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Available structures
PDBOrtholog search: PDBe RCSB
AliasesUSP11, UHX1, ubiquitin specific peptidase 11
External IDsMGI: 2384312 HomoloGene: 31252 GeneCards: USP11
Gene location (Human)
X chromosome (human)
Chr.X chromosome (human)[1]
X chromosome (human)
Genomic location for USP11
Genomic location for USP11
BandXp11.3Start47,232,690 bp[1]
End47,248,328 bp[1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr X: 47.23 – 47.25 MbChr X: 20.7 – 20.72 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Ubiquitin carboxyl-terminal hydrolase or Ubiquitin specific protease 11 is an enzyme that in humans is encoded by the USP11 gene.[5][6] USP11 belongs to the Ubiquitin specific proteases family (USPs) which is a sub-family of the Deubiquitinating enzymes (DUBs).USPs are multiple domain proteases and belong to the C19 cysteine proteases sub‒family. Depending on their domain architecture and position there is different homology between the various members. Generally the largest domain is the catalytic domain which harbours the three residue catalytic triad that is included inside conserved motifs (Cys and His boxes). The catalytic domain also contains sequences that are not related with the catalysis function and their role is mostly not clearly understood at present, the length of these sequences varies for each USP and therefore the length of the whole catalytic domain can range from approximately 295 to 850 amino acids.[7] Particular sequences inside the catalytic domain or at the N‒terminus of some USPs have been characterised as UBL (Ubiquitin like) and DUSP (domain present in ubiquitin‒specific proteases) domains respectively. In some cases, regarding the UBL domains, it has been reported to have a catalysis enhancing function as in the case of USP7.[8] In addition, a so‒called DU domain module is the combination of a DUSP domain followed by a UBL domain separated by a linker and is found in USP11 as well as in USP15 and USP4.

USP11 is 963aa protein with a MW of approximately 109.8 kDa and a pI of ~5.28; it shares significant homology with USP15 and along with USP4 forms the DU subfamily. Nevertheless, alignment of the three USPs confirms that USP15 and USP4 are the closest homologues with the identity reaching ~73 % between their UBL1 domains whereas USP11 is the most distant member with an identity of only ~32.3 % when compared to USP15. An UBL2 domain insertion (285aa) is present within the catalytic domain, which encompasses amino acids 310‒931, and the catalytic triad consists of a cysteine, a histidine and an aspartic acid.


Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23[6]


USP11 has been shown to interact with RANBP9.[9]

Model organisms[edit]

Model organisms have been used in the study of USP11 function. A conditional knockout mouse line called Usp11tm1(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[10] Male and female animals underwent a standardized phenotypic screen[11] to determine the effects of deletion.[12][13][14][15] Additional screens performed: In-depth immunological phenotyping[16]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102226 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031066 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Puente XS, Sánchez LM, Overall CM, López-Otín C (July 2003). "Human and mouse proteases: a comparative genomic approach". Nature Reviews. Genetics. 4 (7): 544–58. doi:10.1038/nrg1111. PMID 12838346.
  6. ^ a b "Entrez Gene: USP11 ubiquitin specific peptidase 11".
  7. ^ Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK, Bernards R (December 2005). "A genomic and functional inventory of deubiquitinating enzymes". Cell. 123 (5): 773–86. doi:10.1016/j.cell.2005.11.007. PMID 16325574.
  8. ^ Faesen AC, Dirac AM, Shanmugham A, Ovaa H, Perrakis A, Sixma TK (October 2011). "Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase". Molecular Cell. 44 (1): 147–59. doi:10.1016/j.molcel.2011.06.034. PMID 21981925.
  9. ^ Ideguchi H, Ueda A, Tanaka M, Yang J, Tsuji T, Ohno S, Hagiwara E, Aoki A, Ishigatsubo Y (October 2002). "Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM". The Biochemical Journal. 367 (Pt 1): 87–95. doi:10.1042/BJ20011851. PMC 1222860. PMID 12084015.
  10. ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  11. ^ a b "International Mouse Phenotyping Consortium".
  12. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  13. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  14. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  15. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (July 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  16. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading[edit]