ENTH Epsin N-terminal homology (ENTH) domain
SMART ACC:	SM000273
Description:	-
InterPro ACC:	IPR013809
InterPro abstract:	The ENTH (Epsin N-terminal homology) 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 α-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 [ PUBMED:11911874 … expand The ENTH (Epsin N-terminal homology) 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 α-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 [ PUBMED:11911874 ]. An N-terminal helix folds back, forming a deep basic groove that forms the binding pocket for the Ins(1,4,5)P3 ligand [ PUBMED:12353027 ]. The ligand is coordinated by residues from surrounding α-helices and all three phosphates are multiply coordinated. The coordination of Ins(1,4,5)P3 suggests that ENTH is specific for particular head groups. Proteins containing this domain have been found to bind PtdIns(4,5)P2 and PtdIns(1,4,5)P3 suggesting that the domain may be 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 [ PUBMED:10048338 ]. 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. collapse
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 10 331 ENTH domains in 10 323 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing ENTH domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing ENTH domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the ENTH domain is listed below. Automatically-derived, secondary literature is also available.

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a ENTH domain which could be assigned to a KEGG orthologous group, and not all proteins containing ENTH domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

InterPro	IPR013809