Since 2012, the interest for TMEM165 increased due to its implication in a rare genetic human disease named TMEM165-CDG (Congenital Disorder(s) of Glycosylation). TMEM165 is a Golgi localized protein, highly conserved through evolution and belonging to the uncharacterized protein family 0016 (UPF0016). Although the precise function of TMEM165 in glycosylation is still controversial, our results highly suggest that TMEM165 would act as a Golgi Ca2+/Mn2+ transporter regulating both Ca2+ and Mn2+ Golgi homeostasis, the latter is required as a major cofactor of many Golgi glycosylation enzymes. Strikingly, we recently demonstrated that besides its role in regulating Golgi Mn2+ homeostasis and consequently Golgi glycosylation, TMEM165 is sensitive to high manganese exposure. Members of the UPF0016 family contain two particularly highly conserved consensus motifs E-φ-G-D-[KR]-[TS] predicted to be involved in the ion transport function of UPF0016 members. We investigate the contribution of these two specific motifs in the function of TMEM165 in Golgi glycosylation and in its Mn2+ sensitivity. Our results show the crucial importance of these two conserved motifs and underline the contribution of some specific amino acids in both Golgi glycosylation and Mn2+ sensitivity.

中文翻译：

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解剖TMEM165在高尔基糖基化中的功能及其对Mn2 +的敏感性。

自2012年以来，由于TMEM165与一种罕见的遗传性人类疾病TMEM165-CDG（先天性糖基化）有关，因此对TMEM165的兴趣有所增加。TMEM165是高尔基体定位的蛋白质，通过进化高度保守，属于未鉴定的蛋白质家族0016（UPF0016）。尽管TMEM165在糖基化中的确切功能仍存在争议，但我们的研究结果高度提示TMEM165可以作为高尔基Ca2 + / Mn2 +转运蛋白，同时调节Ca2 +和Mn2 +高尔基体内稳态，后者是许多高尔基糖基化酶的主要辅因子。令人惊讶的是，我们最近证明，TMEM165除了在调节高尔基Mn2 +稳态以及因此在高尔基糖基化中的作用外，还对高锰暴露敏感。UPF0016家族的成员包含两个特别保守的共有基序E-φ-GD-[KR]-[TS]，预计它们参与UPF0016成员的离子转运功能。我们调查这两个特定的基序在高尔基糖基化及其对Mn2 +敏感性中TMEM165的功能的贡献。我们的结果显示了这两个保守基序的至关重要性，并强调了某些特定氨基酸在高尔基糖基化和Mn2 +敏感性中的贡献。