Alternative titles; symbols
HGNC Approved Gene Symbol: YKT6
Cytogenetic location: 7p13 Genomic coordinates (GRCh38): 7:44,200,978-44,214,294 (from NCBI)
For an explanation of the SNARE hypothesis, see 603215. YKT6 is a v-SNARE involved in endoplasmic reticulum-Golgi transport.
McNew et al. (1997) isolated S. cerevisiae Ykt6p as an interacting partner of the cis Golgi target membrane-associated SNARE Sed5p. They identified human YKT6 by comparison of the yeast sequence with an EST database, and cloned the human cDNA by PCR from a pancreatic cDNA library. Ykt6 and its homologs are highly conserved from yeast to human. Human YKT6 protein shares 47% and 57% sequence identity with S. cerevisiae and C. elegans homologs, respectively.
Ykt6 is an essential gene that codes for a novel vesicle-associated SNARE functioning at the endoplasmic reticulum/Golgi transport step in the yeast secretory pathway. McNew et al. (1997) demonstrated that depletion of Ykt6p results in the accumulation of the p1 precursor of the vacuolar enzyme carboxypeptidase Y and morphologic abnormalities consistent with a defect in secretion. Membrane localization of Ykt6p is essential for protein function and is normally mediated by isoprenylation. However, replacement of the isoprenylation motif with a bona fide transmembrane anchor results in a functional protein confirming that membrane localization, but not isoprenylation per se, is required for function. McNew et al. (1997) demonstrated that human YKT6 could complement the loss of Ykt6p.
Tochio et al. (2001) performed in vitro studies which revealed that the N-terminal domain of Ykt6p plays an important biologic role in its function, which includes influencing the kinetics and proper assembly of SNARE complexes.
Atomic Structure
By nuclear magnetic resonance (NMR) spectroscopy, Tochio et al. (2001) reported the atomic structure of the N-terminal domain of Ykt6p. The N-terminal structure of Ykt6p differed entirely from that of syntaxin (see 186590) and resembled the overall fold of the actin regulatory protein profilin (see 176610). Like some syntaxins, Ykt6p adopted a folded-back conformation in which the Ykt6p N-terminus bound to its C-terminal core domain.
McNew, J. A., Sogaard, M., Lampen, N. M., Machida, S., Ye, R. R., Lacomis, L., Tempst, P., Rothman, J. E., Sollner, T. H. Ykt6p, a prenylated SNARE essential for endoplasmic reticulum-Golgi transport. J. Biol. Chem. 272: 17776-17783, 1997. [PubMed: 9211930] [Full Text: https://doi.org/10.1074/jbc.272.28.17776]
Tochio, H., Tsui, M. M. K., Banfield, D. K., Zhang, M. An autoinhibitory mechanism for nonsyntaxin SNARE proteins revealed by the structure of Ykt6p. Science 293: 698-702, 2001. [PubMed: 11474112] [Full Text: https://doi.org/10.1126/science.1062950]