USP16
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 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator (PubMed:17914355). Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3 (H3S10ph), and is required for chromosome segregation when cells enter into mitosis (PubMed:17914355). In resting B- and T-lymphocytes, phosphorylation by AURKB leads to enhance its activity, thereby maintaining transcription in resting lymphocytes. Regulates Hox gene expression via histone H2A deubiquitination (PubMed:17914355). Prefers nucleosomal substrates (PubMed:17914355). Does not deubiquitinate histone H2B (PubMed:17914355). Also deubiquitinates non-histone proteins, such as ribosomal protein RPS27A: deubiquitination of monoubiquitinated RPS27A promotes maturation of the 40S ribosomal subunit (PubMed:32129764). Also mediates deubiquitination of tektin proteins (TEKT1, TEKT2, TEK3, TEKT4 and TEKT5), promoting their stability.
Involvement in disease
A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.
Post-translational modifications
Phosphorylated at the onset of mitosis and dephosphorylated during the metaphase/anaphase transition. Phosphorylation by AURKB enhances the deubiquitinase activity.
Sequence Similarities
Belongs to the peptidase C19 family. USP16 subfamily.
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.
Cellular localization
- Nucleus
- Cytoplasm
Alternative names
MSTP039, USP16, Ubiquitin carboxyl-terminal hydrolase 16, Deubiquitinating enzyme 16, Ubiquitin thioesterase 16, Ubiquitin-processing protease UBP-M, Ubiquitin-specific-processing protease 16