Phylogenetic analysis of the formin homology 2 domain
Phylogenetic analysis of the formin homology 2 domain
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DOI：
10.1091/mbc.e04-07-0565
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Peterson, KJ
中科院分区：
文献类型：
--
作者：
Higgs, HN;Peterson, KJ
成蛋白是真核生物肌动蛋白丝组装和延伸的关键调节因子，许多物种拥有多种成蛋白异构体。基于基本特征的命名系统是可取的，这有助于新成蛋白的快速鉴定和特性描述。在本文中，我们试图通过对成蛋白同源2（FH2）结构域进行系统发育分析来使成蛋白家族系统化。FH2结构域是所有成蛋白共有的一个独立折叠区域，它本身就能影响肌动蛋白动力学。通过数据库搜索，我们从26种真核生物物种中鉴定出101个FH2结构域，其中包括小鼠中的15个。序列比对显示在FH2结构域的“ knob环”区域有一个高度保守的酵母特异性插入片段，其功能影响未知。使用最小进化（ME）、最大简约（MP）和最大似然（ML）算法进行的系统发育分析有力地支持了七个后生动物类群的存在。酵母的FH2结构域与所有其他真核生物（包括后生动物、其他真菌、植物和原生生物）分离。非FH2区域的序列比较支持三个后生动物类群（Dia、DAAM和FRL）之间的关系，并检验了先前鉴定的卷曲螺旋和透明蛋白自调节结构域序列。这种分析使得基于序列关系的成蛋白命名系统成为可能，同时也为确定这些蛋白质的生化和细胞活性提供了策略。
Formin proteins are key regulators of eukaryotic actin filament assembly and elongation, and many species possess multiple formin isoforms. A nomenclature system based on fundamental features would be desirable, to aid the rapid identification and characterization of novel formins. In this article, we attempt to systematize the formin family by performing phylogenetic analyses of the formin homology 2 (FH2) domain, an independently folding region common to all formins, which alone can influence actin dynamics. Through database searches, we identify 101 FH2 domains from 26 eukaryotic species, including 15 in mice. Sequence alignments reveal a highly conserved yeast-specific insert in the "knob loop" region of the FH2 domain, with unknown functional consequences. Phylogenetic analysis using minimum evolution (ME), maximum parsimony (MP), and maximum likelihood (ML) algorithms strongly supports the existence of seven metazoan groups. Yeast FH2 domains segregate from all other eukaryotes, including metazoans, other fungi, plants, and protists. Sequence comparisons of non-FH2 regions support relationships between three metazoan groups (Dia, DAAM, and FRL) and examine previously identified coiled-coil and Diaphanous auto-regulatory domain sequences. This analysis allows for a formin nomenclature system based on sequence relationships, as well as suggesting strategies for the determination of biochemical and cellular activities of these proteins.