Epsin 1 is a polyubiquitin-selective clathrin-associated sorting protein

Traffic. 2006 Mar;7(3):262-81. doi: 10.1111/j.1600-0854.2006.00383.x.


Epsin 1 engages several core components of the endocytic clathrin coat, yet the precise mode of operation of the protein remains controversial. The occurrence of tandem ubiquitin-interacting motifs (UIMs) suggests that epsin could recognize a ubiquitin internalization tag, but the association of epsin with clathrin-coat components or monoubiquitin is reported to be mutually exclusive. Here, we show that endogenous epsin 1 is clearly an integral component of clathrin coats forming at the cell surface and is essentially absent from caveolin-1-containing structures under normal conditions. The UIM region of epsin 1 associates directly with polyubiquitin chains but has extremely poor affinity for monoubiquitin. Polyubiquitin binding is retained when epsin synchronously associates with phosphoinositides, the AP-2 adaptor complex and clathrin. The enrichment of epsin within clathrin-coated vesicles purified from different tissue sources varies and correlates with sorting of multiubiquitinated cargo, and in cultured cells, polyubiquitin, rather than non-conjugable monoubiquitin, promotes rapid internalization. As epsin interacts with eps15, which also contains a UIM region that binds to polyubiquitin, epsin and eps15 appear to be central components of the vertebrate poly/multiubiquitin-sorting endocytic clathrin machinery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport / chemistry
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Adaptor Proteins, Vesicular Transport / ultrastructure
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium-Binding Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Clathrin-Coated Vesicles / physiology*
  • Clathrin-Coated Vesicles / ultrastructure
  • Endocytosis
  • Epidermal Growth Factor / pharmacology
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Molecular Sequence Data
  • Phosphoproteins / metabolism
  • Polyubiquitin / chemistry
  • Polyubiquitin / genetics
  • Polyubiquitin / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Calcium-Binding Proteins
  • EPS15 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • epsin
  • Polyubiquitin
  • Epidermal Growth Factor
  • Glutathione Transferase