OTUD5 Data Analysis

HGNC Gene Name
OTU deubiquitinase 5
HGNC Gene Symbol
OTUD5
Identifiers
hgnc:25402 NCBIGene:55593 uniprot:Q96G74
Orthologs
mgi:1859615 rgd:1563027
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for OTUD5
Number of Papers
27 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
UBR5 ubiquitin protein ligase E3 component n-recognin 5 0.773 BioGRID INDRA (6) -0.11 -0.72 6.67e-02
TRIP12 thyroid hormone receptor interactor 12 0.284 Reactome (1) -0.26 -1.51 5.30e-06
HIRA histone cell cycle regulator 0.218 -0.23 -1.34 8.20e-05
VCPIP1 valosin containing protein interacting protein 1 0.217 Reactome (4) 0.00 -0.07 9.64e-01
FBXW7 F-box and WD repeat domain containing 7 0.201 Reactome (3)
CYBA cytochrome b-245 alpha chain -0.197 Reactome (2) -0.18 -1.10 1.95e-03
GOLGA7 golgin A7 0.196 Reactome (2) -0.35 -1.99 3.11e-10

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with OTUD5using 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:0070535 histone H2A K63-linked ubiquitination Biological Process 1.17e-06 5.40e-04 2.37e-04
GO:1900045 negative regulation of protein K63-linked ubiquitination Biological Process 3.26e-06 1.51e-03 2.66e-04
GO:1902915 negative regulation of protein polyubiquitination Biological Process 5.24e-06 2.43e-03 2.66e-04
GO:0033182 regulation of histone ubiquitination Biological Process 5.24e-06 2.43e-03 2.66e-04
GO:1900044 regulation of protein K63-linked ubiquitination Biological Process 7.69e-06 3.56e-03 3.12e-04
GO:1902914 regulation of protein polyubiquitination Biological Process 2.94e-05 1.36e-02 8.57e-04
GO:1902275 regulation of chromatin organization Biological Process 2.95e-05 1.37e-02 8.57e-04
GO:0033522 histone H2A ubiquitination Biological Process 3.49e-05 1.61e-02 8.85e-04
GO:1903320 regulation of protein modification by small protein conjugation or removal Biological Process 5.27e-05 2.44e-02 1.19e-03
GO:0045738 negative regulation of DNA repair Biological Process 6.51e-05 3.01e-02 1.32e-03
GO:0031057 negative regulation of histone modification Biological Process 9.97e-05 4.62e-02 1.84e-03

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out OTUD5 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
MMP1 matrix metallopeptidase 1 8.01e-01 3.39e-25 7.49e-21
CST3 cystatin C -5.12e-01 2.75e-06 3.04e-02

Gene Set Enrichment Analysis

There were too few differentially expressed genes to run a meaningful GSEA.

Literature Mining

INDRA was used to automatically assemble known mechanisms related to OTUD5 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
OTUD5 deubiquitinates TRAF3. 10 / 13
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For example, the deubiquitinase DUBA reverses TRAF3 ubiquitination, disconnecting TRAF3 from its substrates TBK1 and IKKɛ [38].

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Two close relatives of DUBA, OTUB1 and OTUB2, were shown to reduce TRAF3 ubiquitination coupled with decreased anti-viral signaling responses in Sendai virus infected HEK 293T cells.

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DUBA deubiquitinates TRAF3 to downregulate its interaction with TBK1 and consequent activation of IRF-3 (Kayagaki et al., 2007).

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Cellular protein DUBA specifically deubiquitinates TRAF3 that is critical for activation of IRF3, resulting in inhibiting phosphorylation of IRF3.

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DUBA interacts with and de-ubiquitinates TRAF3, thereby attenuating TLR dependent and TLR independent antiviral responses XREF_BIBR.

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TRIAD3A dependent TRAF3 proteasomal destruction, like TRAF3 de-ubiquitination by DUBA, halts the activation of TBK1 and IKKepsilon and subsequent IFN production.

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Interestingly, the newly identified cellular DUB, DUBA, inhibits the ubiquitination of TRAF3, an adaptor of RIG-I signaling, and negatively regulates the type I IFN signaling pathway 21.

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Cellular protein DUBA specifically deubiquitinates TRAF3 that is critical for activation of IRF3, resulting in inhibiting phosphorylation of IRF3 (Kayagaki et al., 2007; Wang et al., 2011).

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For example, the deubiquitinase DUBA reverses TRAF3 ubiquitination, disconnecting TRAF3 from its substrates TBK1 and IKKe [38] .

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DUBA deubiquitinates TRAF3 to down-regulate its interaction with TBK1 and consequent activation of IRF-3.
OTUD5 deubiquitinates TP53. 8 / 8
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To verify that the deubiquitination of p53 by OTUD5 is specific, MDM2 was also tested in the in vitro deubiquitination assay and found thatMDM2 can not be deubiquitinated by OTUD5 (XREF_FIG).

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In this study, we provide new evidences that OTUD5 can also function to deubiquitinate and stabilize p53.

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OTUD1, OTUD5 and USP11 directly deubiquitinating p53 and functional proteins were required for p53 stabilization [XREF_BIBR - XREF_BIBR].

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Review

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We show that (1) OTUD5 is a novel p53 interacting protein; (2) OTUD5 deubiquitinates p53, leading to the stabilization of p53; (3) OTUD5 can help in the stabilization and activation of p53 in response to DNA damage; (4) OTUD5 is required for p53 induced apoptosis in response to DNA damage.

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Overall, OTUD5 deubiquitinates p53, leading to the stabilization of p53.

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To verify that the deubiquitination of p53 by OTUD5 is specific, MDM2 was also tested in the in vitro deubiquitination assay.

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Another DUB, OTUD5, interacts and deubiquitylates p53 in response to DNA damage stress.
OTUD5 deubiquitinates UBR5. 2 / 2
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When DUBA deubiquitylates UBR5 and rescues it from degradation, UBR5 is free to polyubiquitylate RORgammaT, driving its degradation and consequently limiting Th17 differentiation.

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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 ROR纬t in response to TGF-尾 signalling.?
OTUD5 deubiquitinates MDM2. 1 / 1
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As shown in XREF_FIG, MDM2 can not be deubiquitinated by OTUD5.
OTUD5 deubiquitinates PDCD5. 1 / 1
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Conversely, PDCD5 knockdown greatly attenuated the effect of OTUD5 on p53 activation.
OTUD5 deubiquitinates TRAF3 on lysine. 1 / 1
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biopax:reactome
No evidence text available
OTUD5 deubiquitinates TRAF5. 1 / 1
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ubibrowser
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.
OTUD5 leads to the deubiquitination of DDX58. 1 / 1
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Other DUBs that target the RIG-I and MDA5 pathway include CYLD and DUBA which target RIG-I and TRAF3 ubiquitination respectively (XREF_FIG).
OTUD5 deubiquitinates PDCD5 on K97. 1 / 1
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OTUD5 thus deubiquitinates PDCD5 at Lys97 and Lys98 subsequently regulating p53 levels.
OTUD5 deubiquitinates Interferon. 1 / 1
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TRIAD3A dependent TRAF3 proteasomal destruction, like TRAF3 de-ubiquitination by DUBA, halts the activation of TBK1 and IKKepsilon and subsequent IFN production.
OTUD5 deubiquitinates TRAF2. 1 / 1
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ubibrowser
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.
OTUD5 deubiquitinates PDCD5 on K98. 1 / 1
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OTUD5 thus deubiquitinates PDCD5 at Lys97 and Lys98 subsequently regulating p53 levels.
OTUD5 deubiquitinates TRAF6. 1 / 1
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ubibrowser
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.
OTUD5 deubiquitinates IKBKE. 1 / 1
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TRIAD3A dependent TRAF3 proteasomal destruction, like TRAF3 de-ubiquitination by DUBA, halts the activation of TBK1 and IKKepsilon and subsequent IFN production.

Other Statements

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
OTUD5 affects TP53
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OTUD5 activates TP53.
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OTUD5 activates TP53. 6 / 8
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The function of OTUD5 is required to allow the rapid activation of p53 dependent transcription and a p53 dependent apoptosis in response to DNA damage stress.

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Deubiquitinase OTUD5 mediates the sequential activation of PDCD5 and p53 in response to genotoxic stress.

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OTU deubiquitinase (OTUD5) binds to PDCD5inresponseto etoposide treatment and effectively mediates the sequential activation of both PDCD5 and P53.

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Overexpression of OTUD5 efficiently enhanced the activation of both PDCD5 and p53.

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The knockdown of OTUD5 inactivated p53 and PDCD5, promoting the proliferation and metastasis of NSCLC cells while inhibiting their apoptosis.

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To this end, 1mug of p53 and increasing amounts of Flag-OTUD5 were cotransfected into H1299 cells.
OTUD5 inhibits TP53.
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OTUD5 inhibits TP53. 1 / 3
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The knockdown of OTUD5 inactivated p53 and PDCD5, promoting the proliferation and metastasis of NSCLC cells while inhibiting their apoptosis.
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OTUD5 decreases the amount of TP53.
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OTUD5 decreases the amount of TP53. 1 / 2
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Using shRNA mediated depletion of OTUD5 in U2OS cells caused marked decrease of p53 protein levels with no effect on p53 mRNA levels (XREF_FIG).
OTUD5 affects Interferon
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They showed that reducing the expression of DUBA augments the IFN response to poly(I:C) whereas ectopic expression of DUBA blocks the IFN response.

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It has been demonstrated that the deubiquitinating enzymes A20 and CYLD inhibit NF-kappaB signaling by targeting TRAF6 upstream of IKK, while the deubiquitinating protein DUBA inhibits type I interferon activity by targeting TRAF3.

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DUBA inhibits type I IFN production in the absence of IL-1RI signaling.

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OTUD5 has been shown to suppress the type I interferon dependent innate immune response by cleaving the polyubiquitin chain from an essential type I interferon adaptor protein.

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For example, DUBA, a member of the Otubain (OTUB) family, has been shown to deubiquitinate TRAF3 and negatively regulate TLR3- and RIG-I and MDA5-mediated IFN induction.

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For example, DUBA, a member of the Otubain (OTUB) family, has been shown to deubiquitinate TRAF3 and negatively regulate TLR3- and RIG-I/MDA5-mediated IFN induction (52).

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The activation of TLR4 and TLR3 stimulates the K 63 -linked ubiquitination of TRAF3, which is required for the activation of IRF3 and the production of type I IFNs, and DUBA removes K 63 -linked ubiquitin chains from TRAF3, thereby inhibiting type I IFN responses.

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Indeed, DUBA and OTUD5, a DUB which selectively disassembles Lys63 linked ubiquitin chains on TRAF3, has been shown to suppress the production of type I interferon by reducing the level of TRAF3-TBK1 interaction XREF_BIBR.
OTUD5 affects PDCD5
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OTUD5 activates PDCD5.
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OTUD5 activates PDCD5. 5 / 8
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Studies have shown that OTUD5 can activate the programmed cell death 5 (PDCD5, a tumor suppressor; Park et al., xref ).
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OTU deubiquitinase (OTUD5) binds to PDCD5inresponseto etoposide treatment and effectively mediates the sequential activation of both PDCD5 and P53.

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The knockdown of OTUD5 inactivated p53 and PDCD5, promoting the proliferation and metastasis of NSCLC cells while inhibiting their apoptosis.

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Overexpression of OTUD5 efficiently enhanced the activation of both PDCD5 and p53.

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Deubiquitinase OTUD5 mediates the sequential activation of PDCD5 and p53 in response to genotoxic stress.
OTUD5 inhibits PDCD5.
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OTUD5 inhibits PDCD5. 1 / 1
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The knockdown of OTUD5 inactivated p53 and PDCD5, promoting the proliferation and metastasis of NSCLC cells while inhibiting their apoptosis.
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OTUD5 affects TRAF3
| 1 8
OTUD5 inhibits TRAF3.
| 1 5
OTUD5 inhibits TRAF3. 6 / 6
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TRAF3 are inhibited by DUBA, OTUB1 and UCHL1 that specilally remove TRAF3 K63‐linked ubiquitination.

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Structural data suggest that 1) Toll and IL-1R (TIR) domain containing regulators (BCAP, SIGIRR, and ST2) interfere with TIR domain signalosome formation; 2) major deubiquitinases such as A20, CYLD, and DUBA prevent association of TRAF6 and TRAF3 with their partners, inaddition to removing K63 linked ubiquitin chains that serve as a docking platform for downstream effectors; 3) alternative downstream pathways of TLRs also restrict signaling by competing to bind common partners through shared binding sites.

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TRAF3 activation can in turn be negated by DUBA, a DUB specifically binding TRAF3 and deconjugating its K63 chains [32] .

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TRAF3 activation is negatively regulated by SOCS3 and DUBA.

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TRAF3 activation is inhibited by SOCS3 and DUBA and TRAF 6 is targeted by numerous inhibitors including A20, USP4, CYLD, and others [73,74].
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TRAF3 are inhibited by DUBA, OTUB1 and UCHL1 that specilally remove TRAF3 K63‐linked ubiquitination.
OTUD5 activates TRAF3.
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OTUD5 activates ubiquitinated TRAF3. 1 / 1
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Expression of DUBA cleaves Lys63-linked ubiquitin chains on TRAF3 and depletion of DUBA increases ubiquitinated TRAF3.
OTUD5 activates TRAF3. 1 / 1
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Moreover, the adaptor proteins TRAF3 and TRAF6 are targeted by the cellular proteins DUBA and A20 XREF_BIBR, XREF_BIBR, and TBK1 is sequestered by SIKE XREF_BIBR.
OTUD5 increases the amount of TRAF3.
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OTUD5 increases the amount of TRAF3. 1 / 1
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DUBA cleaves the K63-linked polyubiquitin chains of TRAF3 and depletion of DUBA increases the level of ubiquinated TRAF3 both in steady-state cells and in ligands-stimulated cells.

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It has been reported that OTUD5 could suppress the type I interferon dependent innate immune response by cleaving the polyubiquitin chain from an essential type I interferon adaptor protein TRAF3.

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OTUD5 has been shown to suppress the type I interferon dependent innate immune response by cleaving the polyubiquitin chain from an essential type I interferon adaptor protein.

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Three human DUBs, CYLD, A20 and DUBA, have been shown to negatively regulate the innate immune response by removing K63-based chains [55, 56] , and USP15 inhibits the NFkB pathway by removing K48-Ub from IkBa, preventing its degradation [57] .

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Cellular proteins DUBA and CYLD also negatively regulate the innate immune response.

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DUBA, a member of the ovarian tumor (OTU) domain containing cysteine protease superfamily, was shown to suppress the type I IFN dependent innate immune response by cleaving the K63 polyubiquitin chain on TRAF3.

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Three human DUBs, CYLD, A20 and DUBA, have been shown to negatively regulate the innate immune response by removing K63 based chains XREF_BIBR, XREF_BIBR, and USP15 inhibits the NFkappaB pathway by removing K48-Ub from IkappaBalpha, preventing its degradation XREF_BIBR.

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Three human DUBs, CYLD, A20 and DUBA, have been shown to negatively regulate the innate immune response by removing K63-based chains [55], [56], and USP15 inhibits the NFκB pathway by removing K48-Ub from IκBα, preventing its degradation [57].
OTUD5 affects cell growth
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OTUD5 knockdown promoted cell growth in a TRIM25-dependent manner .

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Through an unbiased RNAi screen, knockdown of OTUD5 is shown to significantly accelerate cell growth.

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In the current study , we find that OTUD5 knockdown accelerates cell growth in a TRIM25-dependent manner .

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OTUD5 knockdown accelerated cell growth .

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Through an unbiased RNAi screen , knockdown of OTUD5 is shown to significantly accelerate cell growth .
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The function of OTUD5 is required to allow the rapid activation of p53 dependent transcription and a p53 dependent apoptosis in response to DNA damage stress.

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Knockdown of OTUD5 accelerated the proliferation , migration , and invasion of A549 cells , and inhibited their apoptosis Next , A549 cells were used for the following experiment .
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It was proved that OTUD5 inhibited the proliferation and metastasis of NSCLC cells but promoted their apoptosis via regulating p53 and PDCD5 .
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Knockdown of OTUD5 clearly impeded the apoptosis, consistent with a weaker activation of p53 (XREF_FIG).
OTUD5 affects IRF3
| 1 3
OTUD5 inhibits IRF3.
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OTUD5 inhibits IRF3. 3 / 3
| 1 2

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These results suggest that DUBA inhibits IRF3 by functioning as a K63-specific DUB that antagonizes the function of TRAF3.

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Removal of Lys 63 -linked polyubiquitin chains from RIG-I and TRAF3 by cylindromatosis (CYLD) and deubiquitinating enzyme A (DUBA), respectively, inhibits the RIG-I-dependent activation of IRF3.

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These results suggest that DUBA inhibits IRF3 by functioning as a K63 specific DUB that antagonizes the function of TRAF3.
OTUD5 activates IRF3.
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OTUD5 activates IRF3. 1 / 1
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RNAi of DUBA enhances IRF3 activation, whereas overexpression of DUBA has the opposite effect.
OTUD5 affects IL17A
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OTUD5 inhibits IL17A.
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OTUD5 inhibits IL17A. 2 / 2
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OTUD5 inhibits the production of IL-17A by blocking the UBR5-mediated proteasomal degradation of RORgammat17 .

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T-cell specific loss of DUBA therefore results in reduced levels of UBR5, stabilization of RORgammaT, and increased IL-17A production in response to TCR stimulation 76.
OTUD5 decreases the amount of IL17A.
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OTUD5 decreases the amount of IL17A. 1 / 1
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Accumulation of the deubiquitinating enzyme DUBA (OTUD5) negatively regulates RORgammat stability and IL-17 expression in T cells by stabilizing the ubiquitin ligase UBR5, which ubiquitinates RORgammat in response to TGF-beta, leading to RORgammat degradation and decreased IL-17 expression.
OTUD5 activates IL17A.
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OTUD5 activates IL17A. 1 / 1
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On the other hand, DUBA deficient Tregs, which still have immunosuppressive functions in vitro and in vivo, can produce IL-17A under TCR stimulation.
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As DUBA protein is also increased in macrophages by LPS stimulation, it may also function as part of a negative feedback circuit.

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As OTUD5 is induced by LPS stimulation , it might act as a negative feedback regulator of IFN signaling by targeting TRAF3 [ 119 ] .

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As DUBA protein is also increased in macrophages by LPS stimulation, it may also function as part of a negative feedback circuit.Another OTU DUB family protein, the tumor suppressor, CYLD, has been identified as a negative regulator of RIG-I by two groups [61, 62] .
OTUD5 affects DDX58
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OTUD5 inhibits DDX58. 3 / 3
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For example, DUBA, a member of the Otubain (OTUB) family, has been shown to deubiquitinate TRAF3 and negatively regulate TLR3- and RIG-I and MDA5-mediated IFN induction.

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For example, DUBA, a member of the Otubain (OTUB) family, has been shown to deubiquitinate TRAF3 and negatively regulate TLR3- and RIG-I/MDA5-mediated IFN induction (52).

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In addition, A20, NLRX1, PIN1, DUBA and Triad3A deregulate RIG-I mediated signaling by inhibiting MAVS, IRF3 and TRAF3.
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Thus, OTUD5 controls neural cell fate commitment by regulating chromatin accessibility at neural- and neural crest specific enhancers to enable activation of transcriptional networks that drive the differentiation program.
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Intriguingly, this separation-of-function mutant (OTUD5 DeltaCterm) failed to support neural crest differentiation and showed aberrant CNS precursor formation (XREF_FIG and fig.
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Indeed, knockout of Otud5 is embryonic lethal in mice and OTUD5 depleted hESCs are defective in neuroectodermal differentiation, which can be rescued by re-expression of wild-type OTUD5 [XREF_BIBR].
IFNG affects OTUD5
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IFNG activates OTUD5.
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IFNG activates OTUD5. 2 / 2
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OTUD5 expression was enhanced by IFN-gamma through a p38 / MAPK-dependent mechanism and the AS-induced knockdown of OTUD5 in LPMCs of IBD patients and colitic mice reduced TNF-alpha .

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Recently, OTUD5 was found to be up-regulated in the intestinal inflammatory tissues of IBD patients and TNBS-induced colitis mice, and IFN-γ was found to up-regulate OTUD5’s expression through a p38/MAPK-dependent mechanism.
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IFNG increases the amount of OTUD5.
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IFNG increases the amount of OTUD5. 1 / 1
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OTUD5 expression was enhanced by IFN-gamma through a p38 and MAPK dependent mechanism and the AS induced knockdown of OTUD5 in LPMCs of IBD patients and colitic mice reduced TNF-alpha.
Doxorubicin affects OTUD5
1 | 2
Doxorubicin inhibits OTUD5.
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As shown in XREF_FIG after Doxorubicin treatment depletion of OTUD5 clearly prevented the efficient deubiquitination of p53 that is associated with protein accumulation (XREF_FIG).
Doxorubicin decreases the amount of OTUD5.
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Doxorubicin decreases the amount of OTUD5. 1 / 1
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ctd
No evidence text available
Doxorubicin activates OTUD5.
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U2OS cells transfected with scramble shRNA or OTUD5 shRNA were treated with Doxorubicin.
Vasotocin affects OTUD5
| 1 1
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XREF_FIG d, AVT also decreases Otud4, Otud5 and Otud7b in addition to Otub1 and c-Maf.

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As shown in Fig. 5d , AVT also decreases Otud4 , Otud5 and Otud7b in addition to Otub1 / c-Maf .
PDCD5 affects OTUD5
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PDCD5 activates OTUD5. 2 / 2
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Therefore , it was concluded that OTUD5 could impede the proliferation , migration , and invasion of HCC827 cells while facilitating their apoptosis , and the role of OTUD5 was partly mediated by PDCD5 .
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Conversely, PDCD5 knockdown greatly attenuated the effect of OTUD5 on p53 activation.
OTUD5 affects TLR3
| 2
OTUD5 inhibits TLR3. 2 / 2
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For example, DUBA, a member of the Otubain (OTUB) family, has been shown to deubiquitinate TRAF3 and negatively regulate TLR3- and RIG-I and MDA5-mediated IFN induction.

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For example, DUBA, a member of the Otubain (OTUB) family, has been shown to deubiquitinate TRAF3 and negatively regulate TLR3- and RIG-I/MDA5-mediated IFN induction (52).
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Pirinixic acid decreases the amount of OTUD5.
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Pirinixic acid decreases the amount of OTUD5. 1 / 1
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ctd
No evidence text available
Pirinixic acid activates OTUD5.
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ctd
No evidence text available
UBR5 affects OTUD5
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UBR5 inhibits OTUD5.
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UBR5 bound to OTUD5 inhibits OTUD5. 1 / 1
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DUBA interacted with the ubiquitin ligase UBR5, which suppressed DUBA abundance in naive T cells.
UBR5 activates OTUD5.
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UBR5 activates OTUD5. 1 / 1
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UBR5 destabilizes DUBA through ubiquitylation, whereas DUBA stabilizes UBR5 in activated T cells by attenuating degradative auto-ubiquitylation, triggering UBR5 mediated ubiquitylation of the transcription factor RORyt in response to TGF-beta [XREF_BIBR].
OTUD5 affects TRAF6
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OTUD5 inhibits TRAF6.
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OTUD5 inhibits TRAF6. 1 / 1
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Structural data suggest that 1) Toll and IL-1R (TIR) domain containing regulators (BCAP, SIGIRR, and ST2) interfere with TIR domain signalosome formation; 2) major deubiquitinases such as A20, CYLD, and DUBA prevent association of TRAF6 and TRAF3 with their partners, inaddition to removing K63 linked ubiquitin chains that serve as a docking platform for downstream effectors; 3) alternative downstream pathways of TLRs also restrict signaling by competing to bind common partners through shared binding sites.
OTUD5 activates TRAF6.
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OTUD5 activates TRAF6. 1 / 1
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Moreover, the adaptor proteins TRAF3 and TRAF6 are targeted by the cellular proteins DUBA and A20 XREF_BIBR, XREF_BIBR, and TBK1 is sequestered by SIKE XREF_BIBR.
Zinc atom affects OTUD5
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Zinc atom increases the amount of OTUD5. 1 / 1
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ctd
No evidence text available
Urethane affects OTUD5
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Urethane increases the amount of OTUD5. 1 / 1
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ctd
No evidence text available
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Methotrexate decreases the amount of OTUD5. 1 / 1
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ctd
No evidence text available
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Lead diacetate increases the amount of OTUD5. 1 / 1
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ctd
No evidence text available
Ketone body affects OTUD5
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Ketone body increases the amount of OTUD5. 1 / 1
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ctd
No evidence text available
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Hsa-miR-885-3p decreases the amount of OTUD5. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-6873-5p decreases the amount of OTUD5. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-6858-3p decreases the amount of OTUD5. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-6836-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6782-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6766-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6756-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6722-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-664b-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-654-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-650 affects OTUD5
1 |
Hsa-miR-650 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6132 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-608 affects OTUD5
1 |
Hsa-miR-608 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-575 affects OTUD5
1 |
Hsa-miR-575 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-541-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-520a-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-505-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4712-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4693-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4676-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4651 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4443 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4417 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3612 decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-339-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-328-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3120-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1909-3p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1273d decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1260b decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-let-7e-5p decreases the amount of OTUD5. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Folic acid affects OTUD5
1 |
Folic acid decreases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
Dioxygen affects OTUD5
1 |
Dioxygen increases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
Clofibrate affects OTUD5
1 |
Clofibrate decreases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
Choline affects OTUD5
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Choline decreases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
Bisphenol A affects OTUD5
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Bisphenol A increases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
1 |
Benzo[a]pyrene increases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
All-trans-retinoic acid increases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
Abrine affects OTUD5
1 |
Abrine increases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
Ubiquitin affects OTUD5
| 1
| 1

reach
An intricate web of interactions involving the phosphate and the C-terminal tail of ubiquitin cause DUBA to fold around its substrate, revealing why phosphorylation is essential for deubiquitinase activity.
TRAF3 affects OTUD5
| 1
TRAF3 inhibits OTUD5. 1 / 1
| 1

reach
TRAF3 activation is negatively regulated by Suppressor of Cytokine Signalling 3 (SOCS3) and Deubiquitinating Enzyme A (DUBA) [XREF_BIBR].
TGFB affects OTUD5
| 1
TGFB activates OTUD5. 1 / 1
| 1

eidos
In immunomodulation , TGF-beta stimulation leads to excessive OTUD5 production .

reach
TRAF3 activation is negatively regulated by Suppressor of Cytokine Signalling 3 (SOCS3) and Deubiquitinating Enzyme A (DUBA) [XREF_BIBR].
SP1 affects OTUD5
1 |
SP1 decreases the amount of OTUD5. 1 / 1
1 |

biopax:msigdb
No evidence text available

eidos
d The level of ubiquitinated TRIM25 increased following OTUD5 depletion by siRNA in the Hep3B cells .
RIPK1 affects OTUD5
| 1
RIPK1 activates OTUD5. 1 / 1
| 1

reach
Meylan and colleagues have shown that RIP3 inhibits RIP1 by competition, down-regulating the TRIF–RIP1-induced NF-κB pathway.40 Similarly to DUBA, A20 is a de-ubiquitinating enzyme that has been found to act in the cytoplasm as a negative regulator of TLR responses, affecting RIP1 and TRAF6 and thereby terminating TLR-induced NF-κB signalling.
PAX4 affects OTUD5
1 |
PAX4 decreases the amount of OTUD5. 1 / 1
1 |

biopax:msigdb
No evidence text available

reach
The function of OTUD5 is required to allow the rapid activation of p53 dependent transcription and a p53 dependent apoptosis in response to DNA damage stress.

reach
Interferon type I (IFN-I) responses are triggered by pattern-recognition receptors (PRRs), and DUBA (OTUD5) was shown to negatively regulate this immune signaling pathway [29] .
| PMC

eidos
Studies have shown that OTUD5 can activate the programmed cell death 5 ( PDCD5 , a tumor suppressor ; Park et al ., 2015 ) .
| PMC
OTUD5 affects maleate(2-)
| 1
| 1

reach
Recently, a male specific multiple congenital anomaly disorder caused by pathogenic variants in OTUD5 was reported by two groups.
| 1

reach
OTUD5 promotes innate antiviral and antitumor immunity through deubiquitinating and stabilizing STING.
OTUD5 affects doxorubicin
| 1
| 1

reach
OTUD5 knockdown also enhanced the resistance of NSCLC cells to doxorubicin and cisplatin.
OTUD5 affects cisplatin
| 1
| 1

reach
OTUD5 knockdown also enhanced the resistance of NSCLC cells to doxorubicin and cisplatin.

eidos
Two different lung tumor cell lines , H1299 and A549 , were used to investigate whether siRNA-mediated depletion of OTUD5 also promoted cell proliferation .
| 1

eidos
In response to genotoxic stress , OTUD5 interacts with p53-PDCD5 to reduce its ubiquitination ( Luo , 2013 ; Park et al ., 2015 ) .
OTUD5 affects Ubiquitin
| 1
| 1

reach
An intricate web of interactions involving the phosphate and the C-terminal tail of ubiquitin cause DUBA to fold around its substrate, revealing why phosphorylation is essential for deubiquitinase activity.
OTUD5 affects TRIM25
| 1
OTUD5 increases the amount of TRIM25. 1 / 1
| 1

reach
Further investigation reveals that OTUD5 depletion leads to the enhanced transcriptional activity of TRIM25 and the inhibited expression of PML by altering the ubiquitination level of TRIM25.
OTUD5 affects TNF
| 1
OTUD5 activates TNF. 1 / 1
| 1

reach
OTUD5 expression was enhanced by IFN-gamma through a p38 and MAPK dependent mechanism and the AS induced knockdown of OTUD5 in LPMCs of IBD patients and colitic mice reduced TNF-alpha.
OTUD5 affects TLR9
| 1
OTUD5 activates TLR9. 1 / 1
| 1

reach
DUBA short interference RNA augmented the TLR9 dependent type I IFN response.
OTUD5 affects TGFB
| 1
OTUD5 inhibits TGFB. 1 / 1
| 1

reach
For example, deubiquitinase DUBA can suppress RORgammat protein stability in TGF-beta stimulated Th17 cells [XREF_BIBR].
| PMC
OTUD5 affects STING1
| 1
OTUD5 activates STING1. 1 / 1
| 1

reach
Similarly, OTUD5 promotes the protein stability of STING via cleaving the K48-linked polyubiquitin chains.
OTUD5 affects PML
| 1
OTUD5 decreases the amount of PML. 1 / 1
| 1

reach
Further investigation reveals that OTUD5 depletion leads to the enhanced transcriptional activity of TRIM25 and the inhibited expression of PML by altering the ubiquitination level of TRIM25.
OTUD5 affects Neoplasms
| 1
| 1

eidos
Briefly , OTUD5 potentially inhibits tumor progression by regulating PML transcription by deubiquitinating TRIM25 ( Fig. 8g ) .
OTUD5 affects IL6
| 1
OTUD5 inhibits IL6. 1 / 1
| 1

reach
DUBA knockdown by siRNA transfection in Il1r1 -/- BMDCs (XREF_FIG) resulted in significantly increased IL-10 and IFN-beta production and decreased secretion of IL-6, but not TNF, in CpG stimulated Il1r1 -/- BMDCs (XREF_FIG).
OTUD5 affects IFNB1
| 1
OTUD5 activates IFNB1. 1 / 1
| 1

reach
DUBA knockdown by siRNA transfection in Il1r1 -/- BMDCs (XREF_FIG) resulted in significantly increased IL-10 and IFN-beta production and decreased secretion of IL-6, but not TNF, in CpG stimulated Il1r1 -/- BMDCs (XREF_FIG).
OTUD5 affects HES
| 1
OTUD5 inhibits HES. 1 / 1
| 1

reach
To corroborate these results and exclude any off-target effects originating from clonal selection during iPSC reprogramming, we next generated control or OTUD5 depleted hES H1 cells and subjected them to neural conversion.
| PMC
| 1
| 1

reach
Given that TRAF3 may be dispensable for RIG-I signalling XREF_BIBR, it can not be excluded, however, that DUBA also targets other E3 ligases like TRAF2, 5 and 6.
OTUD5 affects DNA repair
| 1
| 1

eidos
Studies have shown that OTUD5 could inhibit DNA damage repair by regulating the FACT histone chaperone complex ( de Vivo et al ., 2019 ) .
| PMC

eidos
In order to study whether OTUD5 can inhibit NSCLC via regulating p53 expression , OTUD5 siRNA and a p53 overexpressing plasmid were used to construct an si-OTUD5 / p53 group , an si-OTUD5 group , a p53 group , and an si-NC group , respectively .
| PMC
| 1

eidos
Our findings reveal a mechanism whereby OTUD5 regulates gene transcription and suppresses tumorigenesis by deubiquitinating TRIM25 , providing a potential target for oncotherapy .
OTUD5 is modified
| 1
OTUD5 is produced. 1 / 1
| 1

trips
Here, we found that OTU deubiquitinase 5 (OTUD5) was bound to PDCD5 in response to etoposide treatment and increased the stability of PDCD5 by mediating deubiquitination of PDCD5 at Lys-97/98.
MIR937 affects OTUD5
| 1
MIR937 inhibits OTUD5. 1 / 1
| 1

eidos
Moreover , hsa-mir-137 , hsa-mir-1913 , hsa-mir-937 , hsa-mir-607 , hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5 .
MIR607 affects OTUD5
| 1
MIR607 inhibits OTUD5. 1 / 1
| 1

eidos
Moreover , hsa-mir-137 , hsa-mir-1913 , hsa-mir-937 , hsa-mir-607 , hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5 .
MIR3149 affects OTUD5
| 1
| 1

eidos
Moreover , hsa-mir-137 , hsa-mir-1913 , hsa-mir-937 , hsa-mir-607 , hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5 .
MIR1913 affects OTUD5
| 1
| 1

eidos
Moreover , hsa-mir-137 , hsa-mir-1913 , hsa-mir-937 , hsa-mir-607 , hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5 .
MIR144 affects OTUD5
| 1
MIR144 inhibits OTUD5. 1 / 1
| 1

eidos
Moreover , hsa-mir-137 , hsa-mir-1913 , hsa-mir-937 , hsa-mir-607 , hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5 .
MIR137 affects OTUD5
| 1
MIR137 inhibits OTUD5. 1 / 1
| 1

eidos
Moreover , hsa-mir-137 , hsa-mir-1913 , hsa-mir-937 , hsa-mir-607 , hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5 .
LEF1 affects OTUD5
1 |
LEF1 decreases the amount of OTUD5. 1 / 1
1 |

biopax:msigdb
No evidence text available
1 |
L-methionine decreases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
Interferon affects OTUD5
| 1
Interferon deubiquitinates OTUD5. 1 / 1
| 1

reach
Several mechanisms dampen IFNα/β production, for example, deubiquitinating enzyme A (DUBA) is a negative regulator of IFNα/β downstream of multiple induction pathways [7].
IL1R1 affects OTUD5
| 1
IL1R1 inhibits OTUD5. 1 / 1
| 1

reach
DUBA knockdown by siRNA transfection in Il1r1 -/- BMDCs (XREF_FIG) resulted in significantly increased IL-10 and IFN-beta production and decreased secretion of IL-6, but not TNF, in CpG stimulated Il1r1 -/- BMDCs (XREF_FIG).
IL1 affects OTUD5
| 1
IL1 activates OTUD5. 1 / 1
| 1

reach
In other systems, IL-1 signaling has been shown to trigger the downregulation of deubiquitinating enzyme A (DUBA), which selectively cleaves K63 linked ubiquitin chains from TRAF3 to limit type I IFN responses.
Grape Seed Proanthocyanidins decreases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
FOXO4 affects OTUD5
1 |
FOXO4 decreases the amount of OTUD5. 1 / 1
1 |

biopax:msigdb
No evidence text available
FOXN1 affects OTUD5
1 |
FOXN1 decreases the amount of OTUD5. 1 / 1
1 |

biopax:msigdb
No evidence text available
1 |
Dietary Fats increases the amount of OTUD5. 1 / 1
1 |

ctd
No evidence text available
BPTF affects OTUD5
1 |
BPTF decreases the amount of OTUD5. 1 / 1
1 |

biopax:msigdb
No evidence text available
1 |
Aroclor 1254 decreases the amount of OTUD5. 1 / 1
1 |

ctd