USP13

Description

The USP13 (ubiquitin specific peptidase 13) is a protein-coding gene located on chromosome 3.

Ubiquitin carboxyl-terminal hydrolase 13 is an enzyme that in humans is encoded by the USP13 gene.

USP13 is a deubiquitinase that removes ubiquitin tags from various target proteins, including BECN1, MITF, SKP2, and USP10. This activity is involved in a range of cellular processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression, and DNA damage response. USP13 plays a role in regulating autophagy by deubiquitinating BECN1, a key autophagy regulator. This stabilizes the PIK3C3/VPS34-containing complexes. USP13 also forms a deubiquitination complex with NEDD4, which further stabilizes VPS34 to promote autophagy. USP13 deubiquitinates USP10, a critical regulator of p53/TP53 stability. Interestingly, the PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting a regulatory loop where these complexes control p53/TP53 protein levels through USP10 and USP13. In ERAD, USP13 is recruited by nuclear UFD1 and deubiquitinates SKP2, thereby regulating the process. USP13 also regulates ERAD through deubiquitination of UBL4A, a component of the BAG6/BAT3 complex. Notably, USP13 stabilizes SIAH2 independently of its deubiquitinase activity by binding to ubiquitinated SIAH2 and inhibiting its autoubiquitination. USP13 regulates cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB. It also contributes to maintaining genomic stability and activating the DNA replication checkpoint by regulating RAP80 and TOPBP1. USP13 deubiquitinates HMGB1, a multifunctional protein, driving its nucleocytoplasmic localization and secretion. USP13 positively regulates type I and type II interferon signaling by deubiquitinating STAT1, but negatively regulates antiviral response by deubiquitinating STING1. USP13 interacts with UFD1, SIAH2 (via UBA domains), BAG6, AMFR (via UBA 2 domain), and UBL4A. The interaction with BAG6 is direct and may mediate UBL4A deubiquitination, while the interaction with AMFR is also direct. The interaction with UBL4A may be indirect via BAG6. USP13 also interacts with NEDD4.

USP13 is also known as ISOT3, IsoT-3.

Associated Diseases

WES Whole Exome Sequencing