S chool of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK.
Metallomics. 2024 Oct 4;16(10). doi: 10.1093/mtomcs/mfae045.
The mammalian retina contains high amounts of metals/metalloid-selenium. Their dyshomeostases are associated with certain retinal diseases. We carried out this bioinformatics study to identify the relationships between putative retinal metal/selenium binding proteins, their molecular functions, and biological processes. Identification of putative mouse metal/selenium binding proteins was based on known binding motifs, domains, patterns, and profiles. Annotations were obtained from Uniprot keywords 'metal binding', 'metal ion co-factors', 'selenium proteins'. Protein functions were estimated by associative frequency with key words in UniProt annotations. The raw data of five mouse proteomics PRIDE datasets (available to date) were downloaded and processed with Mascot against the mouse taxa of Uniprot (SwissProt/Trembl) and MaxQuant (version 1.6.10.43) for qualitative and quantitative datasets, respectively. Clinically relevant variants were evaluated using archives and aggregated information in ClinVar. The 438 proteins common to all the retina proteomics datasets were used to identify over-represented Gene Ontology categories. The putative mouse retinal metal/metalloid binding proteins identified are mainly involved in: (1) metabolic processes (enzymes), (2) homeostasis, (3) transport (vesicle mediated, transmembrane, along microtubules), (4) cellular localization, (5) regulation of signalling and exocytosis, (6) organelle organization, (7) (de)phosphorylation, and (8) complex assembly. Twenty-one proteins were identified as involved in response to light stimulus and/or visual system development. An association of metal ion binding proteins rhodopsin, photoreceptor specific nuclear receptor, calcium binding protein 4 with disease-related mutations in inherited retinal conditions was identified, where the mutations affected an area within or in close proximity to the metal binding site or domain. These findings suggest a functional role for the putative metal/metalloid binding site in retinal proteins in certain retinal disorders.
哺乳动物视网膜中含有大量的金属/类金属-硒。它们的动态平衡失调与某些视网膜疾病有关。我们进行了这项生物信息学研究，以确定假定的视网膜金属/硒结合蛋白与其分子功能和生物学过程之间的关系。
鉴定假定的小鼠金属/硒结合蛋白是基于已知的结合基序、结构域、模式和图谱。注释来自 Uniprot 关键词“金属结合”、“金属离子辅因子”、“硒蛋白”。通过与 UniProt 注释中的关键字的关联频率来估计蛋白质的功能。迄今为止，共下载了五个小鼠蛋白质组学 PRIDE 数据集的原始数据，并使用 Mascot 对 UniProt（SwissProt/Trembl）和 MaxQuant（版本 1.6.10.43）的小鼠分类进行定性和定量数据集分析。使用 ClinVar 中的档案和聚合信息评估临床相关变体。将所有视网膜蛋白质组学数据集共有的 438 种蛋白质用于识别过度表达的基因本体类别。
鉴定出的假定的小鼠视网膜金属/类金属结合蛋白主要参与：（1）代谢过程（酶），（2）动态平衡，（3）运输（囊泡介导、跨膜、沿微管），（4）细胞定位，（5）信号转导和胞吐作用的调节，（6）细胞器组织，（7）（去）磷酸化，和（8）复合物组装。有 21 种蛋白被鉴定为参与对光刺激和/或视觉系统发育的反应。鉴定出金属离子结合蛋白视紫红质、感光细胞特异性核受体、钙结合蛋白 4 与遗传性视网膜疾病相关的突变之间存在关联，这些突变影响金属结合部位或结构域内或附近的区域。这些发现表明，某些视网膜疾病中视网膜蛋白的假定金属/类金属结合部位在功能上起作用。
