García-Cano Jesús, Martinez-Martinez Arturo, Sala-Gaston Joan, Pedrazza Leonardo, Rosa Jose Luis
Ubiquitylation and Cell Signalling Lab, IDIBELL, Departament de Ciències Fisiològiques, Universitat de Barcelona, Barcelona, Spain.
Front Physiol. 2019 Aug 7;10:1014. doi: 10.3389/fphys.2019.01014. eCollection 2019.
Homologous to the E6AP carboxyl terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain-containing proteins (HERCs) belong to the superfamily of ubiquitin ligases. HERC proteins are divided into two subfamilies, Large and Small HERCs. Despite their similarities in terms of both structure and domains, these subfamilies are evolutionarily very distant and result from a convergence phenomenon rather than from a common origin. Large HERC genes, and , are present in most metazoan taxa. They encode very large proteins (approximately 5,000 amino acid residues in a single polypeptide chain) that contain more than one RCC1-like domain as a structural characteristic. Accumulating evidences show that these unusually large proteins play key roles in a wide range of cellular functions which include neurodevelopment, DNA damage repair, and cell proliferation. To better understand the origin, evolution, and function of the Large HERC family, this minireview provides with an integrated overview of their structure and function and details their physiological implications. This study also highlights and discusses how dysregulation of these proteins is associated with severe human diseases such as neurological disorders and cancer.
与E6相关蛋白羧基末端（HECT）和染色体凝聚调节因子1（RCC1）样结构域包含蛋白（HERC）属于泛素连接酶超家族。HERC蛋白分为两个亚家族，即大HERC和小HERC。尽管它们在结构和结构域方面有相似之处，但这些亚家族在进化上非常遥远，是趋同现象的结果而非共同起源。大HERC基因 和 存在于大多数后生动物类群中。它们编码非常大的蛋白质（单条多肽链中约有5000个氨基酸残基），其结构特征是含有一个以上的RCC1样结构域。越来越多的证据表明，这些异常大的蛋白质在广泛的细胞功能中起关键作用，包括神经发育、DNA损伤修复和细胞增殖。为了更好地理解大HERC家族的起源、进化和功能，本综述对其结构和功能进行了综合概述，并详细阐述了它们的生理意义。本研究还强调并讨论了这些蛋白质的失调如何与严重的人类疾病如神经疾病和癌症相关联。
