USP15
Description
The USP15 (ubiquitin specific peptidase 15) is a protein-coding gene located on chromosome 12.
Ubiquitin carboxyl-terminal hydrolase 15 is an enzyme that in humans is encoded by the USP15 gene. Ubiquitin is a highly conserved protein involved in the regulation of intracellular protein breakdown, cell cycle regulation, and stress response, which is released from degraded proteins by disassembly of the polyubiquitin chains. The disassembly process is mediated by ubiquitin-specific proteases (USPs).
== See also == USP1 (MIM 603478).
USP15 is a hydrolase that removes ubiquitin from target proteins and plays a role in various cellular processes. It is known to regulate TGF-beta receptor signaling, NF-kappa-B, and RNF41/NRDP1-PRKN pathways. It acts as a key regulator of TGF-beta receptor signaling, promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2, and/or SMAD3), thereby activating TGF-beta target genes. USP15 also deubiquitinates and stabilizes TGFBR1, enhancing TGF-beta signaling. It can deubiquitinate monoubiquitinated substrates, Lys-27-, Lys-48-, and Lys-63-linked polyubiquitin chains. USP15 may regulate gene expression and DNA repair through deubiquitination of histone H2B. It functions as an inhibitor of mitophagy by counteracting parkin's activity, hydrolyzing Lys-48- and Lys-63-linked polyubiquitin chains attached to target proteins like MFN2. USP15 is associated with the COP9 signalosome complex (CSN) and regulates NF-kappa-B by deubiquitinating NFKBIA and deubiquitinating substrates bound to VCP. It is involved in endosome organization by mediating deubiquitination of SQSTM1, releasing target vesicles for transport into the cell periphery. USP15 acts as a negative regulator of antifungal immunity by mediating Lys-27-linked deubiquitination of CARD9, inactivating CARD9.
USP15 is also known as UNPH-2, UNPH4.
