. Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex. Nature 404, 355-62
5. The Sec1 family: a novel family of proteins involved in synaptic transmission and general secretion. J. Neurochem. 66, 889-97