USP16

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.

Full Name

USP16

Function

Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. 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. 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. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.

Biological Process

Biological Process cell division Source:UniProtKB-KW
Biological Process cellular response to DNA damage stimulus Source:UniProtKB1 Publication
Biological Process chromatin organization Source:UniProtKB-KW
Biological Process histone deubiquitination Source:UniProtKB1 Publication
Biological Process histone H2A K63-linked deubiquitination Source:UniProtKB1 Publication
Biological Process mitotic cell cycle Source:UniProtKB1 Publication
Biological Process mitotic nuclear division Source:UniProtKB-UniRule
Biological Process monoubiquitinated histone H2A deubiquitination Source:UniProtKB
Biological Process positive regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:UniProtKB
Biological Process positive regulation of translational elongation Source:UniProtKB1 Publication
Biological Process protein deubiquitination Source:Reactome
Biological Process protein homotetramerization Source:UniProtKB1 Publication
Biological Process regulation of cell cycle Source:InterPro
Biological Process regulation of transcription by RNA polymerase II Source:UniProtKB
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Cellular Location

Nucleus

Involvement in disease

A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.

PTM

Phosphorylated at the onset of mitosis and dephosphorylated during the metaphase/anaphase transition. Phosphorylation by AURKB enhances the deubiquitinase activity.