This gene encodes a deubiquitinating enzyme that is phosphorylated at the onset of mitosis and then dephosphorylated at the metaphase/anaphase transition. It can deubiquitinate H2A, one of two major ubiquitinated proteins of chromatin, in vitro and a mutant form of the protein was shown to block cell division. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008],catalytic activity:Ubiquitin C-terminal thioester + H(2)O = ubiquitin + a thiol.,disease:A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.,domain:The UBP-type zinc finger binds 3 zinc ions that form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. It recognizes the C-terminal tail of free ubiquitin.,function:Specifically deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at ‘Ser-10’ of histone H3, and is required for chromosome segregation when cells enter into mitosis. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.,PTM:Phosphorylated at the onset of mitosis and dephosphorylated during the metaphase/anaphase transition. The phosphorylated form of the protein is also enzymatically active.,similarity:Belongs to the peptidase C19 family. USP16 subfamily.,similarity:Contains 1 UBP-type zinc finger.,subunit:Homotetramer.,tissue specificity:Present in all the tissues examined including fetal brain, lung, liver, kidney, and adult heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.,