USP8 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 8
HGNC Gene Symbol
USP8
Identifiers
hgnc:12631 NCBIGene:9101 uniprot:P40818
Orthologs
mgi:1934029 rgd:1304979
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP8
Number of Papers
261 retrieved on 2022-05-22

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type
PTPN23 protein tyrosine phosphatase non-receptor type 23 0.563 INDRA (4) 0.50 2.65 8.26e-23
UBAP1 ubiquitin associated protein 1 0.454 0.30 1.57 2.78e-08
HGS hepatocyte growth factor-regulated tyrosine kinase substrate 0.438 INDRA (10) Reactome (8) 0.15 0.72 1.29e-02
STAMBP STAM binding protein 0.377 INDRA (6) Reactome (3) 0.32 1.68 2.51e-09 97.75 kd
CLTC clathrin heavy chain 0.346 Reactome (3) 0.35 1.83 6.25e-11
VPS37A VPS37A subunit of ESCRT-I 0.343 0.37 1.97 1.48e-12
VPS36 vacuolar protein sorting 36 homolog 0.324 0.49 2.60 6.28e-22

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP8using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value
GO:0016197 endosomal transport Biological Process 1.62e-11 3.62e-09 1.45e-09
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Biological Process 4.73e-11 1.06e-08 2.12e-09
GO:0036452 ESCRT complex Cellular Component 1.13e-10 2.54e-08 3.38e-09
GO:0036257 multivesicular body organization Biological Process 1.38e-07 3.08e-05 3.08e-06
GO:0072666 establishment of protein localization to vacuole Biological Process 4.64e-07 1.04e-04 8.30e-06
GO:0072665 protein localization to vacuole Biological Process 1.15e-06 2.58e-04 1.72e-05
GO:0007032 endosome organization Biological Process 2.40e-06 5.38e-04 3.07e-05
GO:0000813 ESCRT I complex Cellular Component 5.24e-06 1.17e-03 5.86e-05
GO:0031902 late endosome membrane Cellular Component 1.03e-05 2.31e-03 1.02e-04
GO:0007034 vacuolar transport Biological Process 1.29e-05 2.89e-03 1.13e-04
GO:0061919 process utilizing autophagic mechanism Biological Process 1.39e-05 3.11e-03 1.13e-04
GO:0032509 endosome transport via multivesicular body sorting pathway Biological Process 3.21e-05 7.19e-03 2.39e-04
GO:0071985 multivesicular body sorting pathway Biological Process 5.76e-05 1.29e-02 3.96e-04
GO:0006623 protein targeting to vacuole Biological Process 6.90e-05 1.55e-02 4.33e-04
GO:0005770 late endosome Cellular Component 7.25e-05 1.62e-02 4.33e-04
GO:0016236 macroautophagy Biological Process 1.19e-04 2.67e-02 6.68e-04
GO:0016050 vesicle organization Biological Process 1.60e-04 3.58e-02 8.40e-04
GO:0005769 early endosome Cellular Component 1.98e-04 4.43e-02 9.30e-04

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP8 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
UBC ubiquitin C 1.04e+00 6.19e-71 3.07e-67
MT1X metallothionein 1X 7.01e-01 1.97e-20 4.89e-17
NAMPT nicotinamide phosphoribosyltransferase 6.54e-01 6.29e-11 1.04e-07
STC1 stanniocalcin 1 7.22e-01 2.65e-09 3.28e-06
MSMO1 methylsterol monooxygenase 1 7.25e-01 1.55e-08 1.54e-05
CD74 CD74 molecule -6.58e-01 4.80e-08 3.54e-05
FTL ferritin light chain 4.07e-01 4.99e-08 3.54e-05
UBB ubiquitin B 2.64e-01 6.06e-08 3.75e-05
HSPA5 heat shock protein family A (Hsp70) member 5 3.75e-01 1.12e-07 6.14e-05
IFIT3 interferon induced protein with tetratricopeptide repeats 3 6.13e-01 2.62e-07 1.30e-04
HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 7.84e-01 3.22e-07 1.45e-04
BIRC5 baculoviral IAP repeat containing 5 -4.06e-01 5.22e-07 2.04e-04
PGK1 phosphoglycerate kinase 1 3.44e-01 5.34e-07 2.04e-04
GDF15 growth differentiation factor 15 8.81e-01 5.99e-07 2.12e-04
C15orf48 chromosome 15 open reading frame 48 6.20e-01 6.66e-07 2.20e-04
MMP1 matrix metallopeptidase 1 3.63e-01 7.19e-07 2.23e-04
BNIP3 BCL2 interacting protein 3 4.47e-01 8.46e-07 2.30e-04
HMGN2 high mobility group nucleosomal binding domain 2 -3.11e-01 8.11e-07 2.30e-04
SQSTM1 sequestosome 1 5.55e-01 8.83e-07 2.30e-04
CXCL8 C-X-C motif chemokine ligand 8 8.94e-01 9.39e-07 2.33e-04
AKR1C3 aldo-keto reductase family 1 member C3 5.45e-01 1.32e-06 3.12e-04
IFIT1 interferon induced protein with tetratricopeptide repeats 1 8.67e-01 1.44e-06 3.25e-04
INSIG1 insulin induced gene 1 6.74e-01 2.05e-06 4.42e-04
TP53 tumor protein p53 -6.81e-01 2.25e-06 4.64e-04
NDRG1 N-myc downstream regulated 1 7.20e-01 3.88e-06 7.67e-04
TXNRD1 thioredoxin reductase 1 5.40e-01 4.03e-06 7.67e-04
IDI1 isopentenyl-diphosphate delta isomerase 1 4.85e-01 8.97e-06 1.65e-03
CDCA8 cell division cycle associated 8 -5.98e-01 1.02e-05 1.73e-03
FDPS farnesyl diphosphate synthase 3.57e-01 1.05e-05 1.73e-03
HMGA1 high mobility group AT-hook 1 -3.75e-01 1.01e-05 1.73e-03
TNFSF15 TNF superfamily member 15 6.57e-01 1.50e-05 2.40e-03
CD59 CD59 molecule (CD59 blood group) -3.32e-01 2.80e-05 4.33e-03
KLF6 Kruppel like factor 6 3.92e-01 3.09e-05 4.41e-03
RAB13 RAB13, member RAS oncogene family 3.80e-01 3.11e-05 4.41e-03
TUBB4B tubulin beta 4B class IVb -4.04e-01 2.97e-05 4.41e-03
CSF1 colony stimulating factor 1 5.59e-01 3.75e-05 5.15e-03
FDFT1 farnesyl-diphosphate farnesyltransferase 1 5.93e-01 4.70e-05 6.29e-03
SOD2 superoxide dismutase 2 4.25e-01 4.95e-05 6.46e-03
FTH1 ferritin heavy chain 1 4.34e-01 5.68e-05 7.21e-03
HIGD2A HIG1 hypoxia inducible domain family member 2A 3.80e-01 5.82e-05 7.21e-03
NAV3 neuron navigator 3 7.64e-01 6.30e-05 7.62e-03
DNMT1 DNA methyltransferase 1 -3.99e-01 7.07e-05 8.34e-03
IGFBP4 insulin like growth factor binding protein 4 -3.01e-01 8.00e-05 9.19e-03
SKA2 spindle and kinetochore associated complex subunit 2 -4.63e-01 8.16e-05 9.19e-03
HMGA2 high mobility group AT-hook 2 6.27e-01 9.09e-05 1.00e-02
SAT1 spermidine/spermine N1-acetyltransferase 1 4.00e-01 9.34e-05 1.01e-02
RPS28 ribosomal protein S28 7.26e-01 9.76e-05 1.03e-02
CAVIN2 caveolae associated protein 2 -8.39e-01 1.17e-04 1.20e-02
AXL AXL receptor tyrosine kinase -4.59e-01 1.44e-04 1.46e-02
DBI diazepam binding inhibitor, acyl-CoA binding protein 2.49e-01 1.52e-04 1.50e-02
DDX41 DEAD-box helicase 41 5.89e-01 1.55e-04 1.50e-02
IQGAP3 IQ motif containing GTPase activating protein 3 -5.41e-01 1.62e-04 1.54e-02
PLAUR plasminogen activator, urokinase receptor 3.30e-01 1.71e-04 1.60e-02
ERRFI1 ERBB receptor feedback inhibitor 1 4.67e-01 2.20e-04 2.02e-02
HERPUD1 homocysteine inducible ER protein with ubiquitin like domain 1 5.74e-01 2.24e-04 2.02e-02
NAMPTP1 nicotinamide phosphoribosyltransferase pseudogene 1 5.04e-01 2.63e-04 2.33e-02
RPL3P4 ribosomal protein L3 pseudogene 4 6.07e-01 2.90e-04 2.52e-02
PLIN2 perilipin 2 4.28e-01 3.11e-04 2.66e-02
BTG1 BTG anti-proliferation factor 1 5.27e-01 3.30e-04 2.77e-02
SLC7A11 solute carrier family 7 member 11 5.85e-01 3.43e-04 2.83e-02
LRRC75A leucine rich repeat containing 75A -2.90e-01 3.74e-04 3.04e-02
CD44 CD44 molecule (Indian blood group) 3.19e-01 3.89e-04 3.11e-02
NUCKS1 nuclear casein kinase and cyclin dependent kinase substrate 1 -2.83e-01 4.94e-04 3.89e-02
POLR1A RNA polymerase I subunit A -7.11e-01 5.07e-04 3.93e-02
EIF2S3 eukaryotic translation initiation factor 2 subunit gamma -4.20e-01 5.16e-04 3.93e-02
ATP5IF1 ATP synthase inhibitory factor subunit 1 2.33e-01 6.46e-04 4.85e-02
IGFBP7 insulin like growth factor binding protein 7 -3.66e-01 6.77e-04 4.93e-02
NUSAP1 nucleolar and spindle associated protein 1 -3.67e-01 6.69e-04 4.93e-02
AKR1B1 aldo-keto reductase family 1 member B 2.74e-01 6.93e-04 4.98e-02

Gene Set Enrichment Analysis

The GSEA method was applied for all genes whose knockout resulted in at least 20 significantly differentially expressed genes.

ID Name p-value p-value (adj.) log2 Error ES NES
msig:M5925 HALLMARK_E2F_TARGETS 9.51e-20 3.24e-16 1.15e+00 -6.03e-01 -2.68e+00
go:0007049 cell cycle 5.77e-16 9.83e-13 1.03e+00 -3.71e-01 -1.91e+00
go:0005694 chromosome 3.16e-15 3.58e-12 1.01e+00 -4.12e-01 -2.04e+00
reactome:R-HSA-1640170 Cell Cycle 7.03e-15 5.99e-12 9.97e-01 -4.42e-01 -2.15e+00
go:0051301 cell division 1.90e-14 1.29e-11 9.76e-01 -4.74e-01 -2.26e+00
go:0022402 cell cycle process 9.22e-14 5.24e-11 9.55e-01 -3.79e-01 -1.92e+00
reactome:R-HSA-69278 Cell Cycle, Mitotic 2.13e-13 1.04e-10 9.44e-01 -4.49e-01 -2.14e+00
go:0000278 mitotic cell cycle 5.09e-13 2.17e-10 9.21e-01 -3.96e-01 -1.96e+00
msig:M5901 HALLMARK_G2M_CHECKPOINT 1.93e-12 7.29e-10 8.99e-01 -5.45e-01 -2.39e+00
go:0140014 mitotic nuclear division 2.96e-11 1.01e-08 8.51e-01 -5.31e-01 -2.31e+00
go:0000793 condensed chromosome 1.54e-10 4.77e-08 8.27e-01 -5.54e-01 -2.37e+00
go:0007059 chromosome segregation 1.96e-10 5.55e-08 8.27e-01 -5.05e-01 -2.24e+00
go:0051276 chromosome organization 2.52e-10 6.60e-08 8.14e-01 -3.64e-01 -1.82e+00
go:0048285 organelle fission 3.85e-10 9.38e-08 8.14e-01 -4.82e-01 -2.18e+00
msig:M5891 HALLMARK_HYPOXIA 7.72e-10 1.75e-07 8.01e-01 5.68e-01 2.42e+00
msig:M5924 HALLMARK_MTORC1_SIGNALING 2.84e-09 6.04e-07 7.75e-01 4.58e-01 2.10e+00
go:0010564 regulation of cell cycle process 6.80e-09 1.29e-06 7.61e-01 -3.83e-01 -1.86e+00
reactome:R-HSA-69618 Mitotic Spindle Checkpoint 6.77e-09 1.29e-06 7.61e-01 -5.89e-01 -2.33e+00
go:0098813 nuclear chromosome segregation 7.66e-09 1.37e-06 7.48e-01 -5.07e-01 -2.19e+00
reactome:R-HSA-68877 Mitotic Prometaphase 3.19e-08 5.43e-06 7.20e-01 -4.88e-01 -2.12e+00
go:0098687 chromosomal region 4.13e-08 6.70e-06 7.20e-01 -4.43e-01 -2.01e+00
go:0000775 chromosome, centromeric region 4.59e-08 7.11e-06 7.20e-01 -5.11e-01 -2.18e+00
go:0000819 sister chromatid segregation 5.63e-08 8.33e-06 7.20e-01 -5.08e-01 -2.14e+00
reactome:R-HSA-69620 Cell Cycle Checkpoints 9.74e-08 1.38e-05 7.05e-01 -4.40e-01 -1.98e+00
go:0000070 mitotic sister chromatid segregation 1.05e-07 1.43e-05 7.05e-01 -5.48e-01 -2.25e+00
go:0006259 DNA metabolic process 1.15e-07 1.51e-05 7.05e-01 -3.65e-01 -1.78e+00
go:0016126 sterol biosynthetic process 1.47e-07 1.85e-05 6.90e-01 6.90e-01 2.41e+00
reactome:R-HSA-5663220 RHO GTPases Activate Formins 1.52e-07 1.85e-05 6.90e-01 -5.31e-01 -2.16e+00
msig:M7963 KEGG_CELL_CYCLE 1.62e-07 1.91e-05 6.90e-01 -5.83e-01 -2.23e+00
go:0006974 cellular response to DNA damage stimulus 2.00e-07 2.27e-05 6.90e-01 -3.61e-01 -1.75e+00
reactome:R-HSA-2500257 Resolution of Sister Chromatid Cohesion 2.54e-07 2.75e-05 6.75e-01 -5.40e-01 -2.18e+00
go:0008202 steroid metabolic process 2.58e-07 2.75e-05 6.75e-01 5.31e-01 2.22e+00
go:0051726 regulation of cell cycle 2.71e-07 2.80e-05 6.75e-01 -3.30e-01 -1.65e+00
go:1901617 organic hydroxy compound biosynthetic process 3.40e-07 3.40e-05 6.75e-01 5.57e-01 2.26e+00
go:0000776 kinetochore 4.07e-07 3.85e-05 6.75e-01 -5.37e-01 -2.17e+00
go:0006260 DNA replication 4.06e-07 3.85e-05 6.75e-01 -4.66e-01 -2.03e+00
go:0006281 DNA repair 5.03e-07 4.63e-05 6.59e-01 -3.93e-01 -1.85e+00
go:0042175 nuclear outer membrane-endoplasmic reticulum membrane network 5.66e-07 5.07e-05 6.59e-01 3.16e-01 1.66e+00
reactome:R-HSA-556833 Metabolism of lipids 6.20e-07 5.41e-05 6.59e-01 3.79e-01 1.83e+00
go:0006323 DNA packaging 6.43e-07 5.48e-05 6.59e-01 -5.31e-01 -2.14e+00
go:0006694 steroid biosynthetic process 6.88e-07 5.72e-05 6.59e-01 5.77e-01 2.26e+00
go:0005819 spindle 9.75e-07 7.91e-05 6.44e-01 -4.27e-01 -1.92e+00
reactome:R-HSA-8957322 Metabolism of steroids 1.05e-06 8.36e-05 6.44e-01 5.96e-01 2.27e+00
go:0000228 nuclear chromosome 1.25e-06 9.66e-05 6.44e-01 -3.87e-01 -1.82e+00
go:0000779 condensed chromosome, centromeric region 1.54e-06 1.14e-04 6.44e-01 -5.34e-01 -2.11e+00
go:0005773 vacuole 1.54e-06 1.14e-04 6.44e-01 3.52e-01 1.76e+00
go:0006629 lipid metabolic process 2.68e-06 1.94e-04 6.27e-01 3.33e-01 1.70e+00
go:1901615 organic hydroxy compound metabolic process 2.74e-06 1.94e-04 6.27e-01 4.46e-01 1.99e+00
go:0006873 cellular ion homeostasis 2.99e-06 2.07e-04 6.27e-01 4.15e-01 1.91e+00
go:0006261 DNA-dependent DNA replication 3.05e-06 2.07e-04 6.27e-01 -5.25e-01 -2.08e+00
go:0000226 microtubule cytoskeleton organization 3.22e-06 2.15e-04 6.27e-01 -3.93e-01 -1.81e+00
go:0051783 regulation of nuclear division 4.14e-06 2.66e-04 6.11e-01 -4.91e-01 -2.04e+00
go:0034508 centromere complex assembly 4.09e-06 2.66e-04 6.11e-01 -6.96e-01 -2.24e+00
go:0044770 cell cycle phase transition 4.54e-06 2.86e-04 6.11e-01 -3.57e-01 -1.70e+00
reactome:R-HSA-194315 Signaling by Rho GTPases 4.75e-06 2.94e-04 6.11e-01 -4.03e-01 -1.81e+00
go:0002252 immune effector process 5.19e-06 3.16e-04 6.11e-01 3.09e-01 1.63e+00
go:0015630 microtubule cytoskeleton 6.17e-06 3.69e-04 6.11e-01 -3.22e-01 -1.59e+00
go:0046165 alcohol biosynthetic process 6.86e-06 4.03e-04 6.11e-01 5.73e-01 2.21e+00
msig:M5890 HALLMARK_TNFA_SIGNALING_VIA_NFKB 8.01e-06 4.62e-04 5.93e-01 4.87e-01 2.03e+00
go:0006325 chromatin organization 8.49e-06 4.74e-04 5.93e-01 -3.51e-01 -1.68e+00
reactome:R-HSA-68886 M Phase 8.36e-06 4.74e-04 5.93e-01 -3.80e-01 -1.78e+00
msig:M16848 KEGG_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION 9.61e-06 5.28e-04 5.93e-01 6.56e-01 2.19e+00
go:0044430 1.14e-05 6.15e-04 5.93e-01 -3.12e-01 -1.56e+00
go:0034097 response to cytokine 1.16e-05 6.20e-04 5.93e-01 2.96e-01 1.55e+00
go:0005783 endoplasmic reticulum 1.33e-05 6.87e-04 5.93e-01 2.67e-01 1.46e+00
reactome:R-HSA-73894 DNA Repair 1.31e-05 6.87e-04 5.93e-01 -4.13e-01 -1.84e+00
reactome:R-HSA-168249 Innate Immune System 1.45e-05 7.37e-04 5.93e-01 3.01e-01 1.57e+00
reactome:R-HSA-195258 RHO GTPase Effectors 1.54e-05 7.71e-04 5.76e-01 -4.12e-01 -1.83e+00
go:0044843 cell cycle G1/S phase transition 1.75e-05 8.53e-04 5.76e-01 -4.48e-01 -1.92e+00
go:0006333 chromatin assembly or disassembly 1.75e-05 8.53e-04 5.76e-01 -5.05e-01 -1.99e+00
msig:M5913 HALLMARK_INTERFERON_GAMMA_RESPONSE 1.83e-05 8.78e-04 5.76e-01 5.06e-01 2.06e+00
msig:M5893 HALLMARK_MITOTIC_SPINDLE 1.88e-05 8.91e-04 5.76e-01 -4.53e-01 -1.91e+00
go:0044437 2.29e-05 1.07e-03 5.76e-01 3.55e-01 1.72e+00
go:0048878 chemical homeostasis 2.32e-05 1.07e-03 5.76e-01 3.20e-01 1.60e+00
go:0007346 regulation of mitotic cell cycle 2.99e-05 1.32e-03 5.76e-01 -3.38e-01 -1.62e+00
go:0000785 chromatin 3.15e-05 1.36e-03 5.57e-01 -3.65e-01 -1.70e+00
go:0050801 ion homeostasis 3.20e-05 1.36e-03 5.57e-01 3.65e-01 1.72e+00
go:0071824 protein-DNA complex subunit organization 3.17e-05 1.36e-03 5.57e-01 -4.27e-01 -1.85e+00
go:0008608 attachment of spindle microtubules to kinetochore 3.39e-05 1.43e-03 5.57e-01 -6.94e-01 -2.17e+00
msig:M11266 KEGG_LYSOSOME 3.81e-05 1.58e-03 5.57e-01 5.50e-01 2.12e+00
go:0034728 nucleosome organization 4.20e-05 1.72e-03 5.57e-01 -5.03e-01 -1.95e+00
reactome:R-HSA-162587 HIV Life Cycle 4.50e-05 1.83e-03 5.57e-01 -4.56e-01 -1.90e+00
go:0055065 metal ion homeostasis 4.82e-05 1.93e-03 5.57e-01 3.81e-01 1.75e+00
go:0002274 myeloid leukocyte activation 5.05e-05 2.00e-03 5.57e-01 3.27e-01 1.62e+00
go:0006952 defense response 5.26e-05 2.06e-03 5.57e-01 2.87e-01 1.52e+00
reactome:R-HSA-191273 Cholesterol biosynthesis 5.46e-05 2.09e-03 5.57e-01 7.66e-01 2.19e+00
reactome:R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 5.44e-05 2.09e-03 5.57e-01 6.40e-01 2.14e+00
go:0051983 regulation of chromosome segregation 5.66e-05 2.14e-03 5.57e-01 -5.08e-01 -1.95e+00
reactome:R-HSA-168325 Viral Messenger RNA Synthesis 5.77e-05 2.16e-03 5.57e-01 -6.17e-01 -2.06e+00
reactome:R-HSA-2990846 SUMOylation 6.11e-05 2.26e-03 5.38e-01 -4.63e-01 -1.88e+00
go:0060968 regulation of gene silencing 6.16e-05 2.26e-03 5.38e-01 -4.96e-01 -1.93e+00
go:1901701 cellular response to oxygen-containing compound 6.61e-05 2.40e-03 5.38e-01 3.09e-01 1.59e+00
go:0051290 protein heterotetramerization 7.02e-05 2.52e-03 5.38e-01 -7.32e-01 -2.06e+00
reactome:R-HSA-68962 Activation of the pre-replicative complex 7.12e-05 2.53e-03 5.38e-01 -7.02e-01 -2.06e+00
msig:M5892 HALLMARK_CHOLESTEROL_HOMEOSTASIS 7.42e-05 2.58e-03 5.38e-01 5.82e-01 2.12e+00
go:0018205 peptidyl-lysine modification 7.42e-05 2.58e-03 5.38e-01 -4.09e-01 -1.80e+00
go:0051607 defense response to virus 8.06e-05 2.77e-03 5.38e-01 4.38e-01 1.87e+00
go:0031055 chromatin remodeling at centromere 8.14e-05 2.77e-03 5.38e-01 -6.76e-01 -2.11e+00
reactome:R-HSA-69190 DNA strand elongation 1.09e-04 3.67e-03 5.38e-01 -6.70e-01 -2.09e+00
go:0007010 cytoskeleton organization 1.19e-04 3.97e-03 5.38e-01 -3.07e-01 -1.51e+00
go:0019218 regulation of steroid metabolic process 1.21e-04 3.99e-03 5.38e-01 5.95e-01 2.06e+00
go:1901698 response to nitrogen compound 1.35e-04 4.37e-03 5.19e-01 3.06e-01 1.55e+00
go:0071103 DNA conformation change 1.36e-04 4.37e-03 5.19e-01 -4.04e-01 -1.75e+00
go:0051321 meiotic cell cycle 1.49e-04 4.73e-03 5.19e-01 -4.82e-01 -1.92e+00
go:0008610 lipid biosynthetic process 1.55e-04 4.83e-03 5.19e-01 3.53e-01 1.64e+00
go:0001775 cell activation 1.54e-04 4.83e-03 5.19e-01 2.81e-01 1.49e+00
go:0043486 histone exchange 1.57e-04 4.86e-03 5.19e-01 -6.11e-01 -2.02e+00
reactome:R-HSA-2555396 Mitotic Metaphase and Anaphase 1.60e-04 4.91e-03 5.19e-01 -3.94e-01 -1.73e+00
go:0005125 cytokine activity 1.66e-04 5.06e-03 5.19e-01 5.96e-01 1.99e+00
go:0016925 protein sumoylation 1.72e-04 5.20e-03 5.19e-01 -5.71e-01 -1.97e+00
go:0043044 ATP-dependent chromatin remodeling 1.80e-04 5.39e-03 5.19e-01 -5.37e-01 -1.96e+00
go:0000922 spindle pole 1.91e-04 5.67e-03 5.19e-01 -4.54e-01 -1.83e+00
go:0034724 DNA replication-independent nucleosome organization 1.97e-04 5.72e-03 5.19e-01 -6.03e-01 -2.00e+00
reactome:R-HSA-983231 Factors involved in megakaryocyte development and platelet production 1.97e-04 5.72e-03 5.19e-01 -5.27e-01 -1.96e+00
msig:M5898 HALLMARK_DNA_REPAIR 2.04e-04 5.89e-03 5.19e-01 -4.39e-01 -1.83e+00
go:0090734 site of DNA damage 2.06e-04 5.90e-03 5.19e-01 -5.54e-01 -1.96e+00
go:0006984 ER-nucleus signaling pathway 2.22e-04 6.30e-03 5.19e-01 6.28e-01 2.08e+00
reactome:R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 2.33e-04 6.56e-03 5.19e-01 6.75e-01 2.10e+00
go:0007017 microtubule-based process 2.52e-04 7.00e-03 4.98e-01 -3.30e-01 -1.56e+00
go:0002444 myeloid leukocyte mediated immunity 2.53e-04 7.00e-03 4.98e-01 3.12e-01 1.54e+00
reactome:R-HSA-5693532 DNA Double-Strand Break Repair 2.91e-04 8.01e-03 4.98e-01 -4.69e-01 -1.83e+00
go:0006310 DNA recombination 2.97e-04 8.02e-03 4.98e-01 -4.14e-01 -1.77e+00
reactome:R-HSA-176187 Activation of ATR in response to replication stress 2.96e-04 8.02e-03 4.98e-01 -6.55e-01 -2.01e+00
go:1901700 response to oxygen-containing compound 3.01e-04 8.07e-03 4.98e-01 2.67e-01 1.43e+00
msig:M16853 KEGG_DNA_REPLICATION 3.04e-04 8.09e-03 4.98e-01 -6.26e-01 -1.99e+00
go:0040029 regulation of gene expression, epigenetic 3.19e-04 8.42e-03 4.98e-01 -3.73e-01 -1.66e+00
reactome:R-HSA-73886 Chromosome Maintenance 3.35e-04 8.77e-03 4.98e-01 -5.13e-01 -1.88e+00
go:0045787 positive regulation of cell cycle 3.49e-04 9.01e-03 4.98e-01 -3.68e-01 -1.65e+00
go:0072507 divalent inorganic cation homeostasis 3.53e-04 9.01e-03 4.98e-01 4.23e-01 1.80e+00
go:0031935 regulation of chromatin silencing 3.54e-04 9.01e-03 4.98e-01 -7.17e-01 -1.98e+00
go:0035861 site of double-strand break 3.50e-04 9.01e-03 4.98e-01 -5.72e-01 -1.93e+00
reactome:R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 3.72e-04 9.39e-03 4.98e-01 -5.50e-01 -1.94e+00
go:0050810 regulation of steroid biosynthetic process 3.86e-04 9.66e-03 4.98e-01 5.98e-01 2.02e+00
reactome:R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 3.93e-04 9.78e-03 4.98e-01 -6.44e-01 -2.01e+00
go:0006302 double-strand break repair 4.31e-04 1.06e-02 4.98e-01 -4.28e-01 -1.79e+00
msig:M5908 HALLMARK_ANDROGEN_RESPONSE 4.39e-04 1.07e-02 4.98e-01 4.71e-01 1.84e+00
go:0098542 defense response to other organism 4.65e-04 1.13e-02 4.98e-01 3.81e-01 1.70e+00
go:0019216 regulation of lipid metabolic process 4.82e-04 1.16e-02 4.98e-01 3.91e-01 1.72e+00
msig:M15569 KEGG_NOD_LIKE_RECEPTOR_SIGNALING_PATHWAY 5.00e-04 1.20e-02 4.77e-01 6.90e-01 2.00e+00
go:0090068 positive regulation of cell cycle process 5.05e-04 1.20e-02 4.77e-01 -3.88e-01 -1.68e+00
go:0002682 regulation of immune system process 5.14e-04 1.22e-02 4.77e-01 2.67e-01 1.41e+00
go:0019725 cellular homeostasis 5.49e-04 1.29e-02 4.77e-01 2.99e-01 1.49e+00
go:0044433 5.76e-04 1.34e-02 4.77e-01 2.57e-01 1.38e+00
go:0001786 phosphatidylserine binding 6.02e-04 1.39e-02 4.77e-01 -6.83e-01 -1.92e+00
reactome:R-HSA-1280215 Cytokine Signaling in Immune system 6.12e-04 1.41e-02 4.77e-01 2.96e-01 1.50e+00
go:0005774 vacuolar membrane 6.39e-04 1.45e-02 4.77e-01 3.48e-01 1.61e+00
go:1901681 sulfur compound binding 6.38e-04 1.45e-02 4.77e-01 4.36e-01 1.77e+00
go:0009615 response to virus 6.56e-04 1.48e-02 4.77e-01 3.78e-01 1.69e+00
reactome:R-HSA-69242 S Phase 6.74e-04 1.51e-02 4.77e-01 -4.01e-01 -1.70e+00
go:0009607 response to biotic stimulus 6.79e-04 1.51e-02 4.77e-01 2.97e-01 1.48e+00
go:0000790 chromatin 7.11e-04 1.57e-02 4.77e-01 -3.79e-01 -1.65e+00
msig:M5947 HALLMARK_IL2_STAT5_SIGNALING 7.67e-04 1.68e-02 4.77e-01 4.53e-01 1.83e+00
go:0000794 condensed nuclear chromosome 7.69e-04 1.68e-02 4.77e-01 -5.67e-01 -1.93e+00
go:0031349 positive regulation of defense response 8.22e-04 1.78e-02 4.77e-01 3.46e-01 1.59e+00
reactome:R-HSA-4615885 SUMOylation of DNA replication proteins 8.28e-04 1.79e-02 4.77e-01 -5.61e-01 -1.87e+00
go:1903046 meiotic cell cycle process 8.37e-04 1.79e-02 4.77e-01 -4.78e-01 -1.80e+00
go:0050729 positive regulation of inflammatory response 8.64e-04 1.83e-02 4.77e-01 5.51e-01 1.88e+00
go:0061695 transferase complex, transferring phosphorus-containing groups 9.05e-04 1.90e-02 4.77e-01 -4.00e-01 -1.69e+00
reactome:R-HSA-168898 Toll-like Receptor Cascades 9.17e-04 1.92e-02 4.77e-01 4.95e-01 1.87e+00
reactome:R-HSA-375276 Peptide ligand-binding receptors 9.73e-04 2.02e-02 4.77e-01 6.73e-01 1.95e+00
go:0002221 pattern recognition receptor signaling pathway 9.91e-04 2.05e-02 4.55e-01 4.85e-01 1.87e+00
go:0030141 secretory granule 1.01e-03 2.06e-02 4.55e-01 2.86e-01 1.45e+00
reactome:R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 1.03e-03 2.09e-02 4.55e-01 6.43e-01 2.00e+00
go:0000725 recombinational repair 1.05e-03 2.13e-02 4.55e-01 -4.68e-01 -1.77e+00
reactome:R-HSA-167172 Transcription of the HIV genome 1.06e-03 2.14e-02 4.55e-01 -5.04e-01 -1.79e+00
msig:M5932 HALLMARK_INFLAMMATORY_RESPONSE 1.17e-03 2.35e-02 4.55e-01 4.49e-01 1.76e+00
go:0051298 centrosome duplication 1.19e-03 2.38e-02 4.55e-01 -5.61e-01 -1.86e+00
go:0051235 maintenance of location 1.21e-03 2.39e-02 4.55e-01 3.87e-01 1.67e+00
reactome:R-HSA-6798695 Neutrophil degranulation 1.24e-03 2.42e-02 4.55e-01 3.02e-01 1.46e+00
reactome:R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 1.24e-03 2.42e-02 4.55e-01 -6.34e-01 -1.88e+00
go:0051186 1.28e-03 2.49e-02 4.55e-01 3.14e-01 1.49e+00
reactome:R-HSA-4085377 SUMOylation of SUMOylation proteins 1.34e-03 2.59e-02 4.55e-01 -6.10e-01 -1.87e+00
go:0051310 metaphase plate congression 1.42e-03 2.74e-02 4.55e-01 -5.43e-01 -1.81e+00
go:0043621 protein self-association 1.46e-03 2.80e-02 4.55e-01 -6.59e-01 -1.86e+00
go:0055085 transmembrane transport 1.50e-03 2.84e-02 4.55e-01 2.69e-01 1.40e+00
go:0032101 regulation of response to external stimulus 1.50e-03 2.84e-02 4.55e-01 3.16e-01 1.49e+00
go:0042592 homeostatic process 1.52e-03 2.85e-02 4.55e-01 2.52e-01 1.36e+00
go:0099513 polymeric cytoskeletal fiber 1.55e-03 2.89e-02 4.55e-01 -3.31e-01 -1.52e+00
go:0009991 response to extracellular stimulus 1.61e-03 2.99e-02 4.55e-01 3.36e-01 1.54e+00
go:0007292 female gamete generation 1.64e-03 3.03e-02 4.55e-01 -5.52e-01 -1.83e+00
go:0002263 cell activation involved in immune response 1.66e-03 3.06e-02 4.55e-01 2.87e-01 1.43e+00
go:0010469 regulation of signaling receptor activity 1.86e-03 3.38e-02 4.55e-01 3.95e-01 1.68e+00
go:0071453 cellular response to oxygen levels 1.88e-03 3.38e-02 4.55e-01 3.59e-01 1.60e+00
reactome:R-HSA-909733 Interferon alpha/beta signaling 1.87e-03 3.38e-02 4.55e-01 5.88e-01 1.87e+00
go:0019221 cytokine-mediated signaling pathway 1.89e-03 3.38e-02 4.55e-01 2.94e-01 1.44e+00
go:0003682 chromatin binding 1.88e-03 3.38e-02 4.55e-01 -3.28e-01 -1.50e+00
go:0044255 cellular lipid metabolic process 1.93e-03 3.42e-02 4.55e-01 3.08e-01 1.48e+00
go:0009124 nucleoside monophosphate biosynthetic process 2.05e-03 3.62e-02 4.32e-01 -5.52e-01 -1.80e+00
go:0032527 protein exit from endoplasmic reticulum 2.23e-03 3.92e-02 4.32e-01 5.52e-01 1.86e+00
go:0046890 regulation of lipid biosynthetic process 2.24e-03 3.92e-02 4.32e-01 4.39e-01 1.70e+00
go:0018193 peptidyl-amino acid modification 2.26e-03 3.93e-02 4.32e-01 -2.83e-01 -1.38e+00
reactome:R-HSA-176033 Interactions of Vpr with host cellular proteins 2.31e-03 3.96e-02 4.32e-01 -5.81e-01 -1.84e+00
go:0016591 RNA polymerase II, holoenzyme 2.30e-03 3.96e-02 4.32e-01 -4.90e-01 -1.78e+00
go:0048640 negative regulation of developmental growth 2.31e-03 3.96e-02 4.32e-01 5.80e-01 1.85e+00
go:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 2.34e-03 3.98e-02 4.32e-01 5.25e-01 1.77e+00
go:0045087 innate immune response 2.35e-03 3.98e-02 4.32e-01 2.89e-01 1.44e+00
go:1901987 regulation of cell cycle phase transition 2.41e-03 4.05e-02 4.32e-01 -3.22e-01 -1.51e+00
go:0005814 centriole 2.45e-03 4.06e-02 4.32e-01 -4.65e-01 -1.72e+00
go:0071384 cellular response to corticosteroid stimulus 2.44e-03 4.06e-02 4.32e-01 5.57e-01 1.86e+00
go:0051304 chromosome separation 2.47e-03 4.09e-02 4.32e-01 -4.89e-01 -1.77e+00
reactome:R-HSA-2980766 Nuclear Envelope Breakdown 2.51e-03 4.09e-02 4.32e-01 -5.27e-01 -1.80e+00
go:0044786 cell cycle DNA replication 2.52e-03 4.09e-02 4.32e-01 -5.06e-01 -1.75e+00
go:0012506 vesicle membrane 2.52e-03 4.09e-02 4.32e-01 2.95e-01 1.46e+00
go:0010948 negative regulation of cell cycle process 2.54e-03 4.11e-02 4.32e-01 -3.42e-01 -1.54e+00
go:0050662 2.62e-03 4.21e-02 4.32e-01 3.68e-01 1.59e+00
go:0044706 multi-multicellular organism process 2.65e-03 4.24e-02 4.32e-01 4.46e-01 1.74e+00
go:0003697 single-stranded DNA binding 2.71e-03 4.31e-02 4.32e-01 -4.57e-01 -1.71e+00
go:0070848 response to growth factor 2.73e-03 4.32e-02 4.32e-01 2.93e-01 1.43e+00
go:0016301 kinase activity 2.77e-03 4.34e-02 4.32e-01 -3.30e-01 -1.51e+00
go:0007584 response to nutrient 2.77e-03 4.34e-02 4.32e-01 4.33e-01 1.74e+00
go:0002443 leukocyte mediated immunity 2.78e-03 4.34e-02 4.32e-01 2.73e-01 1.37e+00
reactome:R-HSA-69473 G2/M DNA damage checkpoint 2.81e-03 4.36e-02 4.32e-01 -5.02e-01 -1.77e+00
go:0005875 microtubule associated complex 2.81e-03 4.36e-02 4.32e-01 -4.54e-01 -1.70e+00
go:1901699 cellular response to nitrogen compound 2.84e-03 4.37e-02 4.32e-01 3.09e-01 1.47e+00
go:0018394 peptidyl-lysine acetylation 2.95e-03 4.52e-02 4.32e-01 -4.51e-01 -1.70e+00
go:0007080 mitotic metaphase plate congression 3.02e-03 4.62e-02 4.32e-01 -5.75e-01 -1.82e+00
go:0051129 negative regulation of cellular component organization 3.08e-03 4.67e-02 4.32e-01 -3.16e-01 -1.48e+00
go:0002753 cytoplasmic pattern recognition receptor signaling pathway 3.07e-03 4.67e-02 4.32e-01 5.51e-01 1.79e+00
reactome:R-HSA-4551638 SUMOylation of chromatin organization proteins 3.13e-03 4.71e-02 4.32e-01 -5.16e-01 -1.74e+00
msig:M5938 HALLMARK_REACTIVE_OXYGEN_SPECIES_PATHWAY 3.14e-03 4.72e-02 4.32e-01 5.10e-01 1.77e+00
reactome:R-HSA-449147 Signaling by Interleukins 3.18e-03 4.75e-02 4.32e-01 2.93e-01 1.40e+00
reactome:R-HSA-917937 Iron uptake and transport 3.19e-03 4.75e-02 4.32e-01 5.19e-01 1.73e+00
reactome:R-HSA-72086 mRNA Capping 3.25e-03 4.81e-02 4.32e-01 -5.72e-01 -1.82e+00
go:0005815 microtubule organizing center 3.26e-03 4.81e-02 4.32e-01 -3.01e-01 -1.43e+00
msig:M5937 HALLMARK_GLYCOLYSIS 3.31e-03 4.84e-02 4.32e-01 3.65e-01 1.57e+00
reactome:R-HSA-5693538 Homology Directed Repair 3.34e-03 4.86e-02 4.32e-01 -4.53e-01 -1.70e+00
go:0045540 regulation of cholesterol biosynthetic process 3.45e-03 5.00e-02 4.32e-01 6.17e-01 1.90e+00
go:0031347 regulation of defense response 3.49e-03 5.03e-02 4.32e-01 3.00e-01 1.44e+00
go:0030496 midbody 3.55e-03 5.11e-02 4.32e-01 -3.89e-01 -1.62e+00
go:1990234 transferase complex 3.59e-03 5.13e-02 4.32e-01 -2.83e-01 -1.37e+00
go:0005768 endosome 3.66e-03 5.19e-02 4.32e-01 2.73e-01 1.37e+00
go:0051302 regulation of cell division 3.69e-03 5.22e-02 4.32e-01 -4.47e-01 -1.68e+00
reactome:R-HSA-3108214 SUMOylation of DNA damage response and repair proteins 3.75e-03 5.25e-02 4.32e-01 -4.76e-01 -1.69e+00
go:0070997 neuron death 3.75e-03 5.25e-02 4.32e-01 3.50e-01 1.55e+00
go:0043902 positive regulation of multi-organism process 3.76e-03 5.25e-02 4.32e-01 -3.96e-01 -1.61e+00
go:0014070 response to organic cyclic compound 3.79e-03 5.27e-02 4.32e-01 2.70e-01 1.36e+00
go:0002224 toll-like receptor signaling pathway 3.88e-03 5.34e-02 4.32e-01 4.99e-01 1.77e+00
go:0034504 protein localization to nucleus 3.87e-03 5.34e-02 4.32e-01 -3.63e-01 -1.55e+00
reactome:R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 3.95e-03 5.38e-02 4.07e-01 -5.72e-01 -1.81e+00
go:0007051 spindle organization 3.96e-03 5.38e-02 4.07e-01 -3.95e-01 -1.62e+00
go:0005876 spindle microtubule 3.93e-03 5.38e-02 4.07e-01 -5.30e-01 -1.81e+00
reactome:R-HSA-177243 Interactions of Rev with host cellular proteins 4.04e-03 5.45e-02 4.07e-01 -5.66e-01 -1.80e+00
msig:M15798 KEGG_MELANOMA 4.05e-03 5.45e-02 4.07e-01 -5.94e-01 -1.76e+00
go:0036260 RNA capping 4.27e-03 5.65e-02 4.07e-01 -5.54e-01 -1.79e+00
go:0005657 replication fork 4.26e-03 5.65e-02 4.07e-01 -5.00e-01 -1.76e+00
go:0016772 transferase activity, transferring phosphorus-containing groups 4.24e-03 5.65e-02 4.07e-01 -3.08e-01 -1.46e+00
msig:M9809 KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION 4.28e-03 5.65e-02 4.07e-01 5.07e-01 1.75e+00
go:0099503 secretory vesicle 4.32e-03 5.66e-02 4.07e-01 2.69e-01 1.38e+00
go:0097110 scaffold protein binding 4.36e-03 5.69e-02 4.07e-01 -5.92e-01 -1.76e+00
go:0030545 receptor regulator activity 4.44e-03 5.77e-02 4.07e-01 3.88e-01 1.60e+00
msig:M15913 KEGG_RIG_I_LIKE_RECEPTOR_SIGNALING_PATHWAY 4.58e-03 5.91e-02 4.07e-01 6.55e-01 1.87e+00
go:0005506 iron ion binding 4.58e-03 5.91e-02 4.07e-01 5.10e-01 1.70e+00
reactome:R-HSA-382551 Transport of small molecules 4.63e-03 5.91e-02 4.07e-01 3.02e-01 1.43e+00
go:0080134 regulation of response to stress 4.65e-03 5.92e-02 4.07e-01 2.44e-01 1.31e+00
go:0007276 gamete generation 4.70e-03 5.94e-02 4.07e-01 -3.44e-01 -1.52e+00
go:1902930 regulation of alcohol biosynthetic process 4.73e-03 5.97e-02 4.07e-01 5.82e-01 1.82e+00
go:0031023 microtubule organizing center organization 4.88e-03 6.11e-02 4.07e-01 -4.21e-01 -1.61e+00
go:1904949 ATPase complex 4.88e-03 6.11e-02 4.07e-01 -4.54e-01 -1.66e+00
go:0000281 mitotic cytokinesis 4.97e-03 6.18e-02 4.07e-01 -4.96e-01 -1.74e+00
go:1903513 endoplasmic reticulum to cytosol transport 5.05e-03 6.23e-02 4.07e-01 6.03e-01 1.87e+00
go:0006270 DNA replication initiation 5.08e-03 6.23e-02 4.07e-01 -5.99e-01 -1.73e+00
reactome:R-HSA-6803529 FGFR2 alternative splicing 5.09e-03 6.23e-02 4.07e-01 -5.77e-01 -1.77e+00
reactome:R-HSA-73762 RNA Polymerase I Transcription Initiation 5.05e-03 6.23e-02 4.07e-01 -5.22e-01 -1.73e+00
go:0002684 positive regulation of immune system process 5.12e-03 6.25e-02 4.07e-01 2.63e-01 1.33e+00
go:0045177 apical part of cell 5.21e-03 6.29e-02 4.07e-01 3.86e-01 1.61e+00
reactome:R-HSA-5633007 Regulation of TP53 Activity 5.23e-03 6.29e-02 4.07e-01 -3.99e-01 -1.59e+00
msig:M18937 KEGG_NUCLEOTIDE_EXCISION_REPAIR 5.24e-03 6.29e-02 4.07e-01 -5.20e-01 -1.72e+00
go:0051984 positive regulation of chromosome segregation 5.24e-03 6.29e-02 4.07e-01 -5.87e-01 -1.74e+00
go:0045814 negative regulation of gene expression, epigenetic 5.30e-03 6.32e-02 4.07e-01 -4.48e-01 -1.66e+00
go:0071559 response to transforming growth factor beta 5.31e-03 6.32e-02 4.07e-01 3.70e-01 1.55e+00
go:0006915 apoptotic process 5.42e-03 6.42e-02 4.07e-01 2.28e-01 1.26e+00
reactome:R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 5.43e-03 6.42e-02 4.07e-01 -5.68e-01 -1.78e+00
go:0008306 associative learning 5.57e-03 6.56e-02 4.07e-01 6.25e-01 1.81e+00
go:0097194 execution phase of apoptosis 5.65e-03 6.62e-02 4.07e-01 -4.77e-01 -1.64e+00
go:0044450 5.64e-03 6.62e-02 4.07e-01 -4.13e-01 -1.61e+00
go:0060548 negative regulation of cell death 5.80e-03 6.76e-02 4.07e-01 2.50e-01 1.30e+00
go:0002039 p53 binding 6.14e-03 7.11e-02 4.07e-01 -5.23e-01 -1.71e+00
go:1901796 regulation of signal transduction by p53 class mediator 6.19e-03 7.15e-02 4.07e-01 -4.00e-01 -1.64e+00
reactome:R-HSA-5578749 Transcriptional regulation by small RNAs 6.23e-03 7.15e-02 4.07e-01 -4.60e-01 -1.64e+00
go:1990841 promoter-specific chromatin binding 6.23e-03 7.15e-02 4.07e-01 -6.16e-01 -1.74e+00
go:0045786 negative regulation of cell cycle 6.30e-03 7.18e-02 4.07e-01 -2.95e-01 -1.40e+00
go:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress 6.29e-03 7.18e-02 4.07e-01 5.38e-01 1.78e+00
go:0071396 cellular response to lipid 6.33e-03 7.18e-02 4.07e-01 3.00e-01 1.41e+00
go:0005643 nuclear pore 6.35e-03 7.19e-02 4.07e-01 -4.70e-01 -1.67e+00
reactome:R-HSA-69306 DNA Replication 6.39e-03 7.20e-02 4.07e-01 -3.81e-01 -1.57e+00
go:0010332 response to gamma radiation 6.42e-03 7.22e-02 4.07e-01 -5.61e-01 -1.77e+00
reactome:R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 6.53e-03 7.32e-02 4.07e-01 5.94e-01 1.82e+00
go:0031491 nucleosome binding 6.76e-03 7.55e-02 4.07e-01 -4.60e-01 -1.65e+00
reactome:R-HSA-180746 Nuclear import of Rev protein 6.84e-03 7.61e-02 4.07e-01 -5.67e-01 -1.74e+00
go:0051208 sequestering of calcium ion 6.95e-03 7.71e-02 4.07e-01 5.76e-01 1.80e+00
go:0006826 iron ion transport 7.13e-03 7.74e-02 4.07e-01 5.42e-01 1.72e+00
reactome:R-HSA-1839126 FGFR2 mutant receptor activation 7.18e-03 7.74e-02 4.07e-01 -6.09e-01 -1.74e+00
go:0033044 regulation of chromosome organization 7.13e-03 7.74e-02 4.07e-01 -3.30e-01 -1.48e+00
go:0016491 oxidoreductase activity 7.18e-03 7.74e-02 4.07e-01 2.56e-01 1.30e+00
go:0033273 response to vitamin 7.04e-03 7.74e-02 4.07e-01 5.29e-01 1.72e+00
go:0097191 extrinsic apoptotic signaling pathway 7.17e-03 7.74e-02 4.07e-01 -3.83e-01 -1.56e+00
go:0001816 cytokine production 7.15e-03 7.74e-02 4.07e-01 2.95e-01 1.40e+00
go:0032103 positive regulation of response to external stimulus 7.05e-03 7.74e-02 4.07e-01 3.78e-01 1.57e+00
msig:M5109 KEGG_PYRIMIDINE_METABOLISM 7.13e-03 7.74e-02 4.07e-01 -4.29e-01 -1.61e+00
go:0070482 response to oxygen levels 7.21e-03 7.75e-02 4.07e-01 2.99e-01 1.41e+00
msig:M5945 HALLMARK_HEME_METABOLISM 7.28e-03 7.77e-02 4.07e-01 3.64e-01 1.54e+00
go:0002764 immune response-regulating signaling pathway 7.27e-03 7.77e-02 4.07e-01 3.06e-01 1.42e+00
go:0045111 intermediate filament cytoskeleton 7.50e-03 7.99e-02 4.07e-01 -4.80e-01 -1.69e+00
go:0005794 Golgi apparatus 7.59e-03 8.06e-02 4.07e-01 2.36e-01 1.26e+00
go:0071407 cellular response to organic cyclic compound 7.70e-03 8.12e-02 4.07e-01 2.98e-01 1.40e+00
go:0002573 myeloid leukocyte differentiation 7.70e-03 8.12e-02 4.07e-01 4.00e-01 1.57e+00
go:0006812 cation transport 7.73e-03 8.12e-02 4.07e-01 2.75e-01 1.35e+00
go:1900117 regulation of execution phase of apoptosis 7.77e-03 8.14e-02 4.07e-01 -6.08e-01 -1.71e+00
go:0032154 cleavage furrow 8.03e-03 8.39e-02 3.81e-01 -5.14e-01 -1.68e+00
go:0006885 regulation of pH 8.09e-03 8.42e-02 3.81e-01 4.88e-01 1.63e+00
go:0048585 negative regulation of response to stimulus 8.11e-03 8.42e-02 3.81e-01 2.39e-01 1.28e+00
go:1905818 regulation of chromosome separation 8.22e-03 8.48e-02 3.81e-01 -4.69e-01 -1.62e+00
reactome:R-HSA-73933 Resolution of Abasic Sites (AP sites) 8.21e-03 8.48e-02 3.81e-01 -5.53e-01 -1.74e+00
go:0030001 metal ion transport 8.28e-03 8.52e-02 3.81e-01 3.03e-01 1.41e+00
go:0006289 nucleotide-excision repair 8.32e-03 8.53e-02 3.81e-01 -4.09e-01 -1.56e+00
go:0030554 adenyl nucleotide binding 8.34e-03 8.53e-02 3.81e-01 -2.62e-01 -1.30e+00
msig:M5906 HALLMARK_ESTROGEN_RESPONSE_EARLY 8.51e-03 8.60e-02 3.81e-01 3.99e-01 1.56e+00
go:0061982 meiosis I cell cycle process 8.44e-03 8.60e-02 3.81e-01 -4.90e-01 -1.65e+00
go:0005770 late endosome 8.50e-03 8.60e-02 3.81e-01 3.45e-01 1.48e+00
go:0070603 SWI/SNF superfamily-type complex 8.49e-03 8.60e-02 3.81e-01 -4.57e-01 -1.63e+00
reactome:R-HSA-113418 Formation of the Early Elongation Complex 8.57e-03 8.63e-02 3.81e-01 -5.36e-01 -1.73e+00
reactome:R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 8.68e-03 8.70e-02 3.81e-01 5.09e-01 1.71e+00
reactome:R-HSA-983189 Kinesins 8.72e-03 8.71e-02 3.81e-01 -5.58e-01 -1.71e+00
go:0050000 chromosome localization 8.83e-03 8.80e-02 3.81e-01 -4.74e-01 -1.67e+00
go:0030968 endoplasmic reticulum unfolded protein response 8.87e-03 8.80e-02 3.81e-01 3.97e-01 1.56e+00
go:0021510 spinal cord development 9.07e-03 8.96e-02 3.81e-01 -5.81e-01 -1.71e+00
go:0007062 sister chromatid cohesion 9.07e-03 8.96e-02 3.81e-01 -4.84e-01 -1.66e+00
reactome:R-HSA-983712 Ion channel transport 9.25e-03 9.06e-02 3.81e-01 4.79e-01 1.69e+00
go:0051784 negative regulation of nuclear division 9.28e-03 9.06e-02 3.81e-01 -5.05e-01 -1.67e+00
go:0000075 cell cycle checkpoint 9.26e-03 9.06e-02 3.81e-01 -3.57e-01 -1.51e+00
go:0006665 sphingolipid metabolic process 9.42e-03 9.17e-02 3.81e-01 5.23e-01 1.73e+00
reactome:R-HSA-9614085 FOXO-mediated transcription 9.51e-03 9.23e-02 3.81e-01 5.06e-01 1.71e+00
reactome:R-HSA-168638 NOD1/2 Signaling Pathway 9.55e-03 9.24e-02 3.81e-01 6.30e-01 1.80e+00
go:0033218 amide binding 9.66e-03 9.27e-02 3.81e-01 3.55e-01 1.53e+00
go:0045935 positive regulation of nucleobase-containing compound metabolic process 9.65e-03 9.27e-02 3.81e-01 -3.53e-01 -1.50e+00
go:0043543 protein acylation 9.62e-03 9.27e-02 3.81e-01 -3.79e-01 -1.53e+00
go:0007093 mitotic cell cycle checkpoint 9.80e-03 9.35e-02 3.81e-01 -3.75e-01 -1.52e+00
go:1902850 microtubule cytoskeleton organization involved in mitosis 9.85e-03 9.35e-02 3.81e-01 -4.07e-01 -1.56e+00
msig:M8104 KEGG_AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR_METABOLISM 9.80e-03 9.35e-02 3.81e-01 5.13e-01 1.66e+00
go:0033043 regulation of organelle organization 9.83e-03 9.35e-02 3.81e-01 -2.60e-01 -1.29e+00
go:0010941 regulation of cell death 1.00e-02 9.48e-02 3.81e-01 2.29e-01 1.25e+00
go:1901989 positive regulation of cell cycle phase transition 1.01e-02 9.49e-02 3.81e-01 -4.46e-01 -1.59e+00
go:0022853 active ion transmembrane transporter activity 1.01e-02 9.49e-02 3.81e-01 4.82e-01 1.63e+00
reactome:R-HSA-5696398 Nucleotide Excision Repair 1.01e-02 9.49e-02 3.81e-01 -3.87e-01 -1.53e+00
reactome:R-HSA-1226099 Signaling by FGFR in disease 1.02e-02 9.58e-02 3.81e-01 -5.38e-01 -1.71e+00
go:0032886 regulation of microtubule-based process 1.04e-02 9.68e-02 3.81e-01 -3.74e-01 -1.52e+00
go:0099080 supramolecular complex 1.04e-02 9.68e-02 3.81e-01 -2.94e-01 -1.39e+00
reactome:R-HSA-167287 HIV elongation arrest and recovery 1.05e-02 9.77e-02 3.81e-01 -5.43e-01 -1.70e+00
go:1903573 negative regulation of response to endoplasmic reticulum stress 1.06e-02 9.77e-02 3.81e-01 5.24e-01 1.67e+00
go:0043620 regulation of DNA-templated transcription in response to stress 1.06e-02 9.77e-02 3.81e-01 3.76e-01 1.56e+00
go:0090382 phagosome maturation 1.06e-02 9.77e-02 3.81e-01 6.27e-01 1.79e+00
reactome:R-HSA-199992 trans-Golgi Network Vesicle Budding 1.07e-02 9.78e-02 3.81e-01 4.39e-01 1.63e+00
go:0006970 response to osmotic stress 1.07e-02 9.80e-02 3.81e-01 5.09e-01 1.71e+00
go:0051480 regulation of cytosolic calcium ion concentration 1.09e-02 9.94e-02 3.81e-01 4.26e-01 1.62e+00
go:0048524 positive regulation of viral process 1.09e-02 9.94e-02 3.81e-01 -4.00e-01 -1.54e+00
go:0043628 ncRNA 3'-end processing 1.10e-02 9.94e-02 3.81e-01 -5.52e-01 -1.68e+00
go:0015078 proton transmembrane transporter activity 1.10e-02 9.94e-02 3.81e-01 3.99e-01 1.55e+00
reactome:R-HSA-177929 Signaling by EGFR 1.10e-02 9.94e-02 3.81e-01 5.68e-01 1.76e+00
go:0045071 negative regulation of viral genome replication 1.10e-02 9.94e-02 3.81e-01 5.17e-01 1.71e+00

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP8 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP8 deubiquitinates SMO. 10 / 14
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In addition, it has been reported that the deubiquitinase Usp8 could deubiquitinate Smo to influence Hh signaling activity.

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Although our observations support the notion that USP8 deubiquitinates Smo and prevents localization to early endosomes, we are not suggesting that USP8 play an exclusive role in the inhibition of Smo endocytosis.

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As shown in XREF_FIG, USP8, but not the other DUBs, reduced the ubiquitination of Myc-Smo.

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Using an in vivo RNAi screen, we identified ubiquitin specific protease 8 (USP8) as a deubiquitinase that down-regulates Smo ubiquitination.

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Review

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In addition, it has been reported that the deubiquitinase Usp8 could deubiquitinate Smo to influence Hh signaling activity (Li et al., 2012; Xia et al., 2012).

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In addition, we provide evidence that the non visual beta-arrestin Krz acts in parallel with Smo ubiquitination to promote its internalization and that Smo ubiquitination is antagonized by the deubiquitinating enzyme UBPY.

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However, we found that UBPY decreases Smo ubiquitination regardless of the Hh signaling states and that the association between UBPY and Smo is not significantly affected by either Hh stimulation or Smo phosphorylation, suggesting that Smo deubiquitination by UBPY is unlikely to be a major mechanism by which Hh inhibits Smo ubiquitination, although we can not rule out the possibility that Hh regulates UBPY binding to Smo in a subtle way that escaped the detection by our coimmunoprecipitation assay.

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Taken together, these results suggest that UBPY can reverse Smo ubiquitination to promote its cell surface accumulation and induce low but not high levels of Hh pathway activation.

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Hh promotes the formation of a Smo and USP8 complex, and USP8 further promotes the accumulation of Smo at the cell surface and prevents localization to the early endosomes by deubiquitinating Smo, leading to increased Hh signaling activity.
USP8 deubiquitinates EGFR. 10 / 13
| 1 11

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In an elegant and comprehensive analysis of corticotroph adenoma, Reincke et al demonstrated that heterozygous somatic USP8 single nucleotide mutation or deletions at or adjacent to the 14-3-3 protein binding domain make USP8 resistant to 14-3-3 protein binding and more prone to proteolytic cleavage, which, in turn, leads to higher rate of USP8 induced EGFR deubiquitination activity upon binding of EGF to its receptor.

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USP8 (also known as UBPY) deubiquitylates EGFR on early endosomes, rescuing EGFR from degradation 107, 108 .

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Before incorporation into MVBs, the EGFR is deubiquitinated by Usp8.

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However, we can not fully exclude the other possibility that the UBPY S680A expression resulted in a reduction in the cellular Ub conjugating activity toward activated EGFR in some way.The fact that U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III.

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Some studies showed that AMSH [31] and UBPY [32, 33] prevent EGFR down-regulation by deubiquitinating EGFR.

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While AMSH is required for sorting of EGFR into MVEs and degradation in lysosomes XREF_BIBR, deubiquitination of EGFR by USP8 protects it from lysosomal degradation XREF_BIBR.

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If USP8 deubiquitylates EGFR at the MVB, this facilitates EGFR 's progression toward degradation in the lysosome and, thus, aids receptor down-regulation.

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Review

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Furthermore we demonstrated that both EGFR and EGFR-ErbB2 TM are deubiquitinated by the deubiquitination enzyme Usp8, although deubiquitination of ErbB2 was less efficient than that of EGFR [10].
USP8 deubiquitinates CHMP1B. 7 / 7
| 6

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Thus, deubiquitination of CHMP1B by USP8 at the endosomal membrane may favor CHMP1B oligomerization and co-assembly with IST1 in vivo.

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Furthermore, we have demonstrated that USP8 deubiquitinates CHMP1B.

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From 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.

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We demonstrate further that CHMP1B is deubiquitinated by the ubiquitin specific protease USP8 (syn. UBPY)

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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.

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Our results thus strongly suggest that USP8 deubiquitinates CHMP1B.

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Finally, we observed that the ubiquitination level of endogenous CHMP1B was higher in partially Usp8 silenced cells compared to control cells, strengthening the hypothesis that USP8 deubiquitinates CHMP1B (XREF_FIG).
USP8 deubiquitinates PRKN. 6 / 6
| 5

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Finally, deubiquitination of Parkin by USP8 is required for Parkin recruitment to CCCP intoxicated mitochondria and to promote stress induced mitophagy in vitro.

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Our findings suggested that H 2 S promoted mitophagy formation by increasing S sulfhydration of USP8, which enhanced deubiquitination of parkin through the recruitment of parkin in mitochondria.

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This process is negatively regulated by USP15 [XREF_BIBR] and USP30 [XREF_BIBR], which deubiquitinate mitochondrial Parkin-targets, while it is supported by USP8, which deubiquitinates Parkin itself [XREF_BIBR].

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USP8 deubiquitylation of auto-ubiquitylated Parkin is required for its localization to depolarized mitochondria, and thereby for efficient activation of mitophagy [XREF_BIBR].

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Whilst the phosphatase that dephosphorylates p-Ub remains unknown, two DUBs have been identified that deubiquitylate Parkin directed substrates, USP30 and USP15, and USP8 has also been reported to reverse Parkin autoubiquitylation.

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USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin.
USP8 deubiquitinates CLOCK. 5 / 5
| 5

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As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK and CYC transcriptional activity.

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Since deubiquitylation of CLK by USP8 decreases its activity XREF_BIBR, it will be interesting to investigate whether CK2alpha phosphorylation affects CLK ubiquitylation.

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CLK deubiquitylation by USP8 reinforces transcriptional repression by PER complexes, whereas CLK ubiquitylation and decreased phosphorylation may be involved in shifting CLK to a transcriptionally active state.

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This rhythm in ubiquitylation is mediated by UBIQUITIN SPECIFIC PROTEASE 8 (USP8), which deubiquitylates CLK to downregulate CLK-CYC activity from ~ ZT18-ZT4, thereby reinforcing PER dependent repression [XREF_BIBR].

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CLOCK deubiquitylation by USP8 inhibits CLK and CYC transcription in Drosophila.
USP8 deubiquitinates SQSTM1. 4 / 4
| 4

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USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR].

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USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR].

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USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction.

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USP8 overexpression leads to deubiquitination of p62 protein, suppressing its autophagic activity (Peng et al. 2020).
USP8 deubiquitinates HGS. 4 / 4
| 4

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We provide evidence that Ubpy interacts with and deubiquitylates Hrs.

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Mop recruits Ubpy to promote the deubiquitination of Hrs.

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Studies have shown that USP8 also interacts with and deubiquitinate Hrs, demonstrating multiple roles of USP8 in both cargo de-ubiquitination and ESCRT-0 stability during development, which is helpful to address the mechanisms of Hh signaling.

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Previous studies showed that Hrs is deubiquitinated by Ubpy.
Modified USP8 leads to the deubiquitination of SMO. 4 / 4
| 4

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Overexpression of Flag-USP8 in S2 cells reduced Smo ubiquitination (XREF_FIG, lane 3, top panel), whereas knockdown of USP8 by RNAi enhanced the levels of ubiquitinated Smo (XREF_FIG, lane 2, top panel), which was consistent with the data from the screen.

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Consistent with UBPY being able to counteract Smo ubiquitination independent of Hh signaling states, overexpression of UBPY reduced Smo ubiquitination in S2 cells both in the absence and presence of Hh (XREF_FIG).

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The overexpression of USP8 down-regulated Smo ubiquitination and increased Smo accumulation.

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Moreover, overexpression of USP8 prevents Smo ubiquitination and elevates Smo accumulation, leading to increased Hh signaling activity.
USP8 deubiquitinates STAM. 4 / 4
| 3

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USP8 modulates EGFR trafficking by regulating STAM de-ubiquitination on early endosomes 11.

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In addition, we identified STAM and NFX1, which are known to be deubiquitylated by USP8 and USP9 respectively.

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USP8 deubiquitinates STAM, preventing its degradation by the proteasome [XREF_BIBR], and Nrdp1, an E3 required for the lysosomal degradation of EGFR family members ErbB3 and ErbB4 [XREF_BIBR].

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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.
USP8 deubiquitinates KCNN4. 3 / 3
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Further, overexpression of wild-type USP8 accelerates channel deubiquitylation, while either a catalytically inactive mutant USP8 or siRNA mediated knockdown of USP8 enhanced accumulation of ubiquitylated KCa3.1, thereby inhibiting channel degradation.

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Further, we demonstrated that KCa3.1 is initially ubiquitylated following endocytosis and then deubiquitylated by USP8 prior to lysosomal degradation XREF_BIBR.

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USP8 deubiquitinates GJA1. 3 / 3
| 2

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USP8 reduces both multiple monoubiquitination and polyubiquitination of Cx43 to prevent autophagy mediated degradation.

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The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43

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USP8 interacts with and deubiquitinates Cx43, removing monoubiquitin moieties as well as K63- and K48 linked ubiquitin chains.
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, K929, Y1092, Y1016, Y1197, K970, and Y1069 on K716. 3 / 3
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USP8 deubiquitinates KDR. 3 / 3
| 3

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USP8 depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system.

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We now provide evidence that USP8 de-ubiquitinates VEGFR2.

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Conversely, the de-ubiquitinating enzyme, USP8, is shown to mediate de-ubiquitination of VEGFR2, regulating VEGFR2 trafficking, proteolysis, and signal transduction 39.
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K737, K754, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K867. 3 / 3
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USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, K929, Y1092, Y1016, K716, Y1197, and Y1069 on K970. 3 / 3
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USP8 deubiquitinates ERBB2. 3 / 3
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ERBB2 is a target for USP8-mediated deubiquitination

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We recently showed that Usp8 also deubiquitinates ERBB2, albeit to a much lesser extent than EGFR [17].

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We recently showed that Usp8 also deubiquitinates ErbB2, albeit to a much lesser extent than EGFR [10].
USP8 deubiquitinates SEC31A. 3 / 3
| 2

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We concluded that USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion.

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Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion

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Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A.
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K754, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K737. 3 / 3
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USP8 deubiquitinates LRIG1. 3 / 3
| 2

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To determine whether endogenous USP8 deubiquitinates LRIG1, we used shUSP8 to decrease the level of endogenous USP8 in EBC1 cells.

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Also, when over-expressed, USP8 decreases LRIG1 ubiquitination by SAIT301 treatment (XREF_FIG).
USP8 deubiquitinates NTRK2. 3 / 3
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TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation.

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TrkB deubiquitination by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation.

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TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation.
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K754. 3 / 3
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USP8 deubiquitinates RNF41. 3 / 3
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We found that the carboxy terminal domain of Nrdp1 binds to the rhodanese domain of USP8, and that USP8 very efficiently deubiquitinates and stabilizes Nrdp1.

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USP8 deubiquitinates STAM, preventing its degradation by the proteasome [XREF_BIBR], and Nrdp1, an E3 required for the lysosomal degradation of EGFR family members ErbB3 and ErbB4 [XREF_BIBR].

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USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K929. 3 / 3
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USP8 deubiquitinates SHANK3. 3 / 3
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USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels

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USP8 acts to deubiquitinate SHANK3, which prevents its proteasomal mediated degradation and enhances overall dendritic spine stability.

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USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity Dependent Protein Levels.
USP8 deubiquitinates ITCH. 2 / 2
| 1

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USP8 and USP9X deubiquitinate ITCH to induce ubiquitination and degradation of the anti-apoptotic protein c-FLIP, leading to apoptosis in glioblastoma [XREF_BIBR], or to anoikis in pancreatic ductal adenocarcinoma [XREF_BIBR].

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USP8 leads to the deubiquitination of F2RL1. 2 / 2
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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.

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USP8 and AMSH mediate deubiquitination of PAR2 and its sorting from endosomes to lysosomes [XREF_BIBR].
USP8 deubiquitinates GRIA. 2 / 2
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Furthermore, shRNA mediated knockdown of USP8 is sufficient to enhance the basal level of AMPAR ubiquitination in primary neurons.

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In addition to USP46, USP8 can also deubiquitinate mammalian AMPARs indicating that multiple regulatory mechanisms exist to control AMPAR ubiquitination levels (Scudder et al., 2014).
USP8 deubiquitinates HIF1A. 2 / 2
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HIF1alpha deubiquitination by USP8 is essential for ciliogenesis in normoxia.

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Review
USP8 deubiquitinates LEPR. 2 / 2
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Bland and colleagues suggested that leptin increases the expression of USP8, which in turn deubiquitylates the leptin receptor by cleaving Lys48-ubiquitin chains, among other (still unknown) chain types.

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USP8 deubiquitinates the leptin receptor and is necessary for leptin mediated synapse formation.
USP8 deubiquitinates EPG5. 2 / 2
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We propose that deubiquitination of EPG5 by USP8 guards the autophagic flux in ESCs to maintain their stemness.

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Mechanistically, USP8 directly removes non-classical K63-linked ubiquitin chains from EPG5 at Lysine 252, leading to enhanced interaction between EPG5 and LC3.
USP8 deubiquitinates SNCA. 2 / 2
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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 α-synuclein in vitro

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Another deubiquitinase, USP8, removes K63-linked ubiquitin chains of α-synuclein and prevents its lysosomal degradation.
Mutated USP8 leads to the deubiquitination of EGFR. 2 / 2
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The identified USP8 mutants increase EGFR deubiquitination to inhibit EGF induced EGFR downregulation, leading to augmented and more sustained EGFR signaling.

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USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells.
USP8 leads to the deubiquitination of ARL6IP4. 2 / 2
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Consistent with this idea, overexpression of wild-type USP8 decreased the ubiquitination of the FLIP (S) E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP (S) interaction, whereas siRNA mediated suppression of USP8 increased AIP4 ubiquitination.

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Consistent with this idea, over-expression of WT USP8 decreased ubiquitination of the FLIP S E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP S interaction, while siRNA mediated suppression of USP8 increased AIP4 ubiquitination.
USP8 deubiquitinates CYT1. 2 / 2
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Finally, even though CYT-1 shows ligand induced K63 polyubiquitination, it is not subjected to deubiquitination by the K63 polyubiquitin specific AMSH deubiquitinating enzyme, while CYT-1 is slightly deubiquitinated by USP8.

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Finally, CYT-1 is not subjected to deubiquitination by the K63 polyubiquitin specific AMSH DUB enzyme, while CYT-1 is slightly deubiquitinated by USP8.
USP8 deubiquitinates RNF128. 2 / 2
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These data further demonstrate that the two isoforms of Otubain 1 have opposing effects on GRAIL and that Otubain 1 ARF-1 recruits the ubiquitin specific protease 8 (USP-8) to promote GRAIL deubiquitination and stabilization.

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This unexpected function of otubain-1 might be mediated through the inhibition of USP8, a DUB that binds to and deubiquitylates GRAIL; however, it is not known how otubain-1 might inhibit USP8.
USP8 leads to the deubiquitination of CFLAR. 2 / 2
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USP8 directly deubiquitylates and stabilizes FLIPL

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USP8 and USP9X deubiquitinate ITCH to induce ubiquitination and degradation of the anti-apoptotic protein c-FLIP, leading to apoptosis in glioblastoma [XREF_BIBR], or to anoikis in pancreatic ductal adenocarcinoma [XREF_BIBR].
USP8 deubiquitinates EPS15. 2 / 2
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UBPY also deubiquitinated Eps15 in vitro, suggesting that Eps15 is a cellular substrate for UBPY.

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No evidence text available
USP8 deubiquitinates LDLR. 2 / 2
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We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway.

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We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway.
USP8 deubiquitinates FZD5 on lysine. 1 / 1
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No evidence text available
USP8 deubiquitinates LRIG1 on lysine. 1 / 1
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No evidence text available
USP8 deubiquitinates GRIA1. 1 / 1
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Synaptic Strength Is Bidirectionally Controlled by Opposing Activity-Dependent Regulation of Nedd4-1 and USP8
USP8 deubiquitinates SFRP4. 1 / 1
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Review
USP8 deubiquitinates CBL-Y1045F. 1 / 1
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Indeed, the Y1045F and Y1091F Cbl binding site mutants are deubiquitinated by Usp8, suggesting that this ubiquitination signal may represent mono- or oligo-ubiquitin (Figs. 7 and 8, upper panel, arrow[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP8 deubiquitinates KIF23. 1 / 1
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No evidence text available
USP8 deubiquitinates CBL. 1 / 1
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The Cbl binding site mutants of EGFR (Y1045F) and EGFR-ErbB2 (Y1091F) are also deubiquitinated by Usp8 both with and without EGF stimulation (Figs. 7 and 8).
USP8 deubiquitinates Smoothened. 1 / 1
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Smoothened, a key component of Hedgehog pathway, is deubiquitinated by USP8 34 and activation of Hedgehog pathway induces ACTH secretion 35.
USP8 leads to the deubiquitination of TRAF6. 1 / 1
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USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction.
USP8 deubiquitinates EGFR-Y1045F. 1 / 1
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The Cbl binding site mutants of EGFR (Y1045F) and EGFR-ErbB2 (Y1091F) are also deubiquitinated by Usp8 both with and without EGF stimulation (Figs. 7 and 8).
USP8 deubiquitinates ERVK-18. 1 / 1
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Furthermore we demonstrated that both EGFR and EGFR-ErbB2 TM are deubiquitinated by the deubiquitination enzyme Usp8, although deubiquitination of ErbB2 was less efficient than that of EGFR [10].
USP8 deubiquitinates EGF. 1 / 1
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However, we can not fully exclude the other possibility that the UBPY S680A expression resulted in a reduction in the cellular Ub conjugating activity toward activated EGFR in some way.The fact that U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP8 deubiquitinates FZD. 1 / 1
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In contrast, Fzd receptors are deubiquitinated by UBPY and ubiquitin specific protease 6 and 8 (USP6 and USP8).
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USP8 deubiquitinates ERBB3. 1 / 1
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USP8 regulates another EGFR family member, ErbB3 by modulating Nrdp1 (neuregulin-receptor-degradation protein-1)
USP8 deubiquitinates BIRC6. 1 / 1
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No evidence text available
USP8 deubiquitinates NTRK1. 1 / 1
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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
USP8 deubiquitinates CASP8. 1 / 1
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Our data are consistent with the recent findings that USP8 directly deubiquitylates and stabilizes the long isoform of FLICE like inhibitory protein (FLIP L) in cervical cancer cell line ME-180, which was derived from the metastatic site of epidermoid carcinoma.
USP8 deubiquitinates CFTR. 1 / 1
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For example, in this and a previous study we observed that neither USP34, nor USP8 deubiquitinate CFTR, and only USP10 activity was inhibited by Cif XREF_BIBR, XREF_BIBR.
USP8 deubiquitinates MET. 1 / 1
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USP8 deubiquitinates NFX1. 1 / 1
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In addition, we identified STAM and NFX1, which are known to be deubiquitylated by USP8 and USP9 respectively.
USP8 deubiquitinates MCPH1. 1 / 1
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BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1
USP8 deubiquitinates FZD4 on lysine. 1 / 1
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No evidence text available
USP8 leads to the deubiquitination of BECN1. 1 / 1
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USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction.
USP8 deubiquitinates SCNN1A. 1 / 1
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USP8 interacted with ENaC, as detected by co-immunoprecipitation, and it deubiquitinated ENaC.
USP8 in the endosome deubiquitinates EGFR in the endosome. 1 / 1
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We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes.
USP8 leads to the deubiquitination of TCHP. 1 / 1
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Conversely, deubiquitination of TCHP is mediated by ubiquitin-specific peptidase 8 (USP8) [50].
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USP8 deubiquitinates BACE1. 1 / 1
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The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation
Modified USP8 leads to the deubiquitination of LRIG1. 1 / 1
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SAIT301 treatment significantly enhanced the ubiquitination of LRIG1, whereas over-expression of USP8 markedly diminished the ubiquitination of LRIG1 (XREF_FIG).
Threonine-phosphorylated USP8 deubiquitinates RNF41. 1 / 1
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No evidence text available
USP8 deubiquitinates USP46. 1 / 1
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In addition to USP46, USP8 can also deubiquitinate mammalian AMPARs indicating that multiple regulatory mechanisms exist to control AMPAR ubiquitination levels (Scudder et al., 2014).
USP8 deubiquitinates FZD8 on lysine. 1 / 1
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