NUMBER SwissProt ID (DUB) SwissProt ID (Substrate) SwissProt AC (DUB) SwissProt AC (Substrate) Gene Symbol (DUB) Gene Symbol (Substrate) SOURCE SOURCEID SENTENCE DUBTYPE COUNT type species 1 UBP13_ARATH DAR2_ARATH Q84WU2 Q0WSN2 UBP13 DAR2 MEDLINE 32209225 UBP12 and UBP13 negatively regulate the activity of the ubiquitin-dependent peptidases DA1, DAR1 and DAR2 USP 1 Other A.thaliana 2 UBP13_ARATH NAC92_ARATH Q84WU2 Q9FKA0 UBP13 NAC92 MEDLINE 31050353 We found that UBP12/UBP13 can deubiquitinate polyubiquitinated ORE1 in vitro and increase the stability of ORE1 in vivo in MG132/cycloheximide-chase experiments USP 1 Other A.thaliana 3 Q7JMS4_CAEEL CEP1_CAEEL Q7JMS4 Q20646 cyld-1 cep-1 MEDLINE 29394249 29394249 Other 1 Other C.elegans 4 Q93875_CAEEL FBRL_CAEEL Q93875 Q22053 usp-33 fib-1 MEDLINE 31914708 31914708 USP 1 Other C.elegans 5 UBP46_CAEEL GLR1_CAEEL P34547 P34299 usp-46 glr-1 MEDLINE 32587090 We have previously shown that the DUB ubiquitin-specific protease 46 (USP-46) removes ubiquitin from the glutamate receptor GLR-1 and regulates its trafficking and degradation in Caenorhabditis elegans We found that the WD40-repeat proteins WDR-20 and WDR-48 bind and stimulate the catalytic activity of USP-46 USP 1 Other C.elegans 6 Q7JMS4_CAEEL AP1M_CAEEL Q7JMS4 P35602 cyld-1 unc-101 MEDLINE 29394249 29394249 other 1 Other C.elegans 7 Q9VDD8_DROME Q95SH2_DROME Q9VDD8 Q95SH2 Usp8 Chmp1 MEDLINE 29933386 29933386 USP 1 Other D.melanogaster 8 CALYP_DROME H2A_DROME Q7K5N4 P84051 calypso His2A:CG33865 MEDLINE 30349006 30349006 UCH 1 Other D.melanogaster 9 CALYP_DROME H2AV_DROME Q7K5N4 P08985 calypso His2Av MEDLINE 31130514 31130514 UCH 1 Other D.melanogaster 10 TRA1_DROME H2B_DROME Q8I8U7 P02283 Nipped-A His2B:CG33910 MEDLINE 31538360 Nipped-A regulates the Drosophila circadian clock via histone deubiquitination Other 1 Other D.melanogaster 11 Q9W0L7_DROME YAP1_DROME Q9W0L7 Q45VV3 Usp10 yki MEDLINE 31795326 Here, we provide evidence that the deubiquitinating enzyme ubiquitin-specific protease 10 (Usp10) binds Yki to counteract Yki ubiquitination and stabilize Yki protein in Drosophila S2 cells Other 1 Other D.melanogaster 12 Q9VDD8_DROME MARF_DROME Q9VDD8 Q7YU24 Usp8 Marf MEDLINE 30988163 A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional mitochondrial fusion protein Mitofusin (MFN) identified USP8 prominently influencing MFN levels USP 1 Other D.melanogaster 13 F1RBA1_DANRE Q05AN5_DANRE F1RBA1 Q05AN5 usp38 bbs4 MEDLINE 31723061 31723061 USP 1 Other D.rerio 14 E7EYZ1_DANRE PIS4A_DANRE E7EYZ1 F1R4C4 usp18 pias4a MEDLINE 28165509 28165509 USP 1 Other D.rerio 15 E7EZD6_DANRE F1QS48_DANRE E7EZD6 F1QS48 usp4 smad4a MEDLINE 28468752 28468752 USP 1 Other D.rerio 16 UBP3_HUMAN DDX58_HUMAN Q9Y6I4 O95786 USP3 DDX58 MEDLINE 24366338 USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors USP 1 Training data H.sapiens 17 UBP13_HUMAN TOPB1_HUMAN Q92995 Q92547 USP13 TOPBP1 MEDLINE 33592542 Mechanistically, USP13 binds to TopBP1 and stabilizes TopBP1 by deubiquitination USP 1 Other H.sapiens 18 UBP7_HUMAN ARMC5_HUMAN Q93009 Q96C12 USP7 ARMC5 MEDLINE 33544460 By screening a deubiquitinase library, we identified USP7 as a potential ARMC5 associated deubiquitinase USP 1 Other H.sapiens 19 UBP8_HUMAN CXA1_HUMAN P40818 P17302 USP8 GJA1 MEDLINE 29626091 The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43 USP 1 Training data H.sapiens 20 UBP21_HUMAN FOSL1_HUMAN Q9UK80 P15407 USP21 FOSL1 MEDLINE 31947604 These results demonstrate that USP21 enhances Fra-1 stability and AP-1 target gene expression by deubiquitinating Fra-1 USP 1 Other H.sapiens 21 USP9X_HUMAN TTK_HUMAN Q93008 P33981 USP9X TTK MEDLINE 29721084 Conclusions: In summary, our data demonstrated that the USP9X-TTK axis may play a critical role in NSCLC, and could be considered as a potential therapeutic target. USP 1 Training data H.sapiens 22 UBP16_HUMAN RS27A_HUMAN Q9Y5T5 P62979 USP16 RPS27A MEDLINE 32129764 USP16 counteracts mono-ubiquitination of RPS27a and promotes maturation of the 40S ribosomal subunit USP 1 Other H.sapiens 23 ATX3_HUMAN GBRAP_HUMAN P54252 O95166 ATXN3 GABARAP MEDLINE 31625269 The Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy Josephin 1 Other H.sapiens 24 UBP1_HUMAN ESR1_HUMAN O94782 P03372 USP1 ESR1 MEDLINE 33123289 Immuno-precipitation assays indicate that USP1 associates with ERALPHA and promotes its stability possibly via inhibiting ERALPHA K48-linked poly-ubiquitination USP 1 Other H.sapiens 25 UBP18_HUMAN ISG15_HUMAN Q9UMW8 P05161 USP18 ISG15 MEDLINE 28242811 Prior work implicated the IFN-stimulated gene 15 (ISG15) deubiquitinase (DUB) USP18 as having antineoplastic activity by regulating lung cancer growth and oncoprotein stability USP 1 Other H.sapiens 26 UBP7_HUMAN MAF_HUMAN Q93009 O75444 USP7 MAF MEDLINE 31822558 These results therefore demonstrated that USP7 is a deubiquitinase of Maf proteins and promotes MM cell survival in association with Maf stability USP 1 Other H.sapiens 27 ATX3_HUMAN MLP3C_HUMAN P54252 Q9BXW4 ATXN3 MAP1LC3C MEDLINE 31625269 The Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy Josephin 1 Other H.sapiens 28 UBP21_HUMAN RIPK1_HUMAN Q9UK80 Q13546 USP21 RIPK1 MEDLINE 25680095 The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation. USP 1 Training data H.sapiens 29 UBP26_HUMAN ANDR_HUMAN Q9BXU7 P10275 USP26 AR MEDLINE 20501646 Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity. USP 1 Training data H.sapiens 30 UBP22_HUMAN EGFR_HUMAN Q9UPT9 P00533 USP22 EGFR MEDLINE 29981430 Additionally, USP22 sustained the activation of multiple EGFR downstream signaling pathways, including STAT3, AKT/mTOR and MEK/ERK pathways, in lung ADC cell lines H1975 and PC9. USP 1 Training data H.sapiens 31 UBP19_HUMAN TRAF3_HUMAN O94966 Q13114 USP19 TRAF3 MEDLINE 28391724 USP19 suppresses cellular type I interferon signaling by targeting TRAF3 for deubiquitination USP 1 Training data H.sapiens 32 ATX3_HUMAN PRKN_HUMAN P54252 O60260 ATXN3 PRKN MEDLINE 20940148 Moreover, ataxin-3 deubiquitinates parkin directly in vitro and in cells Josephin 1 Training data H.sapiens 33 OTUB2_HUMAN TRAF6_HUMAN Q96DC9 Q9Y4K3 OTUB2 TRAF6 MEDLINE 19996094 Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6 OTU 1 Training data H.sapiens 34 UBP4_HUMAN RB_HUMAN Q13107 P06400 USP4 RB1 MEDLINE 25121098 USP4, reported as an oncogenic protein, is known to interact with the pocket proteins (Rb, p107, and p130) although no deubiquitinating activity has been reported USP 1 Training data H.sapiens 35 CYLD_HUMAN DDX58_HUMAN Q9NQC7 O95786 CYLD DDX58 MEDLINE 27279133 SDC4 likely promotes redistribution of RIG-I and CYLD in a perinuclear pattern post viral infection, and thus enhances the RIG-I-CYLD interaction and potentiates the K63-linked deubiquitination of RIG-I. USP 1 Training data H.sapiens 36 UBP4_HUMAN TRAF6_HUMAN Q13107 Q9Y4K3 USP4 TRAF6 MEDLINE 28755289 The downregulation of USP4 expression may promote microglial activation and subsequent neuronal inflammation through NF-kappaB by attenuating the deubiquitination of TRAF6 USP 1 Training data H.sapiens 37 ATX3_HUMAN CHIP_HUMAN P54252 Q9UNE7 ATXN3 STUB1 MEDLINE 23653622 Indeed, ataxin-3 not only deubiquitinated CHIP, but also trimmed Ub conjugates on CHIP substrates, thereby regulating the length of Ub chains. Josephin 1 Training data H.sapiens 38 OTUD5_HUMAN XRCC5_HUMAN Q96G74 P13010 OTUD5 XRCC5 MEDLINE 30980112 In summary, our study demonstrates that OTUD5 is a specific deubiquitinase for Ku80 and establishes OTUD5 as an important and positive regulator of NHEJ repair. OTU 1 Training data H.sapiens 39 STABP_HUMAN EGFR_HUMAN O95630 P00533 STAMBP EGFR MEDLINE 34102455 STAMBP may deubiquitinate EGFR by localizing in early endosomes and increase EGFR membrane localization in LUAD cells. Other 1 Other H.sapiens 40 USP9X_HUMAN BCL9_HUMAN Q93008 O00512 USP9X BCL9 MEDLINE 31073027 Here, using MCF-7, HeLa, HEK293T, MDA-MB-231, and Sf9 cells, along with immunoblotting and immunofluorescence, nano-HPLC-MS/MS, deubiquitination, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assays, we report that BCL9 physically associates with a protein deubiquitinase, ubiquitin-specific peptidase 9, X-linked (USP9X), and that USP9X removes Lys-63-linked polyubiquitin on Lys-212 of BCL9 USP 1 Other H.sapiens 41 UBP7_HUMAN MPIP1_HUMAN Q93009 P30304 USP7 CDC25A MEDLINE 32860838 Furthermore, in a co-immunoprecipitation assay, we found that HAUSP interacts with and deubiquitinates Cdc25A both exogenously and endogenously USP 1 Other H.sapiens 42 BAP1_HUMAN STK11_HUMAN Q92560 Q15831 BAP1 STK11 MEDLINE 32819560 BAP1 regulates AMPK-mTOR signalling pathway through deubiquitinating and stabilizing tumour-suppressor LKB1 UCH 1 Other H.sapiens 43 UBP7_HUMAN SOCS1_HUMAN Q93009 O15524 USP7 SOCS1 MEDLINE 31691271 USP7 physically interacts with suppressor of cytokine signaling 1 (SOCS1) and enhances SOCS1 protein stability by deubiquitination effects, which in turn restricts IFN-I-induced activation of Janus kinase-signal transducer and activator of transcription 1 signaling USP 1 Other H.sapiens 44 UBP8_HUMAN STAM1_HUMAN P40818 Q92783 USP8 STAM MEDLINE 16996268 UBPY function is essential for effective downregulation but is likely to be multifaceted, encompassing activity against both K63-linked and K48-linked polyubiquitin chains and including regulation of the stability of ESCRT-associated proteins such as STAM, by reversing their ubiquitination. USP 1 Other H.sapiens 45 UBP4_HUMAN P53_HUMAN Q13107 P04637 USP4 TP53 MEDLINE 25121098 Regulation of p53 is also subject to other DUBs, such as USP4, USP10, USP29, and USP42 [171]. USP 1 Training data H.sapiens 46 UBP28_HUMAN FBXW7_HUMAN Q96RU2 Q969H0 USP28 FBXW7 MEDLINE 26410034 We discuss mechanisms that regulate ubiquitination by Fbw7, including ubiquitin-specific proteases such as USP28 that counteract Fbw7 activity and thereby stabilise oncoproteins. USP 1 Training data H.sapiens 47 UCHL1_HUMAN NFKB1_HUMAN P09936 P19838 UCHL1 NFKB1 MEDLINE 30305579 It was showed that UCH-L1 over-expression inhibited NF-KAPPAB activation and decrease IL-6 and IL-8 levels, while knockdown of it enhanced NF-KAPPAB activation and increase IL-6 and IL-8 levels during TNF-alpha treatment. UCH 1 Training data H.sapiens 48 UBP11_HUMAN PP1A_HUMAN P51784 P62136 USP11 PPP1CA MEDLINE 31521612 Mechanically, USP11 stabilized PPP1CA by deubiquitinating and protecting it from proteasome-mediated degradation USP 1 Other H.sapiens 49 OTUD4_HUMAN MAVS_HUMAN Q01804 Q7Z434 OTUD4 MAVS MEDLINE 30410068 Induction of OTUD4 by viral infection promotes antiviral responses through deubiquitinating and stabilizing MAVS OTU 1 Training data H.sapiens 50 UBP13_HUMAN ACLY_HUMAN Q92995 P53396 USP13 ACLY MEDLINE 30319415 USP13, the main regulator of ovarian cancer energy metabolism, specifically deubiquitinates and stabilizes oxoglutarate dehydrogenase and ATP citrate lyase, which can catalyze fatty acid synthesis, glutaminolysis and mitochondrial respiration. USP 1 Training data H.sapiens 51 UBP20_HUMAN ADRB2_HUMAN Q9Y2K6 P07550 USP20 ADRB2 MEDLINE 26445063 26445063 USP 1 Training data H.sapiens 52 UBP33_HUMAN ADRB2_HUMAN Q8TEY7 P07550 USP33 ADRB2 MEDLINE 26445063 26445063 USP 1 Training data H.sapiens 53 UBP3_HUMAN MPIP1_HUMAN Q9Y6I4 P30304 USP3 CDC25A MEDLINE 32415280 USP3 was identified as a deubiquitinase of Cdc25A USP 1 Other H.sapiens 54 UBP15_HUMAN APC_HUMAN Q9Y4E8 P25054 USP15 APC MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 55 USP9X_HUMAN CTNB1_HUMAN Q93008 P35222 USP9X CTNNB1 MEDLINE 29080116 Additionally, DUBs USP14, USP15, USP47, and Fam/USP9X have been reported to prevent BETA-CATENIN turnover by inhibiting its Ub-proteasomal degradation USP 1 Training data H.sapiens 56 UBP33_HUMAN ARRB1_HUMAN Q8TEY7 P49407 USP33 ARRB1 MEDLINE 19363159 We now report the discovery that the deubiquitinating enzyme ubiquitin-specific protease 33 (USP33) binds beta-arrestin2 and leads to the deubiquitination of beta-arrestins USP 1 Training data H.sapiens 57 UBP7_HUMAN ASXL1_HUMAN Q93009 Q8IXJ9 USP7 ASXL1 MEDLINE 26189775 26189775 USP 1 Training data H.sapiens 58 UBP2_HUMAN AURKA_HUMAN O75604 O14965 USP2 AURKA MEDLINE 29449607 In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP 1 Training data H.sapiens 59 UBP13_HUMAN MITF_HUMAN Q92995 O75030 USP13 MITF MEDLINE 28544818 However, deubiquitinase USP13 can stabilize MITF expression and prolong its half-life. USP 1 Training data H.sapiens 60 VCIP1_HUMAN SNTG2_HUMAN Q96JH7 Q9NY99 VCPIP1 SNTG2 MEDLINE 27404360 Syn5 is monoubiquitinated by the ubiquitin ligase HACE1 in early mitosis and deubiquitinated by the deubiquitinase VCIP135 in late mitosis OTU 1 Other H.sapiens 61 BRCC3_HUMAN NUMA1_HUMAN P46736 Q14980 BRCC3 NUMA1 MEDLINE 26195665 importantly, BRISC promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). JAMM 1 Training data H.sapiens 62 UBP44_HUMAN CDC20_HUMAN Q9H0E7 Q12834 USP44 CDC20 MEDLINE 28188342 Usp44, however, counteracts the activity of the APC/C by deubiquitinating Cdc20, thereby preventing premature Mad2-dissociation and SAC silencing USP 1 Training data H.sapiens 63 UBP4_HUMAN DDX58_HUMAN Q13107 O95786 USP4 DDX58 MEDLINE 23388719 Furthermore, USP4 was found to interact with RIG-I and remove K48-linked polyubiquitination chains from RIG-I. USP 1 Training data H.sapiens 64 USP9X_HUMAN STMN1_HUMAN Q93008 P16949 USP9X STMN1 MEDLINE 23112048 In this report, we find that Usp9x, a deubiquitinating enzyme, stably associates with the SMN complex via directly interacting with SMN. USP 1 Other H.sapiens 65 OTU6A_HUMAN AURKA_HUMAN Q7L8S5 O14965 OTUD6A AURKA MEDLINE 33669244 OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A OTU 1 Other H.sapiens 66 UBP7_HUMAN AURKA_HUMAN Q93009 O14965 USP7 AURKA MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 67 UBP46_HUMAN PHLP1_HUMAN P62068 O60346 USP46 PHLPP1 MEDLINE 25121098 SP1 [137] and USP46 [138] are other DUBs known to deubiquitinate PHLPP1 USP 1 Training data H.sapiens 68 UCHL1_HUMAN SC5A7_HUMAN P09936 Q9GZV3 UCHL1 SLC5A7 MEDLINE 24525247 These data provide novel and potentially important evidence that UCHL1 may play a role in the regulation of cholinergic function by affecting CHT ubiquitination and degradation UCH 1 Other H.sapiens 69 OTUB1_HUMAN TAU_HUMAN Q96FW1 P10636 OTUB1 MAPT MEDLINE 28083634 Focusing on Tau deubiquitination, we here identify Otub1 as a Tau-deubiquitinating enzyme. Otub1 directly affected Lys48-linked Tau deubiquitination OTU 1 Training data H.sapiens 70 UBP35_HUMAN AURKB_HUMAN Q9P2H5 Q96GD4 USP35 AURKB MEDLINE 29764563 Recently, we have found that USP35 acts as a deubiquitinating enzyme (DUB) for Aurora B and affects its stability during cell division, thus being involved in the regulation of mitosis. USP 1 Training data H.sapiens 71 SNUT2_HUMAN AURKB_HUMAN Q53GS9 Q96GD4 USP39 AURKB MEDLINE 25121098 USP39 deubiquitinates Aurora B kinase maintaining spindle assembly checkpoint integrity [103] while USP44 stabilizes Mad2/Cdc20 complex inhibiting premature activation of the APC/CCdh1 complex USP 1 Training data H.sapiens 72 UBP1_HUMAN SNAI1_HUMAN O94782 O95863 USP1 SNAI1 MEDLINE 33926817 UBIQUITIN SPECIFIC PEPTIDASE 1 promotes hepatic fibrosis through positive regulation of CXCL1 by deubiquitinating SNAIL USP 1 Other H.sapiens 73 CSN5_HUMAN CUL4A_HUMAN Q92905 Q13619 COPS5 CUL4A MEDLINE 12732143 Figure 4|in vitro deneddylation assay also demonstrated that CSN could de-ubiquitinat Cul4a JAMM 1 Other H.sapiens 74 UBP36_HUMAN DHX33_HUMAN Q9P275 Q9H6R0 USP36 DHX33 MEDLINE 29273634 Collectively, these results support that Usp36 is essential for cell and organism viability because of its role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, by regulating DHX33 stability. USP 1 Training data H.sapiens 75 UBP36_HUMAN EZH2_HUMAN Q9P275 Q15910 USP36 EZH2 MEDLINE 31434700 Furthermore, we identify USP36 as the deubiquitinating enzyme which deubiquitinates EZH2 at K222 USP 1 Other H.sapiens 76 UBP19_HUMAN SYVN1_HUMAN O94966 Q86TM6 USP19 SYVN1 MEDLINE 27827840 We demonstrate that USP19 rescues HRD1 from proteasomal degradation by deubiquitination of K48-linked ubiquitin chains USP 1 Training data H.sapiens 77 CYLD_HUMAN NLRP6_HUMAN Q9NQC7 P59044 CYLD NLRP6 MEDLINE 32424362 Here, we demonstrate that the deubiquitinase Cyld prevents excessive interleukin 18 (IL-18) production in the colonic mucosa by deubiquitinating NLRP6 USP 1 Other H.sapiens 78 CYLD_HUMAN TRAF6_HUMAN Q9NQC7 Q9Y4K3 CYLD TRAF6 MEDLINE 28335430 Moreover, additional studies showed that CYLD specifically deubiquitinates polyubiquitin chains at K63 of different substrates (e.g., TRAF2 and TRAF6), or tyrosine kinase receptors such as TrkA. USP 1 Training data H.sapiens 79 UBP8_HUMAN ERBB3_HUMAN P40818 P21860 USP8 ERBB3 MEDLINE 25121098 USP8 regulates another EGFR family member, ErbB3 by modulating Nrdp1 (neuregulin-receptor-degradation protein-1) USP 1 Training data H.sapiens 80 OTU7B_HUMAN TRAF3_HUMAN Q6GQQ9 Q13114 OTUD7B TRAF3 MEDLINE 23334419 OTUD7B controls non-canonical NF-kappaB activation through deubiquitination of TRAF3 OTU 1 Training data H.sapiens 81 UBP4_HUMAN PPIA_HUMAN Q13107 P62937 USP4 PPIA MEDLINE 29396555 Mechanistically, cyclophilin A (CypA) was identified as an important molecule for USP4-mediated oncogenic activity in HCC. USP 1 Training data H.sapiens 82 OTUB1_HUMAN TRAF3_HUMAN Q96FW1 Q13114 OTUB1 TRAF3 MEDLINE 19996094 Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6 OTU 1 Training data H.sapiens 83 CYLD_HUMAN NOX4_HUMAN Q9NQC7 Q9NPH5 CYLD NOX4 MEDLINE 28751569 Moreover, Nox4 was deubiquitinated via a direct interaction with the ubiquitin-specific protease domain of CYLD. USP 1 Training data H.sapiens 84 ATX3_HUMAN RHEB_HUMAN P54252 Q15382 ATXN3 RHEB MEDLINE 33157014 Mechanistically, we identified ATXN3 as a Ub-Rheb deubiquitinase whose lysosomal localization is blocked by active Rag heterodimer in response to amino acid stimulation Josephin 1 Other H.sapiens 85 UBP22_HUMAN BMI1_HUMAN Q9UPT9 P35226 USP22 BMI1 MEDLINE 29788550 All these findings indicate USP22 as a novel deubiquitinase of BMI1 in glioma USP 1 Training data H.sapiens 86 UBP14_HUMAN AURKB_HUMAN P54578 Q96GD4 USP14 AURKB MEDLINE 28662510 The Deubiquitinating Enzyme USP14 Regulates Leukemic Chemotherapy Drugs-Induced Cell Apoptosis by Suppressing Ubiquitination of Aurora Kinase B USP 1 Training data H.sapiens 87 ATX3_HUMAN BAD_HUMAN P54252 Q92934 ATXN3 BAD MEDLINE 28279784 28279784 Josephin 1 Training data H.sapiens 88 ATX3_HUMAN BAX_HUMAN P54252 Q07812 ATXN3 BAX MEDLINE 28279784 28279784 Josephin 1 Training data H.sapiens 89 UBP10_HUMAN AAPK1_HUMAN Q14694 Q13131 USP10 PRKAA1 MEDLINE 26876938 The deubiquitinase USP10 specifically removes ubiquitination on AMPKA to facilitate AMPKA phosphorylation by LKB1 USP 1 Other H.sapiens 90 UBP49_HUMAN FKBP5_HUMAN Q70CQ1 Q13451 USP49 FKBP5 MEDLINE 28363942 Mechanistically, USP49 deubiquitinates and stabilizes FKBP51, which in turn enhances PHLPP's capability to dephosphorylate AKT Furthermore, USP49 inhibited pancreatic cancer cell proliferation and enhanced cellular response to gemcitabine in a FKBP51-AKT-dependent manner. USP 1 Training data H.sapiens 91 UBP18_HUMAN NEMO_HUMAN Q9UMW8 Q9Y6K9 USP18 IKBKG MEDLINE 26240016 USP18 negatively regulates NF-kappaB signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms USP 1 Training data H.sapiens 92 ATX3_HUMAN BECN1_HUMAN P54252 Q14457 ATXN3 BECN1 MEDLINE 28445460 28445460 Josephin 1 Other H.sapiens 93 UBP48_HUMAN GLI1_HUMAN Q86UV5 P08151 USP48 GLI1 MEDLINE 28623188 Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1 USP 1 Training data H.sapiens 94 UBP49_HUMAN FKBP4_HUMAN Q70CQ1 Q02790 USP49 FKBP4 MEDLINE 28363942 Mechanistically, USP49 deubiquitinates and stabilizes FKBP51, which in turn enhances PHLPP's capability to dephosphorylate AKT Furthermore, USP49 inhibited pancreatic cancer cell proliferation and enhanced cellular response to gemcitabine in a FKBP51-AKT-dependent manner. USP 1 Other H.sapiens 95 UBP19_HUMAN BECN1_HUMAN O94966 Q14457 USP19 BECN1 MEDLINE 26988033 USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1 USP 1 Training data H.sapiens 96 UBP7_HUMAN YAP1_HUMAN Q93009 P46937 USP7 YAP1 MEDLINE 30679505 Here, we show that Hippo pathway attenuates the binding of a ubiquitin-specific protease Usp7 to Yki, which regulates Hippo signaling through deubiquitinating Yki USP 1 Other H.sapiens 97 OTUB1_HUMAN ESR1_HUMAN Q96FW1 P03372 OTUB1 ESR1 UNIPROT UBP46_HUMAN Deubiquitinates estrogen receptor alpha (ESR1) OTU 1 Other H.sapiens 98 UBP11_HUMAN SPRTN_HUMAN P51784 Q9H040 USP11 SPRTN MEDLINE 33567341 USP11 mediates repair of DNA-protein crosslinks by deubiquitinating SPRTN metalloprotease USP 1 Other H.sapiens 99 UBP11_HUMAN BMI1_HUMAN P51784 P35226 USP11 BMI1 MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 100 PSDE_HUMAN GRB2_HUMAN O00487 P62993 PSMD14 GRB2 MEDLINE 31634528 PSMD14 inhibits degradation of GRB2 via deubiquitinating this oncoprotein in HCC cells JAMM 1 Other H.sapiens 101 UBP7_HUMAN BMI1_HUMAN Q93009 P35226 USP7 BMI1 MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 102 UBP15_HUMAN BMR1A_HUMAN Q9Y4E8 P36894 USP15 BMPR1A MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 103 USP9X_HUMAN EGLN3_HUMAN Q93008 Q9H6Z9 USP9X EGLN3 MEDLINE 34112167 USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1Bbeta via deubiquitinating EGLN3 USP 1 Other H.sapiens 104 UBP28_HUMAN BRAF_HUMAN Q96RU2 P15056 USP28 BRAF MEDLINE 29880484 Here, we demonstrate that the deubiquitinating enzyme USP28 functions through a feedback loop to destabilize RAF family members. USP 1 Training data H.sapiens 105 UBP15_HUMAN BRAP_HUMAN Q9Y4E8 Q7Z569 USP15 BRAP MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 106 BAP1_HUMAN BRCA1_HUMAN Q92560 P38398 BAP1 BRCA1 MEDLINE 25121098 BAP1 also controls G1/S cell cycle progression by regulating BRCA-1 [111], Ying Yang 1 (YY-1), and host cell factor 1 (HCF-1) UCH 1 Training data H.sapiens 107 CYLD_HUMAN SMAD7_HUMAN Q9NQC7 O15105 CYLD SMAD7 MEDLINE 24756567 This showed that CYLD can bind to SMAD7 and deubiquitinate SMAD7 at Lysine 360 and 374 residues, which are required for the activation of TAK1 and p38 signaling USP 1 Training data H.sapiens 108 UBP11_HUMAN BRCA2_HUMAN P51784 P51587 USP11 BRCA2 MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 109 UBP19_HUMAN GCR_HUMAN O94966 P04150 USP19 NR3C1 MEDLINE 29901692 Thus, USP19 modulates GR levels and in so doing may modulate both insulin and glucocorticoid signaling, two critical pathways that control protein turnover in muscle and overall glucose homeostasis. USP 1 Training data H.sapiens 110 UBP7_HUMAN EZH2_HUMAN Q93009 Q15910 USP7 EZH2 MEDLINE 32453339 USP7 deubiquitinates and stabilizes EZH2 in prostate cancer cells USP 1 Other H.sapiens 111 TNAP3_HUMAN RIPK2_HUMAN P21580 O43353 TNFAIP3 RIPK2 MEDLINE 26834734 Activation of RIPK2 depends on its K63 ubiquitination by E3 ligases, whereas the deubiquitinating enzyme A20 counter regulates RIPK2 activity by cleaving K63-polyubiquitin chains from RIPK2. OTU 1 Training data H.sapiens 112 CYLD_HUMAN RIPK2_HUMAN Q9NQC7 O43353 CYLD RIPK2 MEDLINE 26834734 CYLD-mediated K63 deubiquitination of RIPK2 resulted in an impaired activation of both NF-kappaB and ERK1/2 pathways, reduced production of proinflammatory cytokines interleukin-6 (IL-6), IL-12, anti-listerial reactive oxygen species (ROS) and nitric oxide (NO), and, finally, impaired pathogen control. USP 1 Training data H.sapiens 113 BAP1_HUMAN KLF5_HUMAN Q92560 Q13887 BAP1 KLF5 MEDLINE 26419610 BAP1 interacts directly with KLF5 and stabilizes KLF5 via deubiquitination UCH 1 Training data H.sapiens 114 UBP4_HUMAN RIPK1_HUMAN Q13107 Q13546 USP4 RIPK1 MEDLINE 23313255 USP4 directly interacts with receptor-interacting protein 1 (RIP1) and deubiquitinates K63-linked ubiquitination from RIP1 USP 1 Training data H.sapiens 115 U17L2_HUMAN BRD4_HUMAN Q6R6M4 O60885 USP17L2 BRD4 MEDLINE 30057199 Here, we demonstrate that the deubiquitinase DUB3 binds to BRD4 and promotes its deubiquitination and stabilization. USP 1 Training data H.sapiens 116 UBP7_HUMAN BUB3_HUMAN Q93009 O43684 USP7 BUB3 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 117 UBP20_HUMAN SNAI2_HUMAN Q9Y2K6 O43623 USP20 SNAI2 MEDLINE 32943575 Here, we conducted comprehensive gain- and loss-of-function screens using a human DUB cDNA library of 65 genes and an siRNA library of 98 genes, and identified USP20 as a deubiquitinase (DUB) that regulates SNAI2 ubiquitination and stability USP 1 Other H.sapiens 118 SNUT2_HUMAN ZEB1_HUMAN Q53GS9 P37275 USP39 ZEB1 MEDLINE 33649471 Deubiquitinase USP39 and E3 ligase TRIM26 balance the level of ZEB1 ubiquitination and thereby determine the progression of hepatocellular carcinoma USP 1 Other H.sapiens 119 UBP10_HUMAN KLF4_HUMAN Q14694 O43474 USP10 KLF4 MEDLINE 31748695 The deubiquitinase USP10 regulates KLF4 stability and suppresses lung tumorigenesis USP 1 Other H.sapiens 120 PSDE_HUMAN SNAI1_HUMAN O00487 O95863 PSMD14 SNAI1 MEDLINE 29331416 Furthermore, knockdown of PSMD14 significantly blocks SNAIL-induced EMT and then suppresses tumor cell migration and invasion in vitro and tumor metastasis in vivo. JAMM 1 Training data H.sapiens 121 UBP30_HUMAN MFN2_HUMAN Q70CQ3 O95140 USP30 MFN2 MEDLINE 29178074 USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and MFN2. USP 1 Training data H.sapiens 122 OTUB1_HUMAN BIRC2_HUMAN Q96FW1 Q13490 OTUB1 BIRC2 MEDLINE 23524849 Here, we describe the identification of OTUB1 as a c-IAP-associated deubiquitinating enzyme that regulates C-IAP1 stability. OTUB1 disassembles K48-linked polyubiquitin chains from C-IAP1 in vitro and in vivo within the TWEAK receptor-signalling complex. OTU 1 Training data H.sapiens 123 UBP5_HUMAN CAC1H_HUMAN P45974 O95180 USP5 CACNA1H MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 124 UBP15_HUMAN CASP3_HUMAN Q9Y4E8 P42574 USP15 CASP3 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 125 UBP5_HUMAN CTNB1_HUMAN P45974 P35222 USP5 CTNNB1 MEDLINE 30555744 Mechanistically, we found that USP5 deubiquitinated BETA-CATENIN, prevented ubiquitination mediated BETA-CATENIN degradation and promoted BETA-CATENIN nuclear accumulation, leading to the activation of Wnt/BETA-CATENIN signal pathway in NSCLC cells USP 1 Other H.sapiens 126 U17L2_HUMAN DDX58_HUMAN Q6R6M4 O95786 USP17L2 DDX58 MEDLINE 20368735 Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling. USP 1 Other H.sapiens 127 OTUD1_HUMAN SMUF1_HUMAN Q5VV17 Q9HCE7 OTUD1 SMURF1 MEDLINE 33361422 Furthermore, OTUD1 induced upregulation of the E3 ubiquitin ligase Smurf1 by deubiquitinating Smurf1, and Smurf1 degraded MAVS in MDBK cells in a ubiquitination-dependent manner, ultimately inhibiting IFN-I production OTU 1 Training data H.sapiens 128 TNAP3_HUMAN CASP8_HUMAN P21580 Q14790 TNFAIP3 CASP8 MEDLINE 25121098 Apo2L induces both K48 and K63-linked polyubiquitination of caspase 8 OTU 1 Training data H.sapiens 129 UBP13_HUMAN UBL4A_HUMAN Q92995 P11441 USP13 UBL4A MEDLINE 24424410 we identify USP13 as a gp78-associated DUB that eliminates ubiquitin conjugates from Ubl4A to maintain the functionality of Bag6 USP 1 Other H.sapiens 130 TRIM2_HUMAN SNAI1_HUMAN Q9C040 O95863 TRIM2 SNAI1 MEDLINE 32536816 TRIM2 directly deubiquitinates and stabilizes Snail1 protein, mediating proliferation and metastasis of lung adenocarcinoma Other 1 Other H.sapiens 131 UBP21_HUMAN FOXM1_HUMAN Q9UK80 Q08050 USP21 FOXM1 MEDLINE 30865895 USP21 increases the stability of FOXM1, and USP21 binds and deubiquitinates FOXM1 in vivo and in vitro, indicating a direct enzyme-substrate relationship USP 1 Other H.sapiens 132 U17L2_HUMAN LGMN_HUMAN Q6R6M4 Q99538 USP17L2 LGMN MEDLINE 24610907 We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90alpha to subsequently promote pro-AEP intracellular stability as well as secretion. USP 1 Other H.sapiens 133 UBP37_HUMAN CCNA2_HUMAN Q86T82 P20248 USP37 CCNA2 MEDLINE 25347529 Flow cytometry analysis of the HBx-expressing cells showed deregulation of cell cycle apparently due to the enhanced gene expression and stabilization of USP37 protein and deubiquitination of Cyclin A by USP37 USP 1 Training data H.sapiens 134 UBP26_HUMAN SMAD7_HUMAN Q9BXU7 O15105 USP26 SMAD7 MEDLINE 28381482 USP26 regulates TGF-b signaling by deubiquitinating and stabilizing SMAD7 USP 1 Other H.sapiens 135 UBP14_HUMAN CCNB1_HUMAN P54578 P14635 USP14 CCNB1 MEDLINE 31474315 CyclinB1 deubiquitination by USP14 regulates cell cycle progression in breast cancer USP 1 Other H.sapiens 136 UBP2_HUMAN CCND1_HUMAN O75604 P24385 USP2 CCND1 MEDLINE 26643174 Usp2 is a deubiquitination enzyme targeting various factors including CyclinD1 in cancer cells and PTH receptor 1 in osteoblasts USP 1 Training data H.sapiens 137 UBP44_HUMAN MD2L1_HUMAN Q9H0E7 Q13257 USP44 MAD2L1 MEDLINE 25121098 USP39 deubiquitinates aurora B kinase maintaining spindle assembly checkpoint integrity [103] while USP44 stabilizes Mad2/Cdc20 complex inhibiting premature activation of the APC/CCdh1 complex USP 1 Training data H.sapiens 138 UBP28_HUMAN CCNE1_HUMAN Q96RU2 P24864 USP28 CCNE1 MEDLINE 26410034 . This study pointed towards USP28 as an oncogene, potentially acting via stabilisation of c-Myc and cyclin E1. USP 1 Training data H.sapiens 139 UBP25_HUMAN TCPD_HUMAN Q9UHP3 P50991 USP25 CCT4 MEDLINE 25755282 USP25 catalyzed deubiquitination of the TRiC protein and stabilized the chaperonin, thereby reducing accumulation of misfolded polyglutamine protein aggregates. USP 1 Training data H.sapiens 140 OTU7B_HUMAN CDC16_HUMAN Q6GQQ9 Q13042 OTUD7B CDC16 MEDLINE 29973362 Here, we demonstrate that Cezanne/OTUD7B is a cell cycle-regulated DUB that opposes the ubiquitination of APC/C targets. OTU 1 Training data H.sapiens 141 MINY1_HUMAN YAP1_HUMAN Q8N5J2 P46937 MINDY1 YAP1 MEDLINE 34315490 CONCLUSION: In general, our findings establish a previously undocumented catalytic role for MINDY1 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of bladder cancer. MINDY 1 Other H.sapiens 142 UBP47_HUMAN CADH1_HUMAN Q96K76 P12830 USP47 CDH1 MEDLINE 29080116 USP47 can be recruited to AJs and suppress the ubiquitination of E-cadherin, thus inhibiting its resultant proteasomal degradation USP 1 Training data H.sapiens 143 JOS1_HUMAN SOCS1_HUMAN Q15040 O15524 JOSD1 SOCS1 MEDLINE 28355105 JOSD1 Negatively Regulates Type-I Interferon Antiviral Activity by Deubiquitinating and Stabilizing SOCS1 Josephin 1 Other H.sapiens 144 EIF3H_HUMAN SNAI1_HUMAN O15372 O95863 EIF3H SNAI1 MEDLINE 32867821 Moreover, we identified EIF3H as a novel deubiquitinating enzyme of Snail JAMM 1 Other H.sapiens 145 BRCC3_HUMAN JAK2_HUMAN P46736 O60674 BRCC3 JAK2 MEDLINE 30755420 Endogenous JAK2 and phospho-JAK2 were rapidly K63-ubiquitinated upon TPO stimulation, and this action was augmented in cells depleted of the BRISC core components KIAA0157, MERIT40, or BRCC36 JAMM 1 Other H.sapiens 146 USP9X_HUMAN CADH1_HUMAN Q93008 P12830 USP9X CDH1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 147 UBP37_HUMAN CDN1B_HUMAN Q86T82 P46527 USP37 CDKN1B MEDLINE 22665064 Ectopically expressed wild-type USP37 formed a complex with p27, promoted its deubiquitination and stabilization and blocked cell proliferation. USP 1 Training data H.sapiens 148 TNAP3_HUMAN RIPK3_HUMAN P21580 Q9Y572 TNFAIP3 RIPK3 MEDLINE 32599618 Mechanistically, ABIN3 is rapidly recruited to the TNF-RSC complex, which interacts and coordinates with deubiquitinating enzyme A20 to control the K63 deubiquitination modification and subsequent activation of the critical necroptosis kinase, RIPK3, to suppress necroptosis OTU 1 Training data H.sapiens 149 USP9X_HUMAN PEX5_HUMAN Q93008 P50542 USP9X PEX5 MEDLINE 26367801 In addition, PEX5P can be deubiquitinated by the deubiquitinase USP9X USP 1 Training data H.sapiens 150 UBP10_HUMAN CFTR_HUMAN Q14694 P13569 USP10 CFTR MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 151 PAN2_HUMAN CTIP_HUMAN Q504Q3 Q99708 PAN2 RBBP8 MEDLINE 33097710 Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847 USP 1 Other H.sapiens 152 UBP7_HUMAN CHK1_HUMAN Q93009 O14757 USP7 CHEK1 MEDLINE 31601781 31601781 USP 1 Training data H.sapiens 153 UBP4_HUMAN TRAF2_HUMAN Q13107 Q12933 USP4 TRAF2 MEDLINE 22029577 Ubiquitin-specific protease 4 (USP4) targets TRAF2 and TRAF6 for deubiquitination and inhibits TNFalpha-induced cancer cell migration USP 1 Training data H.sapiens 154 UCHL1_HUMAN NTRK2_HUMAN P09936 Q16620 UCHL1 NTRK2 MEDLINE 28500221 Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory via Its Deubiquitinating Effect on TrkB UCH 1 Training data H.sapiens 155 UBP8_HUMAN S22A6_HUMAN P40818 Q4U2R8 USP8 SLC22A6 MEDLINE 32818533 Results We demonstrated that USP8 overexpression in hOAT1-expressing cells led to an increased hOAT1 transporter activity and expression, which correlated well with a reduced hOAT1 ubiquitination USP 1 Other H.sapiens 156 BAP1_HUMAN HCFC1_HUMAN Q92560 P51610 BAP1 HCFC1 MEDLINE 29069806 The tumor suppressor BAP1 associates with ASXL1/2 to form the core Polycomb complex PR-DUB, which catalyzes the removal of mono-ubiquitin from several substrates including histone H2A. This complex also mediates the poly-deubiquitination of HCFC1, OGT and PCG1-alpha, preventing them from proteasomal degradation. UCH 1 Training data H.sapiens 157 OTUL_HUMAN ATG13_HUMAN Q96BN8 O75143 OTULIN ATG13 MEDLINE 32543267 Together, our study provides evidence that LUBAC and OTULIN cooperatively regulate autophagy initiation and autophagosome maturation by mediating the linear ubiquitination and the stabilization of ATG13. Other 1 Other H.sapiens 158 ATX3_HUMAN IF4G2_HUMAN P54252 P78344 ATXN3 EIF4G2 MEDLINE 17000876 We present evidence that atx3 may promote p97-associated deubiquitination to facilitate the transfer of polypeptides from p97 to the proteasome Josephin 1 Other H.sapiens 159 UBP46_HUMAN HGFL_HUMAN P62068 P26927 USP46 MST1 MEDLINE 34029571 Moreover, USP46 acts as a deubiquitinating enzyme of MST1 to potentiate MST1 kinase activity to suppress tumor growth and metastasis, indicating that USP46 activation may represent a potential treatment strategy for HCC. USP 1 Other H.sapiens 160 UBP8_HUMAN SHAN3_HUMAN P40818 Q9BYB0 USP8 SHANK3 MEDLINE 29735556 USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels USP 1 Training data H.sapiens 161 UBP33_HUMAN PPM1A_HUMAN Q8TEY7 P35813 USP33 PPM1A MEDLINE 30308513 USP33 could deubiquitinate PPM1A (protein phosphatase, Mg2+/Mn2 + dependent 1A), a phosphatase for Smad2/3 USP 1 Other H.sapiens 162 UBP4_HUMAN PDPK1_HUMAN Q13107 O15530 USP4 PDPK1 MEDLINE 22347420 By screening a library of ubiquitin proteases, we further identify the Ubiquitin-Specific Protease 4 (USP4) as an enzyme that removes ubiquitin from PDK1 in vivo and in vitro and co-localizes with PDK1 at the plasma membrane when the two proteins are overexpressed, indicating direct deubiquitination. USP 1 Training data H.sapiens 163 TNAP3_HUMAN TRAF6_HUMAN P21580 Q9Y4K3 TNFAIP3 TRAF6 MEDLINE 25121098 The targets of A20-mediated deubiquitination are K63-linked ubiquitinated TRAF6 and RIP1 OTU 1 Training data H.sapiens 164 CYLD_HUMAN BCL3_HUMAN Q9NQC7 P20749 CYLD BCL3 MEDLINE 26763122 In this region, CYLD associates with its substrate Bcl-3 and prevents the nuclear localization of Bcl3 USP 1 Training data H.sapiens 165 UBP13_HUMAN MYC_HUMAN Q92995 P01106 USP13 MYC MEDLINE 27923907 In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP 1 Other H.sapiens 166 UBP25_HUMAN CD3D_HUMAN Q9UHP3 P04234 USP25 CD3D MEDLINE 22590560 Thus, the ability of USP25 to both bind and cleave ubiquitin appears to be required to exert the rescue effect on CD3DELTA. USP 1 Other H.sapiens 167 UBP28_HUMAN CHK2_HUMAN Q96RU2 O96017 USP28 CHEK2 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 168 UBP7_HUMAN CHFR_HUMAN Q93009 Q96EP1 USP7 CHFR MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 169 UCHL3_HUMAN SMAD1_HUMAN P15374 Q15797 UCHL3 SMAD1 MEDLINE 21453705 Ubiquitin C-terminal hydrolase-L3 regulates Smad1 ubiquitination and osteoblast differentiation UCH 1 Other H.sapiens 170 USP9X_HUMAN CP131_HUMAN Q93008 Q9UPN4 USP9X CEP131 MEDLINE 30319415 USP9X can also regulate and stabilize CEP131, a centriolar satellite protein, ultimately promoting breast carcinogenesis, indicating that USP9X is a significant regulator of centrosome biogenesis and revealing a critical role for the USP9X/CEP131 axis in breast carcinogenesis USP 1 Training data H.sapiens 171 UCHL5_HUMAN PRP19_HUMAN Q9Y5K5 Q9UMS4 UCHL5 PRPF19 MEDLINE 23220010 Ubiquitin C-terminal Hydrolase 37, a novel predictor for hepatocellular carcinoma recurrence, promotes cell migration and invasion via interacting and deubiquitinating PRP19. UCH 1 Other H.sapiens 172 UBP10_HUMAN KSYK_HUMAN Q14694 P43405 USP10 SYK MEDLINE 32015510 Here, we validated USP10 as a DUB that stabilises SYK by showing that targeted loss of USP10 by genetic KO or KD leads to ubiquitin-mediated degradation of SYK protein in AML cells, with no effect on SYK transcription USP 1 Other H.sapiens 173 UBP37_HUMAN SNAI1_HUMAN Q86T82 O95863 USP37 SNAI1 MEDLINE 31998374 USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein via Deubiquitination USP 1 Other H.sapiens 174 UCHL5_HUMAN NOS2_HUMAN Q9Y5K5 P35228 UCHL5 NOS2 MEDLINE 20634424 In this study, we show that Rpn13 is involved in iNOS degradation and is required for iNOS interaction with the deubiquitination protein UCH37. UCH 1 Training data H.sapiens 175 UBP11_HUMAN IKKA_HUMAN P51784 O15111 USP11 CHUK MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 176 UBP15_HUMAN IKKA_HUMAN Q9Y4E8 O15111 USP15 CHUK MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 177 OTUD1_HUMAN YAP1_HUMAN Q5VV17 P46937 OTUD1 YAP1 MEDLINE 29891922 Here, we report that YAP is subject to non-proteolytic, K63-linked polyubiquitination by the SCFSKP2 E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1 OTU 1 Training data H.sapiens 178 USP9X_HUMAN KDM4C_HUMAN Q93008 Q9H3R0 USP9X KDM4C MEDLINE 33558705 Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C USP 1 Other H.sapiens 179 UBP7_HUMAN UVSSA_HUMAN Q93009 Q2YD98 USP7 UVSSA MEDLINE 29323787 The central region of UVSSA, which contains the tumor necrosis factor receptor-associated factor (TRAF)-binding motif, is required for the interaction with the N-terminal TRAF domain of USP7. Here, we showed that UVSSA is mono-ubiquitinated in vitro and identified a lysine residue (Lys414 ) in UVSSA as the target of ubiquitination. The deubiquitination activity of USP7 was inhibited by the ubiquitin-conjugating enzyme UbcH6. Lys414 was also modified by poly-ubiquitin chains in vivo. USP 1 Other H.sapiens 180 UBP29_HUMAN CLSPN_HUMAN Q9HBJ7 Q9HAW4 USP29 CLSPN MEDLINE 24632611 USP29 controls the stability of checkpoint adaptor Claspin by deubiquitination USP 1 Training data H.sapiens 181 UBP14_HUMAN CXCR4_HUMAN P54578 P61073 USP14 CXCR4 MEDLINE 19106094 Co-localization of CXCR4 and USP14 also is time-dependent following CXCL12 stimulation USP 1 Training data H.sapiens 182 UBP28_HUMAN CLSPN_HUMAN Q96RU2 Q9HAW4 USP28 CLSPN MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 183 UBP13_HUMAN NLRP3_HUMAN Q92995 Q96P20 USP13 NLRP3 MEDLINE 33243234 Moreover, we demonstrated that USP13 is a key enzyme for Paxillin-mediated NLRP3 deubiquitination upon ATP treatment USP 1 Other H.sapiens 184 UBP26_HUMAN SNAI1_HUMAN Q9BXU7 O95863 USP26 SNAI1 MEDLINE 30763716 In this study, we screened a DUB library and found USP26 is a potent deubiquitinase mediating Snail stabilization USP 1 Other H.sapiens 185 UBP5_HUMAN TRAF6_HUMAN P45974 Q9Y4K3 USP5 TRAF6 MEDLINE 32214906 In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6 USP 1 Other H.sapiens 186 UBP20_HUMAN CLSPN_HUMAN Q9Y2K6 Q9HAW4 USP20 CLSPN MEDLINE 25355518 USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling USP 1 Training data H.sapiens 187 UBP3_HUMAN CLSPN_HUMAN Q9Y6I4 Q9HAW4 USP3 CLSPN MEDLINE 31900278 Moreover, we found that Smo reduced Claspin polyubiquitination and proteasomal degradation by promoting USP3 transcription USP 1 Other H.sapiens 188 PCDB3_HUMAN NFKB1_HUMAN Q9Y5E6 P19838 PCDHB3 NFKB1 MEDLINE 29537081 The tumor-suppressive effects of PCDHB3 are partially due to inhibition of NF-kappaB transcriptional activity through K63 deubiquitination of p50 at lysine 244/252, which increases the binding affinity of inactive p50 homodimer to kappaB DNA, resulting in competitive inhibition of the transcription of NF-kappaB target genes by p65 dimers. Other 1 Training data H.sapiens 189 UBP7_HUMAN CLSPN_HUMAN Q93009 Q9HAW4 USP7 CLSPN MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 190 CYLD_HUMAN NR2C2_HUMAN Q9NQC7 P49116 CYLD NR2C2 MEDLINE 26763122 Other identified CYLD substrates include TNF receptor associated factor 7 (TRAF7), TRAF interacting protein (TRIP), transforming growth factor beta-activated kinase 1 (TAK1), NF-kappa-B essential modifier (NEMO), lymphocyte cell specific protein-tyrosine kinase (LCK), receptor-interacting protein 1 (RIP1), retinoic acid inducible gene (RIG), and polo-like kinase 1 (PLK1) USP 1 Training data H.sapiens 191 UBP7_HUMAN CNBP1_HUMAN Q93009 Q9NSA3 USP7 CTNNBIP1 MEDLINE 29045831 29045831 USP 1 Other H.sapiens 192 OTUD4_HUMAN XPC_HUMAN Q01804 Q01831 OTUD4 XPC MEDLINE 24366067 Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. OTU 1 Other H.sapiens 193 UCHL1_HUMAN IL8_HUMAN P09936 P10145 UCHL1 CXCL8 MEDLINE 30305579 It was showed that UCH-L1 over-expression inhibited NF-kappaB activation and decrease IL-6 and IL-8 levels, while knockdown of it enhanced NF-kappaB activation and increase IL-6 and IL-8 levels during TNF-alpha treatment. UCH 1 Training data H.sapiens 194 UBP7_HUMAN DAXX_HUMAN Q93009 Q9UER7 USP7 DAXX MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 195 UBP25_HUMAN TRAF6_HUMAN Q9UHP3 Q9Y4K3 USP25 TRAF6 MEDLINE 23042150 Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act2. USP 1 Other H.sapiens 196 CSN5_HUMAN PD1L1_HUMAN Q92905 Q9NZQ7 COPS5 CD274 MEDLINE 27866850 Deubiquitination and Stabilization of PD-L1 by CSN5 JAMM 1 Training data H.sapiens 197 UBP15_HUMAN RORG_HUMAN Q9Y4E8 P51449 USP15 RORC MEDLINE 27430721 Knockdown of USP15 or expression of inactive USP15 impaired Th17 differentiation, suggesting a positive role for USP15-mediated deubiquitination of RORGAMMAT in Th17 differentiation. USP 1 Training data H.sapiens 198 UBP11_HUMAN TGFR2_HUMAN P51784 P37173 USP11 TGFBR2 MEDLINE 29724812 Together, these data suggest that deubiquitination of TGFBR2 by USP11 effectively spares TGFBR2 from proteasomal degradation to promote EMT and metastasis. USP 1 Training data H.sapiens 199 USP9X_HUMAN DDI1_HUMAN Q93008 Q8WTU0 USP9X DDI1 MEDLINE 31130875 31130875 USP 1 Other H.sapiens 200 UBP13_HUMAN UIMC1_HUMAN Q92995 Q96RL1 USP13 UIMC1 MEDLINE 28569838 USP13, in turn, deubiquitinates RAP80 and promotes RAP80 recruitment and proper DDR. USP 1 Training data H.sapiens 201 UBP21_HUMAN DDX58_HUMAN Q9UK80 O95786 USP21 DDX58 MEDLINE 27341175 Another study demonstrated that USP21 deubiquitinates RIG-1, an essential protein in antiviral immune defense. USP 1 Training data H.sapiens 202 CYLD_HUMAN DLG4_HUMAN Q9NQC7 P78352 CYLD DLG4 MEDLINE 28973854 CYLD-mediated PSD-95 deubiquitination, mobilizing and depleting PSD-95 from synapses. USP 1 Training data H.sapiens 203 UBP7_HUMAN DNMT1_HUMAN Q93009 P26358 USP7 DNMT1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 204 UBP14_HUMAN DVL2_HUMAN P54578 O14641 USP14 DVL2 MEDLINE 23958854 Usp14 deubiquitinates K63-linked polyubiquitin chains of Dvl USP 1 Training data H.sapiens 205 USP9X_HUMAN BMAL1_HUMAN Q93008 O00327 USP9X ARNTL MEDLINE 29626158 Here, we use affinity purification and mass spectrometry analysis to identify probable ubiquitin carboxyl-terminal hydrolase FAF-X (USP9X) as an interacting protein of the core clock protein aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL or BMAL1). USP 1 Training data H.sapiens 206 UBP7_HUMAN MARH7_HUMAN Q93009 Q9H992 USP7 MARCHF7 MEDLINE 29080116 It has been proposed that USP7 may reverse self-ubiquitination of the Ub E3 ligase MARCH7, thus stabilizing MARCH7 which has been known to regulate the expression levels of E-cadherin and beta-catenin USP 1 Training data H.sapiens 207 OTU7B_HUMAN EGFR_HUMAN Q6GQQ9 P00533 OTUD7B EGFR MEDLINE 25121098 USP21 and Cezanne or OTUD7B negatively regulate NFkappaB signaling by deubiquitinating and inactivating RIP1 upon TNF-alpha stimulation, providing a feedback loop in the proinflammatory signaling OTU 1 Training data H.sapiens 208 UBP10_HUMAN SL9A3_HUMAN Q14694 P48764 USP10 SLC9A3 MEDLINE 33095475 Ubiquitin-specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity USP 1 Other H.sapiens 209 UBP8_HUMAN EGFR_HUMAN P40818 P00533 USP8 EGFR MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 210 USP9X_HUMAN IF4B_HUMAN Q93008 P23588 USP9X EIF4B MEDLINE 29228324 USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1 USP 1 Training data H.sapiens 211 CYLD_HUMAN ARHGC_HUMAN Q9NQC7 Q9NZN5 CYLD ARHGEF12 MEDLINE 23405219 Mechanistically, CYLD does not interact with RhoA; instead, it interacts with and deubiquitinates leukemia-associated RhoGEF (LARG). USP 1 Training data H.sapiens 212 BRCC3_HUMAN NLRP3_HUMAN P46736 Q96P20 BRCC3 NLRP3 MEDLINE 32941940 CONCLUSION: BRCC3 and JOSD2 mediate NLRP3-R779C deubiquitination, which promotes NLRP3 inflammasome activation and the risk of developing VEOIBD. JAMM 1 Training data H.sapiens 213 OTUD3_HUMAN P53_HUMAN Q5T2D3 P04637 OTUD3 TP53 MEDLINE 32571254 Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells OTU 1 Other H.sapiens 214 UBP14_HUMAN ELOV6_HUMAN P54578 Q9H5J4 USP14 ELOVL6 MEDLINE 30425250 Among the potential substrates identified, we show that fatty acid synthase (FASN), a key enzyme involved in hepatic lipogenesis, is a bona fide substrate of USP14. USP 1 Training data H.sapiens 215 UBP2_HUMAN ELOV6_HUMAN O75604 Q9H5J4 USP2 ELOVL6 MEDLINE 29449607 In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP 1 Training data H.sapiens 216 UBP7_HUMAN ERCC6_HUMAN Q93009 Q03468 USP7 ERCC6 MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 217 UBP7_HUMAN ERR1_HUMAN Q93009 P11474 USP7 ESRRA MEDLINE 31518603 Deubiquitination and stabilization of estrogen receptor alpha by UBIQUITIN-SPECIFIC PROTEASE 7 promotes breast tumorigenesis USP 1 Other H.sapiens 218 STABP_HUMAN PAR2_HUMAN O95630 P55085 STAMBP F2RL1 MEDLINE 19684015 Expression of the catalytically inactive mutants, AMSH(D348A) and UBPY(C786S), caused an increase in PAR(2) ubiquitination and trapped the receptor in early endosomes, thereby preventing lysosomal trafficking and degradation. Other 1 Training data H.sapiens 219 UBP7_HUMAN SIR7_HUMAN Q93009 Q9NRC8 USP7 SIRT7 MEDLINE 28655758 Ubiquitin-specific peptidase 7 (USP7)-mediated deubiquitination of the histone deacetylase SIRT7 regulates gluconeogenesis USP 1 Training data H.sapiens 220 UBP10_HUMAN TRAF6_HUMAN Q14694 Q9Y4K3 USP10 TRAF6 MEDLINE 25861989 We found TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-kappaB activation upon DNA damage. USP 1 Training data H.sapiens 221 UBP14_HUMAN ANDR_HUMAN P54578 P10275 USP14 AR MEDLINE 29353883 Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G0/G1 to S phase transition and inducing apoptosis. USP 1 Training data H.sapiens 222 UBP8_HUMAN PAR2_HUMAN P40818 P55085 USP8 F2RL1 MEDLINE 19684015 Expression of the catalytically inactive mutants, AMSH(D348A) and UBPY(C786S), caused an increase in PAR(2) ubiquitination and trapped the receptor in early endosomes, thereby preventing lysosomal trafficking and degradation. USP 1 Training data H.sapiens 223 UBP1_HUMAN FACD2_HUMAN O94782 Q9BXW9 USP1 FANCD2 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 224 ATX3_HUMAN KLF4_HUMAN P54252 O43474 ATXN3 KLF4 MEDLINE 31563563 Subsequent immunoprecipitation assays confirmed that ATXN3 bound to KLF4, mediating the deubiquitination and stabilization of KLF4 protein levels Josephin 1 Other H.sapiens 225 UBP7_HUMAN MYCN_HUMAN Q93009 P04198 USP7 MYCN MEDLINE 27618649 HAUSP deubiquitinates and stabilizes N-MYC in neuroblastoma USP 1 Training data H.sapiens 226 UBP22_HUMAN F16P1_HUMAN Q9UPT9 P09467 USP22 FBP1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 227 OTUB2_HUMAN TRAF3_HUMAN Q96DC9 Q13114 OTUB2 TRAF3 MEDLINE 19996094 Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6 OTU 1 Training data H.sapiens 228 UBP5_HUMAN FOXM1_HUMAN P45974 Q08050 USP5 FOXM1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 229 UBP4_HUMAN PRP31_HUMAN Q13107 Q8WWY3 USP4 PRPF31 MEDLINE 28088760 USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3 USP 1 Other H.sapiens 230 UBP7_HUMAN FOXO1_HUMAN Q93009 Q12778 USP7 FOXO1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 231 UBP7_HUMAN FOXO3_HUMAN Q93009 O43524 USP7 FOXO3 MEDLINE 25121098 USP7 deubiquitinates checkpoint with forkhead and RING finger domains protein (Chfr), which in turn ubiquitinates histone deacetylase 1 (HDAC1), leading to upregulation of p21Cip1/Waf1 and induction of G1 arrest USP 1 Training data H.sapiens 232 UBP15_HUMAN SMAD1_HUMAN Q9Y4E8 Q15797 USP15 SMAD1 MEDLINE 28245560 reports have suggested that USP15 acts as a key regulator of TGF-b receptor-signaling pathways by deubiquitinating the TGF-b receptor itself and its downstream transducers receptor-regulated SMADs (R-SMADs), including SMAD1, SMAD2, and SMAD3, thus activating the TGF-b target genes. USP 1 Other H.sapiens 233 UBP7_HUMAN FOXO4_HUMAN Q93009 P98177 USP7 FOXO4 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 234 ZRAN1_HUMAN HECD1_HUMAN Q9UGI0 Q9ULT8 ZRANB1 HECTD1 MEDLINE 33853758 The E3 ubiquitin ligase HECTD1 was then validated as a substrate of TRABID and used UbiCREST and Ub-AQUA proteomics to show that HECTD1 preferentially assembles K29- and K48-linked ubiquitin chains OTU 1 Other H.sapiens 235 UBP14_HUMAN GABR1_HUMAN P54578 Q9UBS5 USP14 GABBR1 MEDLINE 26817839 Post-endocytotic Deubiquitination and Degradation of the Metabotropic gamma-Aminobutyric Acid Receptor by the Ubiquitin-specific Protease 14 USP 1 Training data H.sapiens 236 UBP21_HUMAN GATA3_HUMAN Q9UK80 P23771 USP21 GATA3 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 237 UBP8_HUMAN NTRK1_HUMAN P40818 P04629 USP8 NTRK1 MEDLINE 28335430 Recent studies have attempted to identify the specific DUBs associated with TrkA, where Ceriani and collaborators described an interaction between TrkA and USP8 (USP-family) in PC12 cells USP 1 Training data H.sapiens 238 OTUB2_HUMAN GLI2_HUMAN Q96DC9 P10070 OTUB2 GLI2 MEDLINE 30241937 Here we have identified the eubiquitinating enzyme otubain2 (OTUB2) as a regulator of Gli2 protein degradation OTU 1 Other H.sapiens 239 USP9X_HUMAN GPSM1_HUMAN Q93008 Q86YR5 USP9X GPSM1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 240 UCHL3_HUMAN RAD51_HUMAN P15374 Q06609 UCHL3 RAD51 MEDLINE 27941124 UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2. UCH 1 Other H.sapiens 241 UBP8_HUMAN BACE1_HUMAN P40818 P56817 USP8 BACE1 MEDLINE 27302062 The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation USP 1 Training data H.sapiens 242 UBP13_HUMAN UBP10_HUMAN Q92995 Q14694 USP13 USP10 UNIPROT UBP28_HUMAN Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 USP 1 Other H.sapiens 243 UBP13_HUMAN SKP2_HUMAN Q92995 Q13309 USP13 SKP2 UNIPROT USP9Y_HUMAN Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and Ubp10 USP 1 Other H.sapiens 244 OTUB1_HUMAN UB2E1_HUMAN Q96FW1 P51965 OTUB1 UBE2E1 MEDLINE 30282802 OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination OTU 1 Training data H.sapiens 245 UBP8_HUMAN GRIA1_HUMAN P40818 P42261 USP8 GRIA1 MEDLINE 25505317 Synaptic Strength Is Bidirectionally Controlled by Opposing Activity-Dependent Regulation of Nedd4-1 and USP8 USP 1 Training data H.sapiens 246 UBP46_HUMAN GRIA1_HUMAN P62068 P42261 USP46 GRIA1 MEDLINE 26237995 This Editorial Highlight discusses the relevance of a study published in the current issue of Journal of Neurochemistry, in which the authors Huo and collaborators now identified ubiquitin-specific peptidase 46 (USP46) as a specific AMPAR deubiquitinase. USP 1 Training data H.sapiens 247 UBP15_HUMAN IKBA_HUMAN Q9Y4E8 P25963 USP15 NFKBIA UNIPROT UBP47_HUMAN regulates NF-kappa-B by mediating deubiquitination of NFKBIA USP 1 Other H.sapiens 248 UCHL1_HUMAN IL6_HUMAN P09936 P05231 UCHL1 IL6 MEDLINE 30305579 It was showed that UCH-L1 over-expression inhibited NF-kappaB activation and decrease IL-6 and IL-8 levels, while knockdown of it enhanced NF-kappaB activation and increase IL-6 and IL-8 levels during TNF-alpha treatment. UCH 1 Training data H.sapiens 249 UBP15_HUMAN SQSTM_HUMAN Q9Y4E8 Q13501 USP15 SQSTM1 UNIPROT UBP13_HUMAN Involved in endosome organization by mediating deubiquitination of SQSTM1 USP 1 Other H.sapiens 250 UCHL1_HUMAN NOX4_HUMAN P09936 Q9NPH5 UCHL1 NOX4 MEDLINE 25915537 These findings indicate that H2O2 levels regulated by UCH-L1 are necessary for cell invasion to occur and demonstrate that UCH-L1 promotes cell invasion by up-regulating H2O2 via deubiquitination of NOX4 UCH 1 Training data H.sapiens 251 UBP11_HUMAN NF2L2_HUMAN P51784 Q16236 USP11 NFE2L2 MEDLINE 33531626 We further found that USP11 deubiquitinates NRF2; this modification stabilizes NRF2 USP 1 Other H.sapiens 252 UBP15_HUMAN TBK1_HUMAN Q9Y4E8 Q9UHD2 USP15 TBK1 MEDLINE 32814047 Ubiquitin-Conjugating Enzyme 2S Enhances Viral Replication by Inhibiting Type I IFN Production through Recruiting USP15 to Deubiquitinate TBK1 USP 1 Other H.sapiens 253 UBP7_HUMAN FOXP3_HUMAN Q93009 Q9BZS1 USP7 FOXP3 MEDLINE 29352742 Furthermore, cambogin (10 muM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7-mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS-treated cells. USP 1 Training data H.sapiens 254 UBP18_HUMAN NR2C2_HUMAN Q9UMW8 P49116 USP18 NR2C2 MEDLINE 26240016 USP18 negatively regulates NF-kappaB signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms USP 1 Training data H.sapiens 255 OTU7B_HUMAN CTNB1_HUMAN Q6GQQ9 P35222 OTUD7B CTNNB1 MEDLINE 33599243 RNA-sequencing and biochemical studies showed that Cezanne drives VSMC proliferation by regulating CCN family member 1 (CCN1) by targeting BETA-CATENIN for deubiquitination OTU 1 Other H.sapiens 256 UBP3_HUMAN P53_HUMAN Q9Y6I4 P04637 USP3 TP53 MEDLINE 28807825 Depletion of USP3 lead to accelerated degradation of p53 in normal cells thereby enhanced cell proliferation and transformation USP 1 Training data H.sapiens 257 UBP33_HUMAN MYC_HUMAN Q8TEY7 P01106 USP33 MYC MEDLINE 33718387 USP33 could bind and deubiquitinate c-Myc USP 1 Other H.sapiens 258 UBP6_HUMAN NMDZ1_HUMAN P35125 Q05586 USP6 GRIN1 MEDLINE 31841517 The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability USP 1 Other H.sapiens 259 UBP7_HUMAN H2B2E_HUMAN Q93009 Q16778 USP7 H2BC21 MEDLINE 32884836 Here we present evidence that UHRF1 and USP7 oppositely control ubiquitination of histones H3 and H2B in S phase of the cell cycle and that DNMT1 binds both ubiquitinated H3 and H2B USP 1 Other H.sapiens 260 UBP15_HUMAN MFN2_HUMAN Q9Y4E8 O95140 USP15 MFN2 UNIPROT UBP15_HUMAN Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2 USP 1 Other H.sapiens 261 UBP28_HUMAN STAT3_HUMAN Q96RU2 P40763 USP28 STAT3 MEDLINE 30881015 Immunoprecipitation was performed to assess whether USP28 interacted with STAT3 or deubiquitinated STAT3 USP 1 Other H.sapiens 262 UBP11_HUMAN IF2B3_HUMAN P51784 O00425 USP11 IGF2BP3 MEDLINE 33594305 IGF2BP3 was protected by USP11 from degradation via deubiquitination USP 1 Other H.sapiens 263 UBP15_HUMAN TET2_HUMAN Q9Y4E8 Q6N021 USP15 TET2 MEDLINE 32948596 Here, we report that USP15 is a TET2 deubiquitinase and inhibitor USP 1 Other H.sapiens 264 UBP10_HUMAN SKP2_HUMAN Q14694 Q13309 USP10 SKP2 MEDLINE 31044085 Further investigations show that USP10 as a novel deubiquitinase of SKP2 amplifies the activation of Bcr-Abl via mediating deubiquitination and stabilization of SKP2 in CML cells USP 1 Other H.sapiens 265 UBP1_HUMAN ULK1_HUMAN O94782 O75385 USP1 ULK1 MEDLINE 30335599 Here, we identified USP1 (ubiquitin specific peptidase 1) as a key player in the modulation of ULK1 K63-linked deubiquitination USP 1 Other H.sapiens 266 UBP6_HUMAN NMD3A_MOUSE P35125 A2AIR5 USP6 Grin3a MEDLINE 31841517 USP6 deubiquitinates NMDAR at the PSD, thereby facilitating NMDAR stabilization, resulting in increased NMDAR function and synaptic activity and enhanced cognition. USP 1 Other H.sapiens 267 UBP8_HUMAN MCPH1_HUMAN P40818 Q8NEM0 USP8 MCPH1 MEDLINE 25733871 BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1 USP 1 Other H.sapiens 268 UBP4_HUMAN HDAC2_HUMAN Q13107 Q92769 USP4 HDAC2 MEDLINE 26411366 USP4 inhibits p53 and NF-kappaB through deubiquitinating and stabilizing HDAC2 USP 1 Other H.sapiens 269 BAP1_HUMAN H2AX_HUMAN Q92560 P16104 BAP1 H2AFX MEDLINE 28031783 28031783 UCH 1 Training data H.sapiens 270 U17L2_HUMAN H2AX_HUMAN Q6R6M4 P16104 USP17L2 H2AFX MEDLINE 28762656 Dub3 controls DNA damage signalling by direct deubiquitination of H2AX USP 1 Training data H.sapiens 271 BAP1_HUMAN OGT1_HUMAN Q92560 O15294 BAP1 OGT MEDLINE 29069806 The tumor suppressor BAP1 associates with ASXL1/2 to form the core Polycomb complex PR-DUB, which catalyzes the removal of mono-ubiquitin from several substrates including histone H2A. This complex also mediates the poly-deubiquitination of HCFC1, OGT and PCG1-alpha, preventing them from proteasomal degradation. UCH 1 Training data H.sapiens 272 USP9X_HUMAN CEP55_HUMAN Q93008 Q53EZ4 USP9X CEP55 MEDLINE 28620049 Collectively, our experiments identified USP9X as an integral component of the centrosome where it functions to stabilize PCM1 and CEP55 and promote centrosome biogenesis. USP 1 Training data H.sapiens 273 UBP10_HUMAN SNX3_HUMAN Q14694 O60493 USP10 SNX3 UNIPROT UBP10_HUMAN A two-hybrid screen identified sorting nexin 3 (SNX3) as a novel substrate of Usp10 USP 1 Other H.sapiens 274 UBP4_HUMAN PRPF3_HUMAN Q13107 O43395 USP4 PRPF3 MEDLINE 28088760 USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3 USP 1 Other H.sapiens 275 UBP5_HUMAN MAF_HUMAN P45974 O75444 USP5 MAF MEDLINE 28933784 Consistent with the high level of c-Maf protein in MM cells, USP5 was also highly expressed. USP 1 Training data H.sapiens 276 UBP14_HUMAN CTNB1_HUMAN P54578 P35222 USP14 CTNNB1 MEDLINE 29080116 Additionally, DUBs USP14, USP15, USP47, and Fam/USP9X have been reported to prevent BETA-CATENIN turnover by inhibiting its Ub-proteasomal degradation USP 1 Training data H.sapiens 277 CYLD_HUMAN AKT1_HUMAN Q9NQC7 P31749 CYLD AKT1 MEDLINE 23300340 We showed that CYLD was a DUB for Akt and suppressed growth factor-mediated ubiquitination and activation of Akt USP 1 Training data H.sapiens 278 CYLD_HUMAN CDN2C_HUMAN Q9NQC7 P42773 CYLD CDKN2C MEDLINE 33654169 In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein USP 1 Other H.sapiens 279 BAP1_HUMAN 1433T_HUMAN Q92560 P27348 BAP1 YWHAQ MEDLINE 29686263 The association between BAP1 and 14-3-3 protein releases the apoptotic inducer protein Bax from 14-3-3 and promotes cell death through the intrinsic apoptosis pathway UCH 1 Training data H.sapiens 280 UBP18_HUMAN M3K7_HUMAN Q9UMW8 O43318 USP18 MAP3K7 MEDLINE 26240016 USP18 negatively regulates NF-kappaB signaling by targeting TAK1 and NEMO for deubiquitination USP 1 Other H.sapiens 281 USP9X_HUMAN IRS2_HUMAN Q93008 Q9Y4H2 USP9X IRS2 MEDLINE 30338032 In a human prostate carcinoma cell line, small interfering RNA (siRNA)-mediated knockdown of USP9X reduced IGF-IR as well as IRS-2 protein levels and increased their ubiquitination USP 1 Other H.sapiens 282 UBP28_HUMAN P53_HUMAN Q96RU2 P04637 USP28 TP53 MEDLINE 27371829 its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo USP 1 Other H.sapiens 283 UBP11_HUMAN H2AX_HUMAN P51784 P16104 USP11 H2AFX MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 284 UBP3_HUMAN H2AX_HUMAN Q9Y6I4 P16104 USP3 H2AFX MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 285 MYSM1_HUMAN STING_HUMAN Q5VVJ2 Q86WV6 MYSM1 STING1 MEDLINE 33086059 MYSM1 subsequently interacts with STING and cleaves STING K63-linked ubiquitination to suppress cGAS-STING signaling JAMM 1 Other H.sapiens 286 BRCC3_HUMAN H2AX_HUMAN P46736 P16104 BRCC3 H2AFX MEDLINE 28778421 BRCA1/2-containing complex36 (BRCC36) is one of the DUBs which localizes at the site of DSBs as a part of the RAP80 complex and deubiquitinates RNF8-dependent H2AX ubiquitination JAMM 1 Training data H.sapiens 287 UBP10_HUMAN H2AZ_HUMAN Q14694 P0C0S5 USP10 H2AFZ MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 288 UBP19_HUMAN HDAC2_HUMAN O94966 Q92769 USP19 HDAC2 MEDLINE 27517492 USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability USP 1 Training data H.sapiens 289 UBP28_HUMAN HIF1A_HUMAN Q96RU2 Q16665 USP28 HIF1A MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 290 UBP3_HUMAN KLF5_HUMAN Q9Y6I4 Q13887 USP3 KLF5 MEDLINE 31624151 We demonstrated that USP3 interacts with KLF5 and stabilizes KLF5 via deubiquitination USP 1 Other H.sapiens 291 ATX3_HUMAN CHK1_HUMAN P54252 O14757 ATXN3 CHEK1 MEDLINE 28180282 Taken together, these findings reveal ATX3 to be a novel deubiquitinase of Chk1, providing a new mechanism of Chk1 stabilization in genome integrity maintenance. Josephin 1 Other H.sapiens 292 UBP8_HUMAN HIF1A_HUMAN P40818 Q16665 USP8 HIF1A MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 293 U17L2_HUMAN FACE2_HUMAN Q6R6M4 Q9Y256 USP17L2 RCE1 MEDLINE 19188362 we show that this effect is caused by the loss of RCE1 catalytic activity as a result of its deubiquitination by USP17 USP 1 Other H.sapiens 294 TNAP3_HUMAN CACO2_HUMAN P21580 Q13137 TNFAIP3 CALCOCO2 MEDLINE 26445063 NDP52 itself has to be activated by the E3 ligase TRAF6 via the attachment of Lys63-linked polyubiquitin chains. A20 counteracts the function of NDP52 in order to prevent an overactivation OTU 1 Training data H.sapiens 295 UBP18_HUMAN FTO_HUMAN Q9UMW8 Q9C0B1 USP18 FTO MEDLINE 33461172 In this study, we demonstrated that the post-translational deubiquitination by USP18 up-regulates the protein but not mRNA of FTO in bladder cancer tissues and cells USP 1 Other H.sapiens 296 CYLD_HUMAN NTRK1_HUMAN Q9NQC7 P04629 CYLD NTRK1 MEDLINE 28335430 Moreover, additional studies showed that CYLD specifically deubiquitinates polyubiquitin chains at K63 of different substrates (e.g., TRAF2 and TRAF6), or tyrosine kinase receptors such as TRKA. USP 1 Training data H.sapiens 297 UBP3_HUMAN CHK1_HUMAN Q9Y6I4 O14757 USP3 CHEK1 MEDLINE 29735693 Herein, we show that the K63-linked ubiquitin chain at CHK1's K132 residue has an inhibitory effect on the kinase activity. Furthermore, we demonstrate that this modification can be removed by ubiquitin-specific protease 3 (USP3), a deubiquitinating enzyme that targets K63-linked ubiquitin chains. USP 1 Training data H.sapiens 298 UBP7_HUMAN NOTC1_HUMAN Q93009 P46531 USP7 NOTCH1 MEDLINE 30224337 In turn, USP7 controls NOTCH1 levels through deubiquitination USP 1 Other H.sapiens 299 OTUB2_HUMAN LMBL1_HUMAN Q96DC9 Q9Y468 OTUB2 L3MBTL1 MEDLINE 24560272 Mechanistically, OTUB2 suppresses RNF8-mediated L3MBTL1 ubiquitination and Lys 63-linked ubiquitin chain formation in a deubiquitinating activity-dependent manner. OTU 1 Other H.sapiens 300 UBP48_HUMAN H2A1B_HUMAN Q86UV5 P04908 USP48 HIST1H2AE MEDLINE 29335415 USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A USP 1 Training data H.sapiens 301 BAP1_HUMAN H2A1_HUMAN Q92560 P0C0S8 BAP1 HIST1H2AM MEDLINE 28031783 28031783 UCH 1 Training data H.sapiens 302 BRCC3_HUMAN H2A1_HUMAN P46736 P0C0S8 BRCC3 HIST1H2AM MEDLINE 28031783 28031783 JAMM 1 Training data H.sapiens 303 MYSM1_HUMAN H2A1_HUMAN Q5VVJ2 P0C0S8 MYSM1 HIST1H2AM MEDLINE 28031783 28031783 JAMM 1 Training data H.sapiens 304 UBP28_HUMAN JUN_HUMAN Q96RU2 P05412 USP28 JUN MEDLINE 26410034 At present, the list of USP28 substrates shared with Fbw7 encompasses c-Myc, cyclin E1 [89], c-Jun, NICD1 [90], and HIF1 USP 1 Training data H.sapiens 305 OTUD3_HUMAN PTEN_HUMAN Q5T2D3 P60484 OTUD3 PTEN MEDLINE 26280536 Here, we report OTUD3 as a deubiquitylase of PTEN. OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN. OTU 1 Training data H.sapiens 306 UBP22_HUMAN H2A1_HUMAN Q9UPT9 P0C0S8 USP22 HIST1H2AM MEDLINE 26880980 USP22 was found to hydrolyze monoubiquitin tagged to uH2A and to antagonize PcG or hydrolyze monoubiquitin from uH2B to regulate MLL-trithorax-mediated trimethylation of histone H3 lysine-4 USP 1 Training data H.sapiens 307 UBP4_HUMAN RBL2_HUMAN Q13107 Q08999 USP4 RBL2 MEDLINE 25121098 USP4, reported as an oncogenic protein, is known to interact with the pocket proteins (Rb, p107, and p130) although no deubiquitinating activity has been reported USP 1 Training data H.sapiens 308 UBP51_HUMAN ZEB1_HUMAN Q70EK9 P37275 USP51 ZEB1 MEDLINE 29119051 By screening a human deubiquitinase library, we identified USP51 as a deubiquitinase that binds, deubiquitinates, and stabilizes ZEB1. USP 1 Training data H.sapiens 309 UBP26_HUMAN H2A1_HUMAN Q9BXU7 P0C0S8 USP26 HIST1H2AM MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 310 UBP16_HUMAN H2A1_HUMAN Q9Y5T5 P0C0S8 USP16 HIST1H2AM MEDLINE 28778421 USP3 and USP16 function to remove ubiquitin from histone H2A during the DDR USP 1 Training data H.sapiens 311 UBP37_HUMAN H2A1_HUMAN Q86T82 P0C0S8 USP37 HIST1H2AM MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 312 UBP49_HUMAN PTEN_HUMAN Q70CQ1 P60484 USP49 PTEN MEDLINE 31001918 Further studies indicated that USP49 deubiquitinated PTEN and stabilized PTEN protein, which suggested that USP49 inhibited PI3K/AKT signaling by stabilizing PTEN in NSCLC cells USP 1 Other H.sapiens 313 USP9X_HUMAN RICTR_HUMAN Q93008 Q6R327 USP9X RICTOR MEDLINE 33378666 USP9X removes Lys63-linked ubiquitin from RICTOR to promote its interaction with mTOR, thereby facilitating mTORC2 signaling USP 1 Other H.sapiens 314 UBP21_HUMAN H2A1_HUMAN Q9UK80 P0C0S8 USP21 HIST1H2AM MEDLINE 27190257 In this study, we report that H2Aub markedly decreases in hepatocellular carcinoma. Usp21, a H2A deubiquitinase, is probably responsible for decrease in H2Aub. USP 1 Training data H.sapiens 315 UBP44_HUMAN H2A1_HUMAN Q9H0E7 P0C0S8 USP44 HIST1H2AM MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 316 UBP15_HUMAN CTNB1_HUMAN Q9Y4E8 P35222 USP15 CTNNB1 MEDLINE 29080116 Additionally, DUBs USP14, USP15, USP47, and Fam/USP9X have been reported to prevent BETA-CATENIN turnover by inhibiting its Ub-proteasomal degradation USP 1 Training data H.sapiens 317 UBP12_HUMAN H2A1_HUMAN O75317 P0C0S8 USP12 HIST1H2AM MEDLINE 28063927 It was shown that USP12 deubiquitinates histones H2A and H2B both in vitro and in vivo USP 1 Training data H.sapiens 318 UBP3_HUMAN H2A1_HUMAN Q9Y6I4 P0C0S8 USP3 HIST1H2AM MEDLINE 28778421 USP3 and USP16 function to remove ubiquitin from histone H2A during the DDR USP 1 Training data H.sapiens 319 UBP18_HUMAN SNAI1_HUMAN Q9UMW8 O95863 USP18 SNAI1 MEDLINE 32742193 Conclusion: USP18 could promote the proliferation, migration, and invasion of colorectal cancer by deubiquitinating and stabilizing the Snail1 protein in colorectal cancer. USP 1 Other H.sapiens 320 UBP44_HUMAN F16P1_HUMAN Q9H0E7 P09467 USP44 FBP1 MEDLINE 31497353 USP44 suppresses pancreatic cancer progression and overcomes gemcitabine resistance by deubiquitinating FBP1 USP 1 Other H.sapiens 321 UBP5_HUMAN WT1_HUMAN P45974 P19544 USP5 WT1 MEDLINE 31845546 We further identified that USP5 deubiquitinated WT1 and stabilized its expression USP 1 Other H.sapiens 322 UBP10_HUMAN H2B1C_HUMAN Q14694 P62807 USP10 HIST1H2BI MEDLINE 29288197 The deubiquitinase (DUB) Ubp10 is thought to promote heterochromatic silencing by maintaining low H2B-Ub at sub-telomeres USP 1 Training data H.sapiens 323 UBP15_HUMAN H2B1C_HUMAN Q9Y4E8 P62807 USP15 HIST1H2BI MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 324 UBP3_HUMAN H2B1C_HUMAN Q9Y6I4 P62807 USP3 HIST1H2BI MEDLINE 17980597 Here we identify the ubiquitin-specific protease 3 USP3 as a deubiquitinating enzyme for uH2A and uH2B USP 1 Training data H.sapiens 325 UBP22_HUMAN H2B1C_HUMAN Q9UPT9 P62807 USP22 HIST1H2BI MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 326 CYLD_HUMAN TBK1_HUMAN Q9NQC7 Q9UHD2 CYLD TBK1 MEDLINE 18636086 CYLD removes polyubiquitin chains from RIG-I as well as from TANK binding kinase 1 (TBK1), the kinase that phosphorylates IRF3, coincident with an inhibition of the IRF3 signalling pathway. USP 1 Other H.sapiens 327 UBP42_HUMAN H2B1C_HUMAN Q9H9J4 P62807 USP42 HIST1H2BI MEDLINE 25336640 Depletion of USP42 increased H2B ubiquitylation at a model promoter and decreased both basal and induced transcription from a number of promoters USP 1 Training data H.sapiens 328 CYLD_HUMAN CNTN2_HUMAN Q9NQC7 Q02246 CYLD CNTN2 MEDLINE 21824392 RESULTS: We show here that the deubiquitinase CYLD physically interacts with Tax and negatively regulates the ubiquitination of this viral protein USP 1 Other H.sapiens 329 UBP21_HUMAN MP2K2_HUMAN Q9UK80 P36507 USP21 MAP2K2 MEDLINE 29706623 The deubiquitinase USP21 stabilizes MEK2 to promote tumor growth USP 1 Training data H.sapiens 330 UBP12_HUMAN MDM2_HUMAN O75317 Q00987 USP12 MDM2 MEDLINE 29755129 We find that USP12 deubiquitinates MDM2 and AR, which in turn controls the levels of the TP53 tumour suppressor and AR oncogene in prostate cancer. USP 1 Training data H.sapiens 331 OTU1_HUMAN ITCH_HUMAN Q5VVQ6 Q96J02 YOD1 ITCH MEDLINE 28416659 Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH stability OTU 1 Training data H.sapiens 332 OTUB1_HUMAN XCT_HUMAN Q96FW1 Q9UPY5 OTUB1 SLC7A11 MEDLINE 30709928 In this study, we utilized biochemial purification to identify the ubiquitin hydrolase OTUB1 as a key factor in modulating SLC7A11 stability OTU 1 Other H.sapiens 333 ZRAN1_HUMAN PK3C3_HUMAN Q9UGI0 Q8NEB9 ZRANB1 PIK3C3 MEDLINE 33637724 Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34 OTU 1 Other H.sapiens 334 U17L2_HUMAN MPIP1_HUMAN Q6R6M4 P30304 USP17L2 CDC25A UNIPROT UBP8_HUMAN mediates deubiquitination of CDC25A, preventing CDC25A degradation by the proteasome during the G1/S and G2/M phases promoting cell-cycle progression USP 1 Other H.sapiens 335 UBP22_HUMAN CSN5_HUMAN Q9UPT9 Q92905 USP22 COPS5 MEDLINE 32665011 Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination USP 1 Other H.sapiens 336 UBP27_HUMAN H2B1C_HUMAN A6NNY8 P62807 USP27X HIST1H2BI MEDLINE 27132940 In contrast, depletion of non-enzymatic components, ATXN7L3 or ENY2, results in increased H2Bub1. These observations led us to discover two H2Bub1 DUBs, USP27X and USP51, which function independently of SAGA and compete with USP22 for ATXN7L3 and ENY2 for activity. USP 1 Training data H.sapiens 337 UBP7_HUMAN H2B1C_HUMAN Q93009 P62807 USP7 HIST1H2BI MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 338 UBP49_HUMAN H2B1C_HUMAN Q70CQ1 P62807 USP49 HIST1H2BI MEDLINE 23824326 USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing USP 1 Training data H.sapiens 339 USP9X_HUMAN RN115_HUMAN Q93008 Q9Y4L5 USP9X RNF115 MEDLINE 30689267 Conversely, overexpression of USP9X resulted in an accumulation of RNF115 protein, accompanied by a decrease in its ubiquitination USP 1 Other H.sapiens 340 U17LO_HUMAN HDAC2_HUMAN Q0WX57 Q92769 USP17L30 HDAC2 MEDLINE 26617781 USP17-mediated deubiquitination and stabilization of HDAC2 in cigarette smoke extract-induced inflammation USP 1 Training data H.sapiens 341 U17LO_HUMAN RORG_HUMAN Q0WX57 P51449 USP17L30 RORC MEDLINE 25070893 The E3 deubiquitinase USP17 is a positive regulaTOR of retinoic acid-related orphan nuclear recepTOR gammat (RORgammat) in Th17 cells USP 1 Training data H.sapiens 342 CYLD_HUMAN MIB2_HUMAN Q9NQC7 Q96AX9 CYLD MIB2 MEDLINE 25565632 To dissect CYLD function we used a proteomics approach to identify CYLD interacting proteins and identified MIB2, an ubiquitin ligase enzyme involved in Notch signalling, as a protein which interacts with CYLD USP 1 Other H.sapiens 343 U17LO_HUMAN SDS3_HUMAN Q0WX57 Q9H7L9 USP17L30 SUDS3 MEDLINE 21239494 The deubiquitinating activity of USP17 on SDS3 negatively regulates SDS3-associated HDAC activity USP 1 Training data H.sapiens 344 UBP12_HUMAN H2B1C_HUMAN O75317 P62807 USP12 HIST1H2BI MEDLINE 28063927 It was shown that USP12 deubiquitinates histones H2A and H2B both in vitro and in vivo USP 1 Training data H.sapiens 345 UBP51_HUMAN H2B1C_HUMAN Q70EK9 P62807 USP51 HIST1H2BI MEDLINE 27132940 In contrast, depletion of non-enzymatic components, ATXN7L3 or ENY2, results in increased H2Bub1. These observations led us to discover two H2Bub1 DUBs, USP27X and USP51, which function independently of SAGA and compete with USP22 for ATXN7L3 and ENY2 for activity. USP 1 Training data H.sapiens 346 BAP1_HUMAN H2A2A_HUMAN Q92560 Q6FI13 BAP1 HIST2H2AA4 MEDLINE 30202049 30202049 UCH 1 Other H.sapiens 347 TNAP3_HUMAN BECN1_HUMAN P21580 Q14457 TNFAIP3 BECN1 MEDLINE 26445063 However, this TRAF6-dependent polyubiquitination of BECLIN 1 is antagonized by the deubiquitinase A20 OTU 1 Training data H.sapiens 348 U17LO_HUMAN FACE2_HUMAN Q0WX57 Q9Y256 USP17L30 RCE1 MEDLINE 19188362 Furthermore, we show that this effect is caused by the loss of RCE1 catalytic activity as a result of its deubiquitination by USP17. USP 1 Training data H.sapiens 349 UBP25_HUMAN MALD2_HUMAN Q9UHP3 Q8N4S9 USP25 MARVELD2 MEDLINE 25755282 USP25 catalyzed deubiquitination of the TRiC protein and stabilized the chaperonin, thereby reducing accumulation of misfolded polyglutamine protein aggregates. 0.75 USP 1 Other H.sapiens 350 UBP44_HUMAN STING_HUMAN Q9H0E7 Q86WV6 USP44 STING1 MEDLINE 31968013 USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA USP 1 Other H.sapiens 351 UBP22_HUMAN PD1L1_HUMAN Q9UPT9 Q9NZQ7 USP22 CD274 MEDLINE 31399419 USP22 Deubiquitinates CD274 to Suppress Anticancer Immunity USP 1 Other H.sapiens 352 UBP48_HUMAN H2A2A_HUMAN Q86UV5 Q6FI13 USP48 HIST2H2AA4 MEDLINE 29335415 USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A USP 1 Other H.sapiens 353 UBP12_HUMAN H2A2C_HUMAN O75317 Q16777 USP12 HIST2H2AC MEDLINE 21183687 USP12 and USP46 prefer nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and in vivo USP 1 Other H.sapiens 354 UBP11_HUMAN E2F1_HUMAN P51784 Q01094 USP11 E2F1 MEDLINE 28992046 Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene expression and activate lung epithelial cells USP 1 Training data H.sapiens 355 UBP29_HUMAN H2A2C_HUMAN Q9HBJ7 Q16777 USP29 HIST2H2AC MEDLINE 23615962 Both USP44 and USP29 promoted efficient deubiquitylation of histone H2A USP 1 Other H.sapiens 356 UBP20_HUMAN TRAF6_HUMAN Q9Y2K6 Q9Y4K3 USP20 TRAF6 MEDLINE 26839314 With purified proteins and in intact cells, our protein interaction studies showed that TRAF6/USP20 association and subsequent USP20-mediated TRAF6 deubiquitination were beta-arrestin2-dependent. USP 1 Training data H.sapiens 357 UBP19_HUMAN LRP6_HUMAN O94966 O75581 USP19 LRP6 MEDLINE 27751231 We show that folding of the Wnt signaling coreceptor LRP6 is promoted by ubiquitination of a specific lysine, retaining it in the ER while avoiding degradation. Subsequent ER exit requires removal of ubiquitin from this lysine by the deubiquitinating enzyme USP19. USP 1 Training data H.sapiens 358 UBP1_HUMAN TAZ_HUMAN O94782 Q16635 USP1 TAZ MEDLINE 33114077 USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer USP 1 Other H.sapiens 359 UBP13_HUMAN PK3C3_HUMAN Q92995 Q8NEB9 USP13 PIK3C3 MEDLINE 32101753 Auto-ubiquitination of NEDD4-1 Recruits USP13 to Facilitate Autophagy through Deubiquitinating VPS34 USP 1 Other H.sapiens 360 UBP19_HUMAN BIRC3_HUMAN O94966 Q13489 USP19 BIRC3 UNIPROT UBP8_HUMAN Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination USP 1 Other H.sapiens 361 USP9X_HUMAN PCM1_HUMAN Q93008 Q15154 USP9X PCM1 MEDLINE 28620049 Collectively, our experiments identified USP9X as an integral component of the centrosome where it functions to stabilize PCM1 and CEP55 and promote centrosome biogenesis. USP 1 Training data H.sapiens 362 UBP5_HUMAN EFTU_HUMAN P45974 P49411 USP5 TUFM MEDLINE 31281542 TUFM was a USP5 deubiquitinating substrate that mediated the cellular effects of USP5 USP 1 Other H.sapiens 363 UBP19_HUMAN BIRC2_HUMAN O94966 Q13490 USP19 BIRC2 UNIPROT UBP19_HUMAN Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination USP 1 Other H.sapiens 364 UBP51_HUMAN H2A2C_HUMAN Q70EK9 Q16777 USP51 HIST2H2AC MEDLINE 27083998 USP51 deubiquitylates H2AK13,15ub and regulates DNA damage response. USP 1 Other H.sapiens 365 TRI11_HUMAN DUS6_HUMAN Q96F44 Q16828 TRIM11 DUSP6 MEDLINE 33970779 Interestingly, we confirmed TRIM11 as a deubiquitinase that regulated DUSP6 accumulation, indicating that lung cancer progression is regulated via the DUSP6-ERK1/2 pathway Other 1 Other H.sapiens 366 OTU6A_HUMAN DNM1L_HUMAN Q7L8S5 O00429 OTUD6A DNM1L MEDLINE 33070427 OTUD6A deubiquitylates and stabilizes Drp1, thereby facilitating regulation of mitochondrial morphology and tumorigenesis. OTU 1 Other H.sapiens 367 UBP33_HUMAN ROBO1_HUMAN Q8TEY7 Q9Y6N7 USP33 ROBO1 MEDLINE 25242263 Robo-interacting ubiquitin-specific protease 33 (USP33) is required for the inhibitory function of Slit2 on CRC cell migration by deubiquitinating and stabilizing Robo1 USP 1 Other H.sapiens 368 UBP3_HUMAN H2A2C_HUMAN Q9Y6I4 Q16777 USP3 HIST2H2AC MEDLINE 24196443 USP3 counteracts RNF168 via deubiquitinating H2A and gammaH2AX at lysine 13 and 15 USP 1 Other H.sapiens 369 UBP2_HUMAN RIPK1_HUMAN O75604 Q13546 USP2 RIPK1 MEDLINE 22179575 We have found that the ubiquitin-specific protease USP2a has a pivotal role in the decision for cell death or survival by the TNFR1 complex. This enzyme is a novel component of the TNFR1 complex that is recruited upon ligand binding and controls the signalling activity of the TNFR1-interacting protein RIP1 by removing its K63-linked ubiquitin chains USP 1 Other H.sapiens 370 OTU7B_HUMAN RIPK1_HUMAN Q6GQQ9 Q13546 OTUD7B RIPK1 MEDLINE 25121098 USP21 and Cezanne or OTUD7B negatively regulate NFkappaB signaling by deubiquitinating and inactivating RIP1 upon TNF-alpha stimulation, providing a feedback loop in the proinflammatory signaling OTU 1 Training data H.sapiens 371 UBP2_HUMAN TRAF2_HUMAN O75604 Q12933 USP2 TRAF2 MEDLINE 22179575 USP2a similarly de-ubiquitinates TRAF2, a ubiquitin-ligase recruited to the TNFR1 complex. USP 1 Other H.sapiens 372 UBP21_HUMAN H2A2C_HUMAN Q9UK80 Q16777 USP21 HIST2H2AC MEDLINE 21179169 Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. USP 1 Other H.sapiens 373 UBP2_HUMAN CRY1_HUMAN O75604 Q16526 USP2 CRY1 MEDLINE 22669941 USP2a protein deubiquitinates and stabilizes the circadian protein CRY1 in response to inflammatory signals USP 1 Other H.sapiens 374 UBP8_HUMAN LDLR_HUMAN P40818 P01130 USP8 LDLR MEDLINE 23382078 We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway USP 1 Other H.sapiens 375 UBP25_HUMAN TRAF5_HUMAN Q9UHP3 O00463 USP25 TRAF5 MEDLINE 23042150 Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1. USP 1 Other H.sapiens 376 UBP14_HUMAN TAAR1_HUMAN P54578 Q96RJ0 USP14 TAAR1 MEDLINE 33762162 Intriguingly, our results showed that USP14 directly interacted with transforming growth factor-beta type 1 receptor (TbeTAR1), and impeded TbeTAR1 ubiquitination and degradation USP 1 Other H.sapiens 377 UBP22_HUMAN H2A2C_HUMAN Q9UPT9 Q16777 USP22 HIST2H2AC UNIPROT UBP22_HUMAN Catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a coactivator. USP 1 Other H.sapiens 378 UBP2_HUMAN TNR6_HUMAN O75604 P25445 USP2 FAS MEDLINE 25121098 USP2a can also deubiquitinate Fas preventing apoptosis in PCa USP 1 Training data H.sapiens 379 UBP19_HUMAN EWS_HUMAN O94966 Q01844 USP19 EWSR1 MEDLINE 30700749 Importantly, stabilization appears to be specific for the fusion protein as it could not be observed neither for EWSR1 nor for FLI1 wild type proteins even though USP19 binds to the N-terminal EWS region to regulate deubiquitination of both EWS-FLI1 and EWSR1 USP 1 Other H.sapiens 380 UBP46_HUMAN H2A2C_HUMAN P62068 Q16777 USP46 HIST2H2AC MEDLINE 21183687 Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46 USP 1 Other H.sapiens 381 U17L2_HUMAN NF2L2_HUMAN Q6R6M4 Q16236 USP17L2 NFE2L2 MEDLINE 34364982 The expression of DUB3 and OTUD1 deubiquitinases, involved in the control of Nrf2 and YAP protein level, respectively, was also investigated USP 1 Other H.sapiens 382 ZC12A_HUMAN TRAF2_HUMAN Q5D1E8 Q12933 ZC3H12A TRAF2 MEDLINE 25121098 Cezanne has been reported to hydrolyze linear K11-Ub chains from RIP1. MCPIP1 also removes K63-Ub from RIP1 and TRAF2 and 6 but its activity is unclear Other 1 Training data H.sapiens 383 UBP44_HUMAN H2A2C_HUMAN Q9H0E7 Q16777 USP44 HIST2H2AC MEDLINE 23615962 Both USP44 and USP29 promoted efficient deubiquitylation of histone H2A USP 1 Other H.sapiens 384 UBP2_HUMAN FAS_HUMAN O75604 P49327 USP2 FASN MEDLINE 15050917 Here we show that the isopeptidase USP2a (ubiquitin-specific protease-2a) interacts with and stabilizes fatty acid synthase (FAS), USP 1 Other H.sapiens 385 UBP2_HUMAN SCNNA_HUMAN O75604 P37088 USP2 SCNN1A MEDLINE 20090362 Fine-tuning of renal sodium reabsorption and excretion depends on the epithelial sodium channel protein (ENaC: protein complex of SCNN1A, SCNN1B, and SCNN1G). The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2. USP 1 Training data H.sapiens 386 BAP1_HUMAN H2A2C_HUMAN Q92560 Q16777 BAP1 HIST2H2AC MEDLINE 28389374 BRCA1 associated protein1 (BAP1) is a tumor suppressor involved in multiple cellular processes such as transcriptional regulation, chromatin modification by deubiquitinating histone 2A, and DNA repair UCH 1 Other H.sapiens 387 MYSM1_HUMAN H2A2C_HUMAN Q5VVJ2 Q16777 MYSM1 HIST2H2AC MEDLINE 26220525 Myb-Like, SWIRM, and MPN domains 1 (MYSM1) is a metalloprotease that deubiquitinates the K119-monoubiquitinated form of histone 2A (H2A), a chromatin marker associated with gene transcription silencing. JAMM 1 Other H.sapiens 388 UBP10_HUMAN PTEN_HUMAN Q14694 P60484 USP10 PTEN MEDLINE 28852924 We further demonstrated that USP10 directly interacted with and stabilized PTEN via deubiquitination USP 1 Training data H.sapiens 389 UBP16_HUMAN H2A2C_HUMAN Q9Y5T5 Q16777 USP16 HIST2H2AC UNIPROT UBP22_HUMAN Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub),UBP-M may deubiquitinate one or more critical proteins that are involved in the condensation of mitotic chromosomes, possibly acting selectively on histones H2A and H3B, the major ubiquitinated proteins of chromatin USP 1 Other H.sapiens 390 UBP16_HUMAN H2B2E_HUMAN Q9Y5T5 Q16778 USP16 HIST2H2BE MEDLINE 20730552 UBP-M may deubiquitinate several critical proteins that are involved in the condensation of mitotic chromosomes, mainly on ubiquitinated proteins of the chromatin such as histones H2A and H2B USP 1 Other H.sapiens 391 UBP3_HUMAN SUZ12_HUMAN Q9Y6I4 Q15022 USP3 SUZ12 MEDLINE 31234902 UBIQUITIN-SPECIFIC PROTEASE 3 promotes cell migration and invasion by interacting with and deubiquitinating SUZ12 in gastric cancer USP 1 Other H.sapiens 392 UBP46_HUMAN H2B2E_HUMAN P62068 Q16778 USP46 HIST2H2BE MEDLINE 21183687 Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46 USP 1 Other H.sapiens 393 UBP4_HUMAN HUWE1_HUMAN Q13107 Q7Z6Z7 USP4 HUWE1 MEDLINE 21522127 USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1 USP 1 Other H.sapiens 394 UBP3_HUMAN H2B2E_HUMAN Q9Y6I4 Q16778 USP3 HIST2H2BE MEDLINE 17980597 USP3 dynamically associates with chromatin and deubiquitinates H2A/H2B in vivo USP 1 Other H.sapiens 395 UBP24_HUMAN DDB2_HUMAN Q9UPU5 Q92466 USP24 DDB2 MEDLINE 27316462 USP24 targeting DDB2 and p53 USP 1 Training data H.sapiens 396 UBP22_HUMAN H2B2E_HUMAN Q9UPT9 Q16778 USP22 HIST2H2BE UNIPROT UBP36_HUMAN Catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a coactivator. USP 1 Other H.sapiens 397 UBP13_HUMAN MCL1_HUMAN Q92995 Q07820 USP13 MCL1 MEDLINE 29335437 Collectively, we nominate USP13 as a novel deubiquitinase which regulates MCL1 turnover in diverse solid tumors and propose that USP13 may be a potential therapeutic target for the treatment of various malignancies. USP 1 Training data H.sapiens 398 OTUB1_HUMAN SMAD2_HUMAN Q96FW1 Q15796 OTUB1 SMAD2 MEDLINE 24071738 OTUB1 enhances TGFbeta signalling by inhibiting the ubiquitylation and degradation of active SMAD2/3 OTU 1 Training data H.sapiens 399 UBP36_HUMAN H2B2E_HUMAN Q9P275 Q16778 USP36 HIST2H2BE UNIPROT UBP44_HUMAN May function as a transcriptional repressor by continually deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) USP 1 Other H.sapiens 400 UBP21_HUMAN BAZ2A_HUMAN Q9UK80 Q9UIF9 USP21 BAZ2A UNIPROT UBP21_HUMAN Deubiquitinates BAZ2A/TIP5 leading to its stabilization USP 1 Other H.sapiens 401 UBP45_HUMAN ERCC1_HUMAN Q70EL2 P07992 USP45 ERCC1 MEDLINE 27316462 USP45 targeting ERCC1 USP 1 Training data H.sapiens 402 UBP44_HUMAN H2B2E_HUMAN Q9H0E7 Q16778 USP44 HIST2H2BE UNIPROT UBP8_HUMAN Acts as a negative regulator of histone H2B (H2BK120ub1) ubiquitination USP 1 Other H.sapiens 403 UBP4_HUMAN SMAD4_HUMAN Q13107 Q13485 USP4 SMAD4 MEDLINE 28468752 USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling USP 1 Other H.sapiens 404 UBP38_HUMAN KDM1A_HUMAN Q8NB14 O60341 USP38 KDM1A MEDLINE 30497519 RESULTS: The deubiquitinase USP38 stabilizes protein LSD1 in cells by binding LSD1 and cleaving its ubiquitin chain to prevent the degradation of LSD1 by the intracellular proteasome USP 1 Other H.sapiens 405 UBP13_HUMAN BECN1_HUMAN Q92995 Q14457 USP13 BECN1 MEDLINE 26445063 While A20 inhibits PtdIns3P signaling by removing the TRAF6-dependent Lys63-linked chains from BECLIN 1, the enzymes USP10 and USP13 prevent PI3K-III complex components from their degradation and, therefore, support autophagy. Interestingly enough, USP10 also stabilizes p53, which, in turn, triggers the degradation of BECLIN 1 and VPS34 in order to prevent autophagy. USP 1 Training data H.sapiens 406 UBP12_HUMAN H2B2E_HUMAN O75317 Q16778 USP12 HIST2H2BE MEDLINE 21183687 USP12 and USP46 prefer nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and in vivo USP 1 Other H.sapiens 407 UBP49_HUMAN H2B2E_HUMAN Q70CQ1 Q16778 USP49 HIST2H2BE UNIPROT UBP4_HUMAN USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing USP 1 Other H.sapiens 408 UBP15_HUMAN H2B2E_HUMAN Q9Y4E8 Q16778 USP15 HIST2H2BE MEDLINE 24526689 The U4/U6 recycling factor SART3 has histone chaperone activity and associates with USP15 to regulate H2B deubiquitination USP 1 Other H.sapiens 409 UBP7_HUMAN HLTF_HUMAN Q93009 Q14527 USP7 HLTF MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 410 UBP18_HUMAN TAB1_HUMAN Q9UMW8 Q15750 USP18 TAB1 MEDLINE 23825189 USP18 is associated with and deubiquitinates the TAK1-TAB1 complex USP 1 Other H.sapiens 411 UBP1_HUMAN ID1_HUMAN O94782 P41134 USP1 ID1 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 412 UBP1_HUMAN ID2_HUMAN O94782 Q02363 USP1 ID2 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 413 MINY4_HUMAN FOXM1_HUMAN Q4G0A6 Q08050 MINDY4 FOXM1 MEDLINE 33142744 FAM188B Interacts with FOXM1 and Regulates Stability via Deubiquitination MINDY 1 Other H.sapiens 414 UBP1_HUMAN ID3_HUMAN O94782 Q02535 USP1 ID3 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 415 USP9X_HUMAN AL1A3_HUMAN Q93008 P47895 USP9X ALDH1A3 MEDLINE 30958800 Collectively, our findings unveil USP9X as a key deubiquitinase for ALDH1A3 protein stabilization and a potential target for GSC-directed therapy. USP 1 Other H.sapiens 416 OTU7B_HUMAN IGF1R_HUMAN Q6GQQ9 P08069 OTUD7B IGF1R MEDLINE 33415003 Conclusion: Mechanistically, Cezanne directly targets IGF-1R by deubiquitination and stabilization OTU 1 Other H.sapiens 417 CYLD_HUMAN TGFR1_HUMAN Q9NQC7 P36897 CYLD TGFBR1 MEDLINE 29235674 Loss of CYLD promotes cell invasion via ALK5 stabilization in oral squamous cell carcinoma USP 1 Training data H.sapiens 418 UBP10_HUMAN RAF1_HUMAN Q14694 P04049 USP10 RAF1 MEDLINE 30281322 USP10 overexpression promoted RAF-1 protein expression, but not mRNA expression, through deubiquitination USP 1 Other H.sapiens 419 UBP11_HUMAN IKKB_HUMAN P51784 O14920 USP11 IKBKB MEDLINE 25121098 Both USP11 and USP15 also negatively regulate and function by deubiquitinating IkappaB to sequester NFkappaB in the cytoplasm USP 1 Training data H.sapiens 420 UBP14_HUMAN IKKB_HUMAN P54578 O14920 USP14 IKBKB MEDLINE 23615914 This study suggests that USP14 removes the ubiquitin chain of I-kappaB, therefore inducing I-IkappaB degradation and increasing cytokine release in lung epithelial cells. USP 1 Training data H.sapiens 421 UBP10_HUMAN RS3_HUMAN Q14694 P23396 USP10 RPS3 MEDLINE 29147007 The mono-ubiquitination of the Rps3 protein is tightly modulated by reciprocal action between the Hel2p E3 ligase and the Ubp3p deubiquitinase in yeasts and the reciprocal action between the RNF123 E3 ligase and the USP10 deubiquitinase in mammalian cells. 0.25 USP 1 Other H.sapiens 422 TNAP3_HUMAN NEMO_HUMAN P21580 Q9Y6K9 TNFAIP3 IKBKG MEDLINE 27775833 27775833 OTU 1 Training data H.sapiens 423 UBP11_HUMAN LPAR1_HUMAN P51784 Q92633 USP11 LPAR1 MEDLINE 27448760 The stability of LPA1 is up-regulated by ubiquitin-specific protease 11 (USP11), which deubiquitinates LPA1 and enhances LPA1-mediated pro-inflammatory effects. USP 1 Training data H.sapiens 424 ATX3_HUMAN PTC1_HUMAN P54252 Q13635 ATXN3 PTCH1 MEDLINE 31253779 Mechanistically, TSPAN8 interacts with PTCH1 and inhibits the degradation of the SHH/PTCH1 complex through recruitment of deubiquitinating enzyme ATXN3 Josephin 1 Other H.sapiens 425 UBP8_HUMAN EPG5_HUMAN P40818 Q9HCE0 USP8 EPG5 MEDLINE 30931944 Mechanistically, USP8 directly removes non-classical K63-linked ubiquitin chains from EPG5 at Lysine 252, leading to enhanced interaction between EPG5 and LC3 USP 1 Other H.sapiens 426 UBP10_HUMAN NEMO_HUMAN Q14694 Q9Y6K9 USP10 IKBKG MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 427 SNUT2_HUMAN STAT1_HUMAN Q53GS9 P42224 USP39 STAT1 MEDLINE 33127822 Furthermore, we found that through novel mechanism USP39 can significantly decrease K6-linked but not K48-linked ubiquitination of STAT1 for degradation USP 1 Other H.sapiens 428 UBP7_HUMAN NEMO_HUMAN Q93009 Q9Y6K9 USP7 IKBKG MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 429 UBP21_HUMAN IL33_HUMAN Q9UK80 O95760 USP21 IL33 MEDLINE 25197364 Furthermore, depletion of USP21 reduces IL-33 protein levels and IL-33-mediated NF-kappaB p65 promoter activity. USP 1 Training data H.sapiens 430 U17LO_HUMAN IL33_HUMAN Q0WX57 O95760 USP17L30 IL33 MEDLINE 26610488 Moreover, IL-33 nuclear function and stability are regulated by the enzyme ubiquitin-specific protease 17 (USP17) through deubiquitination of IL-33 both at the K48 and at the K63 sites. USP 1 Training data H.sapiens 431 UBP7_HUMAN MAFA_HUMAN Q93009 Q8NHW3 USP7 MAFA MEDLINE 31822558 Moreover, USP7 also interacted with c-Maf and MafA and blocked their polyubiquitination and degradation USP 1 Other H.sapiens 432 UBP4_HUMAN IRF4_HUMAN Q13107 Q15306 USP4 IRF4 MEDLINE 28791349 28791349 USP 1 Training data H.sapiens 433 UBP7_HUMAN IRS1_HUMAN Q93009 P35568 USP7 IRS1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 434 BAP1_HUMAN PTEN_HUMAN Q92560 P60484 BAP1 PTEN MEDLINE 34094668 Mechanistically, BAP1 complexed with PTEN and stabilized PTEN via deubiquitination and, furthermore, negatively regulated HCC cell EMT by deactivating the AKT/GSK-3beta/Snail pathway UCH 1 Other H.sapiens 435 UBP38_HUMAN TBK1_HUMAN Q8NB14 Q9UHD2 USP38 TBK1 MEDLINE 27692986 Here we report that USP38 negatively regulates type I IFN signaling by targeting the active form of TBK1 for degradation in vitro and in vivo USP 1 Training data H.sapiens 436 UBP7_HUMAN IRS2_HUMAN Q93009 Q9Y4H2 USP7 IRS2 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 437 U17L2_HUMAN SNAI1_HUMAN Q6R6M4 O95863 USP17L2 SNAI1 MEDLINE 28067227 CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1 USP 1 Other H.sapiens 438 UBP8_HUMAN ITCH_HUMAN P40818 Q96J02 USP8 ITCH MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 439 USP9X_HUMAN ITCH_HUMAN Q93008 Q96J02 USP9X ITCH MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 440 UBP49_HUMAN ABC3G_HUMAN Q70CQ1 Q9HC16 USP49 APOBEC3G MEDLINE 31397674 Here, we found that USP49 directly interacts with A3G and efficiently removes ubiquitin, consequently increasing A3G protein expression and significantly enhancing its anti-HIV-1 activity USP 1 Other H.sapiens 441 UBP15_HUMAN SMAD3_HUMAN Q9Y4E8 P84022 USP15 SMAD3 MEDLINE 25317929 Multiple mono-ubiquitination of SMAD3 can be removed by USP15 and mono-ubiquitination of SMAD4 seems to be removed by FAM/USP9X USP 1 Training data H.sapiens 442 UBP8_HUMAN PRKN_HUMAN P40818 O60260 USP8 PRKN MEDLINE 25216678 USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin USP 1 Training data H.sapiens 443 UBP25_HUMAN TRAF3_HUMAN Q9UHP3 Q13114 USP25 TRAF3 MEDLINE 23674823 Ubiquitin-specific protease 25 regulates TLR4-dependent innate immune responses through deubiquitination of the adaptor protein TRAF3 USP 1 Training data H.sapiens 444 UBP10_HUMAN ITB1_HUMAN Q14694 P05556 USP10 ITGB1 MEDLINE 28851806 Silencing of the DUB USP10 induces a buildup of ubiquitin on integrins beta1 and beta5 in cell lysates, whereas recombinant USP10 removes ubiquitin from these integrin subunits. USP 1 Other H.sapiens 445 UBP10_HUMAN ITB5_HUMAN Q14694 P18084 USP10 ITGB5 MEDLINE 28851806 Silencing of the DUB USP10 induces a buildup of ubiquitin on integrins beta1 and beta5 in cell lysates, whereas recombinant USP10 removes ubiquitin from these integrin subunits. USP 1 Other H.sapiens 446 USP9X_HUMAN KCNH2_HUMAN Q93008 Q12809 USP9X KCNH2 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 447 UBP8_HUMAN KCNN4_HUMAN P40818 O15554 USP8 KCNN4 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 448 UBP22_HUMAN KDM1A_HUMAN Q9UPT9 O60341 USP22 KDM1A MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 449 UBP3_HUMAN PO5F1_HUMAN Q9Y6I4 Q01860 USP3 POU5F1 MEDLINE 34070420 In this study, we generated a ubiquitin-specific protease 3 (USP3) gene knockout using the CRISPR/Cas9 system and demonstrated that USP3 acts as a protein stabilizer of Oct4 by deubiquitinating Oct4 USP 1 Other H.sapiens 450 UBP28_HUMAN ZN304_HUMAN Q96RU2 Q9HCX3 USP28 ZNF304 UNIPROT UBP28_HUMAN Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells USP 1 Other H.sapiens 451 UBP28_HUMAN KDM1A_HUMAN Q96RU2 O60341 USP28 KDM1A MEDLINE 29142505 29142505 USP 1 Training data H.sapiens 452 UBP7_HUMAN KDM1A_HUMAN Q93009 O60341 USP7 KDM1A MEDLINE 29142505 29142505 USP 1 Training data H.sapiens 453 UBP25_HUMAN NOTC1_HUMAN Q9UHP3 P46531 USP25 NOTCH1 MEDLINE 32578360 Furthermore, cellular assays were conducted to confirm that Vismodegib could interact with the evolutionarily related deubiquitinases USP28 and USP25 and down-regulate the levels of the two enzymes' substrate proteins c-Myc, Notch1 and Tankyrase-1/2. USP 1 Other H.sapiens 454 UBP15_HUMAN KEAP1_HUMAN Q9Y4E8 Q14145 USP15 KEAP1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 455 ZC12A_HUMAN KLF4_HUMAN Q5D1E8 O43474 ZC3H12A KLF4 MEDLINE 27919796 27919796 Other 1 Training data H.sapiens 456 USP9X_HUMAN ZBT38_HUMAN Q93008 Q8NAP3 USP9X ZBTB38 MEDLINE 29490077 Molecularly, these functions depend on a deubiquitinase, USP9X, which interacts with ZBTB38, deubiquitinates it, and stabilizes it. USP 1 Other H.sapiens 457 USP9X_HUMAN LATS1_HUMAN Q93008 O95835 USP9X LATS1 MEDLINE 30319415 In addition, USP9X can also function as a tumor suppressor. USP9X strongly interacts with LATS, a core kinase in the Hippo pathway. Increased USP9X expression significantly up-regulates and stabilizes LATS and leads to a decrease in the transport of YAP/TAZ into the nucleus as well as inhibiting of their target genes. USP 1 Training data H.sapiens 458 UBP8_HUMAN LRIG1_HUMAN P40818 Q96JA1 USP8 LRIG1 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 459 UBP4_HUMAN HYAS2_HUMAN Q13107 Q92819 USP4 HAS2 MEDLINE 28604766 USP17 efficiently removed polyubiquitination, whereas USP4 preferentially removed monoubiquitination of 6myc-HAS2.;The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2 and differentially affect its function;USP17 and USP4 differently affect HAS2 ubiquitination, and the stability and function of HAS2 USP 1 Other H.sapiens 460 CYLD_HUMAN NEMO_HUMAN Q9NQC7 Q9Y6K9 CYLD IKBKG MEDLINE 26763122 Other identified CYLD substrates include TNF receptor associated factor 7 (TRAF7), TRAF interacting protein (TRIP), transforming growth factor beta-activated kinase 1 (TAK1), NF-kappa-B essential modifier (NEMO), lymphocyte cell specific protein-tyrosine kinase (LCK), receptor-interacting protein 1 (RIP1), retinoic acid inducible gene (RIG), and polo-like kinase 1 (PLK1) USP 1 Training data H.sapiens 461 UBP22_HUMAN HES1_HUMAN Q9UPT9 Q14469 USP22 HES1 MEDLINE 27341175 A recent study showed that USP22- mediated deubiquitination of Hairy and Enhancer of split 1 (Hes1) is important for neuronal differentiation in the developing brain USP 1 Training data H.sapiens 462 USP9X_HUMAN FBXW7_HUMAN Q93008 Q969H0 USP9X FBXW7 MEDLINE 29346117 The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer USP 1 Other H.sapiens 463 UBP5_HUMAN MAFB_HUMAN P45974 Q9Y5Q3 USP5 MAFB MEDLINE 28933784 USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level USP 1 Other H.sapiens 464 OTUD1_HUMAN MCL1_HUMAN Q5VV17 Q07820 OTUD1 MCL1 MEDLINE 31467488 The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein OTU 1 Other H.sapiens 465 USP9X_HUMAN M3K5_HUMAN Q93008 Q99683 USP9X MAP3K5 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 466 CYLD_HUMAN DVL1_HUMAN Q9NQC7 O14640 CYLD DVL1 MEDLINE 28840581 CYLD negatively regulates the Wnt/beta-catenin signaling pathway by deubiquitinating Dvl proteins USP 1 Training data H.sapiens 467 UBP19_HUMAN MARH6_HUMAN O94966 O60337 USP19 MARCHF6 MEDLINE 25088257 25088257 USP 1 Training data H.sapiens 468 TNAP3_HUMAN RIPK1_HUMAN P21580 Q13546 TNFAIP3 RIPK1 MEDLINE 25121098 The targets of A20-mediated deubiquitination are K63-linked ubiquitinated TRAF6 and RIP1 OTU 1 Training data H.sapiens 469 Q6P468_HUMAN MARH7_HUMAN Q6P468 Q9H992 USP9X MARCHF7 MEDLINE 18410486 hUbiquitome USP 1 Other H.sapiens 470 UBP30_HUMAN MIRO1_HUMAN Q70CQ3 Q8IXI2 USP30 RHOT1 UNIPROT UBP13_HUMAN hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20 USP 1 Other H.sapiens 471 UBP10_HUMAN MLP3B_HUMAN Q14694 Q9GZQ8 USP10 MAP1LC3B MEDLINE 33577797 The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels and autophagic activity USP 1 Other H.sapiens 472 OTUL_HUMAN ACVL1_HUMAN Q96BN8 P37023 OTULIN ACVRL1 MEDLINE 34157307 Conversely, OTULIN deubiquitinates ALK1 to promote Smad1/5 activation Other 1 Other H.sapiens 473 UBP7_HUMAN HIF1A_HUMAN Q93009 Q16665 USP7 HIF1A MEDLINE 27934968 K63-polyubiquitinated HAUSP deubiquitinates HIF-1A and dictates H3K56 acetylation promoting hypoxia-induced tumour progression USP 1 Other H.sapiens 474 UCHL1_HUMAN TAU_HUMAN P09936 P10636 UCHL1 MAPT MEDLINE 29964011 Our results suggest that UCH-L1 may be associated with hippocampal MSF followed the epileptogenesis through mediating phosphorylation of tau UCH 1 Training data H.sapiens 475 USP9X_HUMAN MARH7_HUMAN Q93008 Q9H992 USP9X MARCHF7 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 476 ABRX2_HUMAN NLRP3_HUMAN Q15018 Q96P20 ABRAXAS2 NLRP3 MEDLINE 30787184 ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination Other 1 Other H.sapiens 477 UBP15_HUMAN PRP31_HUMAN Q9Y4E8 Q8WWY3 USP15 PRPF31 MEDLINE 28132030 USP15 regulates dynamic protein-protein interactions of the spliceosome through deubiquitination of PRP31 USP 1 Training data H.sapiens 478 UBP37_HUMAN ZBT16_HUMAN Q86T82 Q05516 USP37 ZBTB16 MEDLINE 23208507 The deubiquitinating enzyme USP37 regulates the oncogenic fusion protein PLZF/RARA stability USP 1 Other H.sapiens 479 USP9X_HUMAN DVL2_HUMAN Q93008 O14641 USP9X DVL2 MEDLINE 31340145 Here, we report that USP9X, a deubiquitylase, and WWP1, an E3 ubiquitin ligase, regulate a ubiquitin rheostat on DVL2, a WNT signaling protein USP 1 Other H.sapiens 480 UBP33_HUMAN IOD2_HUMAN Q8TEY7 Q92813 USP33 DIO2 MEDLINE 22967761 Ubiquitinated D2 can be either targeted to proteasomal degradation or reactivated by deubiquitination, a process that is mediated by the deubiquitinases USP20/33 and is important in adaptive thermogenesis. USP 1 Training data H.sapiens 481 UBP33_HUMAN ARRB2_HUMAN Q8TEY7 P32121 USP33 ARRB2 UNIPROT UBP34_HUMAN Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2) USP 1 Other H.sapiens 482 UCHL1_HUMAN CSN5_HUMAN P09936 Q92905 UCHL1 COPS5 MEDLINE 25121098 UCH-L1 colocalizes with Jab1 sending p27Kip1 to proteasomal degradation, prevents senescence, and ensures proper somatic cell division UCH 1 Training data H.sapiens 483 USP9X_HUMAN MARK4_HUMAN Q93008 Q96L34 USP9X MARK4 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 484 OTUD5_HUMAN UBR5_HUMAN Q96G74 O95071 OTUD5 UBR5 MEDLINE 25470037 DUBA interacted with the ubiquitin ligase UBR5, which suppressed DUBA abundance in naive T cells. DUBA accumulated in activated T cells and stabilized UBR5, which then ubiquitylated RORgammat in response to TGF-beta signalling. OTU 1 Training data H.sapiens 485 UCHL1_HUMAN P53_HUMAN P09936 P04637 UCHL1 TP53 MEDLINE 20395212 These results indicate that UCHL1 could deubiquitinate p53 and p14(ARF) UCH 1 Other H.sapiens 486 UBP4_HUMAN RBL1_HUMAN Q13107 P28749 USP4 RBL1 MEDLINE 25121098 USP4, reported as an oncogenic protein, is known to interact with the pocket proteins (Rb, p107, and p130) although no deubiquitinating activity has been reported USP 1 Training data H.sapiens 487 UBP11_HUMAN SNAI1_HUMAN P51784 O95863 USP11 SNAI1 MEDLINE 30569152 Upregulation of USP11 promotes epithelial-to-mesenchymal transition by deubiquitinating Snail in ovarian cancer USP 1 Other H.sapiens 488 OTU1_HUMAN DESM_HUMAN Q5VVQ6 P17661 YOD1 DES MEDLINE 29080116 YOD1, a DUB from OTU family, deubiquitinates DESMIN. OTU 1 Training data H.sapiens 489 Q6P468_HUMAN MCL1_HUMAN Q6P468 Q07820 USP9X MCL1 MEDLINE 20023629 hUbiquitome USP 1 Other H.sapiens 490 UBP20_HUMAN SQSTM_HUMAN Q9Y2K6 Q13501 USP20 SQSTM1 MEDLINE 32354117 USP20 specifically binds to p62 and acts as a positive regulator for NF-kappaB activation by TNFalpha through deubiquitinating lysine 48 (K48)-linked polyubiquitination, eventually contributing to cell survival USP 1 Other H.sapiens 491 USP9X_HUMAN MCL1_HUMAN Q93008 Q07820 USP9X MCL1 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 492 UBP15_HUMAN MDM2_HUMAN Q9Y4E8 Q00987 USP15 MDM2 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 493 UBP34_HUMAN AXIN2_HUMAN Q70CQ2 Q9Y2T1 USP34 AXIN2 UNIPROT UBP19_HUMAN Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. USP 1 Other H.sapiens 494 UBP34_HUMAN AXIN1_HUMAN Q70CQ2 O15169 USP34 AXIN1 UNIPROT UBP34_HUMAN Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. USP 1 Other H.sapiens 495 UBP2_HUMAN MDM2_HUMAN O75604 Q00987 USP2 MDM2 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 496 USP9X_HUMAN AMOL2_HUMAN Q93008 Q9Y2J4 USP9X AMOTL2 MEDLINE 26598551 we report for the first time that USP9X is a deubiquitinase of Angiomotin-like 2 (AMOTL2) and that AMOTL2 mono-ubiquitination is required for YAP inhibition USP 1 Other H.sapiens 497 UBP19_HUMAN COR2A_HUMAN O94966 Q92828 USP19 CORO2A MEDLINE 27129179 UBIQUITIN SPECIFIC PROTEASE 19 involved in transcriptional repression of retinoic acid receptor by stabilizing CORO2A USP 1 Training data H.sapiens 498 ATX3L_HUMAN KLF5_HUMAN Q9H3M9 Q13887 ATXN3L KLF5 MEDLINE 26079537 Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Kruppel-like factor 5 (KLF5). The Kruppel-like factor 5 (KLF5) has been suggested to promote breast cell proliferation, survival and tumorigenesis. Josephin 1 Other H.sapiens 499 UBP48_HUMAN TRAF2_HUMAN Q86UV5 Q12933 USP48 TRAF2 MEDLINE 28874458 The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions USP 1 Training data H.sapiens 500 UBP26_HUMAN MDM2_HUMAN Q9BXU7 Q00987 USP26 MDM2 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 501 UBP10_HUMAN RS2_HUMAN Q14694 P15880 USP10 RPS2 MEDLINE 34348161 Subsequent deubiquitination of RPS2 and RPS3 by USP10 is critical for recycling of stalled ribosomes in a process known as ribosome-associated quality control USP 1 Other H.sapiens 502 UBP27_HUMAN HES1_HUMAN A6NNY8 Q14469 USP27X HES1 MEDLINE 25846153 Knockdown of Usp22 shortened the half-life of Hes1, delayed its oscillation, and enhanced neuronal differentiation in mouse developing brain, whereas mis-expression of Usp27x reduced neuronal differentiation. USP 1 Training data H.sapiens 503 UBP7_HUMAN UB2E1_HUMAN Q93009 P51965 USP7 UBE2E1 MEDLINE 28073915 UbE2E1/UbcH6 is an E2 ubiquitin-conjugating enzyme that is regulated by USP7 USP 1 Training data H.sapiens 504 USP9X_HUMAN EPS15_HUMAN Q93008 P42566 USP9X EPS15 MEDLINE 26748853 USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15 USP 1 Training data H.sapiens 505 UBP7_HUMAN SL9A3_HUMAN Q93009 P48764 USP7 SLC9A3 MEDLINE 33095475 These findings demonstrate that USP7 and USP10 are DUBs that regulate NHE3 ubiquitination and expression, and reveal a new mechanism of NHE3 inhibition involving DUBs. USP 1 Other H.sapiens 506 UBP7_HUMAN MDM2_HUMAN Q93009 Q00987 USP7 MDM2 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 507 U17L2_HUMAN IFIH1_HUMAN Q6R6M4 Q9BYX4 USP17L2 IFIH1 MEDLINE 20368735 Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling. USP 1 Other H.sapiens 508 UBP7_HUMAN MDM4_HUMAN Q93009 O15151 USP7 MDM4 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 509 UBP8_HUMAN MET_HUMAN P40818 P08581 USP8 MET MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 510 UBP8_HUMAN CFLAR_HUMAN P40818 O15519 USP8 CFLAR MEDLINE 27321185 USP8 directly deubiquitylates and stabilizes FLIPL USP 1 Other H.sapiens 511 UBP48_HUMAN TF65_HUMAN Q86UV5 Q04206 USP48 RELA MEDLINE 30628021 Catalytic domain of deubiquitinylase USP48 directs interaction with Rel homology domain of nuclear factor kappaB transcription factor RelA USP 1 Other H.sapiens 512 USP9X_HUMAN MIB1_HUMAN Q93008 Q86YT6 USP9X MIB1 MEDLINE 27593927 USP9x in turn stimulates JAG1 activity through two mechanisms: (1) through TRB3 deubiquitination and stabilization, and (2) through deubiquitination and activation of Mind Bomb 1, an E3 ligase required for JAG1 ubiquitination-mediated endocytosis and Notch activation. USP 1 Training data H.sapiens 513 UBP2_HUMAN MMP2_HUMAN O75604 P08253 USP2 MMP2 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 514 PSDE_HUMAN ACVR1_HUMAN O00487 Q04771 PSMD14 ACVR1 MEDLINE 31685442 FINDINGS: The deubiquitinase PSMD14 acts as a positive regulator for the initiation of the BMP6 signaling pathway through deubiquitinating K48-linked ALK2 type I receptor ubiquitination mediated by Smurf1 E3 ligase, resulting in increased stability of the ALK2 JAMM 1 Other H.sapiens 515 UBP37_HUMAN CCNA1_HUMAN Q86T82 P78396 USP37 CCNA1 UNIPROT U17L2_HUMAN Deubiquitinase that antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2) USP 1 Other H.sapiens 516 UBP20_HUMAN CTNB1_HUMAN Q9Y2K6 P35222 USP20 CTNNB1 MEDLINE 29867130 Mechanistically, USP20 regulates the deubiquitination of BETA-CATENIN to control its stability, thereby inducing proliferation, invasion and migration of cancer cells USP 1 Other H.sapiens 517 UBP22_HUMAN MMP9_HUMAN Q9UPT9 P14780 USP22 MMP9 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 518 UBP42_HUMAN MMP9_HUMAN Q9H9J4 P14780 USP42 MMP9 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 519 UBP33_HUMAN PRKN_HUMAN Q8TEY7 O60260 USP33 PRKN MEDLINE 31432739 Our findings convincingly demonstrate that USP33 is a novel PRKN deubiquitinase antagonizing its regulatory roles in mitophagy and SH-SY5Y neuron-like cell survival USP 1 Other H.sapiens 520 UBP20_HUMAN HIF1A_HUMAN Q9Y2K6 Q16665 USP20 HIF1A MEDLINE 23750477 USP20 stabilizes HIF-1ALPHA by abolishing von Hippel-Lindau protein (pVHL)-E3 ligase complex-mediated HIF-1ALPHA degradation USP 1 Training data H.sapiens 521 UBP15_HUMAN SMAD2_HUMAN Q9Y4E8 Q15796 USP15 SMAD2 MEDLINE 28245560 reports have suggested that USP15 acts as a key regulator of TGF-b receptor-signaling pathways by deubiquitinating the TGF-b receptor itself and its downstream transducers receptor-regulated SMADs (R-SMADs), including SMAD1, SMAD2, and SMAD3, thus activating the TGF-b target genes. USP 1 Other H.sapiens 522 UBP6_HUMAN MMP9_HUMAN P35125 P14780 USP6 MMP9 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 523 UBP10_HUMAN MSI2H_HUMAN Q14694 Q96DH6 USP10 MSI2 MEDLINE 30604502 USP10 regulates Musashi-2 stability via deubiquitination and promotes tumour proliferation in colon cancer USP 1 Other H.sapiens 524 UBP7_HUMAN CRY2_HUMAN Q93009 Q49AN0 USP7 CRY2 MEDLINE 27123980 We found that ubiquitin-specific protease 7 (USP7 also known as HAUSP) associates with CRY1 and CRY2 and stabilizes CRYs through deubiquitination USP 1 Training data H.sapiens 525 UBP49_HUMAN P53_HUMAN Q70CQ1 P04637 USP49 TP53 MEDLINE 29748582 In our study, we identified USP49 as a novel deubiquitinase (DUB) for p53 from a library consisting of 80 DUBs and found that USP49 has a positive effect on p53 transcriptional activity and protein stability USP 1 Other H.sapiens 526 UBP50_HUMAN WEE1_HUMAN Q70EL3 P30291 USP50 WEE1 MEDLINE 25121098 USP50 regulates HSP90-dependent Wee1 stability preventing mitotic entry, acting as another G2/M checkpoint Other 1 Training data H.sapiens 527 UBP4_HUMAN RORG_HUMAN Q13107 P51449 USP4 RORC MEDLINE 25821221 Ubiquitin-specific protease 4 promotes Th17 cell function under inflammation by deubiquitinating and stabilizing RORGAMMAT USP 1 Training data H.sapiens 528 UBP4_HUMAN IRF8_HUMAN Q13107 Q02556 USP4 IRF8 MEDLINE 28477415 In the present study, we demonstrate that ubiquitin-specific protease (USP)4 physically interacted with interferon regulatory factor 8 (IRF8) function via a K48-linked deubiquitinase, which stabilized IRF8 protein levels in Treg cells. USP 1 Training data H.sapiens 529 UBP12_HUMAN PHLP2_HUMAN O75317 Q6ZVD8 USP12 PHLPP2 MEDLINE 25216524 we demonstrate that Usp12, in complex with Uaf-1 and WDR20, directly deubiquitinates and stabilises the Akt phosphatases PHLPP and PHLPPL resulting in decreased levels of active pAkt. USP 1 Other H.sapiens 530 UBP10_HUMAN NALP7_HUMAN Q14694 Q8WX94 USP10 NLRP7 MEDLINE 33838681 NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer USP 1 Other H.sapiens 531 UBP4_HUMAN AA2AR_HUMAN Q13107 P29274 USP4 ADORA2A UNIPROT UBP33_HUMAN Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. USP 1 Other H.sapiens 532 USP9X_HUMAN MTOR_HUMAN Q93008 P42345 USP9X MTOR MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 533 UBP4_HUMAN CTNB1_HUMAN Q13107 P35222 USP4 CTNNB1 MEDLINE 29080116 Additionally, DUBs USP14, USP15, USP47, and Fam/USP9X have been reported to prevent BETA-CATENIN turnover by inhibiting its Ub-proteasomal degradation USP 1 Training data H.sapiens 534 UBP7_HUMAN RING2_HUMAN Q93009 Q99496 USP7 RNF2 MEDLINE 20800574 Here we identify USP7 as a deubiquitinating enzyme that regulates the ubiquitination state of RING1B USP 1 Training data H.sapiens 535 UBP15_HUMAN PAPD1_HUMAN Q9Y4E8 Q9NVV4 USP15 MTPAP MEDLINE 32839293 USP15 Deubiquitinates TUT1 Associated with RNA Metabolism and Maintains Cerebellar Homeostasis USP 1 Other H.sapiens 536 UBP22_HUMAN MYC_HUMAN Q9UPT9 P01106 USP22 MYC MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 537 UBP28_HUMAN MYC_HUMAN Q96RU2 P01106 USP28 MYC MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 538 UBP15_HUMAN CARD9_HUMAN Q9Y4E8 Q9H257 USP15 CARD9 MEDLINE 33093067 USP15 Deubiquitinates CARD9 to Downregulate C-Type Lectin Receptor-Mediated Signaling USP 1 Other H.sapiens 539 UBP36_HUMAN MYC_HUMAN Q9P275 P01106 USP36 MYC MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 540 USP9X_HUMAN PD1L1_HUMAN Q93008 Q9NZQ7 USP9X CD274 MEDLINE 29992764 CONCLUSION: Our data indicate that USP9X deubiquitinates and stabilizes PD-L1 USP 1 Other H.sapiens 541 UBP38_HUMAN MYC_HUMAN Q8NB14 P01106 USP38 MYC MEDLINE 34102342 USP38 can inhibit the polyubiquitination of c-Myc, thereby increasing c-Myc stability USP 1 Other H.sapiens 542 UBP11_HUMAN VGLL4_HUMAN P51784 Q14135 USP11 VGLL4 MEDLINE 28042509 In this study, we identify deubiquitinating enzyme USP11 as a novel VGLL4 interactor. USP 1 Training data H.sapiens 543 UBP14_HUMAN MACF1_HUMAN P54578 Q9UPN3 USP14 MACF1 MEDLINE 33737492 Here we identified USP14 as a deubiquitinating enzyme that regulated Acf7 ubiquitination and protein levels USP 1 Other H.sapiens 544 UBP13_HUMAN PTEN_HUMAN Q92995 P60484 USP13 PTEN MEDLINE 24270891 Deubiquitylation and stabilization of PTEN by USP13 USP 1 Other H.sapiens 545 UBP49_HUMAN STING_HUMAN Q70CQ1 Q86WV6 USP49 STING1 MEDLINE 30943264 Mechanistically, USP49 removes K63-linked ubiquitin chains from MITA after HSV-1 infection which inhibits the aggregation of MITA and the subsequent recruitment of TBK1 to the signaling complex USP 1 Other H.sapiens 546 UBP37_HUMAN MYC_HUMAN Q86T82 P01106 USP37 MYC MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 547 UBP16_HUMAN NANOG_HUMAN Q9Y5T5 Q9H9S0 USP16 NANOG MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 548 USP9X_HUMAN LATS2_HUMAN Q93008 Q9NRM7 USP9X LATS2 MEDLINE 29183995 Deubiquitylase USP9X suppresses tumorigenesis by stabilizing large tumor suppressor kinase 2 (LATS2) in the Hippo pathway USP 1 Training data H.sapiens 549 UBP21_HUMAN NANOG_HUMAN Q9UK80 Q9H9S0 USP21 NANOG MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 550 UBP4_HUMAN RO52_HUMAN Q13107 P19474 USP4 TRIM21 MEDLINE 16316627 Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity USP 1 Training data H.sapiens 551 UBP3_HUMAN NANOG_HUMAN Q9Y6I4 Q9H9S0 USP3 NANOG MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 552 UBP36_HUMAN PPME1_HUMAN Q9P275 Q9Y570 USP36 PPME1 MEDLINE 29577269 we demonstrate that USP36 regulates PME-1 through its deubiquitinating enzyme activity. USP36 increases PME-1 stability, and depletion of USP36 decreases the PME-1 expression level. USP 1 Training data H.sapiens 553 UBP22_HUMAN NFAC2_HUMAN Q9UPT9 Q13469 USP22 NFATC2 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 554 OTU1_HUMAN TERA_HUMAN Q5VVQ6 P55072 YOD1 VCP MEDLINE 26463207 The activity of the p97-associated deubiquitinylase YOD1 is also required for substrate disposal OTU 1 Training data H.sapiens 555 TNAP3_HUMAN NFKB1_HUMAN P21580 P19838 TNFAIP3 NFKB1 MEDLINE 27775833 27775833 OTU 1 Training data H.sapiens 556 OTUB1_HUMAN PD1L1_HUMAN Q96FW1 Q9NZQ7 OTUB1 CD274 MEDLINE 33328570 Mechanistically, we demonstrate that OTUB1 interacts with and removes K48-linked ubiquitin chains from the PD-L1 intracellular domain in a manner dependent on its deubiquitinase activity to hinder the degradation of PD-L1 through the ERAD pathway OTU 1 Other H.sapiens 557 UBP7_HUMAN NFKB1_HUMAN Q93009 P19838 USP7 NFKB1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 558 UCHL1_HUMAN HIF1A_HUMAN P09936 Q16665 UCHL1 HIF1A MEDLINE 28778421 We revealed that UCHL1 directly interacts with HIF-1ALPHA, mediates the deubiquitination of HIF-1ALPHA, and upregulates HIF-1 activity through the stabilization of HIF1alpha UCH 1 Training data H.sapiens 559 UCHL5_HUMAN IKBA_HUMAN Q9Y5K5 P25963 UCHL5 NFKBIA MEDLINE 20634424 Furthermore, we discovered that IkappaB-alpha, a protein whose proteasomal degradation activates the transcription factor NF-kappaB, is also a substrate for the Rpn13/UCH37 complex. UCH 1 Training data H.sapiens 560 UBP15_HUMAN NF2L1_HUMAN Q9Y4E8 Q14494 USP15 NFE2L1 MEDLINE 27416755 Here, we report that USP15 (Ubiquitin-Specific Protease 15) activates Nrf1 in the nucleus by stabilizing it through deubiquitination. USP 1 Training data H.sapiens 561 USP9X_HUMAN ETS1_HUMAN Q93008 P14921 USP9X ETS1 MEDLINE 28198367 ETS-1 deubiquitination blocks its proteasomal destruction and enhances tumorigenicity, which could be reversed by Usp9x knockdown or inhibition. USP 1 Other H.sapiens 562 UBP11_HUMAN IKBA_HUMAN P51784 P25963 USP11 NFKBIA MEDLINE 19874889 Moreover, knockdown of USP11 expression enhances TNFalpha-induced IkappaBalpha ubiquitination and NF-kappaB activation. USP 1 Training data H.sapiens 563 UBP46_HUMAN DCE1_HUMAN P62068 Q99259 USP46 GAD1 UNIPROT UBP16_HUMAN May act by mediating the deubiquitination of GAD1/GAD67 USP 1 Other H.sapiens 564 UBP47_HUMAN DPOLB_HUMAN Q96K76 P06746 USP47 POLB UNIPROT UBP30_HUMAN Ubiquitin-specific protease that specifically deubiquitinates monoubiquitinated DNA polymerase beta (POLB), stabilizing POLB thereby playing a role in base-excision repair (BER) USP 1 Other H.sapiens 565 UBP47_HUMAN SNAI1_HUMAN Q96K76 O95863 USP47 SNAI1 MEDLINE 29162839 Hypoxia induces epithelial-mesenchymal transition in colorectal cancer cells through ubiquitin-specific protease 47-mediated stabilization of Snail: A potential role of Sox9 USP 1 Training data H.sapiens 566 OTU7B_HUMAN SOX2_HUMAN Q6GQQ9 P48431 OTUD7B SOX2 MEDLINE 30405104 COP1, as the substrate receptor, interacts directly with and ubiquitylates Sox2, while OTUD7B removes polyUb conjugates from Sox2 and increases its stability OTU 1 Training data H.sapiens 567 OTUD5_HUMAN TRI25_HUMAN Q96G74 Q14258 OTUD5 TRIM25 MEDLINE 32826889 OTUD5 cooperates with TRIM25 in transcriptional regulation and tumor progression via deubiquitination activity OTU 1 Other H.sapiens 568 U17L2_HUMAN SNAI2_HUMAN Q6R6M4 O43623 USP17L2 SNAI2 MEDLINE 29088851 In this study, we identified Dub3 as a novel DUB for both Slug and Twist. We further found that Dub3 overexpression increased Slug and Twist protein levels in a dose-dependent manner, whereas Dub3-knockdown decreased their protein levels. USP 1 Other H.sapiens 569 UBP14_HUMAN IKBA_HUMAN P54578 P25963 USP14 NFKBIA MEDLINE 33762162 Furthermore, USP14 could also facilitate IkappaBalpha deubiquitination and degradation, exacerbating IkappaBalpha phosphorylation and NF-kappaB activation USP 1 Other H.sapiens 570 UBP53_HUMAN IKBA_HUMAN Q70EK8 P25963 USP53 NFKBIA MEDLINE 33973730 CONCLUSION: In summary, our data indicate that USP53 inhibits the inactivation of the NF-kappaB pathway by reducing the ubiquitination of IkappaBalpha to further inhibit ccRCC proliferation and metastasis USP 1 Other H.sapiens 571 UCHL1_HUMAN IKBA_HUMAN P09936 P25963 UCHL1 NFKBIA MEDLINE 34288216 Meanwhile, inhibition of UCHL1 blocked the LPS-induced degradation of IkappaBalpha through the ubiquitin-proteasome system UCH 1 Other H.sapiens 572 UBP1_HUMAN IRF1_HUMAN O94782 P10914 USP1 IRF1 MEDLINE 31292489 In addition, we found that downregulation of IRF1 is mediated by its degradation through the ubiquitination-proteasome pathway, and that decreased activity of a deubiquitinase complex containing USP1 and UAF1 is involved in the degradation of IRF1 by Wnt/beta-catenin signaling USP 1 Other H.sapiens 573 UBP7_HUMAN ABL1_HUMAN Q93009 P00519 USP7 ABL1 MEDLINE 33963175 Further studies show that USP7 interacts with BCR-ABL and blocks its polyubiquitination and degradation USP 1 Other H.sapiens 574 UBP22_HUMAN E2F6_HUMAN Q9UPT9 O75461 USP22 E2F6 MEDLINE 34339800 Deubiquitination of the repressor E2F6 by USP22 facilitates AKT activation and tumor growth in hepatocellular carcinoma USP 1 Other H.sapiens 575 UBP14_HUMAN XRCC6_HUMAN P54578 P12956 USP14 XRCC6 MEDLINE 31740976 USP14 is a deubiquitinase for Ku70 and critical determinant of non-homologous end joining repair in autophagy and PTEN-deficient cells USP 1 Other H.sapiens 576 UBP20_HUMAN MK06_HUMAN Q9Y2K6 Q16659 USP20 MAPK6 MEDLINE 28167606 USP20 interacts with and deubiquitinates ERK3 both in vitro and in intact cells USP 1 Other H.sapiens 577 UBP7_HUMAN CCDC6_HUMAN Q93009 Q16204 USP7 CCDC6 MEDLINE 31447003 In the TMA of MPM primary samples, the staining of CCDC6 and of its de-ubiquitinase USP7 showed a significant correlation in the tested primary samples (p = 0.01) USP 1 Other H.sapiens 578 UBP29_HUMAN CGAS_HUMAN Q9HBJ7 Q8N884 USP29 CGAS MEDLINE 32457395 Mechanistically, USP29 constitutively interacts with cGAS, deconjugates K48-linked polyubiquitin chains from cGAS and stabilizes cGAS in uninfected cells or after HSV-1 infection USP 1 Other H.sapiens 579 BAP1_HUMAN NOTC1_HUMAN Q92560 P46531 BAP1 NOTCH1 MEDLINE 31504682 BAP1, a deubiquitinating enzyme (DUB), was further identified as a positive N1ICD regulator, and NUMB facilitates the association between N1ICD and BAP1 to stabilize N1ICD UCH 1 Other H.sapiens 580 USP9X_HUMAN NUAK1_HUMAN Q93008 O60285 USP9X NUAK1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 581 TNAP3_HUMAN OCLN_HUMAN P21580 Q16625 TNFAIP3 OCLN MEDLINE 22031828 We also found that TNFAIP3 deubiquitinates polyubiquitinated occludin OTU 1 Other H.sapiens 582 UBP3_HUMAN SNAI1_HUMAN Q9Y6I4 O95863 USP3 SNAI1 MEDLINE 31266817 USP3 interacts directly with Snail and stabilizes Snail via deubiquitination USP 1 Other H.sapiens 583 UBP3_HUMAN MYCN_HUMAN Q9Y6I4 P04198 USP3 MYCN MEDLINE 33767157 We show that increased USP3 levels reduce K-48- and K-63-linked ubiquitination of MYCN, thus driving up MYCN protein stability USP 1 Other H.sapiens 584 UBP13_HUMAN ODO1_HUMAN Q92995 Q02218 USP13 OGDH MEDLINE 30319415 USP13, the main regulator of ovarian cancer energy metabolism, specifically deubiquitinates and stabilizes oxoglutarate dehydrogenase and ATP citrate lyase, which can catalyze fatty acid synthesis, glutaminolysis and mitochondrial respiration. USP 1 Training data H.sapiens 585 UBP7_HUMAN TRI27_HUMAN Q93009 P14373 USP7 TRIM27 MEDLINE 29688809 Our findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1 USP 1 Training data H.sapiens 586 UBP1_HUMAN PCNA_HUMAN O94782 P12004 USP1 PCNA MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 587 TNAP3_HUMAN M3K5_HUMAN P21580 Q99683 TNFAIP3 MAP3K5 MEDLINE 29227477 we identified the deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes. OTU 1 Training data H.sapiens 588 UBP50_HUMAN ASC_HUMAN Q70EL3 Q9ULZ3 USP50 PYCARD MEDLINE 28094437 The deubiquitinating enzyme, ubiquitin-specific peptidase 50, regulates inflammasome activation by targeting the ASC adaptor protein Other 1 Training data H.sapiens 589 UBP7_HUMAN PCNA_HUMAN Q93009 P12004 USP7 PCNA MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 590 UBP12_HUMAN PHLP1_HUMAN O75317 O60346 USP12 PHLPP1 MEDLINE 25121098 USP11 stabilizes IKK-alpha to stabilize and activate p53 USP 1 Training data H.sapiens 591 U17L2_HUMAN SDS3_HUMAN Q6R6M4 Q9H7L9 USP17L2 SUDS3 MEDLINE 22662218 We previously reported that the USP17 deubiquitinating enzyme having hyaluronan binding motifs (HABMs) interacts with human SDS3 (suppressor of defective silencing 3) and specifically deubiquitinates Lys-63 branched polyubiquitination of SDS3 resulting in negative regulation of histone deacetylase (HDAC) activity in cancer cells USP 1 Other H.sapiens 592 UBP16_HUMAN PLK1_HUMAN Q9Y5T5 P53350 USP16 PLK1 MEDLINE 28188342 ubiquitinspecific peptidase 16 (Usp16) was identified as a PLK1 interacting protein in a co-immunoprecipitation (co-IP) assay in a PBD-dependent manner USP 1 Training data H.sapiens 593 UBP11_HUMAN PML_HUMAN P51784 P29590 USP11 PML MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 594 UBP7_HUMAN PML_HUMAN Q93009 P29590 USP7 PML MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 595 OTUB1_HUMAN FOXM1_HUMAN Q96FW1 Q08050 OTUB1 FOXM1 MEDLINE 27167337 OTUB1-catalyzed deubiquitination of FOXM1 facilitates tumor progression and predicts a poor prognosis in ovarian cancer OTU 1 Training data H.sapiens 596 UBP4_HUMAN RHEB_HUMAN Q13107 Q15382 USP4 RHEB MEDLINE 30514904 EGF enhances the deubiquitination of Rheb through AKT-dependent USP4 phosphorylation, leading to the release of Rheb from the TSC complex USP 1 Other H.sapiens 597 UBP7_HUMAN RARA_HUMAN Q93009 P10276 USP7 RARA MEDLINE 23208507 overexpression or depletion of USP37 caused an increase or decrease of PLZF/RARA protein half-life, correlating with down- or upregulation of PLZF/RARA poly-ubiquitination, respectively. By PLZF/RARA-transduced primary mouse hematopoietic progenitor cells, we demonstrated that Usp37 knockdown alleviated PLZF/RARA-mediated target gene suppression and cell transformation potential USP 1 Other H.sapiens 598 USP9X_HUMAN PTGES_HUMAN Q93008 O14684 USP9X PTGES MEDLINE 31285948 Stabilization of PTGES by deubiquitinase USP9X promotes metastatic features of lung cancer via PGE2 signaling USP 1 Other H.sapiens 599 UBP7_HUMAN PHF8_HUMAN Q93009 Q9UPP1 USP7 PHF8 MEDLINE 27183383 Here, we report that PHF8 physically associates with the deubiquitinase USP7. USP 1 Training data H.sapiens 600 UCHL1_HUMAN HDAC6_HUMAN P09936 Q9UBN7 UCHL1 HDAC6 MEDLINE 28540657 By reducing the production of lysine (K63)-linked ubiquitin chains, UCH-L1 inhibition decreases HDAC6 deacetylase activity and attenuates the interaction of HDAC6 and tau protein, finally leading to tau aggresome formation impairment. UCH 1 Other H.sapiens 601 UBP10_HUMAN NUP62_HUMAN Q14694 P37198 USP10 NUP62 MEDLINE 30469013 USP10 interacted with the ubiquitin receptor p62 and the interaction augmented p62-dependent ubiquitinated protein aggregation and aggresome formation, thereby cooperatively inhibiting apoptosis USP 1 Other H.sapiens 602 UCHL5_HUMAN E2F1_HUMAN Q9Y5K5 Q01094 UCHL5 E2F1 MEDLINE 26396186 Here we identify UCH37 as the first, to our knowledge, deubiquitinating enzyme for E2F1. UCH 1 Training data H.sapiens 603 UBP1_HUMAN FANCI_HUMAN O94782 Q9NVI1 USP1 FANCI MEDLINE 26430909 Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was. USP 1 Training data H.sapiens 604 UBP7_HUMAN REST_HUMAN Q93009 Q13127 USP7 REST MEDLINE 28464229 Collectively, our data demonstrate that the hTPH2 NRSE-mediated promoter repression via NRSF involves class I HDACs and is modulated by the ubiquitin-specific protease 7-mediated deubiquitination and stabilization of NRSF. USP 1 Training data H.sapiens 605 UBP1_HUMAN TBL1R_HUMAN O94782 Q9BZK7 USP1 TBL1XR1 MEDLINE 33102219 USP1 Maintains the Survival of Liver Circulating Tumor Cells by Deubiquitinating and Stabilizing TBLR1 USP 1 Other H.sapiens 606 UBP1_HUMAN RS16_HUMAN O94782 P62249 USP1 RPS16 MEDLINE 34154657 In this study, we revealed that USP1 interacts with RPS16, thereby deubiquitinating and stabilizing RPS16 via its DUB activity on C90 site. USP 1 Other H.sapiens 607 CYLD_HUMAN M3K7_HUMAN Q9NQC7 O43318 CYLD MAP3K7 MEDLINE 22057290 The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation USP 1 Other H.sapiens 608 UBP16_HUMAN MYC_HUMAN Q9Y5T5 P01106 USP16 MYC MEDLINE 33546726 USP16 regulates castration-resistant prostate cancer cell proliferation by deubiquitinating and stablizing c-Myc USP 1 Other H.sapiens 609 UBP7_HUMAN POLH_HUMAN Q93009 Q9Y253 USP7 POLH MEDLINE 25435364 USP7 directly serves as a specific DUB for Poleta USP 1 Other H.sapiens 610 UBP47_HUMAN DPOLL_HUMAN Q96K76 Q9UGP5 USP47 POLL MEDLINE 25121098 DNA Pol beta is a component of the BER complex. It is ubiquitinated by Mule and CHIP and is deubiquitinated by USP47 USP 1 Training data H.sapiens 611 USP9X_HUMAN T2R13_HUMAN Q93008 Q9NYV9 USP9X TAS2R13 MEDLINE 27593927 USP9x in turn stimulates JAG1 activity through two mechanisms: (1) through TRB3 deubiquitination and stabilization, and (2) through deubiquitination and activation of Mind Bomb 1, an E3 ligase required for JAG1 ubiquitination-mediated endocytosis and Notch activation. USP 1 Other H.sapiens 612 UBP7_HUMAN GLI1_HUMAN Q93009 P08151 USP7 GLI1 MEDLINE 26120032 Deubiquitination of Ci/Gli by Usp7/HAUSP regulates Hedgehog Signaling USP 1 Training data H.sapiens 613 UBP36_HUMAN RPA1_HUMAN Q9P275 O95602 USP36 POLR1A MEDLINE 22902402 USP36, the human ortholog of Ubp10, complements the ubp10Delta allele for RNAPI stability, pre-rRNA processing, and cell growth in yeast, suggesting that deubiquitination of RNAPI may be conserved in eukaryotes. USP 1 Other H.sapiens 614 UBP11_HUMAN ARI1A_HUMAN P51784 O14497 USP11 ARID1A MEDLINE 31914402 We identify that the E3 ligase TRIM32 and the deubiquitinase USP11 play key roles in controlling ARID1A stability USP 1 Other H.sapiens 615 PSDE_HUMAN PO5F1_HUMAN O00487 Q01860 PSMD14 POU5F1 MEDLINE 28279784 28279784 JAMM 1 Training data H.sapiens 616 UBP44_HUMAN PO5F1_HUMAN Q9H0E7 Q01860 USP44 POU5F1 MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 617 UBP10_HUMAN SNAI2_HUMAN Q14694 O43623 USP10 SNAI2 MEDLINE 29803676 Here, by using a genome wide siRNA screen for human deubiquitinating enzymes (DUBs), we identified USP10 as a deubiquitinase for Slug in cancer cells. USP 1 Training data H.sapiens 618 UBP7_HUMAN PO5F1_HUMAN Q93009 Q01860 USP7 POU5F1 MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 619 UBP15_HUMAN NRF1_HUMAN Q9Y4E8 Q16656 USP15 NRF1 MEDLINE 27416755 we report that USP15 (Ubiquitin-Specific Protease 15) activates Nrf1 in the nucleus by stabilizing it through deubiquitination USP 1 Other H.sapiens 620 UBP43_HUMAN ZEB1_HUMAN Q70EL4 P37275 USP43 ZEB1 MEDLINE 33391437 Meanwhile, USP43 can deubiquitinate and stabilize the ZEB1 protein, which plays an important role in the function of colorectal cancer. USP 1 Other H.sapiens 621 CSN5_HUMAN SNAI1_HUMAN Q92905 O95863 COPS5 SNAI1 MEDLINE 29755680 Importantly, we demonstrated that COPS5 binds to SNAIL and stabilizes its expression by deubiquitination JAMM 1 Other H.sapiens 622 UBP7_HUMAN TP53B_HUMAN Q93009 Q12888 USP7 TP53BP1 MEDLINE 28930533 53BP1 depletion induces mitotic defects such as disorientation of spindle poles attributed to extra centrosomes or mispositioning of centrosomes, leading to phenotypes similar to those in USP7-deficient cells. USP 1 Training data H.sapiens 623 UBP7_HUMAN NEK2_HUMAN Q93009 P51955 USP7 NEK2 MEDLINE 29863498 Taken together, our data indicate that USP7 stabilizes NEK2 through deubiquitination of NEK2, and inhibition of USP7 with P5091 depletes NEK2 protein USP 1 Other H.sapiens 624 UBP7_HUMAN PPARG_HUMAN Q93009 P37231 USP7 PPARG MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 625 UBP28_HUMAN UCK1_HUMAN Q96RU2 Q9HA47 USP28 UCK1 MEDLINE 31938050 We showed that deubiquitinase USP28 antagonized KLHL2-mediated polyubiquitylation of UCK1. USP 1 Other H.sapiens 626 UBP7_HUMAN CTNB1_HUMAN Q93009 P35222 USP7 CTNNB1 MEDLINE 29045831 USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating BETA-CATENIN Deubiquitination USP 1 Training data H.sapiens 627 UCHL5_HUMAN SMO_HUMAN Q9Y5K5 Q99835 UCHL5 SMO MEDLINE 28992318 The deubiquitinase UCHL5/UCH37 positively regulates Hedgehog signaling by deubiquitinating SMOOTHENED UCH 1 Training data H.sapiens 628 OTUB1_HUMAN NR4A1_HUMAN Q96FW1 P22736 OTUB1 NR4A1 MEDLINE 30905540 We found that OTUB1 interacted with Nur77 to deubiquitinate it, thereby stabilizing Nur77 in an Asp88-dependent manner. OTU 1 Other H.sapiens 629 UBP11_HUMAN PRC1_HUMAN P51784 O43663 USP11 PRC1 MEDLINE 29142505 29142505 USP 1 Training data H.sapiens 630 ATX3_HUMAN HDAC3_HUMAN P54252 O15379 ATXN3 HDAC3 MEDLINE 29802126 ATXN3 Positively Regulates Type I IFN Antiviral Response by Deubiquitinating and Stabilizing HDAC3 Josephin 1 Training data H.sapiens 631 UBP26_HUMAN PRC1_HUMAN Q9BXU7 O43663 USP26 PRC1 MEDLINE 29142505 29142505 USP 1 Training data H.sapiens 632 UBP7_HUMAN PRC1_HUMAN Q93009 O43663 USP7 PRC1 MEDLINE 29142505 29142505 USP 1 Training data H.sapiens 633 UBP27_HUMAN SNAI1_HUMAN A6NNY8 O95863 USP27X SNAI1 MEDLINE 30341066 Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability USP 1 Other H.sapiens 634 UBP18_HUMAN PTEN_HUMAN Q9UMW8 P60484 USP18 PTEN MEDLINE 29142505 29142505 USP 1 Training data H.sapiens 635 UBP7_HUMAN PTEN_HUMAN Q93009 P60484 USP7 PTEN MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 636 UBP28_HUMAN NOTC1_HUMAN Q96RU2 P46531 USP28 NOTCH1 MEDLINE 32578360 Furthermore, cellular assays were conducted to confirm that Vismodegib could interact with the evolutionarily related deubiquitinases USP28 and USP25 and down-regulate the levels of the two enzymes' substrate proteins c-Myc, Notch1 and Tankyrase-1/2. USP 1 Other H.sapiens 637 USP9X_HUMAN BCL10_HUMAN Q93008 O95999 USP9X BCL10 MEDLINE 23690623 Mechanistically, USP9X interacts with Bcl10 of the Carma1-Bcl10-Malt1 (CBM) complex and removes the TCR-induced ubiquitin chain from Bcl10, which facilitates the association of Carma1 with Bcl0-Malt1. USP 1 Other H.sapiens 638 UBP2_HUMAN PTH1R_HUMAN O75604 Q03431 USP2 PTH1R MEDLINE 26643174 Usp2 is a deubiquitination enzyme targeting various factors including CyclinD1 in cancer cells and PTH receptor 1 in osteoblasts USP 1 Training data H.sapiens 639 UBP4_HUMAN TP4A3_HUMAN Q13107 O75365 USP4 PTP4A3 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 640 UBP15_HUMAN FKBP5_HUMAN Q9Y4E8 Q13451 USP15 FKBP5 MEDLINE 33135363 CONCLUSIONS: Our results show that USP15 exacerbates NP degradation by deubiquitinating and stabilizing FKBP5 USP 1 Other H.sapiens 641 UBP22_HUMAN HIF1A_HUMAN Q9UPT9 Q16665 USP22 HIF1A MEDLINE 31776228 RESULTS: USP22 promotes hypoxia-induced HCC stemness and glycolysis by deubiquitinating and stabilising HIF1ALPHA USP 1 Other H.sapiens 642 UCHL3_HUMAN RA51B_HUMAN P15374 O15315 UCHL3 RAD51B MEDLINE 27941124 Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM. UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2. UCH 1 Training data H.sapiens 643 UBP33_HUMAN RALB_HUMAN Q8TEY7 P11234 USP33 RALB MEDLINE 26445063 26445063 USP 1 Training data H.sapiens 644 UBP10_HUMAN AAPK2_HUMAN Q14694 P54646 USP10 PRKAA2 MEDLINE 26876938 The deubiquitinase USP10 specifically removes ubiquitination on AMPKALPHA to facilitate AMPKALPHA phosphorylation by LKB1 USP 1 Training data H.sapiens 645 ATX3_HUMAN TERA_HUMAN P54252 P55072 ATXN3 VCP MEDLINE 17000876 We present evidence that atx3 may promote p97-associated deubiquitination to facilitate the transfer of polypeptides from p97 to the proteasome Josephin 1 Training data H.sapiens 646 UBP7_HUMAN ANDR_HUMAN Q93009 P10275 USP7 AR MEDLINE 26175158 We showed that USP7 associates with AR in an androgen-dependent manner and mediates AR deubiquitination USP 1 Other H.sapiens 647 UBP11_HUMAN RANB9_HUMAN P51784 Q96S59 USP11 RANBP9 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 648 UBP7_HUMAN RB_HUMAN Q93009 P06400 USP7 RB1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 649 UBP10_HUMAN SMAD4_HUMAN Q14694 Q13485 USP10 SMAD4 MEDLINE 31721429 In this study, using a functional screen of USPs siRNA library, we identified ubiquitin-specific proteases USP10 as a deubiquitinating enzyme (DUB) that sustains the protein level of Smad4 and activates TGF-beta signaling USP 1 Other H.sapiens 650 UBP15_HUMAN RBX1_HUMAN Q9Y4E8 P62877 USP15 RBX1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 651 CYLD_HUMAN TF65_HUMAN Q9NQC7 Q04206 CYLD RELA MEDLINE 29394249 29394249 USP 1 Other H.sapiens 652 UBP7_HUMAN TF65_HUMAN Q93009 Q04206 USP7 RELA MEDLINE 25121098 25121098 USP 1 Training data H.sapiens 653 UBP15_HUMAN REST_HUMAN Q9Y4E8 Q13127 USP15 REST MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 654 UBP7_HUMAN MCL1_HUMAN Q93009 Q07820 USP7 MCL1 MEDLINE 32802178 Conclusions: The deubiquitinase USP7-mediated MCL-1 up-regulation enhances arsenic and BaP co-exposure-induced CSC-like property and tumorigenesis, providing the first evidence demonstrating that USP7 stabilizes MCL-1 protein during the tumorigenic process. USP 1 Other H.sapiens 655 USP9X_HUMAN ERG_HUMAN Q93008 P11308 USP9X ERG MEDLINE 24591637 we show that ubiquitin-specific peptidase 9, X-linked (USP9X), a deubiquitinase enzyme, binds ERG in VCaP prostate cancer cells expressing TMPRSS2-ERG and deubiquitinates ERG in vitro. USP 1 Other H.sapiens 656 UBP20_HUMAN RIPK1_HUMAN Q9Y2K6 Q13546 USP20 RIPK1 MEDLINE 30354204 TNF evoked -2-fold more RIPK1 ubiquitination in SMC-DN-USP20-Tg than in control SMCs, and RIPK1 was deubiquitinated by purified USP20 in vitro. USP 1 Training data H.sapiens 657 UBP7_HUMAN RIPK1_HUMAN Q93009 Q13546 USP7 RIPK1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 658 UCHL5_HUMAN NFRKB_HUMAN Q9Y5K5 Q6P4R8 UCHL5 NFRKB MEDLINE 32351584 DRAIC combined with UCHL5 and attenuated binding of UCHL5 and NFRKB, meanwhile promoting the degradation of NFRKB via ubiquitination, and then inhibited the proliferation and metastasis of GC cells, which can be rescued by oeNFRKB UCH 1 Other H.sapiens 659 UBP33_HUMAN CP110_HUMAN Q8TEY7 O43303 USP33 CCP110 MEDLINE 23486064 USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110 USP 1 Training data H.sapiens 660 UBP19_HUMAN FUND1_HUMAN O94966 Q8IVP5 USP19 FUNDC1 MEDLINE 33978709 In response to hypoxia, USP19 binds to and deubiquitinates FUNDC1 at ER-mitochondria contact sites, which facilitates Drp1 oligomerization and Drp1 GTP-binding and hydrolysis activities, thereby promoting mitochondrial division USP 1 Other H.sapiens 661 UBP34_HUMAN RN168_HUMAN Q70CQ2 Q8IYW5 USP34 RNF168 MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 662 UBP15_HUMAN DDX58_HUMAN Q9Y4E8 O95786 USP15 DDX58 MEDLINE 26061460 USP15 specifically removed lysine 63-linked polyubiquitin chains from RIG-I among the essential components in RIG-I-like receptor-dependent pathway USP 1 Other H.sapiens 663 UBP7_HUMAN RN168_HUMAN Q93009 Q8IYW5 USP7 RNF168 MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 664 Q05CD9_HUMAN RNF41_HUMAN Q05CD9 Q9H4P4 USP8 RNF41 MEDLINE 15314180 hUbiquitome USP 1 Other H.sapiens 665 BAP1_HUMAN FOXK2_HUMAN Q92560 Q01167 BAP1 FOXK2 MEDLINE 25451922 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes the ubiquitin-mediated activation of FoxK2 target genes. Okino Y(1), Machida Y(1), Frankland-Searby S(2), Machida YJ(3). Author information: (1)From the Departments of Oncology and. (2)Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905. (3)From the Departments of Oncology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905 machida.yuichi@mayo.edu. BRCA1-associated protein 1 (BAP1), which is frequently mutated in cancer, functions as a deubiquitinase (DUB) for histone H2A.BAP1 represses FoxK2 target genes, and this effect requires BAP1 DUB activity but not interaction with HCF-1 UCH 1 Other H.sapiens 666 OTUB1_HUMAN RFA1_HUMAN Q96FW1 P27694 OTUB1 RPA1 MEDLINE 26403191 PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination OTU 1 Training data H.sapiens 667 UBP35_HUMAN ESR1_HUMAN Q9P2H5 P03372 USP35 ESR1 MEDLINE 34131114 Mechanistically, USP35 enhanced ERALPHA stability by interacting and deubiquitinating ERALPHA, and transcriptional activity of ERALPHA by interacting with ERALPHA in DNA regions containing estrogen response element USP 1 Other H.sapiens 668 UBP8_HUMAN RNF41_HUMAN P40818 Q9H4P4 USP8 RNF41 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 669 UBP11_HUMAN NONO_HUMAN P51784 Q15233 USP11 NONO MEDLINE 33369124 Collectively, these results demonstrate that USP11 is a new deubiquitinase of NONO and that the signalling axis of USP11-NONO is significantly involved in melanoma proliferation. USP 1 Other H.sapiens 670 UBP10_HUMAN CDN2A_HUMAN Q14694 P42771 USP10 CDKN2A MEDLINE 29472714 Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF USP 1 Other H.sapiens 671 USP9X_HUMAN ZAP70_HUMAN Q93008 P43403 USP9X ZAP70 MEDLINE 26936881 Usp9X becomes competent to deubiquitinate ZAP70 through TCR-dependent phosphorylation and enhancement of its catalytic activity and association with the LAT signalosome USP 1 Other H.sapiens 672 U17L2_HUMAN TWST1_HUMAN Q6R6M4 Q15672 USP17L2 TWIST1 MEDLINE 29088851 In this study, we identified Dub3 as a novel DUB for both Slug and Twist. We further found that Dub3 overexpression increased Slug and Twist protein levels in a dose-dependent manner, whereas Dub3-knockdown decreased their protein levels. USP 1 Other H.sapiens 673 U17L2_HUMAN HYAS2_HUMAN Q6R6M4 Q92819 USP17L2 HAS2 MEDLINE 28604766 Several DUBs were found to decrease the ubiquitination of 6myc-HAS2, among which, the most effective were USP17 and USP4. USP17 efficiently removed polyubiquitination, whereas USP4 preferentially removed monoubiquitination of 6myc-HAS2. USP 1 Other H.sapiens 674 UBP15_HUMAN SART3_HUMAN Q9Y4E8 Q15020 USP15 SART3 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 675 UBP11_HUMAN PALB2_HUMAN P51784 Q86YC2 USP11 PALB2 MEDLINE 26649820 PALB2 ubiquitylation suppresses its interaction with BRCA1 and is counteracted by the deubiquitylase USP11 USP 1 Other H.sapiens 676 UBP15_HUMAN TF65_HUMAN Q9Y4E8 Q04206 USP15 RELA MEDLINE 30459344 USP15 overexpression promoted NF-kappaBP65 expression through inhibition of its ubiquitination, whereas NF-kappaBP65 promoted USP15 expression as a positive regulator USP 1 Other H.sapiens 677 UBP8_HUMAN SCNNA_HUMAN P40818 P37088 USP8 SCNN1A MEDLINE 23297398 USP8 interacted with ENaC, as detected by co-immunoprecipitation, and it deubiquitinated ENaC. USP 1 Training data H.sapiens 678 UBP2_HUMAN SCNNB_HUMAN O75604 P51168 USP2 SCNN1B MEDLINE 20090362 The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2. USP 1 Other H.sapiens 679 UBP2_HUMAN SCNNG_HUMAN O75604 P51170 USP2 SCNN1G MEDLINE 20090362 The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2. USP 1 Other H.sapiens 680 UBP18_HUMAN TWST1_HUMAN Q9UMW8 Q15672 USP18 TWIST1 MEDLINE 32368392 USP18 deubiquitinates and stabilizes Twist1 to promote epithelial-mesenchymal transition in glioblastoma cells USP 1 Other H.sapiens 681 UBP8_HUMAN SFRP4_HUMAN P40818 Q6FHJ7 USP8 SFRP4 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 682 UBP7_HUMAN AXIN1_HUMAN Q93009 O15169 USP7 AXIN1 MEDLINE 31519875 USP7 directly interacts with Axin through its TRAF domain, and promotes deubiquitination and stabilization of Axin USP 1 Other H.sapiens 683 UBP2_HUMAN SIR1_HUMAN O75604 Q96EB6 USP2 SIRT1 MEDLINE 29142505 29142505 USP 1 Training data H.sapiens 684 UBP7_HUMAN PAX7_HUMAN Q93009 P23759 USP7 PAX7 MEDLINE 32115872 In this context, previous work showed that Pax7 is ubiquitinated by the E3 ligase Nedd4-1 and interacts with several proteins related to the ubiquitin-proteasome system, including the deubiquitinase Usp7 USP 1 Other H.sapiens 685 UBP22_HUMAN SIR1_HUMAN Q9UPT9 Q96EB6 USP22 SIRT1 MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 686 UBP30_HUMAN MFN1_HUMAN Q70CQ3 Q8IWA4 USP30 MFN1 MEDLINE 29178074 USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2. USP 1 Training data H.sapiens 687 UBP10_HUMAN SIR6_HUMAN Q14694 Q8N6T7 USP10 SIRT6 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 688 UBP19_HUMAN HDAC1_HUMAN O94966 Q13547 USP19 HDAC1 MEDLINE 27517492 USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability USP 1 Training data H.sapiens 689 UBP12_HUMAN ANDR_HUMAN O75317 P10275 USP12 AR MEDLINE 26462181 The AR is known to be regulated by a number of post-translational modifications and we have recently identified the deubiquitinating enzyme Usp12 as a positive regulator of AR USP 1 Training data H.sapiens 690 UBP11_HUMAN CDN1A_HUMAN P51784 P38936 USP11 CDKN1A MEDLINE 29666278 In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21, and stabilizes p21 protein USP 1 Other H.sapiens 691 PAN2_HUMAN ASF1A_HUMAN Q504Q3 Q9Y294 PAN2 ASF1A MEDLINE 29599486 Additionally, we find that USP52 is overexpressed in breast carcinomas, and its level of expression correlates with that of ASF1A. USP 1 Training data H.sapiens 692 USP9X_HUMAN YAP1_HUMAN Q93008 P46937 USP9X YAP1 MEDLINE 29449692 Here we demonstrate that the deubiquitination enzyme USP9X deubiquitinates and stabilizes YAP1, thereby promoting cancer cell survival. USP 1 Training data H.sapiens 693 USP9X_HUMAN SMAD1_HUMAN Q93008 Q15797 USP9X SMAD1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 694 UCHL1_HUMAN SMAD2_HUMAN P09936 Q15796 UCHL1 SMAD2 MEDLINE 32371398 32371398 UCH 1 Other H.sapiens 695 UBP10_HUMAN CCND1_HUMAN Q14694 P24385 USP10 CCND1 MEDLINE 33184448 USP10 interacted with CCND1 and prevented its K48- but not K63-linked polyubiquitination in GBM U251 and HS683 cells, which led to increased CCND1 stability USP 1 Other H.sapiens 696 UCHL1_HUMAN SMAD3_HUMAN P09936 P84022 UCHL1 SMAD3 MEDLINE 32371398 32371398 UCH 1 Other H.sapiens 697 OTUB1_HUMAN SMAD3_HUMAN Q96FW1 P84022 OTUB1 SMAD3 MEDLINE 24071738 OTUB1 enhances TGFbeta signalling by inhibiting the ubiquitylation and degradation of active SMAD2/3 OTU 1 Other H.sapiens 698 UBP4_HUMAN RNPS1_HUMAN Q13107 Q15287 USP4 RNPS1 MEDLINE 27990632 Although RNPS1 is polyubiquitinated by both K48- and K63-linkages, USP4 exclusively deubiquitinates K63-linked polyubiquitin chains of RNPS1. USP 1 Training data H.sapiens 699 UBP1_HUMAN PHLP1_HUMAN O94782 O60346 USP1 PHLPP1 MEDLINE 25121098 USP1 [137] and USP46 [138] are other DUBs known to deubiquitinate PHLPP1, with a similar outcome in other cancers as well. USP 1 Training data H.sapiens 700 UBP44_HUMAN EZH2_HUMAN Q9H0E7 Q15910 USP44 EZH2 MEDLINE 30622230 We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination USP 1 Other H.sapiens 701 UBP7_HUMAN NED4L_HUMAN Q93009 Q96PU5 USP7 NEDD4L MEDLINE 33106424 USP7 deubiquitinates the E3 ubiquitin ligase NEDD4L, which mediates the degradation of SMAD2 USP 1 Other H.sapiens 702 OTUD5_HUMAN PDCD5_HUMAN Q96G74 O14737 OTUD5 PDCD5 MEDLINE 25499082 Conversely, PDCD5 knockdown greatly attenuated the effect of OTUD5 on p53 activation. OTU 1 Training data H.sapiens 703 OTU7B_HUMAN ZAP70_HUMAN Q6GQQ9 P43403 OTUD7B ZAP70 MEDLINE 26903241 Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination OTU 1 Training data H.sapiens 704 UBP15_HUMAN SMAD6_HUMAN Q9Y4E8 O43541 USP15 SMAD6 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 705 UBP47_HUMAN CTNB1_HUMAN Q96K76 P35222 USP47 CTNNB1 MEDLINE 29080116 Additionally, DUBs USP14, USP15, USP47, and Fam/USP9X have been reported to prevent BETA-CATENIN turnover by inhibiting its Ub-proteasomal degradation USP 1 Training data H.sapiens 706 JOS1_HUMAN MCL1_HUMAN Q15040 Q07820 JOSD1 MCL1 MEDLINE 31043700 Mechanistically, we showed that JOSD1 deubiquitinated and stabilized MCL1 to suppress mitochondrial apoptotic signalling Josephin 1 Other H.sapiens 707 OTU7B_HUMAN KDM1A_HUMAN Q6GQQ9 O60341 OTUD7B KDM1A MEDLINE 34050636 OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis OTU 1 Other H.sapiens 708 UBP8_HUMAN CASP1_HUMAN P40818 P29466 USP8 CASP1 MEDLINE 30065070 NS1 recruits the host deubiquitinase USP8 to cleave K11-linked poly-ubiquitin chains from CASPASE-1 at Lys134, thus inhibiting the proteasomal degradation of CASPASE-1 USP 1 Other H.sapiens 709 SNUT2_HUMAN CHK2_HUMAN Q53GS9 O96017 USP39 CHEK2 MEDLINE 30771428 Mechanistically, USP39 deubiquitinates and stabilizes CHK2, which in turn enhances CHK2 stability USP 1 Other H.sapiens 710 USP9X_HUMAN BRCA1_HUMAN Q93008 P38398 USP9X BRCA1 MEDLINE 31512408 Collectively, these results establish USP9X as a deubiquitinase for BRCA1 and reveal a previously unrecognized role of USP9X in the regulation of HR repair and the sensitivity of cancer cells to DNA-damaging agents. USP 1 Other H.sapiens 711 CYLD_HUMAN PLK1_HUMAN Q9NQC7 P53350 CYLD PLK1 MEDLINE 26763122 Other identified CYLD substrates include TNF receptor associated factor 7 (TRAF7), TRAF interacting protein (TRIP), transforming growth factor beta-activated kinase 1 (TAK1), NF-kappa-B essential modifier (NEMO), lymphocyte cell specific protein-tyrosine kinase (LCK), receptor-interacting protein 1 (RIP1), retinoic acid inducible gene (RIG), and polo-like kinase 1 (PLK1) USP 1 Training data H.sapiens 712 UBP15_HUMAN DEK_HUMAN Q9Y4E8 P35659 USP15 DEK MEDLINE 34280614 KIF15 upregulation promotes leiomyosarcoma cell growth via promoting USP15-mediated DEK deubiquitylation USP 1 Other H.sapiens 713 UBP8_HUMAN SMO_HUMAN P40818 Q99835 USP8 SMO MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 714 UBP27_HUMAN B2L11_HUMAN A6NNY8 O43521 USP27X BCL2L11 MEDLINE 27013495 Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK-dependent phosphorylation and can upregulate its expression levels. USP 1 Training data H.sapiens 715 UBP22_HUMAN YAP1_HUMAN Q9UPT9 P46937 USP22 YAP1 MEDLINE 33777217 Moreover, USP22 interacted with and deubiquitinated YAP to prevent YAP turnover USP 1 Other H.sapiens 716 USP9X_HUMAN SMUF1_HUMAN Q93008 Q9HCE7 USP9X SMURF1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 717 XRCC6_HUMAN MCL1_HUMAN P12956 Q07820 XRCC6 MCL1 MEDLINE 24769731 Conversely, expression of exogenous Ku70 in Ku70(-/-) MEF cells restores MCL-1 expression. Other 1 Training data H.sapiens 718 UBP22_HUMAN CCNB1_HUMAN Q9UPT9 P14635 USP22 CCNB1 MEDLINE 27030811 Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1 USP 1 Other H.sapiens 719 UBP7_HUMAN RAD18_HUMAN Q93009 Q9NS91 USP7 RAD18 MEDLINE 25961918 We demonstrate that USP7 associates with Rad18 directly via a consensus USP7-binding motif and can disassemble Rad18-dependent poly-ubiquitin chains both in vitro and in vivo USP 1 Other H.sapiens 720 OTUB1_HUMAN SNAI1_HUMAN Q96FW1 O95863 OTUB1 SNAI1 MEDLINE 29559747 Functionally, OTUB1 facilitates metastasis of esophageal squamous cell carcinoma (ESCC) through promoting Snail protein stability. OTU 1 Training data H.sapiens 721 UBP14_HUMAN NLRC5_HUMAN P54578 Q86WI3 USP14 NLRC5 MEDLINE 26620908 The researchers propose that, after the ubiquitination of NLRC5 at lysine 1178 is catalyzed by TRAF2/6, USP14 specifically removes the polyubiquitin chains from NLRC5 to enhance NLRC5-mediated inhibition of IKK-NF-kappaB signaling, thus forming a coherent feedforward loop to regulate IKK-NF-kappaB activation USP 1 Training data H.sapiens 722 CSN5_HUMAN SNAI2_HUMAN Q92905 O43623 COPS5 SNAI2 MEDLINE 29755680 In this study, we identified COP9 signalosome subunit 5 (COPS5) as a deubiquitinating enzyme of SNAIL by using siRNA library screening. JAMM 1 Training data H.sapiens 723 UBP8_HUMAN NTRK2_HUMAN P40818 Q16620 USP8 NTRK2 MEDLINE 33288548 TrkB deubiquitination by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation USP 1 Other H.sapiens 724 OTUB1_HUMAN UBE2N_HUMAN Q96FW1 P61088 OTUB1 UBE2N MEDLINE 25121098 Although OTUB1 is not catalytically involved in deubiquitinating these K63-linked chains, it may interact with Ubc13 and inhibit the E3 ligase RNF168 OTU 1 Training data H.sapiens 725 UBP20_HUMAN KPYM_HUMAN Q9Y2K6 P14618 USP20 PKM MEDLINE 25708858 From this evidence, it is expected that USP20 would be associated with the metabolic pathway through the regulation of PKM2 ubiquitination. USP 1 Other H.sapiens 726 UBP36_HUMAN SODM_HUMAN Q9P275 P04179 USP36 SOD2 MEDLINE 21268071 we identified a deubiquitinating enzyme USP36 that regulates the protein stability of SOD2 USP 1 Other H.sapiens 727 UBP5_HUMAN SNAI2_HUMAN P45974 O43623 USP5 SNAI2 MEDLINE 30809294 30809294 USP 1 Other H.sapiens 728 USP9X_HUMAN SYUA_HUMAN Q93008 P37840 USP9X SNCA MEDLINE 22361583 We recently found that USP9X deubiquitinates alpha-synuclein, and that this process determines the partition of alpha-synuclein between the proteasomal and autophagy pathways. USP 1 Training data H.sapiens 729 UBP24_HUMAN ULK1_HUMAN Q9UPU5 O75385 USP24 ULK1 MEDLINE 30957634 Our data indicate that USP24 regulates autophagy by affecting ubiquitination and stability of the ULK1 protein USP 1 Other H.sapiens 730 UCHL1_HUMAN SYUA_HUMAN P09936 P37840 UCHL1 SNCA MEDLINE 30126257 The deubiquitination of alpha-synuclein aggregates by USP9X favor their degradation by autophagy, while UCH-L1 contribute to the accumulation of alpha-synuclein by downregulating its lysosomal degradation. UCH 1 Training data H.sapiens 731 UBP8_HUMAN SYUA_HUMAN P40818 P37840 USP8 SNCA MEDLINE 30126257 In addition, this study identifies USP8 as one of the best markers of Lewy bodies in human pigmented neurons in sporadic cases of Parkinson's disease and demonstrates the ability of USP8 to hydrolyze K63-linked ubiquitin chains from alpha-synuclein in vitro. USP 1 Training data H.sapiens 732 PSDE_HUMAN IL1B_HUMAN O00487 P01584 PSMD14 IL1B MEDLINE 30315153 In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1beta by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1beta cleavage JAMM 1 Other H.sapiens 733 UBP14_HUMAN VIME_HUMAN P54578 P08670 USP14 VIM MEDLINE 30319415 Furthermore, USP14 can also deubiquitinate and stabilize vimentin, a vital protein which involves in epithelial-to-mesenchymal transition(EMT) and significantly promotes cell growth, migration and invasion in human gastric cancer USP 1 Training data H.sapiens 734 UBP6_HUMAN JUN_HUMAN P35125 P05412 USP6 JUN MEDLINE 29061731 Based on our data, USP6 is an enzyme that deubiquitinates c-Jun and regulates its downstream cellular functions. USP 1 Training data H.sapiens 735 UBP8_HUMAN SC31A_HUMAN P40818 O94979 USP8 SEC31A MEDLINE 29604273 Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion USP 1 Training data H.sapiens 736 CYLD_HUMAN TRAF7_HUMAN Q9NQC7 Q6Q0C0 CYLD TRAF7 MEDLINE 26763122 Other identified CYLD substrates include TNF receptor associated factor 7 (TRAF7), TRAF interacting protein (TRIP), transforming growth factor beta-activated kinase 1 (TAK1), NF-kappa-B essential modifier (NEMO), lymphocyte cell specific protein-tyrosine kinase (LCK), receptor-interacting protein 1 (RIP1), retinoic acid inducible gene (RIG), and polo-like kinase 1 (PLK1) USP 1 Training data H.sapiens 737 UBP22_HUMAN SOX2_HUMAN Q9UPT9 P48431 USP22 SOX2 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 738 UBP8_HUMAN SOX2_HUMAN P40818 P48431 USP8 SOX2 MEDLINE 31243344 Elevated USP8 subsequently acts as an E3 ligase to promote SOX2 ubiquitination and protein degradation USP 1 Other H.sapiens 739 USP9X_HUMAN SOX2_HUMAN Q93008 P48431 USP9X SOX2 MEDLINE 27919796 27919796 USP 1 Training data H.sapiens 740 OTUB1_HUMAN TRAF6_HUMAN Q96FW1 Q9Y4K3 OTUB1 TRAF6 MEDLINE 19996094 Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6 OTU 1 Training data H.sapiens 741 UBP4_HUMAN M3K7_HUMAN Q13107 O43318 USP4 MAP3K7 MEDLINE 21331078 Using a functional genomic approach, we have identified ubiquitin-specific peptidase 4 (USP4) as a deubiquitinase for TAK1. USP 1 Other H.sapiens 742 UBP13_HUMAN A0A291NLA3_HUMAN Q92995 A0A291NLA3 USP13 SIGIRR MEDLINE 31204278 The deubiquitinase USP13 stabilizes the anti-inflammatory receptor IL-1R8/Sigirr to suppress lung inflammation USP 1 Other H.sapiens 743 UBP8_HUMAN KIF23_HUMAN P40818 Q02241 USP8 KIF23 UNIPROT UBP15_HUMAN Deubiquitinates BIRC6/bruce and KIF23/MKLP1 USP 1 Other H.sapiens 744 UBP7_HUMAN ECT2_HUMAN Q93009 Q9H8V3 USP7 ECT2 MEDLINE 32929379 Co-immunoprecipitation, immunofluorescent stainings, in vivo deubiquitination and in vitro deubiquitination experiments were performed to examine the physical and functional interaction between ECT2 and ubiquitin-specific protease USP7 USP 1 Other H.sapiens 745 UBP36_HUMAN MAD1_HUMAN Q9P275 Q05195 USP36 MXD1 MEDLINE 33647641 Mechanistically, lnc-HZ01 promotes MXD1 mRNA transcription by up-regulating its transcription factor c-JUN and also enhances MXD1 protein stability by up-regulating its deubiquitin enzyme USP36 USP 1 Other H.sapiens 746 USP9X_HUMAN IF4A2_HUMAN Q93008 P60842 USP9X EIF4A1 MEDLINE 29228324 Our results provide evidence that USP9X is a novel regulator of the translation initiation process via deubiquitination of eIF4A1 USP 1 Other H.sapiens 747 UBP14_HUMAN BECN1_HUMAN P54578 Q14457 USP14 BECN1 MEDLINE 27542828 USP14 regulates autophagy by suppressing K63 ubiquitination of BECLIN 1 USP 1 Training data H.sapiens 748 UBP3_HUMAN UIMC1_HUMAN Q9Y6I4 Q96RL1 USP3 UIMC1 MEDLINE 25121098 K63-linked ubiquitin accumulates on Rap80 at the DSB foci with the concerted effect of RNF8, RNF168, and Ubc13, which are clipped off with the assistance of USP3 and BRCC36 to maintain the G2/M checkpoint. USP 1 Training data H.sapiens 749 UBP14_HUMAN TAB2_HUMAN P54578 Q9NYJ8 USP14 TAB2 MEDLINE 29326710 Taken together, our data demonstrate that USP14 can negatively regulate autophagy induction by inhibiting Beclin 1 ubiquitination, interrupting association between TRAF6 and Beclin 1, and affecting TLR4-induced activation of NF-kappaB through deubiquitination of TAB 2 protein USP 1 Training data H.sapiens 750 UBP8_HUMAN EPS15_HUMAN P40818 P42566 USP8 EPS15 UNIPROT OTUB1_HUMAN Deubiquitinates EPS15 and controles tyrosine kinase stability USP 1 Other H.sapiens 751 UBP46_HUMAN ENOA_HUMAN P62068 P06733 USP46 ENO1 MEDLINE 32707136 In addition, we found that USP46 is a bona fide deubiquitinating enzyme to stabilize the protein level of ENO1 through deubiquitination USP 1 Other H.sapiens 752 UBP37_HUMAN EPAS1_HUMAN Q86T82 Q99814 USP37 EPAS1 MEDLINE 32461361 USP37 promotes deubiquitination of HIF2ALPHA in kidney cancer USP 1 Other H.sapiens 753 UBP8_HUMAN BIRC6_HUMAN P40818 Q9NR09 USP8 BIRC6 UNIPROT UBP37_HUMAN Deubiquitinates BIRC6/bruce and KIF23/MKLP1 USP 1 Other H.sapiens 754 TNAP3_HUMAN TRAF2_HUMAN P21580 Q12933 TNFAIP3 TRAF2 MEDLINE 24673262 A tight control in TNF-a led NF-kB activation is exerted byA20 as it targets both RIP1 and TRAF2 through different mechanisms OTU 1 Training data H.sapiens 755 UBP10_HUMAN TAP1_HUMAN Q14694 Q03518 USP10 TAP1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 756 UBP7_HUMAN CRY1_HUMAN Q93009 Q16526 USP7 CRY1 MEDLINE 27123980 We found that ubiquitin-specific protease 7 (USP7 also known as HAUSP) associates with CRY1 and CRY2 and stabilizes CRYs through deubiquitination USP 1 Training data H.sapiens 757 UBP21_HUMAN FOXP3_HUMAN Q9UK80 Q9BZS1 USP21 FOXP3 MEDLINE 27857073 USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes USP 1 Training data H.sapiens 758 UBP11_HUMAN XPC_HUMAN P51784 Q01831 USP11 XPC MEDLINE 29228550 Regulation of XPC deubiquitination by USP11 in repair of UV-induced DNA damage USP 1 Training data H.sapiens 759 UBP15_HUMAN IF4A1_HUMAN Q9Y4E8 P60842 USP15 EIF4A1 MEDLINE 34422211 Platelet-Rich Plasma-Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1 USP 1 Other H.sapiens 760 UBP10_HUMAN TBX21_HUMAN Q14694 Q9UL17 USP10 TBX21 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 761 UBP22_HUMAN TERF1_HUMAN Q9UPT9 P54274 USP22 TERF1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 762 UCHL5_HUMAN TGFR1_HUMAN Q9Y5K5 P36897 UCHL5 TGFBR1 MEDLINE 24756567 Via SMAD7, UCH37 can further be recruited to TbetaRI, where it removes polyubiquitin chains synthesized by SMURF UCH 1 Training data H.sapiens 763 UBP19_HUMAN RN123_HUMAN O94966 Q5XPI4 USP19 RNF123 MEDLINE 25121098 USP19 deubiquitinates Kip1 ubiquitination-promoting complex protein 1 (KPC1) regulating p27Kip1 USP 1 Training data H.sapiens 764 UBP7_HUMAN KAT5_HUMAN Q93009 Q92993 USP7 KAT5 MEDLINE 25121098 USP7 deubiquitinates and stabilizes the acetyltransferase Tip60 to induce p53-dependent apoptotic pathways USP 1 Training data H.sapiens 765 UBP11_HUMAN TGFR1_HUMAN P51784 P36897 USP11 TGFBR1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 766 UBP15_HUMAN TGFR1_HUMAN Q9Y4E8 P36897 USP15 TGFBR1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 767 USP9X_HUMAN SMAD4_HUMAN Q93008 Q13485 USP9X SMAD4 MEDLINE 25317929 Multiple mono-ubiquitination of SMAD3 can be removed by USP15 and mono-ubiquitination of SMAD4 seems to be removed by FAM/USP9X USP 1 Training data H.sapiens 768 CYLD_HUMAN TRAF2_HUMAN Q9NQC7 Q12933 CYLD TRAF2 MEDLINE 28900035 We conclude that PrP traps CYLD, preventing it from binding and deubiquitinating RIP1 and TRAF2. USP 1 Training data H.sapiens 769 UBP8_HUMAN CHM1B_HUMAN P40818 Q7LBR1 USP8 CHMP1B MEDLINE 29933386 Based on these observations, we propose that CHMP1B is dynamically regulated by ubiquitination in response to EGF and that USP8 triggers CHMP1B deubiquitination possibly favoring its subsequent assembly into a membrane-associated ESCRT-III polymer. USP 1 Other H.sapiens 770 UBP21_HUMAN BRCA2_HUMAN Q9UK80 P51587 USP21 BRCA2 MEDLINE 28743957 Together, our findings identify deubiquitination as a means to regulate BRCA2 function and point to USP21 as a potential therapeutic target in BRCA2-proficient tumors. USP 1 Training data H.sapiens 771 UCHL1_HUMAN TGFR1_HUMAN P09936 P36897 UCHL1 TGFBR1 MEDLINE 31857432 Mechanistically, UCHL1 facilitates TGFbeta signaling-induced metastasis by protecting TGFbeta type I receptor and SMAD2 from ubiquitination UCH 1 Other H.sapiens 772 USP9X_HUMAN TRIB3_HUMAN Q93008 Q96RU7 USP9X TRIB3 MEDLINE 27593927 USP9x in turn stimulates JAG1 activity through two mechanisms: (1) through TRB3 deubiquitination and stabilization, and (2) through deubiquitination and activation of Mind Bomb 1, an E3 ligase required for JAG1 ubiquitination-mediated endocytosis and Notch activation. USP 1 Training data H.sapiens 773 UBP10_HUMAN TBP_HUMAN Q14694 P20226 USP10 TBP MEDLINE 26393420 Huwe1 as an E3 ligase targeting TBP for K48-linked ubiquitination and proteasome-mediated degradation; We found that Huwe1 activity on TBP is antagonized by the deubiquitinase USP10, which protects TBP from degradation. USP 1 Other H.sapiens 774 UBP21_HUMAN EZH2_HUMAN Q9UK80 Q15910 USP21 EZH2 MEDLINE 33389794 CONCLUSION: The deubiquitinase USP21 promotes cell proliferation by maintaining the EZH2 protein level in DLBCL USP 1 Other H.sapiens 775 UBP4_HUMAN TGFR1_HUMAN Q13107 P36897 USP4 TGFBR1 MEDLINE 24756567 USP4 is a DUB for TGFbeta type I receptor USP 1 Training data H.sapiens 776 OTUB1_HUMAN MSH2_HUMAN Q96FW1 P43246 OTUB1 MSH2 MEDLINE 33640455 OTUB1 stabilizes mismatch repair protein MSH2 by blocking ubiquitination OTU 1 Other H.sapiens 777 CYLD_HUMAN P53_HUMAN Q9NQC7 P04637 CYLD TP53 MEDLINE 27561390 Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress. USP 1 Other H.sapiens 778 UBP15_HUMAN CASP6_HUMAN Q9Y4E8 P55212 USP15 CASP6 MEDLINE 31952546 We further demonstrated CASPASE-6, as a downstream protein of USP15, was regulated at the post-translational level by deubiquitinating activity of USP15. USP 1 Other H.sapiens 779 UCHL3_HUMAN FOXM1_HUMAN P15374 Q08050 UCHL3 FOXM1 MEDLINE 31598398 Our results demonstrate that UCHL3 deubiquitinated and stabilized FOXM1, thereby potentiating proliferation, migration, and invasion of pancreatic cancer cells. UCH 1 Other H.sapiens 780 USP9X_HUMAN FOXO3_HUMAN Q93008 O43524 USP9X FOXO3 MEDLINE 24990963 Hydroxylation of these sites prevents the binding of USP9x deubiquitinase, thereby promoting the proteasomal degradation of FOXO3A. USP 1 Other H.sapiens 781 UBP13_HUMAN STING_HUMAN Q92995 Q86WV6 USP13 TMEM173 MEDLINE 28534493 Here, we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. USP 1 Training data H.sapiens 782 UBP7_HUMAN NRF1_HUMAN Q93009 Q16656 USP7 NRF1 MEDLINE 33933455 The deubiquitinating enzyme USP7 regulates the transcription factor Nrf1 by modulating its stability in response to toxic metal exposure USP 1 Other H.sapiens 783 UBP21_HUMAN STING_HUMAN Q9UK80 Q86WV6 USP21 TMEM173 MEDLINE 28254948 In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. USP 1 Training data H.sapiens 784 UBP20_HUMAN STING_HUMAN Q9Y2K6 Q86WV6 USP20 TMEM173 MEDLINE 27801882 USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA USP 1 Training data H.sapiens 785 UBP22_HUMAN SHH_HUMAN Q9UPT9 Q15465 USP22 SHH MEDLINE 33568633 Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels USP 1 Other H.sapiens 786 UBP22_HUMAN STING_HUMAN Q9UPT9 Q86WV6 USP22 TMEM173 MEDLINE 29732405 USP22 removes K27-linked ubiquitination on STING through cooperation with USP13 USP 1 Training data H.sapiens 787 UBP5_HUMAN STING_HUMAN P45974 Q86WV6 USP5 TMEM173 MEDLINE 29732405 In addition, the ubiquitination of STING was impaired by USP5, USP13, and USP22. USP 1 Training data H.sapiens 788 OTUL_HUMAN NEMO_HUMAN Q96BN8 Q9Y6K9 OTULIN IKBKG MEDLINE 29444948 Deubiquitination effects of swine OTULIN were identified. The interaction between porcine OTULIN and PRRSV Nsp11 is dependent on the OTU domain. PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to promote removal of linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I IFNs. Other 1 Training data H.sapiens 789 TNAP3_HUMAN IRF7_HUMAN P21580 Q92985 TNFAIP3 IRF7 MEDLINE 20392859 Thus, A20 negatively regulates LMP1-stimulated IRF7 ubiquitination and activity in EBV latency, and its DUB activity is indispensable for this function. OTU 1 Training data H.sapiens 790 UBP35_HUMAN TNIP2_HUMAN Q9P2H5 Q8NFZ5 USP35 TNIP2 MEDLINE 26348204 Collectively, our data indicated that miR let-7a-regulated USP35 can inhibit NF-kappaB activation by deubiquitination and stabilization of ABIN-2 protein and eventually inhibit cell proliferation. USP 1 Training data H.sapiens 791 UBP44_HUMAN AXIN1_HUMAN Q9H0E7 O15169 USP44 AXIN1 MEDLINE 32285989 USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating Wnt/beta-catenin pathway via Axin1 deubiquitination USP 1 Other H.sapiens 792 UBP25_HUMAN TNKS1_HUMAN Q9UHP3 O95271 USP25 TNKS MEDLINE 28619731 USP25 regulates Wnt signaling by controlling the stability of tankyrases USP 1 Training data H.sapiens 793 UBP7_HUMAN MYC_HUMAN Q93009 P01106 USP7 MYC MEDLINE 29899379 Most importantly, we are able to demonstrate that USP7 deubiquitinates and thereby stabilizes c-Myc and that this function is required to maintain neural stem cell fate. USP 1 Training data H.sapiens 794 UBP37_HUMAN IFI27_HUMAN Q86T82 P40305 USP37 IFI27 MEDLINE 22665064 Ectopically expressed wild-type USP37 formed a complex with p27, promoted its deubiquitination and stabilization and blocked cell proliferation. USP 1 Other H.sapiens 795 UBP10_HUMAN FLT3_HUMAN Q14694 P36888 USP10 FLT3 MEDLINE 30319415 USP10, a primary cytoplasmic DUB, acts as an oncogene or a tumor suppressor by regulating various protein substrates, including FLT3, p53, AMPK, PTEN, etc. USP 1 Training data H.sapiens 796 USP9X_HUMAN BECN1_HUMAN Q93008 Q14457 USP9X BECN1 MEDLINE 30126257 Interestingly, Beclin1 and the Bcl-2 family member, MCL-1, compete for their interaction with USP9X, which contributes to their stabilization by protecting them from proteasomal degradation in HEK293T cells USP 1 Training data H.sapiens 797 BRCC3_HUMAN TNKS1_HUMAN P46736 O95271 BRCC3 TNKS MEDLINE 27993934 Cell cycle-regulated ubiquitination of tankyrase 1 by RNF8 and ABRO1/BRCC36 controls the timing of sister telomere resolution JAMM 1 Training data H.sapiens 798 UBP18_HUMAN NOTC1_HUMAN Q9UMW8 P46531 USP18 NOTCH1 MEDLINE 33051403 Mechanistically, USP18 interacts with and removes K48-linked ubiquitin chains from Notch1, thereby stabilizing Notch1 and promoting the Notch1-c-Myc pathway USP 1 Other H.sapiens 799 UBP27_HUMAN DDX58_HUMAN A6NNY8 O95786 USP27X DDX58 MEDLINE 32027733 USP27X negatively regulates antiviral signaling by deubiquitinating RIG-I USP 1 Other H.sapiens 800 UBP30_HUMAN TOM20_HUMAN Q70CQ3 Q15388 USP30 TOMM20 MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 801 UBP30_HUMAN TOM70_HUMAN Q70CQ3 O94826 USP30 TOMM70A MEDLINE 25995186 Similar findings were reported for another DUB: USP30. USP30 overexpression impaired PARKIN-mediated mitophagy by deubiquitinating mitochondrial substrates that include TOM20, TOM70, and the VDACs USP 1 Training data H.sapiens 802 OTUB1_HUMAN DPTOR_HUMAN Q96FW1 Q8TB45 OTUB1 DEPTOR MEDLINE 29382726 OTUB1 protein suppresses mTOR complex 1 (mTORC1) activity by deubiquitinating the mTORC1 inhibitor DEPTOR OTU 1 Training data H.sapiens 803 TRI44_HUMAN HIF1A_HUMAN Q96DX7 Q16665 TRIM44 HIF1A MEDLINE 30089913 TRIM44 functions as a deubiquitinase for hypoxia inducible factor-1alpha (HIF-1ALPHA), which stabilizes HIF-1ALPHA expression during hypoxia and normoxia Other 1 Other H.sapiens 804 UBP22_HUMAN PGH2_HUMAN Q9UPT9 P35354 USP22 PTGS2 MEDLINE 25817787 In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). USP 1 Training data H.sapiens 805 CYLD_HUMAN CEP70_HUMAN Q9NQC7 Q8NHQ1 CYLD CEP70 MEDLINE 26763122 The ciliary function of CYLD is attributed to its deconjugation of the polyubiquitin chain from centrosomal protein of 70 kDa (Cep70), a requirement for Cep70 to interact with gamma -tubulin and localize at the centrosome USP 1 Training data H.sapiens 806 ATX3_HUMAN P53_HUMAN P54252 P04637 ATXN3 TP53 MEDLINE 28801249 28801249 Josephin 1 Training data H.sapiens 807 CYLD_HUMAN PCM1_HUMAN Q9NQC7 Q15154 CYLD PCM1 MEDLINE 31067453 We found that CYLD marshals the centriolar satellites by deubiquitinating and preventing the E3 ligase Mindbomb 1 (MIB1) from marking PCM1 for proteasomal degradation USP 1 Other H.sapiens 808 UBP15_HUMAN SMUF2_HUMAN Q9Y4E8 Q9HAU4 USP15 SMURF2 MEDLINE 26435193 USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination USP 1 Training data H.sapiens 809 UBP20_HUMAN IOD2_HUMAN Q9Y2K6 Q92813 USP20 DIO2 MEDLINE 22967761 Ubiquitinated D2 can be either targeted to proteasomal degradation or reactivated by deubiquitination, a process that is mediated by the deubiquitinases USP20/33 and is important in adaptive thermogenesis. USP 1 Training data H.sapiens 810 UBP10_HUMAN MSH2_HUMAN Q14694 P43246 USP10 MSH2 MEDLINE 26975374 Here we report that ubiquitin-specific peptidase 10 (USP10) interacts with and stabilizes MSH2 USP 1 Training data H.sapiens 811 CYLD_HUMAN RIPK1_HUMAN Q9NQC7 Q13546 CYLD RIPK1 MEDLINE 28900035 We conclude that PrP traps CYLD, preventing it from binding and deubiquitinating RIP1 and TRAF2. USP 1 Training data H.sapiens 812 UBP10_HUMAN BECN1_HUMAN Q14694 Q14457 USP10 BECN1 MEDLINE 26445063 While A20 inhibits PtdIns3P signaling by removing the TRAF6-dependent Lys63-linked chains from BECLIN 1, the enzymes USP10 and USP13 prevent PI3K-III complex components from their degradation and, therefore, support autophagy. Interestingly enough, USP10 also stabilizes p53, which, in turn, triggers the degradation of BECLIN 1 and VPS34 in order to prevent autophagy. USP 1 Training data H.sapiens 813 OTUB1_HUMAN P53_HUMAN Q96FW1 P04637 OTUB1 TP53 MEDLINE 27919796 27919796 OTU 1 Training data H.sapiens 814 UBP2_HUMAN MDM4_HUMAN O75604 O15151 USP2 MDM4 MEDLINE 25121098 USP2 deubiquitinates both Mdm2 and MdmX USP 1 Training data H.sapiens 815 OTUD1_HUMAN P53_HUMAN Q5VV17 P04637 OTUD1 TP53 MEDLINE 28801249 28801249 OTU 1 Training data H.sapiens 816 USP9X_HUMAN ERBB2_HUMAN Q93008 P04626 USP9X ERBB2 MEDLINE 20406983 we have also shown that PS341 and GA differentially affect ErbB2 receptor ubiquitination as well as its association with the E3 ligase, c-Cbl, and the deubiquitylating enzyme, USP9x. USP 1 Other H.sapiens 817 OTUD5_HUMAN P53_HUMAN Q96G74 P04637 OTUD5 TP53 MEDLINE 28801249 28801249 OTU 1 Training data H.sapiens 818 TNAP3_HUMAN P53_HUMAN P21580 P04637 TNFAIP3 TP53 MEDLINE 27775833 27775833 OTU 1 Training data H.sapiens 819 ZRAN1_HUMAN UVRAG_HUMAN Q9UGI0 Q9P2Y5 ZRANB1 UVRAG MEDLINE 30686098 However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux OTU 1 Other H.sapiens 820 UBP4_HUMAN TWST1_HUMAN Q13107 Q15672 USP4 TWIST1 MEDLINE 32549341 Mechanistically, we identified USP4 as a novel deubiquitinase of Twist1 USP 1 Other H.sapiens 821 UBP34_HUMAN AMFR_HUMAN Q70CQ2 Q9UKV5 USP34 AMFR MEDLINE 30585151 The ubiquitin specific protease USP34 protects the ubiquitin ligase gp78 from proteasomal degradation USP 1 Other H.sapiens 822 UBP10_HUMAN P53_HUMAN Q14694 P04637 USP10 TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 823 OTU7B_HUMAN TRAF6_HUMAN Q6GQQ9 Q9Y4K3 OTUD7B TRAF6 MEDLINE 23564640 Cezanne regulates inflammatory responses to hypoxia in endothelial cells by targeting TRAF6 for deubiquitination OTU 1 Training data H.sapiens 824 UBP19_HUMAN NCOA3_HUMAN O94966 Q9Y6Q9 USP19 NCOA3 MEDLINE 34135062 Mechanistically, USP19 removed the K63-linked ubiquitin chain from RORgammat lysine 313, which is essential for recruiting the coactivator SRC3 USP 1 Other H.sapiens 825 UBP11_HUMAN P53_HUMAN P51784 P04637 USP11 TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 826 UBP24_HUMAN P53_HUMAN Q9UPU5 P04637 USP24 TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 827 UBP48_HUMAN SIR6_HUMAN Q86UV5 Q8N6T7 USP48 SIRT6 MEDLINE 33903120 USP48 physically bound and stabilized SIRT6 by K48-linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis USP 1 Other H.sapiens 828 USP9X_HUMAN PSD1_HUMAN Q93008 A5PKW4 USP9X PSD MEDLINE 20339350 USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly USP 1 Training data H.sapiens 829 UBP29_HUMAN P53_HUMAN Q9HBJ7 P04637 USP29 TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 830 UBP25_HUMAN A4_HUMAN Q9UHP3 P05067 USP25 APP MEDLINE 22590560 Similarly to what occurs with CD3delta, overexpression of USP25 increases APP half-life. Again, this effect depends on the catalytic activity of USP25, as catalytically inactive USP25(C178S) does not alter APP turnover (Figure 3B). USP 1 Other H.sapiens 831 UBP49_HUMAN DUS1_HUMAN Q70CQ1 P28562 USP49 DUSP1 MEDLINE 30246457 Moreover, USP49 positively regulated DUSP1 expression through deubiquitinating DUSP1. USP 1 Training data H.sapiens 832 UBP46_HUMAN ANDR_HUMAN P62068 P10275 USP46 AR MEDLINE 29861848 Here we report that the novel small molecule anti-androgen, galeterone targets USP12 and USP46, two highly homologous deubiquitinating enzymes that control the AR-AKT-MDM2-P53 signalling pathway. USP 1 Training data H.sapiens 833 UBP42_HUMAN P53_HUMAN Q9H9J4 P04637 USP42 TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 834 UBP5_HUMAN P53_HUMAN P45974 P04637 USP5 TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 835 UBP7_HUMAN P53_HUMAN Q93009 P04637 USP7 TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 836 USP9X_HUMAN IQCB1_HUMAN Q93008 Q15051 USP9X IQCB1 MEDLINE 28498859 NPHP5 directly binds to a deubiquitinating enzyme USP9X/FAM and two E3 ubiquitin ligases BBS11/TRIM32 and MARCH7/axotrophin. NPHP5 undergoes K63 ubiquitination in a cell cycle dependent manner and K48/K63 ubiquitination upon USP9X depletion or inhibition USP 1 Training data H.sapiens 837 UBP2_HUMAN PER1_HUMAN O75604 O15534 USP2 PER1 MEDLINE 25238854 Recently, we showed that the deubiquitinating enzyme ubiquitin-specific peptidase 2 (USP2) associates with clock proteins and deubiquitinates PERIOD1 (PER1) but does not affect its overall stability. USP 1 Training data H.sapiens 838 USP9X_HUMAN P53_HUMAN Q93008 P04637 USP9X TP53 MEDLINE 28801249 28801249 USP 1 Training data H.sapiens 839 UBP28_HUMAN TP53B_HUMAN Q96RU2 Q12888 USP28 TP53BP1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 840 OTUD5_HUMAN TRAF2_HUMAN Q96G74 Q12933 OTUD5 TRAF2 MEDLINE 24375678 Given that TRAF3 may be dispensable for RIG-I signalling 92, it cannot be excluded, however, that DUBA also targets other E3 ligases like TRAF2, 5 and 6. OTU 1 Training data H.sapiens 841 CYLD_HUMAN LCK_HUMAN Q9NQC7 P06239 CYLD LCK MEDLINE 26763122 Other identified CYLD substrates include TNF receptor associated factor 7 (TRAF7), TRAF interacting protein (TRIP), transforming growth factor beta-activated kinase 1 (TAK1), NF-kappa-B essential modifier (NEMO), lymphocyte cell specific protein-tyrosine kinase (LCK), receptor-interacting protein 1 (RIP1), retinoic acid inducible gene (RIG), and polo-like kinase 1 (PLK1) USP 1 Training data H.sapiens 842 UBP33_HUMAN DUS1_HUMAN Q8TEY7 P28562 USP33 DUSP1 MEDLINE 31857702 Mechanistically, we found that USP33 could inhibit the Lys48 (K48)-linked polyubiquitination of DUSP1 USP 1 Other H.sapiens 843 UBP14_HUMAN DDX58_HUMAN P54578 O95786 USP14 DDX58 MEDLINE 30466171 USP14 promotes K63-linked RIG-I deubiquitination and suppresses antiviral immune responses USP 1 Other H.sapiens 844 UBP7_HUMAN TPP1_HUMAN Q93009 O14773 USP7 TPP1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 845 OTUD5_HUMAN TRAF3_HUMAN Q96G74 Q13114 OTUD5 TRAF3 MEDLINE 28063927 28063927 OTU 1 Training data H.sapiens 846 UBP4_HUMAN ITF2_HUMAN Q13107 P15884 USP4 TCF4 MEDLINE 25121098 DUBs regulate canonical Wnt signaling, by modulating beta-catenin activity. USP4 deubiquitinases TCF4, to suppress beta-catenin dependent transcription USP 1 Training data H.sapiens 847 UBP8_HUMAN ERBB2_HUMAN P40818 P04626 USP8 ERBB2 MEDLINE 21044682 ERBB2 is a target for USP8-mediated deubiquitination USP 1 Training data H.sapiens 848 VCIP1_HUMAN SPRTN_HUMAN Q96JH7 Q9H040 VCPIP1 SPRTN MEDLINE 33567341 Previously, VCPIP1 and USP7 deubiquitinases have been shown to regulate SPRTN OTU 1 Other H.sapiens 849 OTUD5_HUMAN TRAF5_HUMAN Q96G74 O00463 OTUD5 TRAF5 MEDLINE 24375678 Given that TRAF3 may be dispensable for RIG-I signalling 92, it cannot be excluded, however, that DUBA also targets other E3 ligases like TRAF2, 5 and 6. OTU 1 Training data H.sapiens 850 UBP44_HUMAN FOXP3_HUMAN Q9H0E7 Q9BZS1 USP44 FOXP3 MEDLINE 32644293 USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications USP 1 Other H.sapiens 851 UBP7_HUMAN PLK1_HUMAN Q93009 P53350 USP7 PLK1 MEDLINE 31730000 USP7 is a novel Deubiquitinase sustaining PLK1 protein stability and regulating chromosome alignment in mitosis USP 1 Other H.sapiens 852 UBP4_HUMAN NR2C2_HUMAN Q13107 P49116 USP4 NR2C2 MEDLINE 29573006 Mechanistically, hepatocyte USP4 directly bound to and deubiquitinated transforming growth factor-beta activated kinase 1 (TAK1) USP 1 Training data H.sapiens 853 OTUD5_HUMAN TRAF6_HUMAN Q96G74 Q9Y4K3 OTUD5 TRAF6 MEDLINE 24375678 Given that TRAF3 may be dispensable for RIG-I signalling 92, it cannot be excluded, however, that DUBA also targets other E3 ligases like TRAF2, 5 and 6. OTU 1 Training data H.sapiens 854 ZC12A_HUMAN TRAF6_HUMAN Q5D1E8 Q9Y4K3 ZC3H12A TRAF6 MEDLINE 25121098 Cezanne has been reported to hydrolyze linear K11-Ub chains from RIP1. MCPIP1 also removes K63-Ub from RIP1 and TRAF2 and 6 but its activity is unclear Other 1 Training data H.sapiens 855 TRI44_HUMAN TRI17_HUMAN Q96DX7 Q9Y577 TRIM44 TRIM17 MEDLINE 19358823 hUbiquitome Other 1 Other H.sapiens 856 UBP20_HUMAN RAD17_HUMAN Q9Y2K6 O75943 USP20 RAD17 MEDLINE 24923443 Similar to Chk1 and Rad17, which enhance recombinational repair of collapsed replication forks, we demonstrate that USP20 depletion impairs DNA double strand break repair by homologous recombination. USP 1 Training data H.sapiens 857 OTUD1_HUMAN SMAD7_HUMAN Q5VV17 O15105 OTUD1 SMAD7 MEDLINE 29235476 Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7 OTU 1 Training data H.sapiens 858 ZC12A_HUMAN RIPK1_HUMAN Q5D1E8 Q13546 ZC3H12A RIPK1 MEDLINE 25121098 Cezanne has been reported to hydrolyze linear K11-Ub chains from RIP1. MCPIP1 also removes K63-Ub from RIP1 and TRAF2 and 6 but its activity is unclear Other 1 Training data H.sapiens 859 UBP11_HUMAN RAE1L_HUMAN P51784 P78406 USP11 RAE1 MEDLINE 29293652 USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation USP 1 Other H.sapiens 860 UBP15_HUMAN TRI25_HUMAN Q9Y4E8 Q14258 USP15 TRIM25 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 861 UBP37_HUMAN CDT1_HUMAN Q86T82 Q9H211 USP37 CDT1 MEDLINE 27296872 USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication USP 1 Other H.sapiens 862 CYLD_HUMAN TRIPC_HUMAN Q9NQC7 Q14669 CYLD TRIP12 MEDLINE 26763122 Other identified CYLD substrates include TNF receptor associated factor 7 (TRAF7), TRAF interacting protein (TRIP), transforming growth factor beta-activated kinase 1 (TAK1), NF-kappa-B essential modifier (NEMO), lymphocyte cell specific protein-tyrosine kinase (LCK), receptor-interacting protein 1 (RIP1), retinoic acid inducible gene (RIG), and polo-like kinase 1 (PLK1) USP 1 Training data H.sapiens 863 UBP7_HUMAN TRIPC_HUMAN Q93009 Q14669 USP7 TRIP12 MEDLINE 25557975 UBIQUITIN-SPECIFIC PROTEASE 7 accelerates p14(ARF) degradation by deubiquitinating thyroid hormone receptor-interacting protein 12 and promotes hepatocellular carcinoma progression USP 1 Training data H.sapiens 864 UBP5_HUMAN HDAC2_HUMAN P45974 Q92769 USP5 HDAC2 MEDLINE 31727867 Moreover, USP5 interacted with HDAC2, and disruption of USP5 enhanced the ubiquitination of HDAC2 USP 1 Other H.sapiens 865 BAP1_HUMAN GCP3_HUMAN Q92560 Q96CW5 BAP1 TUBGCP3 MEDLINE 25228651 Deubiquitination of gamma-tubulin by BAP1 prevents chromosome instability in breast cancer cells UCH 1 Training data H.sapiens 866 UBP51_HUMAN DGCR8_HUMAN Q70EK9 Q8WYQ5 USP51 DGCR8 MEDLINE 34188037 Upon radiation, the kinase ATM and the deubiquitinase USP51 mediate the activation and stabilization of DGCR8 through phosphorylation and deubiquitination USP 1 Other H.sapiens 867 STABP_HUMAN CXA1_HUMAN O95630 P17302 STAMBP GJA1 MEDLINE 25070368 AMSH-mediated deubiquitination of Cx43 regulates internalization and degradation of gap junctions Other 1 Training data H.sapiens 868 UCHL1_HUMAN UCHL1_HUMAN P09936 P09936 UCHL1 UCHL1 MEDLINE 17259170 Interestingly, UCH-L1 catalyzes its own deubiquitination in an intramolecular manner, thereby regulating the lifetime of this modification. UCH 1 Training data H.sapiens 869 UBP7_HUMAN UHRF1_HUMAN Q93009 Q96T88 USP7 UHRF1 MEDLINE 27775833 27775833 USP 1 Training data H.sapiens 870 ZRAN1_HUMAN EZH2_HUMAN Q9UGI0 Q15910 ZRANB1 EZH2 MEDLINE 29669287 Here we identify ZRANB1 as the EZH2 deubiquitinase OTU 1 Training data H.sapiens 871 OTUD1_HUMAN IRF3_HUMAN Q5VV17 Q14653 OTUD1 IRF3 MEDLINE 30100102 As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63-linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity OTU 1 Training data H.sapiens 872 UBP4_HUMAN UBP4_HUMAN Q13107 Q13107 USP4 USP4 MEDLINE 16472766 UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself USP 1 Training data H.sapiens 873 UBP15_HUMAN VDAC1_HUMAN Q9Y4E8 P21796 USP15 VDAC1 MEDLINE 26445063 26445063 USP 1 Training data H.sapiens 874 UBP30_HUMAN VDAC1_HUMAN Q70CQ3 P21796 USP30 VDAC1 MEDLINE 26445063 26445063 USP 1 Training data H.sapiens 875 UBP35_HUMAN VDAC1_HUMAN Q9P2H5 P21796 USP35 VDAC1 MEDLINE 26445063 26445063 USP 1 Training data H.sapiens 876 UBP11_HUMAN XIAP_HUMAN P51784 P98170 USP11 XIAP MEDLINE 28279784 28279784 USP 1 Training data H.sapiens 877 UBP7_HUMAN XPC_HUMAN Q93009 Q01831 USP7 XPC MEDLINE 28031783 28031783 USP 1 Training data H.sapiens 878 BRCC3_HUMAN FANCG_HUMAN P46736 O15287 BRCC3 FANCG MEDLINE 25132264 we demonstrated that K63Ub-modified FANCG was deubiquitinated by BRCC36 complex in vitro and in vivo JAMM 1 Other H.sapiens 879 PSDE_HUMAN ERBB2_HUMAN O00487 P04626 PSMD14 ERBB2 MEDLINE 25121098 POH1 regulates ErbB2, an EGFR family member JAMM 1 Training data H.sapiens 880 UBP20_HUMAN ULK1_HUMAN Q9Y2K6 O75385 USP20 ULK1 MEDLINE 30126257 The deubiquitination of ULK1 by USP20 allows for its stabilization and promotion of autophagy induction USP 1 Training data H.sapiens 881 UBP50_HUMAN XRCC6_HUMAN Q70EL3 P12956 USP50 XRCC6 MEDLINE 29101126 29101126 Other 1 Training data H.sapiens 882 USP9Y_HUMAN SMAD4_HUMAN O00507 Q13485 USP9Y SMAD4 UNIPROT UBP15_HUMAN Deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33. USP 1 Other H.sapiens 883 BAP1_HUMAN TYY1_HUMAN Q92560 P25490 BAP1 YY1 MEDLINE 25121098 BAP1 also controls G1/S cell cycle progression by regulating BRCA-1 [111], Ying Yang 1 (YY-1), and host cell factor 1 (HCF-1) UCH 1 Training data H.sapiens 884 CSN5_MOUSE PD1L1_MOUSE O35864 Q9EP73 Cops5 Cd274 MEDLINE 33354502 Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5 JAMM 1 Other M.musculus 885 OTU1_MOUSE NEDD4_MOUSE Q8CB27 P46935 Yod1 Nedd4 MEDLINE 31916733 YOD1 Deubiquitinates NEDD4 Involved in the Hippo Signaling Pathway OTU 1 Other M.musculus 886 UBP38_MOUSE JUNB_MOUSE Q8BW70 P09450 Usp38 Junb MEDLINE 30224386 Mechanistically, USP38 directly associated with JunB, deubiquitinated Lys-48-linked poly-ubiquitination of JunB, and consequently blocked TCR-induced JunB turnover USP 1 Other M.musculus 887 UBP15_MOUSE IF4A1_MOUSE Q8R5H1 P60843 Usp15 Eif4a1 MEDLINE 32671073 USP15 Enhances Re-epithelialization Through Deubiquitinating EIF4A1 During Cutaneous Wound Repair USP 1 Other M.musculus 888 UBP2_MOUSE AURKA_MOUSE O88623 P97477 Usp2 Aurka MEDLINE 33530560 USP2 modulates cell cycle progression, and therefore carcinogenesis, via the deubiquitination of cyclins and Aurora-A USP 1 Other M.musculus 889 UBP5_MOUSE SNAI2_MOUSE P56399 P97469 Usp5 Snai2 MEDLINE 30809294 Cycloheximide chase assays and deubiquitination assays confirmed that the effect of USP5 on the deubiquitin of SLUG USP 1 Other M.musculus 890 USP9X_MOUSE ANK3_MOUSE P70398 G5E8K5 Usp9x Ank3 MEDLINE 31813652 Usp9X phosphorylation enhances their interaction, decreases ANKYRIN-G polyubiquitination, and stabilizes ANKYRIN-G to maintain dendritic spine development USP 1 Other M.musculus 891 UBP22_MOUSE IMA1_MOUSE Q5DU02 P52293 Usp22 Kpna2 MEDLINE 32130408 USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2 USP 1 Other M.musculus 892 PSDE_MOUSE CAV1_MOUSE O35593 P49817 Psmd14 Cav1 MEDLINE 30745168 POH1 contributes to hyperactivation of TGF-beta signaling and facilitates hepatocellular carcinoma metastasis through deubiquitinating TGF-beta receptors and caveolin-1 JAMM 1 Other M.musculus 893 UBP7_MOUSE KDM6B_MOUSE Q6A4J8 Q5NCY0 Usp7 Kdm6b MEDLINE 33895173 USP7 promoted the proliferation of mesangial cells and mesangial matrix, and stabilized the JMJD3 protein via deubiquitination in SV40 MES 13 cells USP 1 Other M.musculus 894 OTUD1_MOUSE SMUF1_MOUSE Q9CUB6 Q9CUN6 Otud1 Smurf1 MEDLINE 29734366 Furthermore, OTUD1 upregulates protein levels of intracellular Smurf1 by removing Smurf1 ubiquitination OTU 1 Other M.musculus 895 UBP8_MOUSE M3K7_MOUSE Q80U87 Q62073 Usp8 Map3k7 MEDLINE 30221684 Effect of deubiquitinase USP8 on hypoxia/reoxygenation-induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells USP 1 Other M.musculus 896 UBP1_MOUSE SIX1_MOUSE Q8BJQ2 Q62231 Usp1 Six1 MEDLINE 34079090 Mechanistically, GRP75 provides a platform to recruit the deubiquitinating enzyme USP1 to inhibit K48-linked polyubiquitination of SIX1 USP 1 Other M.musculus 897 UBP18_MOUSE SOX9_MOUSE Q9WTV6 Q04887 Usp18 Sox9 MEDLINE 33694203 Deubiquitinase USP18 regulates reactive astrogliosis by stabilizing SOX9 USP 1 Other M.musculus 898 UBP13_MOUSE MCL1_MOUSE Q5BKP2 P97287 Usp13 Mcl1 MEDLINE 29335437 Collectively, we nominate USP13 as a novel deubiquitinase which regulates MCL1 turnover in diverse solid tumors and propose that USP13 may be a potential therapeutic target for the treatment of various malignancies. USP 1 Other M.musculus 899 USP9X_MOUSE PEG10_MOUSE P70398 Q7TN75 Usp9x Peg10 MEDLINE 30951545 Expressed in a subset of mouse endocrine organs in addition to the placenta, PEG10 was identified as a substrate of the deubiquitinating enzyme USP9X USP 1 Other M.musculus 900 UBP22_MOUSE BRD4_MOUSE Q5DU02 Q9ESU6 Usp22 Brd4 MEDLINE 33826947 Notably, USP22 functioned as a BRD4 deubiquitinase to facilitate BRD4 inflammatory functions USP 1 Other M.musculus 901 UBP11_MOUSE E2F1_MOUSE Q99K46 Q61501 Usp11 E2f1 MEDLINE 34044068 Results from co-immunoprecipitation and ubiquitination assays demonstrated that USP11 interacted with E2F1 and maintained E2F1 protein stability by removing its ubiquitin USP 1 Other M.musculus 902 CYLD_MOUSE RIPK1_MOUSE Q80TQ2 Q60855 Cyld Ripk1 MEDLINE 29352268 In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death USP 1 Other M.musculus 903 UBP7_MOUSE AKT1_MOUSE Q6A4J8 P31750 Usp7 Akt1 MEDLINE 32164484 The deubiquitinase, USP7 (ubiquitin specific peptidase 7), prevented AKT degradation by inhibiting AKT ubiquitination via interaction with AKT USP 1 Other M.musculus 904 UBP19_MOUSE NLRP3_MOUSE Q3UJD6 Q8R4B8 Usp19 Nlrp3 MEDLINE 33097834 In addition, USP19 inhibited the proteasomal degradation of inflammasome-independent NLRP3 by cleaving its polyubiquitin chains USP 1 Other M.musculus 905 US6NL_MOUSE NMDE2_MOUSE Q80XC3 Q01097 Usp6nl Grin2b MEDLINE 31841517 31841517 Other 1 Other M.musculus 906 UBP5_MOUSE DLL4_MOUSE P56399 Q9JI71 Usp5 Dll4 MEDLINE 30586693 Dll4 induction may result from inhibition of the ubiquitin-proteasome pathway, via the deubiquitinating enzyme USP5 USP 1 Other M.musculus 907 UBP7_MOUSE MYC_MOUSE Q6A4J8 P01108 Usp7 Myc MEDLINE 29899379 A complex of the ubiquitin ligase TRIM32 and the deubiquitinase USP7 balances the level of c-Myc ubiquitination and thereby determines neural stem cell fate specification USP 1 Other M.musculus 908 UBP7_MOUSE E9Q605_MOUSE Q6A4J8 E9Q605 Usp7 Chuk MEDLINE 32239614 To probe deeper into the mechanisms, we find that KDF1 associates with a deubiquitinating protease USP7 (ubiquitin-specific peptidase 7), and KDF1 can regulate skin differentiation through deubiquitination and stabilization of IKKALPHA USP 1 Other M.musculus 909 UBP44_MOUSE DDB2_MOUSE Q8C2S0 Q99J79 Usp44 Ddb2 MEDLINE 33937266 Here we show that the tumor suppressor USP44 directly deubiquitinates DDB2 to prevent its premature degradation and is selectively required for CPD repair USP 1 Other M.musculus 910 UBP8_MOUSE SQSTM_MOUSE Q80U87 Q64337 Usp8 Sqstm1 MEDLINE 31241013 Here we report that USP8 (ubiquitin specific peptidase 8) directly interacted with and deubiquitinated SQSTM1 USP 1 Other M.musculus 911 UBP13_MOUSE STING_MOUSE Q5BKP2 Q3TBT3 Usp13 Sting1 MEDLINE 28534493 USP13 negatively regulates antiviral responses by deubiquitinating STING USP 1 Other M.musculus 912 UBP10_MOUSE PTEN_MOUSE P52479 O08586 Usp10 Pten MEDLINE 28852924 We further demonstrated that USP10 directly interacted with and stabilized PTEN via deubiquitination USP 1 Other M.musculus 913 UBP15_MOUSE BARD1_MOUSE Q8R5H1 O70445 Usp15 Bard1 MEDLINE 30874560 Subsequently, USP15 deubiquitinates BARD1 BRCT domain, and promotes BARD1-HP1gamma interaction, resulting in BRCA1/BARD1 retention at DSBs USP 1 Other M.musculus 914 TNAP3_MOUSE M3K5_MOUSE Q60769 O35099 Tnfaip3 Map3k5 MEDLINE 29227477 In screening for proteins that interact with ASK1 in the context of NASH, we identified the deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes OTU 1 Other M.musculus 915 UBP4_MOUSE SMAD4_MOUSE P35123 P97471 Usp4 Smad4 MEDLINE 28468752 USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling USP 1 Other M.musculus 916 UBP19_MOUSE TCAM1_MOUSE Q3UJD6 Q80UF7 Usp19 Ticam1 MEDLINE 31511519 Mechanistically, USP19 interacts with TRIF and catalyzes the removal of TRIF K27-linked polyubiquitin moieties, thereby impairing the recruitment of TRIF to TLR3/4 USP 1 Other M.musculus 917 UBP18_MOUSE M3K7_MOUSE Q9WTV6 Q62073 Usp18 Map3k7 MEDLINE 34235538 Macrophages deficient in USP18 had promoted activation of NF-kappaB, p38 and ERK, and increased ubiquitination of TAK1 USP 1 Other M.musculus 918 USP9X_MOUSE SOX2_MOUSE P70398 P48432 Usp9x Sox2 MEDLINE 31605775 We further identified USP9x as a bona fide deubiquitinase for SOX2 and NGA directly interacts with USP9x in cells USP 1 Other M.musculus 919 PSDE_MOUSE E2F1_MOUSE O35593 Q61501 Psmd14 E2f1 MEDLINE 33456565 Mechanically, PSMD14 inhibited the ubiquitination and degradation of E2F1 to improve the activation of Akt pathway and the transcription of SOX2 JAMM 1 Other M.musculus 920 UBP1_MOUSE KDM4A_MOUSE Q8BJQ2 Q8BW72 Usp1 Kdm4a MEDLINE 32133742 Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability USP 1 Other M.musculus 921 UBP16_MOUSE B1ASP2_MOUSE Q99LG0 B1ASP2 Usp16 Jak1 MEDLINE 34294846 In addition, USP16 interacts with and deubiquitinates JAK1, and thereby promoting lung tumor growth by augmenting JAK1 signaling USP 1 Other M.musculus 922 UBP21_MOUSE GSC_MOUSE Q9QZL6 Q02591 Usp21 Gsc MEDLINE 31253698 These findings suggest that USP21 modulates GSC function through deubiquitination USP 1 Other M.musculus 923 UBP14_MOUSE DDX58_MOUSE Q9JMA1 Q6Q899 Usp14 Ddx58 MEDLINE 30466171 USP14 promotes K63-linked RIG-I deubiquitination and suppresses antiviral immune responses USP 1 Other M.musculus 924 UBP8_MOUSE LEPR_MOUSE Q80U87 P48356 Usp8 Lepr MEDLINE 31199479 USP8 Deubiquitinates the Leptin Receptor and Is Necessary for Leptin-Mediated Synapse Formation USP 1 Other M.musculus 925 UBP13_MOUSE SIGIR_MOUSE Q5BKP2 Q9JLZ8 Usp13 Sigirr MEDLINE 31204278 The deubiquitinase USP13 stabilizes the anti-inflammatory receptor IL-1R8/Sigirr to suppress lung inflammation USP 1 Other M.musculus 926 UBP5_MOUSE E9Q6P9_MOUSE P56399 E9Q6P9 Usp5 Cacna1h MEDLINE 30154101 Furthermore, knockdown of the CaV3.2-targeting deubiquitinating enzyme USP5 or disruption of USP5 binding to CaV3.2 channels in peripheral nociceptors resulted in a robust antihyperalgesic effect in vivo and substantial T-current reduction in vitro USP 1 Other M.musculus 927 UBP18_MOUSE UCP1_MOUSE Q9WTV6 P12242 Usp18 Ucp1 MEDLINE 33380466 Gain of USP18 expression augmented UCP1 protein via reduced ubiquitination USP 1 Other M.musculus 928 UBP16_MOUSE PP2BC_MOUSE Q99LG0 P48455 Usp16 Ppp3cc MEDLINE 31135381 Here, we report that calcineurin A (CNA), encoded by PPP3CB or PPP3CC, is constitutively ubiquitinated on lysine 327, and this polyubiquitin chain is rapidly removed by ubiquitin carboxyl-terminal hydrolase 16 (USP16) in response to intracellular calcium stimulation USP 1 Other M.musculus 929 UBP1_MOUSE AKT1_MOUSE Q8BJQ2 P31750 Usp1 Akt1 MEDLINE 32133736 USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation USP 1 Other M.musculus 930 UBP30_MOUSE ACLY_MOUSE Q3UN04 Q91V92 Usp30 Acly MEDLINE 32221968 IKKbeta phosphorylated and stabilized USP30, which promoted USP30 to deubiquitinate ATP citrate lyase (ACLY) and fatty acid synthase (FASN) USP 1 Other M.musculus 931 UBP47_MOUSE RS2_MOUSE Q8BY87 P25444 Usp47 Rps2 MEDLINE 32370049 USP47 Promotes Tumorigenesis by Negative Regulation of p53 through Deubiquitinating Ribosomal Protein S2 USP 1 Other M.musculus 932 UBP1_MOUSE ID2_MOUSE Q8BJQ2 P41136 Usp1 Id2 MEDLINE 34380645 Recently, the deubiquitinase USP1 was shown to stabilize Id2 and modulate cellular differentiation in osteosarcomas USP 1 Other M.musculus 933 UBP42_MOUSE ZNRF3_MOUSE B2RQC2 Q5SSZ7 Usp42 Znrf3 MEDLINE 33786993 USP42 binds to the Dishevelled interacting region (DIR) of ZNRF3 and stalls the R-spondin-LGR4-ZNRF3 ternary complex by deubiquitinating ZNRF3 USP 1 Other M.musculus 934 UBP13_MOUSE SMAD4_MOUSE Q5BKP2 P97471 Usp13 Smad4 MEDLINE 32434004 Deubiquitinase USP13 promotes extracellular matrix expression by stabilizing Smad4 in lung fibroblast cells USP 1 Other M.musculus 935 UBP7_MOUSE P53_MOUSE Q6A4J8 P02340 Usp7 Tp53 MEDLINE 29795372 It is noteworthy that FAM188B knockdown resulted in a decrease in overall ubiquitination in the p53 immunocomplexes, as well as p53 ubiquitination, because USP7 is involved in p53 deubiquitination USP 1 Other M.musculus 936 ZC12A_MOUSE HIF1A_MOUSE Q5D1E7 Q61221 Zc3h12a Hif1a MEDLINE 29742804 A mechanistic study revealed that MCPIP1 interacted with and maintained hypoxia-inducible factor 1alpha (HIF-1ALPHA) expression by deubiquitinating HIF-1ALPHA Other 1 Other M.musculus 937 ATX3_MOUSE Q3UM33_MOUSE Q9CVD2 Q3UM33 Atxn3 Hdac3 MEDLINE 29802126 ATXN3 Positively Regulates Type I IFN Antiviral Response by Deubiquitinating and Stabilizing HDAC3 Josephin 1 Other M.musculus 938 OTUL_MOUSE OTUL_MOUSE Q3UCV8 Q3UCV8 Otulin Otulin MEDLINE 29950720 29950720 Other 1 Other M.musculus 939 UBP16_MOUSE PP2BA_MOUSE Q99LG0 P63328 Usp16 Ppp3ca MEDLINE 31135381 Our data reveal the physiological function of CNA ubiquitination and its deubiquitinase USP16 in peripheral T cells USP 1 Other M.musculus 940 UBP47_MOUSE SATB1_MOUSE Q8BY87 Q60611 Usp47 Satb1 MEDLINE 30742943 Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression USP 1 Other M.musculus 941 UBP14_MOUSE HIF1A_MOUSE Q9JMA1 Q61221 Usp14 Hif1a MEDLINE 34420039 USP14 maintains HIF1-alpha stabilization via its deubiquitination activity in hepatocellular carcinoma USP 1 Other M.musculus 942 UBP10_MOUSE SIR6_MOUSE P52479 P59941 Usp10 Sirt6 MEDLINE 33170082 Conclusions USP10 functions as a Sirt6 deubiquitinase that induces cardiac myocyte hypertrophy and triggers maladaptive CH USP 1 Other M.musculus 943 UBP4_MOUSE RHEB_MOUSE P35123 Q921J2 Usp4 Rheb MEDLINE 30514904 30514904 USP 1 Other M.musculus 944 OTUB1_MOUSE BRE1A_MOUSE Q7TQI3 Q5DTM8 Otub1 Rnf20 MEDLINE 30282802 30282802 OTU 1 Other M.musculus 945 BAP1_MOUSE AKT1_MOUSE Q99PU7 P31750 Bap1 Akt1 MEDLINE 33758188 Mechanistically, ASXL1-MT cooperates with BAP1 to deubiquitinate and activate AKT UCH 1 Other M.musculus 946 OTUD1_MOUSE IRF3_MOUSE Q9CUB6 P70671 Otud1 Irf3 MEDLINE 32075857 In this study, we found that the ovarian tumor domain containing deubiquitinase OTUD1 deubiquitinated IRF3 and attenuated its function OTU 1 Other M.musculus 947 UBP7_MOUSE MDM2_MOUSE Q6A4J8 P23804 Usp7 Mdm2 MEDLINE 32815035 The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specific-processing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression without MDM2 gene amplification USP 1 Other M.musculus 948 UBP38_MOUSE HDAC1_MOUSE Q8BW70 O09106 Usp38 Hdac1 MEDLINE 31874856 In summary, this study identifies a critical role of USP38 in modulating genome integrity and cancer cell resistance to genotoxic insults by deubiquitinating HDAC1 and regulating its deacetylation activity. USP 1 Other M.musculus 949 UBP20_MOUSE RIPK1_MOUSE Q8C6M1 Q60855 Usp20 Ripk1 MEDLINE 30354204 TNF evoked 2-fold more RIPK1 ubiquitination in SMC-DN-USP20-transgenic than in control SMCs, and RIPK1 was deubiquitinated by purified USP20 in vitro USP 1 Other M.musculus 950 OTUD3_MOUSE ACTN4_MOUSE B1AZ99 P57780 Otud3 Actn4 MEDLINE 34380780 Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it OTU 1 Other M.musculus 951 UBP19_MOUSE M3K7_MOUSE Q3UJD6 Q62073 Usp19 Map3k7 MEDLINE 31127032 Mechanistically, USP19 interacted with TAK1 in a TNF-alpha- or IL-1beta-dependent manner and specifically deconjugated K63- and K27-linked polyubiquitin chains from TAK1, leading to the impairment of TAK1 activity and the disruption of the TAK1-TAB2/3 complex USP 1 Other M.musculus 952 UBP12_MOUSE PPM1B_MOUSE Q9D9M2 P36993 Usp12 Ppm1b MEDLINE 34381028 Mechanistically, USP12 downregulation creates a tumour-promoting secretome resulting from insufficient PPM1B deubiquitination that causes NF-kappaB hyperactivation in tumour cells USP 1 Other M.musculus 953 UBP19_MOUSE TAB1_MOUSE Q3UJD6 Q8CF89 Usp19 Tab1 MEDLINE 31127032 31127032 USP 1 Other M.musculus 954 OTUB1_MOUSE MAF_MOUSE Q7TQI3 P54843 Otub1 Maf MEDLINE 32842143 Therefore, the present study identifies Otub1 as a novel deubiquitinase of c-Maf and establishes that the Otub1/c-Maf axis is a potential therapeutic target for MM. OTU 1 Other M.musculus 955 UBP10_MOUSE NOTC1_MOUSE P52479 Q01705 Usp10 Notch1 MEDLINE 30975888 We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor USP 1 Other M.musculus 956 OTUD4_MOUSE MAVS_MOUSE B2RRE7 Q8VCF0 Otud4 Mavs MEDLINE 30410068 Viral infection leads to the IRF3/7-dependent upregulation of OTUD4 which interacts with MAVS to remove K48-linked polyubiquitin chains, thereby maintaining MAVS stability and promoting innate antiviral signaling OTU 1 Other M.musculus 957 CSN5_MOUSE HXK2_MOUSE O35864 O08528 Cops5 Hk2 MEDLINE 31991125 Mechanistically, we demonstrated that CSN5 attenuated the ubiquitin-proteasome system-mediated degradation of HK2 through its deubiquitinase function JAMM 1 Other M.musculus 958 UBP12_MOUSE BCL10_MOUSE Q9D9M2 Q9Z0H7 Usp12 Bcl10 MEDLINE 33941870 USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10 USP 1 Other M.musculus 959 TRI69_MOUSE M3K5_MOUSE Q80X56 O35099 Trim69 Map3k5 MEDLINE 31178136 Of note, we found that Trim69 directly interacted with and deubiquitinated ASK1 in microglial cells Other 1 Other M.musculus 960 USP9X_MOUSE MCL1_MOUSE P70398 P97287 Usp9x Mcl1 MEDLINE 29335437 While a distinctive feature of MCL1 resides in its efficient ubiquitination and destruction, the deubiquitinase USP9X has been implicated in the preservation of MCL1 expression by removing the polyubiquitin chains USP 1 Other M.musculus 961 OTUD1_MOUSE CARD9_MOUSE Q9CUB6 A2AIV8 Otud1 Card9 MEDLINE 33789983 OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-kappaB and MAPK pathway OTU 1 Other M.musculus 962 UBP7_MOUSE YAP1_MOUSE Q6A4J8 P46938 Usp7 Yap1 MEDLINE 30679505 Usp7 regulates Hippo pathway through deubiquitinating the transcriptional coactivator Yorkie USP 1 Other M.musculus 963 D3ZC84_RAT CXA1_RAT D3ZC84 P08050 Usp9x Gja1 MEDLINE 33857489 The following findings were observed: (1) Expression of USP9X was down-regulated in the kidney tissue of db/db diabetic mice; (2) overexpression of USP9X suppressed high glucose (HG)-induced expressions of EMT markers and extra cellular matrix (ECM) in NRK-52E cells; (3) depletion of USP9X further aggravated EMT process and ECM production in NRK-52E cells; (4) USP9X deubiquitinated Cx43 and suppressed its degradation to regulate EMT process; (5) USP9X deubiquitinated Cx43 by directly binding to the C-terminal Tyr286 of Cx43 USP 1 Other R.norvegicus 964 UBP7_RAT P53_RAT Q4VSI4 P10361 Usp7 Tp53 MEDLINE 33157209 Inhibition of USP7 activated p53 via suppressing deubiquitination, which led to down-regulation of TfR1, accompanied by the decreased ferroptosis and myocardial I/R injury USP 1 Other R.norvegicus 965 D3ZN39_RAT SHAN3_RAT D3ZN39 Q9JLU4 Usp8 Shank3 MEDLINE 29735556 In primary rat neurons, USP8 enhances SHANK3 and SHANK1 protein levels via deubiquitination and increases dendritic spine density USP 1 Other R.norvegicus 966 UBP11_RAT P53_RAT Q5D006 P10361 Usp11 Tp53 MEDLINE 34141823 It was subsequently shown in microglial cells that USP11 stabilized p53 by deubiquitination and p53 targeted the Kruppel-like factor 2 (KLF2) promoter to repress KLF2 transcription, thereby activating the nuclear factor kappaB (NF-kappaB) pathway USP 1 Other R.norvegicus 967 UBP8_YEAST H2B1_YEAST P50102 P02293 UBP8 HTB1 MEDLINE 33010070 H2B ubiquitination and deubiquitination are dynamically regulated by the E3 ligase Bre1 and the deubiquitinase Ubp8 during the reversible yeast-hyphae transition USP 1 Other S.cerevisiae