Dicarboxylate clamp tetratricopeptide repeat (dc
TPR
) motif‐containing proteins are well‐known partners of the heat shock protein (Hsp) 70 and Hsp90 molecular chaperones. Together, they facilitate a variety of intracellular processes, including protein folding and maturation, protein targeting, and protein degradation. An extreme C‐terminal sequence, the EEVD motif, is identical in Hsp70 and Hsp90, and is indispensable for their interaction with dc
TPR
proteins. However, almost no information is available on the existence of other potential dc
TPR
‐interacting proteins. We searched the human protein database for proteins with C‐terminal sequences similar to that of Hsp70/Hsp90 to identify potential partners of dc
TPR
proteins. The search identified 112 proteins containing a Hsp70/Hsp90‐like signature at their C termini. Gene Ontology enrichment analysis of identified proteins revealed enrichment of distinct protein classes, such as molecular chaperones and proteins of the ubiquitin–proteasome system, highlighting the possibility of functional specialization of proteins containing a Hsp70/Hsp90‐like signature. We confirmed interactions of selected proteins containing Hsp70/Hsp90‐like C termini with dc
TPR
proteins both
in vitro
and
in situ
. Analysis of interactions of 10‐amino‐acid peptides corresponding to the C termini of identified proteins with dc
TPR
proteins revealed significant differences in binding strength between various peptides. We propose a hierarchical mode of interaction within the dc
TPR
protein network. These findings describe a novel dc
TPR
protein interaction networks and provide a rationale for selective regulation of protein–protein interactions within this network.