 Abstract
Many cellular functions are regulated through a complex intracellular network of
signal transducers. Specialized protein domains mediate this vast array of interactions
by binding to specific sequences located in target proteins.
One of these protein-protein interaction domain is the EH (for Eps15 homology)
domain, present in three copies in the amino terminus of the tyrosine kinase substrates
Eps15 and Eps15R and shared with other proteins of yeast and nematode. These
eukaryotic signalling modules recognize proteins containing single or multiple NPF
(Asn-Pro-Phe) motifs, such as RAB, NUMB, RabR, NumbR, synaptojanin and epsin.
The peptide motif NPF is established as the essential target for the EH domains of Eps15. Binding is enhanced when Thr or Ser occupy the two positions preceding
NPF and when a hydrophobic or basic residue follows.
Some of the interactions between EH-domain containing proteins and NPF-containing proteins are known to regulate receptor-mediated endocytosis.
Selected references
| Aguilar RC, Watson HA, Wendland B | | The yeast epsin Ent1 is recruited to membranes through multiple
independent interactions. | | J Biol Chem 2003 Jan 14;0() : . | | PMID: 12529323 |
| Chang CP, Lazar CS, Walsh BJ, Komuro M, Collawn JF, Kuhn LA, Tainer JA, Trowbridge IS, Farquhar MG, Rosenfeld MG, et al. | | Ligand-induced internalization of the epidermal growth factor receptor is
mediated by multiple endocytic codes analogous to the tyrosine motif found
in constitutively internalized receptors. | | J Biol Chem 1993 Sep 15;268(26) : 19312-20. | | PMID: 8396132 |
| Cullis DN, Philip B, Baleja JD, Feig LA | | Rab11-FIP2, an Adaptor Protein Connecting Cellular Components Involved in
Internalization and Recycling of Epidermal Growth Factor Receptors. | | J Biol Chem 2002 Dec 20;277(51) : 49158-66. | | PMID: 12364336 |
| Enmon JL, de Beer T, Overduin M | | Solution structure of Eps15's third EH domain reveals coincident Phe-Trp
and Asn-Pro-Phe binding sites. | | Biochemistry 2000 Apr 18;39(15) : 4309-19. | | PMID: 10757979 |
| Kim S, Cullis DN, Feig LA, Baleja JD | | Solution structure of the Reps1 EH domain and characterization of its
binding to NPF target sequences. | | Biochemistry 2001 Jun 12;40(23) : 6776-85. | | PMID: 11389591 |
This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.
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Biological Process |
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Cell growth and/or maintenance
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signal transduction
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intracellular signaling cascade
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endocytosis
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receptor mediated endocytosis
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regulation of endocytosis
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Cellular Component |
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cytosol |
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plasma membrane |
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Molecular Function |
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Binding |
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protein binding |
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protein domain specific binding |
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