MINDY3

MINDY3 (FAM63B) is a member of the MINDY family of deubiquitinases, which possess a structurally unique catalytic domain with no homology to other known DUB families and selectively cleave K48-linked polyubiquitin chains, preferentially trimming long chains from the distal end (PMID:27292798). No experiments directly characterizing MINDY3 itself—as distinct from the founding family member MINDY-1/FAM63A—are present in the available literature; its specific substrates, regulation, and cellular roles remain uncharacterized.

1. 2016 High

   Identification of the MINDY catalytic domain as a novel DUB fold with K48-linkage selectivity established the enzymatic family to which MINDY3 belongs, resolving its previously unannotated catalytic potential.

   Evidence Crystal structure of MINDY-1 with propargylated ubiquitin, in vitro DUB assays with linkage-specific diubiquitin substrates, and active-site mutagenesis

   PMID:27292798

   Open questions at the time

   • All structural and biochemical data derive from the paralog MINDY-1/FAM63A; MINDY3 itself has not been biochemically characterized
   • No cellular substrates or biological processes have been assigned to MINDY3
   • No structural model of MINDY3 exists

• Whether MINDY3 shares the same K48-linkage selectivity, chain-length preference, and catalytic efficiency as MINDY-1, and what its endogenous substrates and physiological roles are, remain entirely open questions.
• No direct enzymatic assay of recombinant MINDY3 has been reported
• No loss-of-function or gain-of-function cellular studies for MINDY3 exist
• Tissue-specific expression and regulation of MINDY3 are unknown