Alternative titles; symbols
HGNC Approved Gene Symbol: SEC62
Cytogenetic location: 3q26.2 Genomic coordinates (GRCh38): 3:169,966,807-169,998,373 (from NCBI)
SEC62 is a component of the translocation machinery for importing proteins into the endoplasmic reticulum (ER) (summary by Han et al., 2019).
The translocation of secretory proteins across the ER membrane is mediated in yeast by Sec62 and other proteins. Daimon et al. (1997) cloned a gene, which they termed HTP1, that is the human homolog of Sec62. The HTP1 cDNA encodes a 399-amino acid polypeptide that is 28% identical to Sec62 and 36% identical to the Drosophila Sec62 homolog, Dtrp1. Northern blot analysis revealed RNAs of about 2.8 kb and 5.5 kb expressed concomitantly at varying levels in all tissues tested.
By searching databases for sequences similar to yeast Sec62, followed by PCR of a HeLa cell cDNA library and RACE of a fetal brain cDNA library, Meyer et al. (2000) cloned SEC62. The deduced protein has 2 membrane-spanning segments. Western blot analysis detected Sec62 in all bovine and rat tissues examined. Immunofluorescence analysis of human hepatoma cells indicated that SEC62 and SEC63 (608648) colocalized with ER proteins.
By Western blot analysis and coimmunoprecipitation of proteins from bovine rough microsomes, Meyer et al. (2000) found that mammalian Sec62 associated with Sec63 and Sec61 (see 609213). Cross-linking experiments indicated that Sec62 specifically interacted with the beta subunit of the Sec61 complex.
Using mutation analysis with protein pull-down assays, Muller et al. (2010) found that the isolated N-terminal domain of human SEC62 (SEC62N) interacted directly with the 26 C-terminal amino acids of SEC63 in a 1:1 ratio. SEC62N also interacted specifically with the 60S ribosomal subunit in canine pancreatic ribosomes, a function not observed with SEC62 orthologs in invertebrates, yeast, and plants. Interaction of SEC62N with ribosomes was sensitive to salt and RNase treatment. Competition studies revealed that SEC62N and the ribosomal tunnel exit-interacting protein ERJ1 (DNAJC1; 611207) competed for an overlapping binding site on ribosomes. Muller et al. (2010) concluded that SEC62 and SEC63, like ERJ1, localize at the ribosomal tunnel exit and function in the transport of polypeptides into the ER.
Han et al. (2019) found that infection by foot-and-mouth disease virus (FMDV) activated the Perk (EIF2AK3; 604032)-Eif2-alpha (EIF2AK3; 603907) and Atf6 (605537) unfolded protein response (UPR) pathways, but suppressed the Ire1-alpha (ERN1; 604033)-Xbp1 (194355) UPR pathway, in both BHK-21 baby hamster kidney cells and PK-15 porcine kidney cells. Overexpression of Sec62 suppressed FMDV protein synthesis and FMDV proliferation in PK-15 cells, whereas Sec62 knockdown increased them. Western blot analysis revealed that Sec62 activated Ire1-alpha by promoting its phosphorylation and stabilization during FMDV infection. Luciferase reporter and quantitative real-time RT-PCR analyses demonstrated that Sec62 stimulated innate antiviral immune responses in PK-15 cells by positively regulating expression of type I interferon and cytokines, independent of virus infection. Further analyses showed that Sec62 suppressed FMDV replication by maintaining the protein levels of Ire1-alpha and Rigi (DDX58; 609631) and positively regulating their downstream Irf3 (603734)/Irf7 (605047) and NFKB (see 164011) signaling pathways.
Hartz (2011) mapped the SEC62 gene to chromosome 3q26.2 based on an alignment of the SEC62 sequence (GenBank BX648539) with the genomic sequence (GRCh37).
Daimon, M., Susa, S., Suzuki, K., Kato, T., Yamatani, K., Sasaki, H. Identification of a human cDNA homologue to the Drosophila translocation protein 1 (Dtrp1). Biochem. Biophys. Res. Commun. 230: 100-104, 1997. [PubMed: 9020021] [Full Text: https://doi.org/10.1006/bbrc.1996.5892]
Han, S., Mao, L., Liao, Y., Sun, S., Zhang, Z., Mo, Y., Liu, H., Zhi, X., Lin, S., Seo, H. S., Guo, H. Sec62 suppresses foot-and-mouth disease virus proliferation by promotion of IRE1-alpha-RIG-I antiviral signaling. J. Immun. 203: 429-440, 2019. [PubMed: 31167774] [Full Text: https://doi.org/10.4049/jimmunol.1801546]
Hartz, P. A. Personal Communication. Baltimore, Md. 12/6/2011.
Meyer, H.-A., Grau, H., Kraft, R., Kostka, S., Prehn, S., Kalies, K.-U., Hartmann, E. Mammalian Sec61 is associated with Sec62 and Sec63. J. Biol. Chem. 275: 14550-14557, 2000. [PubMed: 10799540] [Full Text: https://doi.org/10.1074/jbc.275.19.14550]
Muller, L., de Escauriaza, M. D., Lajoie, P., Theis, M., Jung, M., Muller, A., Burgard, C., Greiner, M., Snapp, E. L., Dudek, J., Zimmermann, R. Evolutionary gain of function for the ER membrane protein Sec62 from yeast to humans. Molec. Biol. Cell 21: 691-703, 2010. [PubMed: 20071467] [Full Text: https://doi.org/10.1091/mbc.e09-08-0730]