ubiquitin carboxyl-terminal hydrolase 4; deubiquitinating enzyme 4; ubiquitin thiolesterase 4; ubiquitin-specific-processing protease 4; ubiquitous nuclear protein homolog (USP4, UNP, UNPH)

Function

• deubiquitinates target proteins including ADORA2A & TRIM21
• deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface
• plays a role in the regulation of quality control in the endoplasmic reticulum (ER)
• thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
• monoubiquitinated by TRIM21
• ubiquitination does not lead to its proteasomal degradation
• autodeubiquitinated
• interacts with RB1 (both dephosphorylated & hypophosphorylated forms)
• interacts with ADORA2A (via cytoplasmic C-terminus)
• interacts with RB1, RBL1 & RBL2

Structure

• belongs to the peptidase C19 family, USP4 subfamily
• contains 1 DUSP domain

Compartment

• cytoplasm, nucleus (putative)
• shuttles between the nucleus & cytoplasm
• exported to the cytoplasm in a CRM1-dependent manner & recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor
• the relative amounts found in the nucleus & cytoplasm vary according to the cell type (putative)

Alternative splicing

named isoforms=2

Expression

• expressed in the hippocampal neurons

Pathology

• overexpressed at protein level in:
  • small cell carcinoma of the lung
  • adenocarcinoma of the lung

More general terms

• ubiquitin C-terminal hydrolase
• phosphoprotein

Additional terms

• ubiquitin (UBCEP2, UBB, UBC)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7375
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7375
• OMIM: https://mirror.omim.org/entry/603486
• UniProt: http://www.uniprot.org/uniprot/Q13107.html