Naslavsky Naava, Caplan Steve
Department of Biochemistry and Molecular Biology and Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
J Cell Sci. 2005 Sep 15;118(Pt 18):4093-101. doi: 10.1242/jcs.02595.
The Eps15-homology (EH) domain is a highly conserved motif comprising approximately 100 residues that is found in proteins from species as diverse as yeast and mammals. Proteins that have an EH domain can carry out a variety of crucial cellular functions ranging from regulation of the actin cytoskeleton, signal transduction and transcriptional regulation to control of the endocytic pathway. EH domains bind to proteins that contain the tripeptide asparagine-proline-phenylalanine (NPF). Although EH domains are typically found at the N-terminus, mammalian cells express four highly homologous C-terminal EH-domain-containing paralogs (EHD1-EHD4), which exhibit broad amino acid conservation throughout the entire sequence. These C-terminal EH-domain-containing proteins also contain a central coiled-coil region involved in oligomerization, as well as an N-terminal nucleotide-binding motif. Recent studies have identified an array of novel binding partners for EHD1-EHD4, including NPF-containing proteins, such as the divalent Rab4/5 effector rabenosyn 5, the cell fate determinant Numb, EH-binding protein 1 (EHBP1) and syndapins I and II. Interactions with the clathrin heavy-chain and components of the internalization machinery have also been described. Indeed, C-terminal EH-domain-containing proteins appear to regulate several key endocytic steps, including internalization and recycling. EHD1 and EHD4 control recycling by regulating the transport of receptors from the recycling compartment to the plasma membrane. EHD1, EHD2 and EHD4 have also been implicated in the internalization of receptors and their transport to early endosomes.
Eps15同源（EH）结构域是一个高度保守的基序，由约100个氨基酸残基组成，存在于从酵母到哺乳动物等多种物种的蛋白质中。具有EH结构域的蛋白质可以执行多种关键的细胞功能，从肌动蛋白细胞骨架的调节、信号转导、转录调控到内吞途径的控制。EH结构域与含有三肽天冬酰胺-脯氨酸-苯丙氨酸（NPF）的蛋白质结合。虽然EH结构域通常位于N端，但哺乳动物细胞表达四种高度同源的含C端EH结构域的旁系同源物（EHD1-EHD4），它们在整个序列中表现出广泛的氨基酸保守性。这些含C端EH结构域的蛋白质还包含一个参与寡聚化的中央卷曲螺旋区域，以及一个N端核苷酸结合基序。最近的研究已经确定了一系列EHD1-EHD4的新型结合伴侣，包括含NPF的蛋白质，如二价Rab4/5效应器rabex-5、细胞命运决定因子Numb、EH结合蛋白1（EHBP1）以及syndapins I和II。与网格蛋白重链和内化机制的成分之间的相互作用也有报道。事实上，含C端EH结构域的蛋白质似乎调节几个关键的内吞步骤，包括内化和再循环。EHD1和EHD4通过调节受体从再循环区室到质膜的运输来控制再循环。EHD1、EHD2和EHD4也与受体的内化及其向早期内体的运输有关。
