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The suppressor of cytokine signaling 2 (SOCS2) is a component of the Cullin5 E3 ubiquitin ligase complex. Here the authors provide insights into substrate recognition and specificity of SOCS2 by determining the crystal structures of the SOCS2-ElonginB-ElonginC in complex with phosphorylated peptides from two of its substrates the growth hormone receptor and erythropoietin receptor.