Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein

Nature. 1993 Sep 30;365(6445):459-62. doi: 10.1038/365459a0.


Clathrin is the structural protein of coated membranes involved in receptor-mediated endocytosis and aspects of Golgi sorting in eukaryotic cells. We have now detected a stoichiometric complex of clathrin with a novel protein of M(r) approximately 100,000 (100K) in lysates of different mammalian cells. Formation of the complex, which also includes the 70K heat-shock protein Hsc70, occurs within 15 min of synthesis. The 100K protein has been identified as valosin-containing protein (VCP; ref. 1), an early substrate for tyrosine phosphorylation on T-cell receptor activation. Further, VCP is the mammalian homologue of yeast Cdc48p (ref. 3) and is a member of a larger gene family that includes putative ATP-binding proteins involved in vesicle transport and fusion, 26S proteasome function, regulation of the expression of human immunodeficiency virus, and assembly of peroxisomes. The association with clathrin and the morphological and catalytic similarity to the chaperonin proteins indicate that VCP may modulate protein-protein interactions in membrane transport processes.

MeSH terms

  • 3T3 Cells
  • Adenosine Triphosphatases
  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Cell Cycle Proteins*
  • Cell Line
  • Clathrin / metabolism*
  • Fungal Proteins / chemistry
  • Heat-Shock Proteins / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neurons / metabolism
  • Precipitin Tests
  • Protein Binding
  • Rats
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / metabolism
  • Valosin Containing Protein


  • Cell Cycle Proteins
  • Clathrin
  • Fungal Proteins
  • Heat-Shock Proteins
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein
  • Vcp protein, mouse
  • Vcp protein, rat