This record contains raw data related to article "Phosphoproteomic mapping of CCR5 and ACKR2 signaling properties" ACKR2 is an atypical chemokine receptor structurally uncoupled from G proteins and unable to activate those signaling pathways used by conventional chemokine receptors to promote cell migration. Nevertheless, ACKR2 regulates inflammation and immune responses by shaping chemokine gradients in tissues by means scavenging inflammatory chemokines. To investigate the signaling pathways downstream ACKR2, a quantitative SILAC-based phosphoproteomic analysis coupled to systems biology approaches based on network analysis was carried out in a HEK293 cell model expressing ACKR2 or its conventional counterpart CCR5, stimulated or not with the common agonist CCL3L1 for short (3 min) and long (30 min) time points. As expected, many of the identified proteins are known to participate in conventional signal transduction pathways and in the regulation of cytoskeleton dynamics. However, our analyses revealed unique phosphorylation and network signatures, suggesting roles for ACKR2 other than its scavenger activity. In conclusion, mapping of phosphorylation events at holistic level indicated that conventional and atypical chemokine receptors differ for signaling properties and provide an unprecedented level of detail of chemokine receptor signaling aimed at identifying potential targets for regulation of ACKR2 and CCR5 function.