High impact information on SEC62

• While bound to Sec61p, the signal sequence forms a helix that is contacted on one side by Sec62p and Sec71p [1].
• We demonstrate that Sec62p, Sec71p and Sec72p form a translocon subcomplex that engages secretory precursors at the membrane site of the ER translocation machinery [2].
• These results confirm previous predictions, based upon genetic interactions between the SEC genes, that Sec61, Sec62 and Sec63 act together to facilitate protein translocation into the ER [3].
• SEC62 encodes a putative membrane protein required for protein translocation into the yeast endoplasmic reticulum [4].
• A potential membrane location for the SEC62 gene product is supported by evaluation of the molecular clone [4].

Biological context of SEC62

• Some form of interaction among the SEC61 (Deshaies, R. J., and R. Schekman. 1987. J. Cell Biol. 105:633-645), SEC62 and SEC63 gene products is suggested by the observation that haploid cells containing any pair of the mutations are inviable at 24 degrees C and show a marked enhancement of the translocation defect [5].
• The DNA sequence of SEC62 predicts a 32-kDa polypeptide with two potential membrane-spanning segments [6].
• SEC62 encodes an essential component of the Sec-complex that is responsible for posttranslational protein translocation across the membrane of the endoplasmic reticulum in Saccharomyces cerevisiae [7].
• The Y. lipolytica SEC62 promoter region was amplified by the inverse polymerase chain reaction (PCR) [8].
• These findings show that phosphorylation of Sec63p is required for tightly recruiting the putative signal-sequence-binding subunit Sec62p to the Sec complex [9].

Anatomical context of SEC62

• SEC62 is required for the import of secretory protein precursors into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae [6].
• The translocation defects of two mutants (sec62 and sec63) have been reproduced in vitro. sec63 microsomes display low and thermolabile translocation activity for prepro-alpha-factor (pp alpha F) synthesized with a cytosol fraction from wild type yeast [5].
• Oligomer formation by the reconstituted Sec61p complex is stimulated by its association with ribosomes or the Sec62/63p complex [10].
• Yeast microsomes contain a heptameric Sec complex involved in post-translational protein transport that is composed of a heterotrimeric Sec61p complex and a tetrameric Sec62-Sec63 complex [11].
• Invertase assembly is only partly affected by the sec62 mutation in vivo and is nearly normal with mutant membranes in vitro [4].

Associations of SEC62 with chemical compounds

• Exchanging either threonine 652 or threonine 654 against the nonphosphorylatable alanines in Sec63p impairs the binding to Sec62p and interferes with the efficient translocation of proteins across the membrane of the endoplasmic reticulum [9].
• Sec62p is predicted to display significant NH2- and COOH-terminal hydrophilic domains on the cytoplasmic surface of the ER membrane [4].

Enzymatic interactions of SEC62

• We show that Sec63p is phosphorylated at its C-terminal domain by the protein kinase CK2 and that this phosphorylation strengthens the interaction between the cytosolic domains of Sec63p and Sec62p [9].

Other interactions of SEC62

• Mutations in SEC62 and SEC63 decrease the ability of Sec61p to be cross-linked to the secretory polypeptide trapped in translocation [12].
• The yeast homologue of the heavy chain-binding protein, BiP (encoded by the KAR2 gene), and the product of the SEC62 gene were present in two fractions having equilibrium densities of 1.146 and 1.192 g/ml, respectively [13].
• Cub fusions that bore the signal sequence of invertase resulted in a much lower Ub reconstitution with Nub-Sec62p than otherwise identical test proteins bearing the signal sequence of prepro-alpha-factor [14].

Analytical, diagnostic and therapeutic context of SEC62

• A combination of subcellular fractionation, detergent and alkali extraction, and indirect immunofluorescence studies indicated that Sec62p is intimately associated with the ER membrane [6].
• Structural and functional dissection of Sec62p, a membrane-bound component of the yeast endoplasmic reticulum protein import machinery [6].
• Y. lipolytica Sec62p behaves as an integral membrane protein as shown by Western blotting [8].

References