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USP15 (ubiquitin specific peptidase 15)

Written2010-12Monica Faronato, Sylvie Urbé, Judy M Coulson
Physiology Department, School of Biomedical Sciences, Faculty of Health, Life Sciences, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK

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Alias_namesubiquitin specific protease 15
Alias_symbol (synonym)KIAA0529
Other aliasUnph-2
HGNC (Hugo) USP15
LocusID (NCBI) 9958
Atlas_Id 44585
Location 12q14.1  [Link to chromosome band 12q14]
Location_base_pair Starts at 62260340 and ends at 62409721 bp from pter ( according to hg19-Feb_2009)  [Mapping USP15.png]
Fusion genes
(updated 2016)
ATP6V0E1 (5q35.1) / USP15 (12q14.1)DYNLT1 (6q25.3) / USP15 (12q14.1)LETM1 (4p16.3) / USP15 (12q14.1)
MON2 (12q14.1) / USP15 (12q14.1)PPM1H (12q14.1) / USP15 (12q14.1)SLC39A9 (14q24.1) / USP15 (12q14.1)
USP15 (12q14.1) / CDH4 (20q13.33)USP15 (12q14.1) / CNTN1 (12q12)USP15 (12q14.1) / PCBP2 (12q13.13)
USP15 (12q14.1) / PDIK1L (1p36.11)USP15 (12q14.1) / PKP4 (2q24.1)USP15 (12q14.1) / SYT1 (12q21.2)
USP15 (12q14.1) / UBR4 (1p36.13)USP15 (12q14.1) / ZCCHC11 (1p32.3)ZCCHC11 (1p32.3) / USP15 (12q14.1)


Note USP15 is a member of the ubiquitin-specific protease (USP) family; these cysteine proteases comprise the largest sub-group of deubiquitinase enzymes (DUBs). USP15 cleaves the isopeptide bonds of polyubiquitin chains, and can cleave linear ubiquitin fusion proteins (Baker et al., 1999).
  Schematic illustrating four human USP15 transcripts. The USP15 reference sequence mRNA (USP15-203) and three alternative splice variants are illustrated. The approximate position and size of exons within the USP15 gene, according to Ensembl, is shown for each splice variant.
Description The USP15 gene spans 145 kb of genomic DNA.
Transcription Four transcripts of the human USP15 gene are described by Ensembl and are summarized in the accompanying diagram and table. According to Entrezgene, USP15 encodes a single reference sequence mRNA of 4611bp (NM_006313.1) composed of 21 exons, which corresponds to USP15-203. However, three other USP15 splice variants utilise several alternative-splicing sites between exon 5 and exon 7 of this reference sequence. USP15-201, a 4698 bp mRNA comprised of 22 exons, is expressed at similar levels to the reference sequence (Angelats et al., 2003). Expression of the remaining variants, USP15-204 and the truncated USP15-202, is less well studied.

Summary table of USP15 transcripts.

NameEnsembl EntrezAceviewSize (bp)Exons
USP15-203ENST00000353364NM_006313.1Variant b461121
USP15-201ENST00000280377 Variant a469822
USP15-204ENST00000393654  462623
USP15-202ENST00000312635 Variant e7177


  Schematic illustrating four human USP15 isoforms. The domain structure is shown for the reference sequence protein (USP15-203) and three alternative isoforms according to Ensembl. DUSP, domain present in ubiquitin-specific proteases; UBL, ubiquitin-like fold; UCH, ubiquitin carboxyl-terminal hydrolase. The cysteine motifs that form the zinc-binding site are shown in purple and the amino acids comprising the catalytic triad are shown in red. The approximate location of nuclear export sequences (triangles) and a putative nuclear localisation signal (inverted triangle) are shown above isoform USP15-203. Differences in amino acid sequence between isoforms are shown in light blue. The UCH is absent in isoform USP15-202, but USP15-201, USP15-203 and USP15-204 are predicted to be catalytically active.
Description Summary table of USP15 protein isoforms.

NameEnsembl EntrezSize (aa)MW (kDa)
USP15-203ENSP00000258123NP_006304.1952 109
USP15-201ENSP00000280377 981 112
USP15-204ENSP00000377264 957 109
USP15-202ENSP00000309240 235 40

All USP15 isoforms encompass a single N-terminal DUSP (domain in USPs) characterised by a novel tripod-like fold with a conserved hydrophobic surface patch that is predicted to participate in protein-protein interaction (de Jong et al., 2006). The ubiquitin carboxyl-terminal hydrolase (UCH) catalytic core of the USPs is typically around 350 amino acids, but consists of six conserved boxes, interspersed by insertion sites for additional sequence that can confer diversity (Ye et al., 2009). The major insertion in USP15 is between boxes 3/4, and embeds an ubiquitin-like fold (UBL) domain within the catalytic domain. UBLs are commonly found in the USPs and in certain other DUB families (Zhu et al., 2007; Komander et al., 2009a). They exhibit low sequence conservation, but have high structural similarity with ubiquitin and have been proposed to play important roles in regulating DUB catalytic function or interactions (Zhu et al., 2007; Ye et al., 2009). The intercalation of a UBL between boxes 3 and 4 of the catalytic domain increases the spacing between two sets of zinc-coordinating cysteine motifs, which form a functional zinc finger that is required for activity (Hetfeld et al., 2005). In the case of USP15, a second UBL is located directly adjacent to the DUSP (Zhu et al., 2007; Ye et al., 2009).
The four USP15 splice variants encode four distinct protein isoforms, which are illustrated in the diagram and summarised in the accompanying table. As a consequence of alternative splicing, isoform USP15-201 has a 29 amino acid insert within the unstructured region between the first UBL domain and the start of the UCH domain, whereas USP15-204 has a substitution of 3 amino acids for 8 residues within the first UBL. Otherwise the three isoforms that retain the catalytic domain are identical. They also retain predicted nuclear export signals (NES) (Soboleva et al., 2005) and, by homology with rat, a functional nuclear localisation signal (NLS) (Park et al., 2000).

Expression USP15 messenger RNA (mRNA) expression is prevalent throughout the tissues of the body, although its levels vary. Human USP15 is least abundant in brain, lung and kidney, consistent with observations for mouse Usp15 and the rat ortholog UBP109 (Park et al., 2000; Angelats et al., 2003). In each species, USP15 is most abundant in testes, and is variously enriched in spleen, heart, skeletal muscle or peripheral blood leukocytes.
Localisation As USP15 harbours both putative NES and NLS, its sub-cellular distribution may in part depend on the cellular context. Rat UBP109 localises to both the cytoplasm and the nuclear compartment, with the latter dependent on a C-terminal NLS (Park et al., 2000) that is conserved across species. Using an Usp15/USP15-specific polyclonal antibody, Soboleva et al. demonstrated that in HeLa (human cervical cancer cells) endogenous USP15 localised to the cytoplasm and nucleolus, but was largely excluded from the nucleoplasm; whilst in NIH3T3 (mouse fibroblast cells), Usp15 localised in the cytoplasm and was enriched proximal to the plasma membrane (Soboleva et al., 2005). Interestingly, GFP-tagged USP15 (isoform USP15-203) adopts a largely cytoplasmic distribution in human cancer cell lines (Urbé, unpublished observation).
Function Human USP15 was cloned and characterized in 1999 (Baker et al., 1999) and belongs to the largest ubiquitin specific protease (USP) group of deubiquitinating enzymes (DUBs). Protein ubiquitination occurs at lysine residues through the concerted action of E1 activating, E2 conjugating and E3 ligase enzymes. Ubiquitin contains seven lysine residues (K6, K11, K27, K29, K33, K48 and K63), which allow poly-ubiquitin chains to assemble through alternative isopeptide bond linkages. In addition, linear ubiquitin chains may be assembled through the amino-terminus and substrate proteins may also be mono-ubiquitinated. Consequently, in addition to the classical K48-poly-ubiquitin tag that targets substrates for proteasome-mediated degradation, ubiquitination has multiple cellular functions including regulation of protein localisation and activity (Pickart and Eddins, 2004). The general role of the DUBs, in addition to processing inactive ubiquitin precursors and keeping the 26S proteasome free of inhibitory ubiquitin chains, is to reverse the ubiquitination of substrate proteins (Amerik and Hochstrasser, 2004). There are approximately 80 active human DUBs that are divided into five families (Komander et al., 2009a). These DUBs are steadily being assigned to specific substrates (Ventii and Wilkinson, 2008), which is increasingly revealing associations with signalling pathways in cancer (Sacco et al., 2010).
USP15 has activity against both mono-ubiquitinated and poly-ubiquitinated substrates; the zinc-binding domain is necessary for USP15 to process poly-ubiquitin chains, but is not required for USP15 to remove ubiquitin from linear ubiquitin-GFP fusion proteins (Hetfeld et al., 2005). Although USP15 is relatively promiscuous in showing little specificity between K48- and K63-linked poly-ubiquitin chains, or between K63 and K11 di-ubiquitin linkages, it has limited activity against K11-linked poly-ubiquitin chains or linear ubiquitin (Komander et al., 2009b; Bremm et al., 2010).
A recent endeavour to map protein partners of the DUBs by mass spectroscopy reported that, in common with USP4 and USP39, USP15 interacts with several proteins involved in mRNA processing and so may play a role in ubiquitin-dependent control of splicing or mRNA decay (Sowa et al., 2009). In addition, various cancer-signalling pathways have been associated with USP15. For example, USP15 was one of twelve DUBs identified from an siRNA screen that impact on the hepatocyte growth factor (HGF)-dependent cell scattering response in non-small cell lung cancer and pancreatic cancer cells (Buus et al., 2009). A number of specific USP15 substrates have also been described, including the human papilloma virus (HPV) E6 oncoprotein (Vos et al., 2009), the RING-box protein Rbx1 (Hetfeld et al., 2005), the adenomatous polyposis coli (APC) tumour suppressor (Huang et al., 2009), and the NF-kB inhibitor IkBa (Schweitzer et al., 2007).
The latter three examples are all connected with the COP9-signalosome (CSN), a conserved multi-protein complex that regulates the cullin-RING ligase (CRL) superfamily of ubiquitin E3 ligases (Wei et al., 2008). CRLs have a core complex comprised of a cullin scaffold and the RING-box protein Rbx1 that recruit alternative adapter and substrate recognition proteins to form diverse E3 complexes with different substrate specificities. The primary function of the CSN is to remove the ubiquitin-like modifier Nedd8 from the cullin component. This both terminates E3 activity and is required for the reassembly of new CRLs (Wei et al., 2008). The CSN plays a role in many cancer-associated pathways including the cell cycle and DNA damage repair, and both CSN and CRL components may be dysregulated in tumours (Richardson and Zundel, 2005). Ubp12p, an S. pombe ortholog of human USP15, was shown through a systematic mass spectrometry screen to bind the CSN (Zhou et al., 2003). This targets Ubp12p to nuclear cullins, where it is proposed to protect against auto-ubiquitination and degradation of CRL components, in particular the substrate-specific adaptors. (Zhou et al., 2003; Wee et al., 2005).
Human USP15 also co-purifies with the CSN complex and was reported to stabilise the CRL core component Rbx1 (Hetfeld et al., 2005), thereby acting as a positive regulator of these E3 ligase complexes. In contrast, other studies suggest USP15 may directly oppose CRL E3 ligase activity by deubiquitinating specific substrates. For example, the CSN is involved in ubiquitin-dependent turnover of the IkBa inhibitor that retains NF-kB in the cytosol (Schweitzer et al., 2007). Phosphorylation of IkBa triggers CRL-mediated poly-ubiquitination of IkBa and subsequent proteasomal degradation, allowing NF-kB to enter the nucleus and activate transcription (Karin and Ben-Neriah, 2000). In response to TNFalpha, IkBa has been reported to interact with the CSN leading to its deubiquitination and stabilisation by CSN-associated USP15 (Schweitzer et al., 2007).
The adenomatous polyposis coli (APC) tumour suppressor and the beta-catenin oncogene are frequently mutated in cancers, particularly of the intestine, leading to constitutive wingless and Int-1 (Wnt) signalling (Clevers, 2006). The CSN is proposed to control the balance of beta-catenin and APC through formation of a regulatory super-complex. Deneddylation by the CSN promotes assembly of the beta-catenin destruction complex, whilst CSN-associated USP15 stabilises APC (Huang et al., 2009). The APC also plays a role in mitotic fidelity through interaction with the plus end-binding protein EB1 that controls microtubule growth and dynamics. In contrast to APC, EB1 is destabilised by USP15, suggesting that this is not a direct substrate, but rather that USP15 stabilises a CRL that accelerates ubiquitination and degradation of EB1 (Peth et al., 2007). It is interesting to speculate that such links with microtubule regulation may underpin recent reports that USP15 levels can influence the taxol sensitivity of cancer cells (Xu et al., 2009; Xie et al., 2010).
VCP/p97 is a large AAA+-type ATPase that acts as a chaperone in many cellular processes. Its basic function is to segregate ubiquitinated proteins from macromolecular complexes, and VCP plays an important role in recognizing and handling misfolded proteins, which are then either handed over for degradation or recycled. The CSN directly interacts with VCP and USP15 can process VCP-bound poly-ubiquitinated substrates, which accumulate following USP15 depletion (Cayli et al., 2009). VCP is implicated in human neurodegenerative disorders where it co-localises with poly-glutamine aggregates and is proposed to act as both an aggregate-formase and an unfoldase (Kakizuka, 2008). Another established VCP-associated cofactor, the DUB Ataxin-3, is subject to polyglutamine repeat expansion, which causes Machado-Joseph disease (Madsen et al., 2009). Although the mechanism is as yet unclear, USP15 was recently associated with this same disorder (Menzies et al., 2010).
Homology USP15 belongs to the peptidase C19 family. The closest paralogs based on sequence homology are USP4 and USP11.


Somatic No mutations have yet been reported for USP15 according to the COSMIC database, which includes data from four studies of 595 renal carcinoma, glioblastoma, breast and colon cancers.

Implicated in

Entity Cervical cancer
Note USP15 plays an oncogenic role in cervical cancer. Specific HPV strains are associated with cervical carcinoma and two HPV oncoproteins, E6 and E7, are expressed in these cancers. E6 hijacks a cellular E3 ubiquitin ligase and forms a complex with p53, whilst E7 binds the retinoblastoma (Rb) protein; in each case the viral oncoproteins facilitate degradation of the cellular tumour suppressor. It was recently found that USP15 interacts with the oncogenic HPV16 E6 protein (Vos et al., 2009). siRNA mediated depletion of USP15 led to a decrease in E6 protein, whilst overexpression of wild-type but not catalytically inactive USP15 promoted the stabilisation of E6. Interesting, another group has shown that E7 is regulated in a similar fashion by USP11 (Lin et al., 2008). Intriguingly, USP4 also has functional Rb binding motifs (Blanchette et al., 2001; DeSalle et al., 2001) that are conserved in USP11 and USP15 (Baker et al., 1999).
Entity Ovarian cancer
Note USP15 was identified from a genome-wide siRNA screen for Paclitaxel-resistance in the cervical cancer cell line HeLa and, in ovarian cancer samples, Paclitaxel-resistant cases (n=3) showed lower expression of USP15 mRNA than drug-sensitive cases (n=6) (Xu et al., 2009). Moreover, USP15 appeared to stabilise caspase-3, suggesting that reduced levels of USP15 may promote cell survival rather than apoptosis in response to drug treatment.
Entity Gastro-intestinal cancers
Note USP15 was also amongst four genes, identified by expression profiling of Docetaxel-sensitive versus resistant cells, which correlated with drug-sensitivity in a panel of gastric cell lines. However, no statistical correlation was established between elevated USP15 transcript levels and Docetaxel-sensitivity in 25 gastric cancer tissues (Xie et al., 2010).
Germline mutations in APC lead to inherited colon cancer and sporadic tumours are associated with beta-catenin stabilisation. Huang et al. show a role for USP15 in stabilizing APC levels through the action of the CSN (Huang et al., 2009).
Entity Machado-Joseph disease
Note USP15 was identified from microarray analysis of a mouse model of spinocerebellar ataxia type 3. In this study, USP15 transcript and protein levels were decreased in both the ataxin-3 model, and in a second huntingtin transgenic model of a polyglutamine disorder; although overexpression of USP15 promoted the accumulation of protein aggregates, this was independent of its activity on poly-ubiquitin chains (Menzies et al., 2010).


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PMID 15571815
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PMID 12532266
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PMID 10444327
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Oncogene. 2001 Sep 6;20(39):5533-7.
PMID 11571651
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Nat Struct Mol Biol. 2010 Aug;17(8):939-47. Epub 2010 Jul 11.
PMID 20622874
Deubiquitinase activities required for hepatocyte growth factor-induced scattering of epithelial cells.
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Curr Biol. 2009 Sep 15;19(17):1463-6. Epub 2009 Aug 20.
PMID 19699092
COP9 signalosome interacts ATP-dependently with p97/valosin-containing protein (VCP) and controls the ubiquitination status of proteins bound to p97/VCP.
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J Biol Chem. 2009 Dec 11;284(50):34944-53. Epub 2009 Oct 13.
PMID 19826004
Wnt/beta-catenin signaling in development and disease.
Clevers H.
Cell. 2006 Nov 3;127(3):469-80. (REVIEW)
PMID 17081971
The de-ubiquitinating enzyme Unp interacts with the retinoblastoma protein.
DeSalle LM, Latres E, Lin D, Graner E, Montagnoli A, Baker RT, Pagano M, Loda M.
Oncogene. 2001 Sep 6;20(39):5538-42.
PMID 11571652
The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is essential to rescue the E3 ligase Rbx1.
Hetfeld BK, Helfrich A, Kapelari B, Scheel H, Hofmann K, Guterman A, Glickman M, Schade R, Kloetzel PM, Dubiel W.
Curr Biol. 2005 Jul 12;15(13):1217-21.
PMID 16005295
The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15.
Huang X, Langelotz C, Hetfeld-Pechoc BK, Schwenk W, Dubiel W.
J Mol Biol. 2009 Aug 28;391(4):691-702. Epub 2009 Jul 1.
PMID 19576224
Roles of VCP in human neurodegenerative disorders.
Kakizuka A.
Biochem Soc Trans. 2008 Feb;36(Pt 1):105-8. (REVIEW)
PMID 18208395
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
Karin M, Ben-Neriah Y.
Annu Rev Immunol. 2000;18:621-63. (REVIEW)
PMID 10837071
Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains.
Komander D, Reyes-Turcu F, Licchesi JD, Odenwaelder P, Wilkinson KD, Barford D.
EMBO Rep. 2009b May;10(5):466-73. Epub 2009 Apr 17.
PMID 19373254
USP11 stabilizes HPV-16E7 and further modulates the E7 biological activity.
Lin CH, Chang HS, Yu WC.
J Biol Chem. 2008 Jun 6;283(23):15681-8. Epub 2008 Apr 11.
PMID 18408009
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Madsen L, Seeger M, Semple CA, Hartmann-Petersen R.
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PMID 19497384
Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3.
Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC.
Brain. 2010 Jan;133(Pt 1):93-104. Epub 2009 Dec 9.
PMID 20007218
Tissue-specificity, functional characterization and subcellular localization of a rat ubiquitin-specific processing protease, UBP109, whose mRNA expression is developmentally regulated.
Park KC, Choi EJ, Min SW, Chung SS, Kim H, Suzuki T, Tanaka K, Chung CH.
Biochem J. 2000 Jul 15;349(Pt 2):443-53.
PMID 10880343
Ubiquitin-dependent proteolysis of the microtubule end-binding protein 1, EB1, is controlled by the COP9 signalosome: possible consequences for microtubule filament stability.
Peth A, Boettcher JP, Dubiel W.
J Mol Biol. 2007 Apr 27;368(2):550-63. Epub 2007 Feb 22.
PMID 17350042
Ubiquitin: structures, functions, mechanisms.
Pickart CM, Eddins MJ.
Biochim Biophys Acta. 2004 Nov 29;1695(1-3):55-72. (REVIEW)
PMID 15571809
The emerging role of the COP9 signalosome in cancer.
Richardson KS, Zundel W.
Mol Cancer Res. 2005 Dec;3(12):645-53. (REVIEW)
PMID 16380502
Emerging roles of deubiquitinases in cancer-associated pathways.
Sacco JJ, Coulson JM, Clague MJ, Urbe S.
IUBMB Life. 2010 Feb;62(2):140-57. (REVIEW)
PMID 20073038
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PMID 17318178
Nuclear-cytoplasmic shuttling of the oncogenic mouse UNP/USP4 deubiquitylating enzyme.
Soboleva TA, Jans DA, Johnson-Saliba M, Baker RT.
J Biol Chem. 2005 Jan 7;280(1):745-52. Epub 2004 Oct 18.
PMID 15494318
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Sowa ME, Bennett EJ, Gygi SP, Harper JW.
Cell. 2009 Jul 23;138(2):389-403. Epub 2009 Jul 16.
PMID 19615732
Protein partners of deubiquitinating enzymes.
Ventii KH, Wilkinson KD.
Biochem J. 2008 Sep 1;414(2):161-75. (REVIEW)
PMID 18687060
The ubiquitin-specific peptidase USP15 regulates human papillomavirus type 16 E6 protein stability.
Vos RM, Altreuter J, White EA, Howley PM.
J Virol. 2009 Sep;83(17):8885-92. Epub 2009 Jun 24.
PMID 19553310
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Nat Cell Biol. 2005 Apr;7(4):387-91. Epub 2005 Mar 27.
PMID 15793566
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Trends Biochem Sci. 2008 Dec;33(12):592-600. Epub 2008 Oct 14. (REVIEW)
PMID 18926707
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Xie L, Wei J, Qian X, Chen G, Yu L, Ding Y, Liu B.
Anticancer Res. 2010 Jun;30(6):2209-16.
PMID 20651371
USP15 plays an essential role for caspase-3 activation during Paclitaxel-induced apoptosis.
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Biochem Biophys Res Commun. 2009 Oct 16;388(2):366-71. Epub 2009 Aug 8.
PMID 19665996
Dissection of USP catalytic domains reveals five common insertion points.
Ye Y, Scheel H, Hofmann K, Komander D.
Mol Biosyst. 2009 Dec;5(12):1797-808. Epub 2009 Jul 17.
PMID 19734957
Fission yeast COP9/signalosome suppresses cullin activity through recruitment of the deubiquitylating enzyme Ubp12p.
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Mol Cell. 2003 Apr;11(4):927-38.
PMID 12718879
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Zhu X, Menard R, Sulea T.
Proteins. 2007 Oct 1;69(1):1-7.
PMID 17597129
Solution structure of the human ubiquitin-specific protease 15 DUSP domain.
de Jong RN, Ab E, Diercks T, Truffault V, Daniels M, Kaptein R, Folkers GE.
J Biol Chem. 2006 Feb 24;281(8):5026-31. Epub 2005 Nov 18.
PMID 16298993


This paper should be referenced as such :
Faronato, M ; Urbé, S ; Coulson, JM
USP15 (ubiquitin specific peptidase 15)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(8):645-651.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)USP15   12613
Entrez_Gene (NCBI)USP15  9958  ubiquitin specific peptidase 15
AliasesUNPH-2; UNPH4
GeneCards (Weizmann)USP15
Ensembl hg19 (Hinxton)ENSG00000135655 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000135655 [Gene_View]  chr12:62260340-62409721 [Contig_View]  USP15 [Vega]
ICGC DataPortalENSG00000135655
TCGA cBioPortalUSP15
AceView (NCBI)USP15
Genatlas (Paris)USP15
SOURCE (Princeton)USP15
Genetics Home Reference (NIH)USP15
Genomic and cartography
GoldenPath hg38 (UCSC)USP15  -     chr12:62260340-62409721 +  12q14.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)USP15  -     12q14.1   [Description]    (hg19-Feb_2009)
EnsemblUSP15 - 12q14.1 [CytoView hg19]  USP15 - 12q14.1 [CytoView hg38]
Mapping of homologs : NCBIUSP15 [Mapview hg19]  USP15 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB011101 AF013990 AF106069 AF153604 AI027693
RefSeq transcript (Entrez)NM_001252078 NM_001252079 NM_006313
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)USP15
Cluster EST : UnigeneHs.434951 [ NCBI ]
CGAP (NCI)Hs.434951
Alternative Splicing GalleryENSG00000135655
Gene ExpressionUSP15 [ NCBI-GEO ]   USP15 [ EBI - ARRAY_EXPRESS ]   USP15 [ SEEK ]   USP15 [ MEM ]
Gene Expression Viewer (FireBrowse)USP15 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9958
GTEX Portal (Tissue expression)USP15
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y4E8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9Y4E8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y4E8
Splice isoforms : SwissVarQ9Y4E8
Catalytic activity : Enzyme3.4.19.12 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   
Domaine pattern : Prosite (Expaxy)DUSP (PS51283)    USP_1 (PS00972)    USP_2 (PS00973)    USP_3 (PS50235)   
Domains : Interpro (EBI)Pept_C19_DUSP    Peptidase_C19_UCH    RNA3'P_cycl/enolpyr_Trfase_a/b    Ub_USP-typ    Ubiquitin-rel_dom    USP_C    USP_CS    USP_dom   
Domain families : Pfam (Sanger)DUSP (PF06337)    Ubiquitin_3 (PF14836)    UCH (PF00443)    USP7_C2 (PF14533)   
Domain families : Pfam (NCBI)pfam06337    pfam14836    pfam00443    pfam14533   
Domain families : Smart (EMBL)DUSP (SM00695)  
Conserved Domain (NCBI)USP15
DMDM Disease mutations9958
Blocks (Seattle)USP15
PDB (SRS)1W6V    3LMN    3PPA    3PV1    3T9L    4A3O    4A3P    5JJW   
PDB (PDBSum)1W6V    3LMN    3PPA    3PV1    3T9L    4A3O    4A3P    5JJW   
PDB (IMB)1W6V    3LMN    3PPA    3PV1    3T9L    4A3O    4A3P    5JJW   
PDB (RSDB)1W6V    3LMN    3PPA    3PV1    3T9L    4A3O    4A3P    5JJW   
Structural Biology KnowledgeBase1W6V    3LMN    3PPA    3PV1    3T9L    4A3O    4A3P    5JJW   
SCOP (Structural Classification of Proteins)1W6V    3LMN    3PPA    3PV1    3T9L    4A3O    4A3P    5JJW   
CATH (Classification of proteins structures)1W6V    3LMN    3PPA    3PV1    3T9L    4A3O    4A3P    5JJW   
Human Protein AtlasENSG00000135655
Peptide AtlasQ9Y4E8
IPIIPI00000728   IPI00219504   IPI01015293   IPI00219505   IPI00165116   IPI01022546   IPI01022030   IPI01022210   IPI01023011   IPI01020757   IPI01022718   IPI01022847   
Protein Interaction databases
IntAct (EBI)Q9Y4E8
Ontologies - Pathways
Ontology : AmiGOcysteine-type endopeptidase activity  thiol-dependent ubiquitin-specific protease activity  transforming growth factor beta receptor binding  protein binding  nucleus  cytoplasm  cytosol  cytosol  ubiquitin-dependent protein catabolic process  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  protein deubiquitination  protein deubiquitination  BMP signaling pathway  monoubiquitinated protein deubiquitination  histone H2B conserved C-terminal lysine deubiquitination  thiol-dependent ubiquitinyl hydrolase activity  identical protein binding  SMAD binding  pathway-restricted SMAD protein phosphorylation  ubiquitinated histone binding  
Ontology : EGO-EBIcysteine-type endopeptidase activity  thiol-dependent ubiquitin-specific protease activity  transforming growth factor beta receptor binding  protein binding  nucleus  cytoplasm  cytosol  cytosol  ubiquitin-dependent protein catabolic process  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  protein deubiquitination  protein deubiquitination  BMP signaling pathway  monoubiquitinated protein deubiquitination  histone H2B conserved C-terminal lysine deubiquitination  thiol-dependent ubiquitinyl hydrolase activity  identical protein binding  SMAD binding  pathway-restricted SMAD protein phosphorylation  ubiquitinated histone binding  
REACTOMEQ9Y4E8 [protein]
REACTOME PathwaysR-HSA-5689880 [pathway]   
NDEx NetworkUSP15
Atlas of Cancer Signalling NetworkUSP15
Wikipedia pathwaysUSP15
Orthology - Evolution
GeneTree (enSembl)ENSG00000135655
Phylogenetic Trees/Animal Genes : TreeFamUSP15
Homologs : HomoloGeneUSP15
Homology/Alignments : Family Browser (UCSC)USP15
Gene fusions - Rearrangements
Fusion : MitelmanATP6V0E1/USP15 [5q35.1/12q14.1]  [t(5;12)(q35;q14)]  
Fusion : MitelmanLETM1/USP15 [4p16.3/12q14.1]  [t(4;12)(p16;q14)]  
Fusion : MitelmanMON2/USP15 [12q14.1/12q14.1]  [t(12;12)(q14;q14)]  
Fusion : MitelmanPPM1H/USP15 [12q14.1/12q14.1]  [t(12;12)(q14;q14)]  
Fusion : MitelmanSLC39A9/USP15 [14q24.1/12q14.1]  [t(12;14)(q14;q24)]  
Fusion : MitelmanUSP15/CDH4 [12q14.1/20q13.33]  [t(12;20)(q14;q13)]  
Fusion : MitelmanUSP15/CNTN1 [12q14.1/12q12]  [t(12;12)(q12;q14)]  
Fusion : MitelmanUSP15/PCBP2 [12q14.1/12q13.13]  [t(12;12)(q13;q14)]  
Fusion : MitelmanUSP15/PKP4 [12q14.1/2q24.1]  [t(2;12)(q24;q14)]  
Fusion : MitelmanUSP15/SYT1 [12q14.1/12q21.2]  [t(12;12)(q14;q21)]  
Fusion: TCGAMON2 12q14.1 USP15 12q14.1 LUAD
Fusion: TCGAPPM1H 12q14.1 USP15 12q14.1 BRCA
Fusion: TCGASLC39A9 14q24.1 USP15 12q14.1 BRCA
Fusion: TCGAUSP15 12q14.1 PCBP2 12q13.13 GBM
Fusion: TCGAUSP15 12q14.1 PKP4 2q24.1 BRCA
Fusion: TCGAUSP15 12q14.1 SYT1 12q21.2 LUAD
Fusion Cancer (Beijing)USP15 [12q14.1]  -  PDIK1L [1p36.11]  [FUSC004348]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerUSP15 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)USP15
Exome Variant ServerUSP15
ExAC (Exome Aggregation Consortium)USP15 (select the gene name)
Genetic variants : HAPMAP9958
Genomic Variants (DGV)USP15 [DGVbeta]
DECIPHERUSP15 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisUSP15 
ICGC Data PortalUSP15 
TCGA Data PortalUSP15 
Broad Tumor PortalUSP15
OASIS PortalUSP15 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICUSP15  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDUSP15
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch USP15
DgiDB (Drug Gene Interaction Database)USP15
DoCM (Curated mutations)USP15 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)USP15 (select a term)
NCG5 (London)USP15
Cancer3DUSP15(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry USP15
NextProtQ9Y4E8 [Medical]
Target ValidationUSP15
Huge Navigator USP15 [HugePedia]
snp3D : Map Gene to Disease9958
BioCentury BCIQUSP15
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9958
Chemical/Pharm GKB GenePA37239
Clinical trialUSP15
canSAR (ICR)USP15 (select the gene name)
PubMed74 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jun 7 12:17:37 CEST 2017

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