 ENTH Domain | |
|
|
Class: Phospholipid binding Structure:
 Despite low primary sequence similarity, the solved structures of various ENTH domains are very similar and are composed of eight alpha helices connected by loops of varying lengths. Three helical hairpins (a1-2, a3-4, and a6-7) are stacked consecutively with a right-handed twist, conferring a rectangular topology to the ENTH domain. A cleft of positively charged residues contributes to phoshoinositide binding. Clusters of basic amino acids present in some but not all ENTH family members (AP180/CALM) have been shown to enrich the affinity for phosphoinositides.
Structure Reference:
Hyman, J. et.al. (2000) J. Cell Biol. 149(3), 537-46. PDB: 1EDU.
| |
|
Domain binding and function:
First identified in the endocytotic protein epsin 1, the epsin NH2-terminal homology (ENTH) domain is a membrane binding motif of approximately 150 amino acids. Proteins containing this domain have been shown to bind to phospholipids including PtdIns(4,5)P2 and PtdIns(1,4,5)P3. Consistent with these findings, the primary function suggested for ENTH domain containing proteins is to act as clathrin adaptors in endocytosis, with binding of the ENTH domain to the phospholipid bilayer allowing recruitment of clathrin components and clathrin accessory factors to the cell membrane. In addition, two ENTH containing proteins (HIP1, HIP1R), shown to localize to clathrin coated pits, also contain a putative actin binding motif (ILWEQ) providing evidence for the elusive link between the actin cytoskeleton and endocytosis.
| |
|
Examples of Proteins:
| ENTH Domain Proteins |
|
Binding partner |
| Epsin1 |  |
PtdIns(4,5)P2 / PtdIns(1,4,5)P3 |
| AP180 | |
PtdIns(4,5)P2 / PtdIns(1,4,5)P3 |
HIP1R
|
|
PI(3,4)P2; PI(3,5)P2
|
|
|
|
| |
|
Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
| |
|
