Epsin: Difference between revisions

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<StructureSection load='5on7' size='340' side='right' caption='Caption for this structure' scene=''>
<StructureSection load='5on7' size='340' side='right' caption='Yeast epsin-2 ENTH complex with PIP2 and sulfate (PDB code [[5on7]])' scene='84/842890/Cv/1'>


== Function ==
== 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<ref>PMID:22942912</ref>.  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 which is a lipid enriched at regions of plasma membrane including endocytic sites.
'''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<ref>PMID:22942912</ref>.  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.


== Disease ==
== Relevance ==


== 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<ref>PMID:25871009</ref>.


== Structural highlights ==
== Structural highlights ==


 
The 3D structure of the complex between epsin-2 ENTH and PIP2 shows two ENTH domains sandwiched around the <scene name='84/842890/Cv/4'>PIP2 molecule with interactions of phosphoinositol group with the ENTH residues including Arg and Lys</scene><ref>PMID:29362354</ref>.
</StructureSection>
</StructureSection>


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[[5lp0]] - Eps-1 ENTH domain - zebrafish<br />
[[5lp0]] - Eps-1 ENTH domain - zebrafish<br />
[[5onf]], [[5loz]] - yEps-1 ENTH domain - yeast<br />
[[5onf]], [[5loz]] - yEps-1 ENTH domain - yeast<br />
[[5ahv]] - yEps-1 ENTH domain + SLA2 ANTH domain - Cryo EM<br />
[[5ahv]], [[7b2l]] - yEps-1 ENTH domain + SLA2 ANTH domain - Cryo EM<br />
[[6enr]], [[4gzc]] - yEps-2 ENTH domain<br />
[[6enr]], [[4gzc]] - yEps-2 ENTH domain<br />
[[4gzd]] - yEps-2 ENTH domain (mutant)<br />
[[4gzd]] - yEps-2 ENTH domain (mutant)<br />
[[5on7]] - yEps-2 ENTH domain + phosphatidylinoitol bisphosphate<br />
[[5on7]] - yEps-2 ENTH domain + PIP2<br />
[[3onk]] - yEps-3 ENTH domain<br />
[[3onk]] - yEps-3 ENTH domain<br />
[[3onl]] - yEps-3 ENTH domain + T-SNARE VTII HABC domain<br />
[[3onl]] - yEps-3 ENTH domain + T-SNARE VTII HABC domain<br />
[[5j08]], [[5cmw]], [[5cmy]] - yEps-5 ENTH domain<br />
[[5j08]], [[5cmw]], [[5cmy]] - yEps-5 ENTH domain<br />
[[5oo7]] - Eps-2 ENTH domain + PIP2 – ''Chaetomium thermophilum''<br />


== References ==
== References ==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky