USP14
Description
The USP14 (ubiquitin specific peptidase 14) is a protein-coding gene located on chromosome 18.
Ubiquitin-specific protease 14 is an enzyme that in humans is encoded by the USP14 gene. This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mice with a mutation that results in reduced expression of the ortholog of this protein are retarded for growth, develop severe tremors by 2 to 3 weeks of age followed by hindlimb paralysis and death by 6 to 10 weeks of age. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. USP14 has been shown to interact with CXCR4.
USP14 is a proteasome-associated deubiquitinase that removes ubiquitin from proteins targeted for degradation by the proteasome. This process ensures the regeneration of ubiquitin for further use in protein degradation. USP14 is a reversibly associated subunit of the proteasome, and a significant portion exists free within the cell. USP14 plays a role in the degradation of CXCR4, a chemokine receptor essential for CXCL12-induced cell chemotaxis. It also functions as a physiological inhibitor of ERAD (endoplasmic reticulum-associated degradation) under non-stressed conditions, preventing the degradation of unfolded ER proteins by interacting with ERN1. USP14 is crucial for the development and function of synapses at neuromuscular junctions. It contributes to the innate immune response against viruses by stabilizing CGAS, a viral DNA sensor, and inhibiting its autophagic degradation. Additionally, USP14 inhibits the OPTN-mediated autophagic degradation of KDM4D, negatively regulating H3K9me2 and H3K9me3.
USP14 is also known as TGT, Ubp6.
