Jump to navigation Jump to search
External IDsGeneCards: [1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)n/an/a
PubMed searchn/an/a
View/Edit Human

Ubiquitin specific protease 4 (USP4) is an enzyme that cleaves ubiquitin from a number of protein substrates.[1] Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals.[2] In the mouse and human the USP4 protein is encoded by a gene containing 22 exons.[3][4][5]

This protein is a member of cysteine peptidase family C19. As a deubiquitinating enzyme it is unusual in having the capacity to cleave ubiquitin-proline bonds.[6] This property may reflect structural flexibility in the active site of the enzyme, and may explain its ability to cleave ubiquitin chains of various linkages. USP4 has substrates of important function in a number of cell signalling pathways, including the NF-κB, TGF-β, Wnt/β-catenin, p53, and spliceosome pathways. Other substrates include the adenosine A2A receptor and the Ro52 (TRIM21) protein.


USP4 has been shown to interact with Retinoblastoma protein.[7]


  1. Gray D (2012). "Chapter 462". In Rawlings & Salvesen. Handbook of Proteolytic Enzymes (3rd ed.). Elsevier. ISBN 9780123822192.
  2. Gupta K, Copeland NG, Gilbert DJ, Jenkins NA, Gray DA (August 1993). "Unp, a mouse gene related to the tre oncogene". Oncogene. 8 (8): 2307–10. PMID 8336951.
  3. Di Fruscio M, Gilchrist CA, Baker RT, Gray DA (May 1998). "Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease". Biochim. Biophys. Acta. 1398 (1): 9–17. doi:10.1016/s0167-4781(98)00035-9. PMID 9602026.
  4. Puente XS, Sanchez LM, Overall CM, Lopez-Otin C (July 2003). "Human and mouse proteases: a comparative genomic approach". Nat Rev Genet. 4 (7): 544–558. doi:10.1038/nrg1111. PMID 12838346.
  5. "Entrez Gene: USP4 ubiquitin specific peptidase 4 (proto-oncogene)".
  6. Gilchrist CA, Gray DA, Baker RT (December 1997). "A ubiquitin-specific protease that efficiently cleaves the ubiquitin-proline bond". J. Biol. Chem. 272 (51): 32280–5. doi:10.1074/jbc.272.51.32280. PMID 9405433.
  7. Blanchette P, Gilchrist CA, Baker RT, Gray DA (September 2001). "Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130". Oncogene. 20 (39): 5533–7. doi:10.1038/sj.onc.1204823. PMID 11571651.

Further reading