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ENTH domain

Class: Phospholipid Binding

Brief description: The ENTH (epsin NH2-terminal homology) domain is approximatel 140 amino acids in length. They were identified from the NH2-terminal of the epsin family of proteins. They were highly conserved in evolution that they were proposed to represent a separately folded module. Through homology searches, ENTH domains have now been found in various other proteins such as CALM and AP180. Despite low primary sequence identity, they share high structural identity. They have been shown to bind PtdIns(4,5)P2 and inositolpolyphosphates with varying affinity.

Structure:

structure The ENTH domain forms a compact globular structure, formed of eight alpha-helices connected by loops of varying length. The general topology of the domain is determined by three helical hairpins that are stacked consecutively with a right hand twist. A cluster of basic residues to bind phosphate groups of PtdIns(4,5)P2 has also been revealed. A cationic phosphoinositide-binding pocket induced by Ins(1,4,5)P3 suggested that hydrophobic residues on the same face of an a-helix, may penetrate the membrane. It has also been proposed that membrane penetration by the epsin 1 ENTH domain is essential for membrane deformation and vesicle budding during clathrin-mediated endocytosis.

Subcellular Localization:

The ENTH domain of epsin-related protein (epsinR) binds PtdIns(4)P, and the ENTH domains of yeast proteins Ent3p and Ent5p have specificity for PtdIns(3,5)P2 . Also, the ENTH domains of Huntingtin-interacting protein1 (HIP1) and HIP1-related protein bind PtdIns(3,4)P2 and PtdIns(3,5)P2. Recently, epsin 1 ENTH domain has been shown to bind inositol-1,4,5-trisphosphate [Ins(1,4,5)P 3].

Get the sequences in a Swiss-Prot/Uniprot pattern and Tab-delimited format.

Browse through the structures available.

Relevant Literature

1. Kay, B.K., Yamabhai, M., Wendland, B. and Emr, S.D. (1999) Identification of a novel domain shared by putative components of the endocytic and cytoskeletal machinery. Protein Sci, 8, 435-438.

2. Itoh, T., Koshiba, S., Kigawa, T., Kikuchi, A., Yokoyama, S. and Takenawa, T. (2001) Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis. Science, 291, 1047-1051.

3. De Camilli, P., Chen, H., Hyman, J., Panepucci, E., Bateman, A. and Brunger, A.T. (2002) The ENTH domain. FEBS Lett, 513, 11-18.

4. Hyman, J., Chen, H., Di Fiore, P.P., De Camilli, P. and Brunger, A.T. (2000) Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF). J Cell Biol, 149, 537-546.