This dataset was generated to identify proteins that associate with DHHC12 in response to amino acid deprivation. HEK293T cells expressing Flag-tagged DHHC12-2CR were cultured in complete or amino acid-deficient medium for 3 h and subjected to Flag co-immunoprecipitation. The eluates were separated by SDS–PAGE, and an approximately 150-kDa band enriched under amino acid-deficient conditions was excised and analyzed by LC–MS/MS. COPA was identified as a candidate amino acid deprivation-enhanced DHHC12-interacting protein and was subsequently validated by co-immunoprecipitation and immunoblotting. These data support the involvement of COPA in the nutrient-dependent regulation of DHHC12 ubiquitination and degradation.