Identification and characterization of Harc, a novel Hsp90-associating relative of Cdc37

J Biol Chem. 2001 Aug 17;276(33):30971-9. doi: 10.1074/jbc.M103889200. Epub 2001 Jun 18.


Although little is known about the precise mechanisms by which the molecular chaperone Hsp90 recognizes its client proteins, Cdc37 has been shown to play a critical role in the targeting of Hsp90 to client protein kinases. Described here is the identification and characterization of a novel 35-kDa human protein that is 31% identical to Cdc37. We have named this novel protein Harc (Hsp90-associating relative of Cdc37). Northern blot analysis revealed the presence of Harc mRNA in several human tissues, including liver, skeletal muscle, and kidney. Biochemical fractionation and immunofluorescent localization of epitope-tagged Harc (i.e. FLAG-Harc) indicated that it is present in the cytoplasm of cells. FLAG-Harc binds Hsp90 but unlike Cdc37 does not bind Src family kinases or Raf-1. Mapping experiments indicate that the central 120 amino acids of both Harc and Cdc37 constitute a Hsp90-binding domain not described previously. FLAG-Harc is basally serine-phosphorylated and hyperphosphorylated when co-expressed with an activated mutant of the Src family kinase Hck. Notably, FLAG-Harc forms complexes with Hsp90, Hsp70, p60Hop, immunophilins, and an unidentified p22 protein but not with the Hsp90 co-chaperone p23. Thus Harc likely represents a novel participant in Hsp90-mediated protein folding, potentially targeting Hsp90 to Hsp70-client protein heterocomplexes.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / analysis
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Oligopeptides
  • Peptides / chemistry
  • Phosphoproteins / chemistry
  • Proto-Oncogene Proteins c-raf / metabolism


  • Carrier Proteins
  • Cdc37 protein, rat
  • Cell Cycle Proteins
  • HSP90 Heat-Shock Proteins
  • Oligopeptides
  • Peptides
  • Phosphoproteins
  • FLAG peptide
  • Proto-Oncogene Proteins c-raf