DUB Portal
A figure showing several modes of information about DUBs.

This DUB portal (which updates automatically each week) provides the integration and analysis of publicly available resources as well as newly collected transcriptomic data following deubiquitinating enzyme (DUB) knockout or inhibition to facilitate the exploration of DUB function in oncology.

This website accompanies the manuscript: Integrating multi-omics data reveals function and therapeutic potential of deubiquitinating enzymes

To assemble a knowledgebase of DUB activities, co-dependent genes, and substrates, we combined targeted experiments using CRISPR libraries and inhibitors with systematic mining of functional genomic databases. Analysis of the Dependency Map, Connectivity Map, Cancer Cell Line Encyclopedia, and protein-protein interaction databases yielded specific hypotheses about DUB function, a subset of which were confirmed in follow-on experiments.

The data in this study, which are browsable below, promise to improve understanding of DUBs as a family as well as the activities of specific DUBs, which have been targeted with investigational cancer therapeutics.

Deubiquitinating enzymes (DUBs) are proteases that remove ubiqutin conjugates from proteins, thereby regulating protein turnover. However, the majority of substrates and pathways regulated by DUBs remain unknown, impeding efforts to prioritize specific proteins for research and drug-development.

Each DUB is listed with the number of papers in PubMed, the number of INDRA statements about deubiquitinating substrates, the number of INDRA statements total (including upstream and downstream processes beyond deubiquitination), and the and the fraction of cell lines in the DepMap that are strongly dependent on each DUB (i.e., cancer cell proliferation is strongly impacted by DUB knockout). Blank values in the "Dependent Cell Lines" column means the DUB was not knocked out in the DepMap dataset. Additionally, we list the Gene Ontology (GO) term most strongly enriched in the top seven co-dependent genes for each DUB and the corresponding p-values. Finally, the "DGEA" column contains the number of differentially expressed genes 96 hours following knockout of the particular DUB in MDAMB231 cells as measured by high-throughput RNAseq. Blank values in "DGEA" refer to DUBs that were not knockout out in the RNAseq experiment.

Click on an individual DUB name for more details and additional data and analysis.

DUB DUB Name DUB Family # Papers # DUB Stmts. # Other Stmts. Dependent Cell Lines # Sig. ORA Gene Sets (DepMap) DGEA # Sig. GSEA Gene Sets (DGEA)
ATXN3 ataxin 3 MJD 786 20 687 1.0% 0
ATXN3L ataxin 3 like MJD 7 1 22 0.0% 0
BAP1 BRCA1 associated protein 1 UCHL 1691 30 437 76.0% 4 10
BRCC3 BRCA1/BRCA2-containing complex subunit 3 JAMM 97 29 197 0.0% 2 1
COPS5 COP9 signalosome subunit 5 JAMM 365 22 589 100.0% 7 52 4
COPS6 COP9 signalosome subunit 6 JAMM 48 11 178 100.0% 0
CYLD CYLD lysine 63 deubiquitinase USP 801 80 875 5.0% 41 28 259
EIF3F eukaryotic translation initiation factor 3 subunit F JAMM 84 2 145 98.0% 21
EIF3H eukaryotic translation initiation factor 3 subunit H JAMM 73 2 130 96.0% 16
JOSD1 Josephin domain containing 1 MJD 16 1 98 9.0% 0 0
JOSD2 Josephin domain containing 2 MJD 12 0 44 0 0
MINDY1 MINDY lysine 48 deubiquitinase 1 MINDY 8 1 83 23.0% 0
MINDY2 MINDY lysine 48 deubiquitinase 2 MINDY 4 0 77 49.0% 0
MINDY3 MINDY lysine 48 deubiquitinase 3 MINDY 2 0 70 0
MINDY4 MINDY lysine 48 deubiquitinase 4 MINDY 1 0 48 0
MINDY4B MINDY family member 4B MINDY 0 0 0 0
MPND MPN domain containing JAMM 20 0 29 5.0% 0 0
MYSM1 Myb like, SWIRM and MPN domains 1 JAMM 65 3 121 0 0
OTUB1 OTU deubiquitinase, ubiquitin aldehyde binding 1 OTU 167 34 327 3.0% 11 0
OTUB2 OTU deubiquitinase, ubiquitin aldehyde binding 2 OTU 38 8 159 0 0
OTUD1 OTU deubiquitinase 1 OTU 40 8 168 0 0
OTUD3 OTU deubiquitinase 3 OTU 32 5 92 1.0% 0
OTUD4 OTU deubiquitinase 4 OTU 29 2 193 0 0
OTUD5 OTU deubiquitinase 5 OTU 30 15 132 48.0% 11 2
OTUD6A OTU deubiquitinase 6A OTU 9 0 39 0.0% 0
OTUD6B OTU deubiquitinase 6B OTU 41 1 49 1.0% 0 9
OTUD7A OTU deubiquitinase 7A OTU 28 14 34 0 2
OTUD7B OTU deubiquitinase 7B OTU 71 20 267 0 0
OTULIN OTU deubiquitinase with linear linkage specificity OTU 97 10 168 1.0% 0
OTULINL OTU deubiquitinase with linear linkage specificity like OTU 2 1 102 0.1% 0
PAN2 poly(A) specific ribonuclease subunit PAN2 USP 115 1 149 7.0% 0 0
PRPF8 pre-mRNA processing factor 8 JAMM 152 1 119 100.0% 14 106
PSMD14 proteasome 26S subunit, non-ATPase 14 102 17 216 100.0% 57 839 913
PSMD7 proteasome 26S subunit, non-ATPase 7 Proteasome 40 1 178 100.0% 6
STAMBP STAM binding protein JAMM 75 17 263 32.0% 4 1
STAMBPL1 STAM binding protein like 1 JAMM 27 3 121 0 0
TNFAIP3 TNF alpha induced protein 3 OTU 1615 16 686 1.0% 17 36 159
UCHL1 ubiquitin C-terminal hydrolase L1 UCHL 2293 31 750 0 11
UCHL3 ubiquitin C-terminal hydrolase L3 UCHL 158 11 193 1.0% 33 77 393
UCHL5 ubiquitin C-terminal hydrolase L5 UCHL 180 27 243 50.0% 8 3
USP1 ubiquitin specific peptidase 1 USP 243 28 385 14.0% 7 0
USP10 ubiquitin specific peptidase 10 USP 216 54 333 69.0% 0 1
USP11 ubiquitin specific peptidase 11 USP 105 54 260 0 0
USP12 ubiquitin specific peptidase 12 USP 62 19 157 0 1
USP13 ubiquitin specific peptidase 13 USP 98 28 301 1.0% 0 2
USP14 ubiquitin specific peptidase 14 USP 315 29 449 9.0% 1 2
USP15 ubiquitin specific peptidase 15 USP 167 75 431 1.0% 1 2
USP16 ubiquitin specific peptidase 16 USP 68 7 135 1.0% 0 10
USP17L1 ubiquitin specific peptidase 17 like family member 1 USP 0 0 3 0
USP17L2 ubiquitin specific peptidase 17 like family member 2 USP 49 25 114 0 0
USP18 ubiquitin specific peptidase 18 USP 327 13 472 16.0% 7 9
USP19 ubiquitin specific peptidase 19 USP 71 18 126 34.0% 0 10
USP2 ubiquitin specific peptidase 2 USP 227 35 360 1.0% 0 14
USP20 ubiquitin specific peptidase 20 USP 54 20 91 0 14
USP21 ubiquitin specific peptidase 21 USP 82 17 55 3.0% 0 1
USP22 ubiquitin specific peptidase 22 USP 241 39 457 1.0% 22 2
USP24 ubiquitin specific peptidase 24 USP 38 9 172 4.0% 0 10
USP25 ubiquitin specific peptidase 25 USP 90 52 344 0 0
USP26 ubiquitin specific peptidase 26 USP 59 5 58 0 2
USP27X ubiquitin specific peptidase 27 X-linked USP 18 11 49 0 1
USP28 ubiquitin specific peptidase 28 USP 124 26 259 1.0% 62 9
USP29 ubiquitin specific peptidase 29 USP 49 6 68 0 9
USP3 ubiquitin specific peptidase 3 USP 69 20 167 0.0% 0 15
USP30 ubiquitin specific peptidase 30 USP 92 11 66 0.0% 0 3
USP31 ubiquitin specific peptidase 31 USP 16 0 75 0 5
USP32 ubiquitin specific peptidase 32 USP 27 0 92 2.0% 10 0
USP33 ubiquitin specific peptidase 33 USP 66 25 128 1.0% 0 0
USP34 ubiquitin specific peptidase 34 USP 50 8 125 1.0% 0 11
USP35 ubiquitin specific peptidase 35 USP 22 8 51 6.0% 2 0
USP36 ubiquitin specific peptidase 36 USP 58 17 114 100.0% 2 3
USP37 ubiquitin specific peptidase 37 USP 49 23 228 80.0% 3 2
USP38 ubiquitin specific peptidase 38 USP 24 2 70 2.0% 47 3
USP39 ubiquitin specific peptidase 39 USP 69 4 119 67.0% 0 10
USP4 ubiquitin specific peptidase 4 USP 171 59 282 6.0% 0 1
USP40 ubiquitin specific peptidase 40 USP 16 0 43 0 0
USP41 ubiquitin specific peptidase 41 USP 9 1 22 0
USP42 ubiquitin specific peptidase 42 USP 31 4 98 1.0% 10 0
USP43 ubiquitin specific peptidase 43 USP 11 1 63 0 0
USP44 ubiquitin specific peptidase 44 USP 56 20 124 1.0% 0 0
USP45 ubiquitin specific peptidase 45 USP 109 3 68 0 0
USP46 ubiquitin specific peptidase 46 USP 61 18 176 0 6
USP47 ubiquitin specific peptidase 47 USP 49 12 178 0.0% 0 0
USP48 ubiquitin specific peptidase 48 USP 54 7 174 1.0% 0 1
USP49 ubiquitin specific peptidase 49 USP 33 9 114 0 0
USP5 ubiquitin specific peptidase 5 USP 127 16 278 100.0% 4 1
USP50 ubiquitin specific peptidase 50 USP 8 5 16 2.0% 0 2
USP51 ubiquitin specific peptidase 51 USP 19 7 53 0.0% 1 0
USP53 ubiquitin specific peptidase 53 USP 27 2 142 2.0% 2 0
USP54 ubiquitin specific peptidase 54 USP 11 0 56 0 0
USP6 ubiquitin specific peptidase 6 USP 215 5 99 14.0% 0 11
USP7 ubiquitin specific peptidase 7 USP 696 148 742 81.0% 47 16
USP8 ubiquitin specific peptidase 8 USP 289 79 299 98.0% 18 69 359
USP9X ubiquitin specific peptidase 9 X-linked USP 340 90 682 92.0% 3 2
USP9Y ubiquitin specific peptidase 9 Y-linked USP 94 1 17 0 2
USPL1 ubiquitin specific peptidase like 1 USP 11 0 74 99.0% 4 813 113
VCPIP1 valosin containing protein interacting protein 1 OTU 21 3 93 35.0% 3 0
YOD1 YOD1 deubiquitinase OTU 56 8 295 0 21 155
ZRANB1 zinc finger RANBP2-type containing 1 OTU 30 7 174 2.0% 0 30 327
ZUP1 zinc finger containing ubiquitin peptidase 1 8 18 168 0