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Epsins have many different domains to interact with various proteins related to endocytosis. At its N-terminus is an ENTH domain that binds phosphatidylinositol (4,5)-bisphosphate, meaning that it binds a lipid of biological membranes. It has also been postulated that this is a site for cargo-binding. In the middle of the epsin sequence are two UIMs (ubiquitin-interacting motifs). The C-terminus contains multiple binding sites, for example for clathrin and AP2 adaptors. As such, epsins are able to bind to membranes with specific cargo and connect them with the endocytosis machinery, so one may understand epsins as something like Swiss army knives for endocytosis. They may be the major membrane curvature-driving proteins in many clathrin-coated vesicle budding events.
Epsin 4, which encodes the protein enthoprotin, now known as clathrin interactor 1 (CLINT1), has been shown to be involved in the genetic susceptibility to schizophrenia in four independent studies. A genetic abnormality in CLINT1 is assumed to change the way internalisation of neurotransmitter receptors occurs in the brains of people with schizophrenia.
The epsin homologue of C.elegans is EPN-1. EPN-1 conserves the UIM, ENTH domain, and clathrin-binding motif.
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