A New Protein Superfamily: TPPP-Like Proteins

The introduction of the term ‘Tubulin Polymerization Promoting Protein (TPPP)-like proteins’ is suggested. They constitute a eukaryotic protein superfamily, characterized by the presence of the p25alpha domain (Pfam05517, IPR008907), and named after the first identified member, TPPP/p25, exhibiting microtubule stabilizing function. TPPP-like proteins can be grouped on the basis of two characteristics: the length of their p25alpha domain, which can be long, short, truncated or partial, and the presence or absence of additional domain(s). TPPPs, in the strict sense, contain no other domains but one long or short p25alpha one (long- and short-type TPPPs, respectively). Proteins possessing truncated p25alpha domain are first described in this paper. They evolved from the long-type TPPPs and can be considered as arthropod-specific paralogs of long-type TPPPs. Phylogenetic analysis shows that the two groups (long-type and truncated TPPPs) split in the common ancestor of arthropods. Incomplete p25alpha domains can be found in multidomain TPPP-like proteins as well. The various subfamilies occur with a characteristic phyletic distribution: e. g., animal genomes/proteomes contain almost without exception long-type TPPPs; the multidomain apicortins occur almost exclusively in apicomplexan parasites. There are no data about the physiological function of these proteins except two human long-type TPPP paralogs which are involved in developmental processes of the brain and the musculoskeletal system, respectively. I predict that the superfamily members containing long or partial p25alpha domain are often intrinsically disordered proteins, while those with short or truncated domain(s) are structurally ordered. Interestingly, members of this superfamily connected or maybe connected to diseases are intrinsically disordered proteins.建议采用“微管蛋白聚合促进蛋白（Tubulin Polymerization Promoting Protein, TPPP）样蛋白”这一术语。该类蛋白构成一类真核蛋白质超家族，核心特征为携带p25alpha结构域（Pfam05517、IPR008907），并以首个被鉴定的成员TPPP/p25命名，该成员具备微管稳定功能。TPPP样蛋白可依据两项特征进行分类：其一为其p25alpha结构域的长度，可分为长型、短型、截短型与部分型；其二为是否携带额外结构域。严格意义上的TPPP仅包含一个长型或短型p25alpha结构域，分别对应长型与短型TPPP。本研究首次报道了携带截短型p25alpha结构域的蛋白，它们起源于长型TPPP，可被视为节肢动物特异性的长型TPPP旁系同源物。系统发育分析表明，长型与截短型TPPP两个类群在节肢动物的共同祖先中发生分化。多结构域TPPP样蛋白中亦可发现不完整的p25alpha结构域。各类亚家族呈现出特征性的物种分布规律：例如，动物基因组/蛋白质组几乎均包含长型TPPP；多结构域顶复皮质蛋白（apicortins）几乎仅存在于顶复门寄生虫中。目前尚无关于该类蛋白生理功能的有效数据，仅发现两种人类长型TPPP旁系同源物分别参与大脑与肌肉骨骼系统的发育过程。本研究预测，携带长型或部分型p25alpha结构域的超家族成员通常为内在无序蛋白，而携带短型或截短型结构域的成员则具有结构化构象。值得注意的是，与疾病存在关联或可能存在关联的该超家族成员均为内在无序蛋白。