USP4

The protein encoded by this gene is a protease that deubiquitinates target proteins such as ADORA2A and TRIM21. The encoded protein shuttles between the nucleus and cytoplasm and is involved in maintaining operational fidelity in the endoplasmic reticulum. Three transcript variants encoding different isoforms have been found for this gene.

Full Name

ubiquitin specific peptidase 4 (proto-oncogene)

Function

Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (PubMed:16316627, PubMed:16472766, PubMed:16339847, PubMed:20595234, PubMed:22347420, PubMed:25404403, PubMed:28604766).
Deubiquitinates PDPK1 (PubMed:22347420).
Deubiquitinates TRIM21 (PubMed:16316627).
Deubiquitinates receptor ADORA2A which increases the amount of functional receptor at the cell surface (PubMed:16339847).
Deubiquitinates HAS2 (PubMed:28604766).
May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3 (PubMed:20595234).
This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP (PubMed:20595234).
May also play a role in the regulation of quality control in the ER (PubMed:16339847).

Biological Process

Biological Process negative regulation of protein ubiquitination Source:UniProtKB1 Publication
Biological Process protein deubiquitination Source:UniProtKB3 Publications
Biological Process protein localization to cell surface Source:UniProtKB1 Publication
Biological Process regulation of protein stability Source:UniProtKB1 Publication
Biological Process spliceosomal tri-snRNP complex assembly Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Cellular Location

Cytoplasm
Nucleus
Shuttles between the nucleus and cytoplasm. Exported to the cytoplasm in a CRM1-dependent manner and recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The relative amounts found in the nucleus and cytoplasm vary according to the cell type.

PTM

Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated.