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The enzyme catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO-1, SUMO-2 and SUMO-3 to their mature forms and deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins. Cleavage of Gly97-/-His98 bond in the SUMO-1 precursor with release of the propeptide His-Ser-Thr-Val. Cleavage of Gly93-/-Val94 bond in the SUMO-2 precursor with release of the propeptide Val94-Thyr. Cleavage of the Gly92-/-Val93 in the SUMO-3 precursor with release of the propeptide Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe. The enzyme catalyzes the desumoylation of SUMO-modified promyelocytic leukemia protein. SENP6 prefers the LRGG-/- sequence versus the QTGG-/- sequence. SENP6 is essential for inner kinetochore assembly.
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