Metalloprotease with deubiquitinase activity that plays important regulator roles in hematopoietic stem cell function, blood cell production and immune response (PubMed:26474655, PubMed:27895164, PubMed:30405132). Participates in the normal programming of B-cell responses to antigen after the maturation process (PubMed:27895164). Within the cytoplasm, plays critical roles in the repression of innate immunity and autoimmunity (PubMed:26474655, PubMed:30405132). Removes 'Lys-63'-linked polyubiquitins from TRAF3 and TRAF6 complexes (PubMed:26474655). Attenuates NOD2-mediated inflammation and tissue injury by promoting 'Lys-63'-linked deubiquitination of RIPK2 component (PubMed:30405132). Suppresses the CGAS-STING1 signaling pathway by cleaving STING1 'Lys-63'-linked ubiquitin chains (PubMed:33086059). In the nucleus, acts as a hematopoietic transcription regulator derepressing a range of genes essential for normal stem cell differentiation including EBF1 and PAX5 in B-cells, ID2 in NK-cell progenitor or FLT3 in dendritic cell precursors (PubMed:22169041, PubMed:24062447, PubMed:25217698 PubMed:26348977). Deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, leading to dissociation of histone H1 from the nucleosome (By similarity). Component of a large chromatin remodeling complex, at least composed of MYSM1, PCAF, RBM10 and KIF11/TRIP5. Binds histones (By similarity). Localizes to the cytoplasm in response to bacterial infection. Contains an N-terminal SANT domain that mediates histone/DNA binding, a central SWIRM domain to mediate interaction with chromatin associated proteins, and a C-terminal MPN domain that contains the metalloprotease activity. Deficient mice elicit hyper-inflammatory responses, are more susceptible to septic shock, more resistant to RNA virus replication but exhibit early death upon DNA viral infection (PubMed:26474655, PubMed:33086059). They also show an impaired B-cell development (PubMed:22169041, PubMed:26348977, PubMed:27895164). In a similar way, NK-cell and dendritic cell development is impaired in deletion mutant (PubMed:25217698, PubMed:24062447). An enhanced systemic inflammation can be observed characterized by higher cytokine levels, as well as the hepatocellular enzyme alanine aminotransferase, a marker of liver damage (PubMed:30405132). Belongs to the peptidase M67A family. MYSM1 subfamily.