This project contains the mass spectrometry data supporting the study of the E3 ubiquitin ligase MKRN1 in regulating therapeutic resistance to KRAS inhibition in pancreatic ductal adenocarcinoma (PDAC). The project includes three independent datasets: 1) AP-MS-based interactome profiling to identify MKRN1-interacting proteins in human PDAC AsPC-1 cells; 2) Comparative LC-MS/MS analysis to map MKRN1-dependent ubiquitination sites on its core substrate YES1; 3) Global quantitative phosphoproteomic profiling of the MKRN1-YES1 axis to identify downstream effectors sustaining MAPK pathway activation in PDAC. All data are associated with the manuscript entitled "Ubiquitin-driven signaling organization sustains MAPK output under KRAS inhibition in pancreatic ductal adenocarcinoma".