USP14
USP14 (ubiquitin specific peptidase 14, also known as TGT or Ubp6) is a proteasome-associated deubiquitinase that releases ubiquitin from proteins targeted for degradation. It helps regenerate ubiquitin at the proteasome and belongs to the peptidase C19 family. Browse Assay Genie's current range of USP14 research reagents below, or read on for the biology behind the target.
USP14 is a deubiquitinating enzyme (DUB) that removes ubiquitin from ubiquitinated proteins delivered to the proteasome, ensuring ubiquitin is regenerated there. It is a reversibly associated proteasome subunit, and a large fraction of the protein exists free of the proteasome within the cell. It also cleaves the ubiquitin moiety from ubiquitin-fused precursors.
Beyond the proteasome, USP14 has several regulatory roles. It is required for degradation of the chemokine receptor CXCR4, which is critical for CXCL12-induced cell chemotaxis. Under non-stressed conditions it acts as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD), inhibiting the degradation of unfolded endoplasmic reticulum proteins through its interaction with ERN1. It is also indispensable for synaptic development and function at neuromuscular junctions.
USP14 contributes to innate antiviral defence by stabilising the viral DNA sensor CGAS and preventing its autophagic degradation. It also inhibits OPTN-mediated selective autophagic degradation of KDM4D, and so negatively regulates H3K9me2 and H3K9me3. The USP14 gene encodes a member of the ubiquitin-specific processing (UBP) family with His and Cys domains, and alternative splice variants encoding different isoforms have been characterised. Its previous HGNC names referred to tRNA-guanine transglycosylase, hence the alias TGT. In mice, a mutation that reduces expression of the ortholog causes growth retardation, severe tremors by 2 to 3 weeks of age, hindlimb paralysis and death by 6 to 10 weeks.
USP14 releases ubiquitin from proteasome-targeted proteins and helps regenerate ubiquitin, making it a key subject for studies of proteasomal degradation.
USP14 is indispensable for synaptic development and function at neuromuscular junctions, and reduced expression in mice produces tremor and paralysis.
USP14 stabilises CGAS to support antiviral defence and inhibits OPTN-mediated autophagic degradation of KDM4D, linking deubiquitination to immune and epigenetic regulation.
USP14 inhibits ERAD through ERN1 under non-stressed conditions and is required for CXCR4 degradation, which underpins CXCL12-induced chemotaxis.
USP14 is a proteasome-associated deubiquitinase that releases ubiquitin from ubiquitinated proteins targeted to the proteasome, ensuring ubiquitin regeneration. It also regulates CXCR4 degradation, inhibits ERAD through ERN1, stabilises CGAS and supports neuromuscular junction function.
USP14 is also known as TGT and Ubp6. Earlier HGNC names, such as ubiquitin specific protease 14 (tRNA-guanine transglycosylase), explain the TGT alias. UniProt calls it ubiquitin carboxyl-terminal hydrolase 14. Alternative splice variants encoding different isoforms have been described.
A mouse ortholog, Usp14, exists. Mice with a mutation reducing its expression show growth retardation, severe tremors from 2 to 3 weeks, hindlimb paralysis and death by 6 to 10 weeks. Check the datasheet of any product for its validated reactivity.
Other ubiquitin specific peptidases and deubiquitinases that act in proteasomal degradation and ubiquitin signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P54578; product specifications from Assay Genie datasheets.