Epsin
Encyclopedia
Epsins are the family of membrane proteins that are important in creating the needed membrane curvature
Membrane curvature
Membrane curvature is the geometrical measure or characterization of the curvature of membranes.The membranes can be naturally occurring or man-made . An example of naturally occurring membrane is the lipid bilayer of cells, also known as cellular membranes. Synthetic membranes can be obtained by...

. Epsins contribute to various needed membrane deformations like endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

 and block vesicle
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 formation during mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

. Epsins have many different domains to interact with various proteins related to endocytosis. At its N-terminus is an ENTH domain
ENTH domain
The Epsin N-terminal homology domain is a structural domain that is found in proteins involved in endocytosis and cytoskeletal machinery.-Structure:...

 that binds Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdInsP2, also known simply as PIP2, is a minor phospholipid component of cell membranes...

, 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
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

-interacting motifs). The C-terminus contains multiple binding sites, for example for clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...

 and AP2 adaptors
AP2 adaptors
The AP2 adaptor complex is a multimeric protein that works on the plasma membrane to internalize cargo in clathrin-mediated endocytosis. It is a stable complex of four adaptins which give rise to a structure that has a core domain and two appendage domains attached to the core domain by polypeptide...

. As such, Epsins are able to bind to a membrane with a specific cargo and connect it with the endocytosis machinery, so one may understand Epsin as something like a Swiss army knife for endocytosis.
They may be the major membrane curvature driving proteins in many clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...

-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.

Epsin homologue of C.elegans is epn-1. EPN-1 conserves UIM, ENTH domain, and Clathrin-binding motif.
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