ubiquitin carboxyl-terminal hydrolase 16; deubiquitinating enzyme 16; ubiquitin thiolesterase 16; ubiquitin-processing protease UBP-M; ubiquitin-specific-processing protease 16 (USP16)
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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, & 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
- thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
- phosphorylated at the onset of mitosis & dephosphorylated during the metaphase/anaphase transition
- the phosphorylated form of the protein is also enzymatically active
Structure
- homotetramer
- the UBP-type Zn+2 finger binds 3 Zn+2 that form a pair of cross-braced ring fingers encapsulated within a third Zn+2 finger in the primary structure
- recognizes the C-terminal tail of free ubiquitin
- belongs to the peptidase C19 family, USP16 subfamily
- contains 1 UBP-type Zn+2 finger
Compartment
nucleus (probable)
Alternative splicing
named isoforms=5
Expression
- present in all the tissues examined including fetal brain, lung, liver, kidney, & adult heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas
Pathology
- chromosomal inversion inv(21)(q21;q22) involving USP16 with RUNX1/AML1 is a cause of chronic myelomonocytic leukemia