Alternative titles; symbols
HGNC Approved Gene Symbol: SGTA
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38) : 19:2,754,715-2,783,273 (from NCBI)
The SGT protein interacts with the parvovirus nonstructural protein NS1. Kordes et al. (1998) used yeast 2-hybrid screening to isolate a human SGT cDNA from a placenta library. The SGT gene encodes a 313-amino acid polypeptide containing 3 tetratricopeptide repeat (TPR) protein-protein interaction motifs. Northern blot analysis revealed SGT expression as a 2.4-kb mRNA at comparable levels in all human tissues tested.
Tobaben et al. (2001) showed that rat Csp (DNAJC5; 611203) interacted with Sgt and Hsc70 (HSPA8; 600816) in a complex located on the synaptic vesicle surface. The complex functioned as an ATP-dependent chaperone that reactivated a denatured substrate. Sgt overexpression in cultured rat hippocampal neurons inhibited neurotransmitter release, suggesting that the Csp/Sgt/Hsc70 complex is important for maintenance of a normal synapse.
By Far Western analysis, Angeletti et al. (2002) demonstrated that SGT bound directly to Hsp70 (see 601113) and its constitutive counterpart, Hsc70, with high affinity. Mutation analysis revealed that the tetratricopeptide repeat (TPR) motifs in the N-terminal half of SGT were required for the interaction. By interacting with Hsp70 and Hsc70, SGT inhibited the ATPase activity of Hsc70 and the refolding activity of Hsp70 and Hsc70. SGT also interacted with Hsp90 (see 140571) via its TPRs, but the overall binding with Hsp90 was weaker than binding with Hsp70 and Hsc70. The cochaperone function of SGT was conserved in yeast, as knockout of Sgt resulted in a yeast strain defective for recovery from severe heat shock.
To understand how the fate of nascent tail-anchored membrane proteins is determined, Shao et al. (2017) reconstituted the core reactions for membrane targeting and ubiquitination of these proteins. They found that the central 6-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induced rapid, private, and committed client transfer to TRC40 (601913) for successful biosynthesis. Commitment to ubiquitination is dictated primarily by comparatively slower client dissociation from SGTA and nonprivate capture by the BAG6 (142590) subunit of the quality control module. Shao et al. (2017) concluded that their results provided a paradigm for how priority and time are encoded within a multichaperone triage system.
Kordes et al. (1998) used fluorescence in situ hybridization to map the SGTA gene to human chromosome 19p13.
Angeletti, P. C., Walker, D., Panganiban, A. T. Small glutamine-rich protein/viral protein U-binding protein is a novel cochaperone that affects heat shock protein 70 activity. Cell Stress Chaperones 7: 258-268, 2002. [PubMed: 12482202] [Full Text: https://doi.org/10.1379/1466-1268(2002)007<0258:sgrpvp>2.0.co;2]
Kordes, E., Savelyeva, L., Schwab, M., Rommelaere, J., Jauniaux, J.-C., Cziepluch, C. Isolation and characterization of human SGT and identification of homologues in Saccharomyces cerevisiae and Caenorhabditis elegans. Genomics 52: 90-94, 1998. [PubMed: 9740675] [Full Text: https://doi.org/10.1006/geno.1998.5385]
Shao, S., Rodrigo-Brenni, M. C., Kivlen, M. H., Hegde, R. S. Mechanistic basis for a molecular triage reaction. Science 355: 298-302, 2017. [PubMed: 28104892] [Full Text: https://doi.org/10.1126/science.aah6130]
Tobaben, S., Thakur, P., Fernandez-Chacon, R., Sudhof, T. C., Rettig, J., Stahl, B. A trimeric protein complex functions as a synaptic chaperone machine. Neuron 31: 987-999, 2001. [PubMed: 11580898] [Full Text: https://doi.org/10.1016/s0896-6273(01)00427-5]