RANBP2/Nup358(Ran结合蛋白2)是核孔蛋白和核孔复合物的关键组分。通过其多种功能(例如SUMO化,调节核质运输)和亚细胞定位(例如在核膜,动车组,环状薄片),它参与许多细胞过程。RANBP2失调或突变导致人类病理的发展,如急性坏死性脑病1(ANE1),癌症,神经退行性疾病,它也参与病毒感染。含有RANBP2基因的染色体区域是高度动态的,具有高度的结构变异和重组事件,导致称为RGPD(RANBP2和GCC2蛋白域)的基因家族的出现,在猿进化过程中有多个基因丢失/复制事件。尽管RGPD同质和进化过程中的维持表明它们可能会给宿主带来优势,它们的功能仍然未知和研究不足。在这次审查中,我们讨论了RANBP2在后生动物及其功能相关病理中的出现和重要性,由其表达水平的改变引起(通过启动子活性,转录后或翻译后修饰),它的定位或基因突变。
Ran-binding protein 2 (
RANBP2)/Nup358 is a nucleoporin and a key component of the nuclear pore complex. Through its multiple functions (e.g., SUMOylation, regulation of nucleocytoplasmic transport) and subcellular localizations (e.g., at the nuclear envelope, kinetochores, annulate lamellae), it is involved in many cellular processes.
RANBP2 dysregulation or mutation leads to the development of human pathologies, such as acute necrotizing encephalopathy 1, cancer, neurodegenerative diseases, and it is also involved in viral infections. The chromosomal region containing the
RANBP2 gene is highly dynamic, with high structural variation and recombination events that led to the appearance of a gene family called
RANBP2 and GCC2 Protein Domains (RGPD), with multiple gene loss/duplication events during ape evolution. Although RGPD homoplasy and maintenance during evolution suggest they might confer an advantage to their hosts, their functions are still unknown and understudied. In this review, we discuss the appearance and importance of
RANBP2 in metazoans and its function-related pathologies, caused by an alteration of its expression levels (through promotor activity, post-transcriptional, or post-translational modifications), its localization, or genetic mutations.