USP14

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. [provided by RefSeq, Jul 2008]

Full Name

Ubiquitin Specific Peptidase 14

Function

Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome (PubMed:18162577, PubMed:28396413).
Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell (PubMed:18162577).
Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (PubMed:19106094).
Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1 (PubMed:19135427).
Indispensable for synaptic development and function at neuromuscular junctions (NMJs) (By similarity).
Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation (PubMed:27666593).

Biological Process

Biological Process chemical synaptic transmission Source:Ensembl
Biological Process innate immune response Source:UniProtKB-KW
Biological Process negative regulation of ER-associated ubiquitin-dependent protein catabolic process Source:ParkinsonsUK-UCL1 Publication
Biological Process positive regulation of NF-kappaB transcription factor activity Source:Reactome
Biological Process proteasome-mediated ubiquitin-dependent protein catabolic process Source:InterPro
Biological Process protein deubiquitination Source:FlyBase1 Publication
Biological Process regulation of chemotaxis Source:UniProtKB1 Publication
Biological Process regulation of proteasomal protein catabolic process Source:UniProtKB1 Publication

Cellular Location

Cytoplasm
Cell membrane