Alternative titles; symbolsVTI1, S. CEREVISIAE, HOMOLOG OF, BVTI1VTI1-LIKE; VTI1LHGNC Approved Gene Symbol: VTI1BCytogenetic location: 14q24.1 Genomic coordi...
Alternative titles; symbols
HGNC Approved Gene Symbol: VTI1B
Cytogenetic location: 14q24.1 Genomic coordinates (GRCh38): 14:67,647,084-67,674,631 (from NCBI)
▼ Cloning and Expression
Membrane traffic in eukaryotic cells requires the interaction of a vesicle-associated soluble NSF attachment protein receptor (v-SNARE) on transport vesicles with a t-SNARE on the target membrane. See 603215. Vti1 is an S. cerevisiae v-SNARE that is essential for viability. Vti1 participates both in Golgi to prevacuolar transport and in traffic to the cis-Golgi. Using a multicopy suppressor screen to identity human proteins that can functionally complement a yeast vti1 deletion mutant, Fischer von Mollard and Stevens (1998) isolated a glioblastoma cDNA encoding VTI1, a human homolog of yeast Vti1. The deduced 232-amino acid human protein contains a C-terminal transmembrane domain and 2 predicted coiled-coil regions. The yeast and human proteins are 29% identical. Expression of human VTI1 in yeast indicated that VTI1 can replace yeast Vti1 in both Golgi transport reactions. Northern blot analysis detected a 1.2-kb VTI1 mRNA in all human tissues tested. Searches of an EST database identified cDNAs encoding a mouse protein with 93% sequence identity to human VTI1.
▼ Biochemical Features
Miller et al. (2007) characterized the molecular details governing the sorting of a SNARE into clathrin-coated vesicles, namely, the direct recognition of the 3-helical bundle H(abc) domain of the mouse SNARE Vti1b by the human clathrin adaptor epsinR (EPNR, also known as CLINT1; 607265). Structures of each domain and of their complex showed that this interaction (dissociation constant 22 microM) is mediated by surface patches composed of approximately 15 residues each, the topographies of which are dependent on each domain's overall fold. Disruption of the interface with point mutations abolished the interaction in vitro and caused Vti1b to become relocalized to late endosomes and lysosomes. Miller et al. (2007) stated that this new class of highly specific, surface-surface interaction between the clathrin coat component and the cargo is distinct from the widely observed binding of short, linear cargo motifs by the assembly polypeptide (AP) complex and GGA adaptors and is therefore not vulnerable to competition from standard motif-containing cargoes for incorporation into clathrin-coated vesicles. Miller et al. (2007) proposed that conceptually similar but mechanistically different interactions direct the post-Golgi trafficking of many SNAREs.