C-terminal EH-domain-containing proteins: consensus for a role in endocytic trafficking, EH?
The Eps15-homology (EH) domain is a highly conserved motif comprising approximately 100 residues that is found in proteins from species as diverse as yeast and mammals. Proteins that have an EH domain can carry out a variety of crucial cellular functions ranging from regulation of the actin cytoskeleton, signal transduction and transcriptional regulation to control of the endocytic pathway. EH domains bind to proteins that contain the tripeptide asparagine-proline-phenylalanine (NPF). Although EH domains are typically found at the N-terminus, mammalian cells express four highly homologous C-terminal EH-domain-containing paralogs (EHD1-EHD4), which exhibit broad amino acid conservation throughout the entire sequence. These C-terminal EH-domain-containing proteins also contain a central coiled-coil region involved in oligomerization, as well as an N-terminal nucleotide-binding motif. Recent studies have identified an array of novel binding partners for EHD1-EHD4, including NPF-containing proteins, such as the divalent Rab4/5 effector rabenosyn 5, the cell fate determinant Numb, EH-binding protein 1 (EHBP1) and syndapins I and II. Interactions with the clathrin heavy-chain and components of the internalization machinery have also been described. Indeed, C-terminal EH-domain-containing proteins appear to regulate several key endocytic steps, including internalization and recycling. EHD1 and EHD4 control recycling by regulating the transport of receptors from the recycling compartment to the plasma membrane. EHD1, EHD2 and EHD4 have also been implicated in the internalization of receptors and their transport to early endosomes.
Naslavsky
Naava
N
Department of Biochemistry and Molecular Biology and Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
Caplan
Steve
S
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C120700:EHD1 protein, human; C406446:EHD2 protein, human; C486206:EPS15 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D033921:Vesicular Transport Proteins