Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins
Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins
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DOI：
10.1093/glycob/cwi014
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发表时间：
2005-04-01
期刊：
影响因子：
4.3
通讯作者：
Moremen, KW
中科院分区：
文献类型：
--
作者：
Mast, SW;Diekman, K;Moremen, KW
在内质网 (ER) 中，错误折叠的蛋白质逆向移位至胞质，并在称为 ER 相关降解 (ERAD) 的过程中被蛋白酶体降解。在此途径的早期，一种拟议的内质网内质网凝集素（EDEM）可识别内质网中错误折叠的糖蛋白，使新生分子脱离折叠途径，并促进其靶向处置。人类总共有 3 个 EDEM 同系物。这些蛋白质的氨基酸序列与其他凝集素不同，但与 I 类甘露糖苷酶（第 47 家族糖苷酶）密切相关。在这项研究中，我们表征了智人的 EDEM 同源物之一，我们将其命名为 EDEM2 (C20orf31)。使用重组产生的 EDEM2，没有观察到 α-1,2 甘露糖苷酶活性。在 HEK293 细胞中，重组 EDEM2 定位于 ER，在那里它可以与错误折叠的 α1-抗胰蛋白酶结合。 EDEM2 的过度表达会加速错误折叠的 α1-抗胰蛋白酶的降解，表明该蛋白参与 ERAD。
In the endoplasmic reticulum (ER), misfolded proteins are retrotranslocated to the cytosol and degraded by the proteasome in a process known as ER-associated degradation (ERAD). Early in this pathway, a proposed lumenal ER lectin, EDEM, recognizes misfolded glycoproteins in the ER, disengages the nascent molecules from the folding pathway, and facilitates their targeting for disposal. In humans there are a total of three EDEM homologs. The amino acid sequences of these proteins are different from other lectins but are closely related to the Class I mannosidases (family 47 glycosidases). In this study, we characterize one of the EDEM homologs from Homo sapiens, which we have termed EDEM2 (C20orf31). Using recombinantly generated EDEM2, no alpha-1,2 mannosidase activity was observed. In HEK293 cells, recombinant EDEM2 is localized to the ER where it can associate with misfolded alpha 1-antitrypsin. Overexpression of EDEM2 accelerates the degradation of misfolded alpha 1-antitrypsin, indicating that the protein is involved in ERAD.