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Function
Epsin (Eps) is essential for cell viability in yeast and for embryo development in higher eukaryotes. Epsins function as adaptors by recognizing ubiquitinated cargo and as endocytic accessory proteins by contributing to endocytic network stability regulation and membrane bending[1]. The N-terminus domain of Eps is called Epsin N-Terminal Homology domain (ENTH). ENTH is a highly conserved ca. 150 amino acid-long domain which binds phosphatidylinoitol 4,5-bisphosphate (PIP2) which is a lipid enriched at regions of plasma membrane including endocytic sites.
Relevance
Epsin deficiency impairs canonical Wnt signaling (affecting regulation of gene transcription) and results in colon cancer resistant phenotype in mice. Epsin upregulation during early stages of tumorigenesis deregulates canonical Wnt signaling and facilitates colon cancer development[2].
Structural highlights
The 3D structure of the complex between epsin-2 ENTH and PIP2 shows two ENTH domains sandwiched around the PIP2 molecule with interactions of phosphoinositol group with the ENTH residues including Arg and Lys[3].
- ↑ Sen A, Madhivanan K, Mukherjee D, Aguilar RC. The epsin protein family: coordinators of endocytosis and signaling. Biomol Concepts. 2012 Apr;3(2):117-126. doi: 10.1515/bmc-2011-0060. PMID:22942912 doi:https://dx.doi.org/10.1515/bmc-2011-0060
- ↑ Chang B, Tessneer KL, McManus J, Liu X, Hahn S, Pasula S, Wu H, Song H, Chen Y, Cai X, Dong Y, Brophy ML, Rahman R, Ma JX, Xia L, Chen H. Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development. Nat Commun. 2015 Mar 16;6:6380. doi: 10.1038/ncomms7380. PMID:25871009 doi:https://dx.doi.org/10.1038/ncomms7380
- ↑ Garcia-Alai MM, Heidemann J, Skruzny M, Gieras A, Mertens HDT, Svergun DI, Kaksonen M, Uetrecht C, Meijers R. Epsin and Sla2 form assemblies through phospholipid interfaces. Nat Commun. 2018 Jan 23;9(1):328. doi: 10.1038/s41467-017-02443-x. PMID:29362354 doi:https://dx.doi.org/10.1038/s41467-017-02443-x
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3D structures of epsin
Updated on 23-February-2023
1inz - hEps epsin N-terminal homology domain ENTH 1-144 - human NMR
1xgw, 2qy7 - hEps-4 ENTH domain
1edu, 1eyh - rEps-1 ENTH domain - rat
1h0a - rEps ENTH domain + inositol triphosphate
5lp0 - Eps-1 ENTH domain - zebrafish
5onf, 5loz - yEps-1 ENTH domain - yeast
5ahv, 7b2l - yEps-1 ENTH domain + SLA2 ANTH domain - Cryo EM
6enr, 4gzc - yEps-2 ENTH domain
4gzd - yEps-2 ENTH domain (mutant)
5on7 - yEps-2 ENTH domain + PIP2
3onk - yEps-3 ENTH domain
3onl - yEps-3 ENTH domain + T-SNARE VTII HABC domain
5j08, 5cmw, 5cmy - yEps-5 ENTH domain
5oo7 - Eps-2 ENTH domain + PIP2 – Chaetomium thermophilum
References
