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AP180 N-Terminal Homology (ANTH) and Epsin N-Terminal Homology (ENTH) Domains: Physiological Functions and Involvement in Disease

  • Sho Takatori
  • Taisuke Tomita
Part of the Advances in Experimental Medicine and Biology book series


The AP180 N-terminal homology (ANTH) and Epsin N-terminal homology (ENTH) domains are crucially involved in membrane budding processes. All the ANTH/ENTH-containing proteins share the phosphoinositide-binding activity and can interact with clathrin or its related proteins via multiple binding motifs. Their function also include promotion of clathrin assembly, induction of membrane curvature, and recruitment of various effector proteins, such as those involved in membrane fission. Furthermore, they play a role in the sorting of specific cargo proteins, thereby enabling the cargos to be accurately transported and function at their appropriate locations. As the structural bases underlying these functions are clarified, contrary to their apparent similarity, the mechanisms by which these proteins recognize lipids and proteins have unexpectedly been found to differ from each other. In addition, studies using knockout mice have suggested that their physiological roles may be more complicated than merely supporting membrane budding processes. In this chapter, we review the current knowledge on the biochemical features of ANTH/ENTH domains, their functions predicted from the phenotypes of animals deficient in these domain-containing proteins, and recent findings on the structural basis enabling specific recognition of their ligands. We also discuss the association of these domains with human diseases. Here we focus on CALM, a protein containing an ANTH domain, which is implicated in the pathogenesis of blood cancers and Alzheimer disease, and discuss how alteration of CALM function is involved in these diseases.


Endocytosis Clathrin Phosphoinositide ANTH ENTH Alzheimer disease 



This work was supported in part by Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS) [17 K15446 to S.T.], Grants-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science [15H02492 to T.T.], by the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from the Japan Agency for Medical Research and Development (AMED) [17dm0207014h0004 to T.T.] and Sunbor Grant from the Suntory Foundation for Life Sciences [to S.T.].

Conflicts of Interest

None declared.


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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical SciencesThe University of TokyoTokyoJapan

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