InterPro domain: IPR036045

Sec1-like molecules have been implicated in a variety of eukaryotic vesicle transport processes including neurotransmitter release by exocytosis [ 1 ].They regulate vesicle transport by binding to a t-SNARE from the syntaxin family. This process is thought to prevent SNARE complex formation, a protein complex required for membrane fusion. Whereas Sec1 molecules are essential for neurotransmitter release and other secretory events, their interaction with syntaxin molecules seems to represent a negative regulatory step in secretion [ 2 ].

Mutations in vacuolar protein sorting-associated protein 33B (VPS33B) account for most cases of arthrogryposis, renal dysfunction and cholestasis syndrome (ARC) [ 3 ]. It is proposed that the VPS33 may play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes [ 4 ].

1. The Sec1 family: a novel family of proteins involved in synaptic transmission and general secretion. J. Neurochem. 66, 889-97
2. The X-ray crystal structure of neuronal Sec1 from squid sheds new light on the role of this protein in exocytosis. Structure 8, 685-94
3. Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. Nat. Genet. 42, 303-12
4. VPS33B regulates protein sorting into and maturation of α-granule progenitor organelles in mouse megakaryocytes. Blood 126, 133-43