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ENTH domain

ENTH domain
Symbol ENTH
Pfam PF01417
InterPro IPR001026
SCOP 1edu
OPM family 39
OPM protein 1h0a
Available PDB structures:

1eyhA:17-140 1h0aA:17-140 1eduA:17-140 1inzA:17-140 1xgwA:21-145

The ENTH (Epsin N-terminal homology) domain a structural domain that was found in proteins involved in endocytosis and cytoskeletal machinery.



This domain is approximately 150 amino acids in length and is always found located at the N-termini of proteins. The domain forms a compact globular structure, composed of 9 alpha-helices connected by loops of varying length. The general topology is determined by three helical hairpins that are stacked consecutively with a right hand twist.[1]. An N-terminal helix folds back, forming a deep basic groove that forms the binding pocket for the Ins(1,4,5)P3 ligand[2]. The lipid ligand is coordinated by residues from surrounding alpha-helices and all three phosphates are multiply coordinated.

Interactions with the lipid bilayer

Proteins containing this domain have been found to bind PtdIns(4,5)P2 and PtdIns(1,4,5)P3 suggesting that the domain is a membrane interacting module. The main function of proteins containing this domain appears to be to act as accessory clathrin adaptors in endocytosis, Epsin is able to recruit and promote clathrin polymerisation on a lipid monolayer, but may have additional roles in signalling and actin regulation[3]. Epsin causes a strong degree of membrane curvature and tubulation, even fragmentation of membranes with a high PtdIns(4,5)P2 content. Epsin binding to membranes facilitates their deformation by insertion of the N-terminal helix into the outer leaflet of the bilayer, pushing the head groups apart. This would reduce the energy needed to curve the membrane into a vesicle, making it easier for the clathrin cage to fix and stabilise the curved membrane. This points to a pioneering role for epsin in vesicle budding as it provides both a driving force and a link between membrane invagination and clathrin polymerisation.

In particular, Epsin-1 shows specificity for the membrane glycophospholipid phosphatidylinositol-4,5-bisphosphate, however not all ENTH domains bind to this molecule. Binding causes tubulation of liposomes and in vivo this membrane-binding function is normally coordinated with clathrin polymerisation.

The N-terminal alpha-helix of this domain is hydrophobic and inserts into the membrane like a wedge and helps to drive membrane curvature.

Human proteins containing this domain



  1. ^ Chen H, Bateman A, de Camilli P, Hyman J, Panepucci E, Brunger AT (2002). "The ENTH domain". FEBS Lett. 513 (1): 11-18. PMID 11911874.
  2. ^ Evans PR, McMahon HT, Ford MG, Mills IG, Peter BJ, Vallis Y, Praefcke GJ (2002). "Curvature of clathrin-coated pits driven by epsin". Nature 419 (6905): 361-366. PMID 12353027.
  3. ^ Kay BK, Yamabhai M, Wendland B, Emr SD (1999). "Identification of a novel domain shared by putative components of the endocytic and cytoskeletal machinery". Protein Sci. 8 (2): 435-438. PMID 10048338.

Further reading

Ford, M.G.J., Mills, I.G., Peter, B.J., Vallis, Y., Praefcke, G.J.K., Evans, P.R. and McMahon, H.T. (2002) Curvature of clathrin-coated pits driven by epsin. Nature 419, 361-366. pubmed

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "ENTH_domain". A list of authors is available in Wikipedia.
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