USP10

Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]

Full Name

Ubiquitin Specific Peptidase 10

Function

Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989).
Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384).

Biological Process

Biological Process autophagy Source:UniProtKB-KW
Biological Process cellular response to DNA damage stimulus Source:UniProtKB1 Publication
Biological Process cellular response to interleukin-1 Source:UniProtKB1 Publication
Biological Process DNA damage response, signal transduction by p53 class mediator Source:UniProtKB1 Publication
Biological Process negative regulation of I-kappaB kinase/NF-kappaB signaling Source:UniProtKB1 Publication
Biological Process protein deubiquitination Source:UniProtKB1 Publication
Biological Process regulation of autophagy Source:UniProtKB1 Publication
Biological Process translesion synthesis Source:Reactome
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Cellular Location

Cytoplasm
Nucleus
Early endosome
Cytoplasmic in normal conditions (PubMed:20096447).
After DNA damage, translocates to the nucleus following phosphorylation by ATM (PubMed:20096447).

PTM

Phosphorylated by ATM following DNA damage, leading to stablization and translocation it to the nucleus.
Ubiquitinated. Deubiquitinated by USP13.