OTUB2 Data Analysis

HGNC Gene Name
OTU deubiquitinase, ubiquitin aldehyde binding 2
HGNC Gene Symbol
OTUB2
Identifiers
hgnc:20351 NCBIGene:78990 uniprot:Q96DC9
Orthologs
mgi:1915399 rgd:1306688
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for OTUB2
Number of Papers
31 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

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with OTUB2using 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

Literature Mining

INDRA was used to automatically assemble known mechanisms related to OTUB2 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

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OTUB2 deubiquitinates L3MBTL1. 7 / 7
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Finally, we investigated whether OTUB2 could deubiquitinate L3MBTL1 in vitro.

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In addition, DSB induced L3MBTL1 ubiquitination (Acs et al., 2011) was also antagonized by OTUB2 in a DUB activity dependent manner.

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These data suggest that the interaction between OTUB2 and L3MBTL1 is constitutive rather than DNA damage dependent.Next, we investigated whether OTUB2 could deubiquitinate L3MBTL1 in vivo.

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However, OTUB2 deubiquitinates L3MBTL1 and suppresses the RNF8 mediated ubiquitination of L3MBTL1, which leads to less recruitment of RAP80 and 53BP1 to DSBs and therefore increases HR.

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Mechanistically, OTUB2 suppresses RNF8-mediated L3MBTL1 ubiquitination and Lys 63-linked ubiquitin chain formation in a deubiquitinating activity-dependent manner.

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Because ubiquitination of L3MBTL1 is a prerequisite for L3MBTL1 removal from damaged chromatin (Acs et al., 2011), we conclude that OTUB2 deubiquitinates L3MBTL1 and suppresses the accelerated removal[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Thus, OTUB2 deubiquitinates L3MBTL1 in vivo and in vitro.
OTUB2 deubiquitinates TRAF3. 7 / 7
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OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR].

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Furthermore, we found that OTUB1 and OTUB2 mediated virus triggered deubiquitination of TRAF3 and -6.

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Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6

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OTUB1 and its paralog OTUB2, deubiquitinate TRAF3 and TRAF6 to inhibit virus triggered signaling pathways that ultimately result in IRF3 and NF-kappaB activation [XREF_BIBR].

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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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It was also shown that two OTUB deubiquitinating enzyme family members, OTUB1 and OTUB2, can deubiquitinate TRAF3 and TRAF6, leading to the inhibition of virus induced IFN-beta expression and cellular antiviral responses.

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It was also shown that two OTUB deubiquitinating enzyme family members, OTUB1 and OTUB2, can deubiquitinate TRAF3 and TRAF6, leading to the inhibition of virus-induced IFN-β expression and cellular antiviral responses (53).
OTUB2 deubiquitinates TRAF6. 5 / 5
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It was also shown that two OTUB deubiquitinating enzyme family members, OTUB1 and OTUB2, can deubiquitinate TRAF3 and TRAF6, leading to the inhibition of virus induced IFN-beta expression and cellular antiviral responses.

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It was also shown that two OTUB deubiquitinating enzyme family members, OTUB1 and OTUB2, can deubiquitinate TRAF3 and TRAF6, leading to the inhibition of virus-induced IFN-β expression and cellular antiviral responses (53).

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OTUB1 and its paralog OTUB2, deubiquitinate TRAF3 and TRAF6 to inhibit virus triggered signaling pathways that ultimately result in IRF3 and NF-kappaB activation [XREF_BIBR].

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OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR].

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Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6
OTUB2 deubiquitinates U2AF2. 3 / 3
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This finding led us to hypothesize that OTUB2 directly interacts with and deubiquitinates U2AF2.

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Of note, U2AF2 deubiquitination by OTUB2 is important for U2AF2 stabilization.

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OTUB2 knockdown significantly enhanced the levels of U2AF2 ubiquitination and K48 linked polyubiquitin chains in H1299 cells, whereas OTUB2 overexpression significantly reduced the levels of U2AF2 ubiquitination and K48 linked polyubiquitin chains in XL-2 cells.
OTUB2 leads to the deubiquitination of GLI2. 1 / 1
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We also found that knockdown of OTUB2 reduced deubiquitination of Gli2 invivo.
OTUB2 leads to the deubiquitination of OTUB2. 1 / 1
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Because the accumulation of RNF168 at DSBs requires the E3 ubiquitin ligase activity of RNF8 and the accumulation of 53BP1, RAP80, and BRCA1 requires recruitment of RNF168 to DSBs (Doil et al., 2009; [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
OTUB2 deubiquitinates Protease. 1 / 1
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A second shared gene of interest is OTU2 that encodes a putative otubain related deubiquitylating protease XREF_BIBR, XREF_BIBR.
OTUB2 leads to the deubiquitination of Histone. 1 / 1
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However, OTUB2 does not suppress histone ubiquitination induced by RNF168 overexpression [XREF_BIBR].

Other Statements

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OTUB2 affects TRAF6
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OTUB2 inhibits TRAF6.
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OTUB2 inhibits TRAF6. 6 / 6
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TRAF6 are inhibited by A20 , CYLD and OTUB2 that specially remove TRAF6 K63-linked ubiquitination .

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TRAF6 are inhibited by A20, CYLD and OTUB2 that specially remove TRAF6 K63‐linked ubiquitination.

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TRAF6 are inhibited by A20, CYLD and OTUB2 that specially remove TRAF6 K63‐linked ubiquitination.

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TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 ( OTUB1 ) and OTUB2 , which remove K63-linked polyubiquitin chains ( Li et al ., 2010b ) .

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TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 (OTUB1) and OTUB2, which remove K63-linked polyubiquitin chains (Li et al., 2010b) .

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TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 (OTUB1) and OTUB2, which remove K63 linked polyubiquitin chains.
OTUB2 activates TRAF6.
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OTUB2 activates TRAF6. 1 / 1
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Mechanistically, OTUB2 overexpression can activate NF-kappaB signaling mostly by stabilizing TRAF6.
OTUB2 affects NFkappaB
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OTUB2 activates NFkappaB.
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Our further investigations revealed that knockdown of OTUB2 significantly suppressed NF-kappaB-driving luciferase activity, and markedly inhibited the phosphorylation of NF-kappaB p65 in liver cancer cells, which indicated that OTUB2 mediated liver cancer cell growth by regulating NF-kappaB signaling.

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Mechanistically, OTUB2 overexpression can activate NF-kappaB signaling mostly by stabilizing TRAF6.

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Knockdown of otubain 2 inhibits liver cancer cell growth by suppressing NF-kappaB signaling.
OTUB2 inhibits NFkappaB.
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Overexpression of OTUB1 and OTUB2 inhibited virus induced activation of IRF3 and NF-kappaB, transcription of the IFNB1 gene as well as cellular antiviral response, whereas knockdown of OTUB1 and OTUB2 had opposite effects.
2,3,7,8-tetrachlorodibenzodioxine increases the amount of OTUB2.
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2,3,7,8-tetrachlorodibenzodioxine decreases the amount of OTUB2.
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OTUB2 affects lactate
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OTUB2 activates lactate. 4 / 4
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Moreover , OTUB2 depletion reduces glucose consumption , lactate production , and cellular ATP production .

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As expected, we verified that OTUB2 overexpression increased ECAR, glucose uptake, and lactate production, while knockdown of OTUB2 impaired the aerobic glycolytic phenotype in different NSCLC cell lines.

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Moreover, OTUB2 depletion reduces glucose consumption, lactate production, and cellular ATP production.

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Conversely, OTUB2 overexpression substantially enhanced glycolytic capability, glucose uptake and extracellular lactate production in XL-2 and H292 cells.
OTUB2 affects U2AF2
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OTUB2 decreases the amount of U2AF2.
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OTUB2 decreases the amount of U2AF2. 2 / 2
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We first examined the mRNA and protein levels of U2AF2 following OTUB2 knockdown or overexpression in MG132 treated NSCLC cell lines wherein global proteasomal activity was inhibited.

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Knockdown of OTUB2 significantly inhibited the U2AF2 protein levels in A549 and H1299 cells but had no impact on U2AF2 mRNA levels.
OTUB2 activates U2AF2.
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OTUB2 activates U2AF2. 2 / 2
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Consistently, OTUB2 overexpression in XL-2 and H292 cells increased the half-life of U2AF2 protein in the presence of CHX.

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Taken together, these results indicate that OTUB2 promotes xenograft tumor growth of NSCLC cells by stabilizing U2AF2 and enhancing the Warburg effect In vivo.
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Valproic acid decreases the amount of OTUB2. 3 / 3
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OTUB2 affects glucose
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OTUB2 activates glucose. 3 / 3
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Moreover, OTUB2 depletion reduces glucose consumption, lactate production, and cellular ATP production.

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As expected, we verified that OTUB2 overexpression increased ECAR, glucose uptake, and lactate production, while knockdown of OTUB2 impaired the aerobic glycolytic phenotype in different NSCLC cell lines.

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Conversely, OTUB2 overexpression substantially enhanced glycolytic capability, glucose uptake and extracellular lactate production in XL-2 and H292 cells.
OTUB2 affects UIMC1
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OTUB2 inhibits UIMC1. 3 / 3
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Taking these findings together, we propose a model whereby OTUB2 inhibits excessive DSB-end protection and allows the initiation of HR by properly regulating the accumulation of RAP80 and 53BP1 at DSB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR [XREF_BIBR, XREF_BIBR].

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Thus, the RNF8-RNF168 axis primarily suppresses HR and promotes non-HR-type DSB repair, e.g. NHEJ, and OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR.
OTUB2 affects TRAF3
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OTUB2 inhibits TRAF3. 3 / 3
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TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 (OTUB1) and OTUB2, which remove K63 linked polyubiquitin chains.

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TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 ( OTUB1 ) and OTUB2 , which remove K63-linked polyubiquitin chains ( Li et al ., 2010b ) .

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TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 (OTUB1) and OTUB2, which remove K63-linked polyubiquitin chains (Li et al., 2010b) .
OTUB2 affects TP53BP1
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OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR [XREF_BIBR, XREF_BIBR].

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Taking these findings together, we propose a model whereby OTUB2 inhibits excessive DSB-end protection and allows the initiation of HR by properly regulating the accumulation of RAP80 and 53BP1 at DSB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Thus, the RNF8-RNF168 axis primarily suppresses HR and promotes non-HR-type DSB repair, e.g. NHEJ, and OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR.

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In contrast, stable overexpression of OTUB2 significantly increased the invasion and migratory abilities of XL-2 and H292 cells.

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We also confirmed that OTUB2 enhanced the proliferation, migration, and invasion abilities of NSCLC cells In vitro.

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Moreover, knockdown of OTUB2 significantly suppressed the invasion and migration abilities of A549 and H1299 cells.
OTUB2 affects IRF3
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OTUB2 inhibits IRF3. 2 / 3
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Overexpression of OTUB1 and OTUB2 inhibited virus induced activation of IRF3 and NF-kappaB, transcription of the IFNB1 gene as well as cellular antiviral response, whereas knockdown of OTUB1 and OTUB2 had opposite effects.

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[172] Because various components are involved in virus induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS mediated but not TBK1- and IRF3 mediated signaling.
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Cell Counting Kit-8 and flow cytometry assay results revealed that overexpression of OTUB2 enhanced cell viability of endometrial cancer cells, while knockdown of OTUB2 inhibited cell viability.

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Cell Counting Kit-8 and flow cytometry assay results revealed that overexpression of OTUB2 enhanced cell viability of endometrial cancer cells , while knockdown of OTUB2 inhibited cell viability .

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Otubain 2 is a novel promoter of beta cell survival as revealed by siRNA high-throughput screens of human pancreatic islets.
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(+)-JQ1 compound decreases the amount of OTUB2. 3 / 3
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Thus, the RNF8-RNF168 axis primarily suppresses HR and promotes non-HR-type DSB repair, e.g. NHEJ, and OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR.

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OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR [XREF_BIBR, XREF_BIBR].

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Taking these findings together, we propose a model whereby OTUB2 inhibits excessive DSB-end protection and allows the initiation of HR by properly regulating the accumulation of RAP80 and 53BP1 at DSB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
OTUB2 affects cell growth
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OTUB2 activates cell growth.
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At the cellular level, knockdown of OTUB2 markedly inhibited liver cancer cell growth.

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Our further investigations revealed that knockdown of OTUB2 significantly suppressed NF-kappaB-driving luciferase activity, and markedly inhibited the phosphorylation of NF-kappaB p65 in liver cancer cells, which indicated that OTUB2 mediated liver cancer cell growth by regulating NF-kappaB signaling.
OTUB2 inhibits cell growth.
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Knockdown of otubain 2 inhibits liver cancer cell growth by suppressing NF-kappaB signaling.
OTUB2 affects MYC
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OTUB2 activates MYC.
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OTUB2 activates MYC. 2 / 2
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OTUB2 may stimulate the Warburg effect by regulating HIF1a and c-Myc in NSCLC cells.

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Collectively, these data indicate that OTUB2 promotes the Warburg effect by modulating HIF1a and c-Myc.
OTUB2 increases the amount of MYC.
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OTUB2 increases the amount of MYC. 1 / 1
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Moreover, it was very intriguing for us to show that OTUB2 promoted the protein expression of HIF1a and c-Myc and induced activation of the AKT and mTOR pathway.
OTUB2 affects HIF1A
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OTUB2 activates HIF1A.
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OTUB2 activates HIF1A. 2 / 2
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Collectively, these data indicate that OTUB2 promotes the Warburg effect by modulating HIF1a and c-Myc.

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OTUB2 may stimulate the Warburg effect by regulating HIF1a and c-Myc in NSCLC cells.
OTUB2 increases the amount of HIF1A.
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OTUB2 increases the amount of HIF1A. 1 / 1
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Moreover, it was very intriguing for us to show that OTUB2 promoted the protein expression of HIF1a and c-Myc and induced activation of the AKT and mTOR pathway.
OTUB2 affects GLI2
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OTUB2 inhibits GLI2.
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OTUB2 inhibits ubiquitinated GLI2. 1 / 1
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Invitro deubiquitination assay showed that ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations.
Mutated OTUB2 inhibits ubiquitinated GLI2. 1 / 1
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Invitro deubiquitination assay showed that ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations.
OTUB2 decreases the amount of GLI2.
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OTUB2 decreases the amount of GLI2. 1 / 1
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Knockdown of OTUB2 decreased Gli2 protein level while the proteasome inhibitor MG-132 treatment restored Gli2 expression.
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Silicon dioxide increases the amount of OTUB2. 2 / 2
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Hsa-miR-6856-3p decreases the amount of OTUB2. 2 / 2
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Hsa-miR-629-3p decreases the amount of OTUB2. 2 / 2
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Hsa-miR-4279 decreases the amount of OTUB2. 2 / 2
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Hsa-miR-1264 decreases the amount of OTUB2. 2 / 2
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Benzo[a]pyrene increases the amount of OTUB2. 2 / 2
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OTUB2 affects UBE2N
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OTUB2 inhibits UBE2N. 2 / 2
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These residues are important for OTUB1 inhibition of E2 activity 4 and are absent in OTUB2, which does not inhibit UBC13 4.

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Interestingly, the corresponding residue is a glutamic acid in OTUB2, which lacks an N-terminal arm and does not inhibit UBC13 4.
OTUB2 affects TAZ
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OTUB2 activates TAZ. 2 / 2
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OTUB2 Promotes Cancer Metastasis via Hippo Independent Activation of YAP and TAZ.

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Importantly, EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation and thereby activate YAP and TAZ.

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These data indicate that the mechanism by which OTUB2 inhibits the DDR is through its deubiquitination activity, which is different from that of OTUB1.Next, we sought to pinpoint the step of DDR signa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Therefore, we excluded the off-target effects of the siRNA and confirmed that OTUB2 indeed suppressed the DDR in a DUB activity dependent manner.
OTUB2 affects BMP2
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OTUB2 increases the amount of BMP2. 2 / 2
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We also found that OTUB2 knockdown suppressed the ALP activity and the expression of the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh and Smo agonists, which indicated OTUB2 may have effect on osteogenic differentiation by regulating Hh signaling.

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OTUB2 knockdown suppressed the alkaline phosphatase activity and the expression of the common osteogenic markers BMP2 and RUNX2 during osteogenesis of mesenchymal stem cells in response to Shh and Smo agonists, suggesting that OTUB2 may play a role in osteogenic differentiation by regulating Hh signaling [64].
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Aflatoxin B1 increases the amount of OTUB2.
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Aflatoxin B1 increases the amount of OTUB2. 1 / 1
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Aflatoxin B1 decreases the amount of OTUB2.
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Aflatoxin B1 decreases the amount of OTUB2. 1 / 1
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OTUB2 affects RUNX2
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OTUB2 increases the amount of RUNX2.
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OTUB2 increases the amount of RUNX2. 1 / 1
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We also found that OTUB2 knockdown suppressed the ALP activity and the expression of the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh and Smo agonists, which indicated OTUB2 may have effect on osteogenic differentiation by regulating Hh signaling.
OTUB2 decreases the amount of RUNX2.
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OTUB2 decreases the amount of RUNX2. 1 / 1
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OTUB2 knockdown suppressed the alkaline phosphatase activity and the expression of the common osteogenic markers BMP2 and RUNX2 during osteogenesis of mesenchymal stem cells in response to Shh and Smo agonists, suggesting that OTUB2 may play a role in osteogenic differentiation by regulating Hh signaling [64].
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Dietary Fats increases the amount of OTUB2.
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Dietary Fats increases the amount of OTUB2. 1 / 1
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Dietary Fats decreases the amount of OTUB2.
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Dietary Fats decreases the amount of OTUB2. 1 / 1
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Vorinostat affects OTUB2
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Vorinostat decreases the amount of OTUB2. 1 / 1
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Vanadium oxoanion increases the amount of OTUB2. 1 / 1
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Valdecoxib affects OTUB2
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Valdecoxib decreases the amount of OTUB2. 1 / 1
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Urethane affects OTUB2
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Urethane decreases the amount of OTUB2. 1 / 1
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Triphenyl phosphate increases the amount of OTUB2. 1 / 1
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Trimellitic anhydride increases the amount of OTUB2. 1 / 1
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Topotecan affects OTUB2
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Topotecan decreases the amount of OTUB2. 1 / 1
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Titanium dioxide decreases the amount of OTUB2. 1 / 1
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Thiocyanate affects OTUB2
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To re-examine the ability of OTUB2 to inhibit 53BP1 foci formation, HeLa cells were transiently transfected with Flag-OTUB2 expression vectors, treated with NCS, and then subjected to Flag and 53BP1 i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Thioacetamide decreases the amount of OTUB2. 1 / 1
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Thimerosal affects OTUB2
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Thimerosal decreases the amount of OTUB2. 1 / 1
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Testosterone increases the amount of OTUB2. 1 / 1
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Tamoxifen affects OTUB2
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Tamoxifen decreases the amount of OTUB2. 1 / 1
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Sodium dichromate decreases the amount of OTUB2. 1 / 1
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Rotenone affects OTUB2
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Rotenone decreases the amount of OTUB2. 1 / 1
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Raloxifene hydrochloride decreases the amount of OTUB2. 1 / 1
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Quercetin affects OTUB2
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Quercetin increases the amount of OTUB2. 1 / 1
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Pirinixic acid decreases the amount of OTUB2. 1 / 1
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Oxaliplatin affects OTUB2
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Oxaliplatin decreases the amount of OTUB2. 1 / 1
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Ormosil affects OTUB2
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Ormosil increases the amount of OTUB2. 1 / 1
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Methylmercury compound decreases the amount of OTUB2. 1 / 1
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Metformin affects OTUB2
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Metformin increases the amount of OTUB2. 1 / 1
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Lucanthone affects OTUB2
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Lucanthone increases the amount of OTUB2. 1 / 1
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Jinfukang affects OTUB2
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Jinfukang increases the amount of OTUB2. 1 / 1
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Isotretinoin decreases the amount of OTUB2. 1 / 1
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Ionomycin affects OTUB2
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Ionomycin increases the amount of OTUB2. 1 / 1
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Indometacin affects OTUB2
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Indometacin increases the amount of OTUB2. 1 / 1
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Hsa-miR-6887-3p decreases the amount of OTUB2. 1 / 1
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Hsa-miR-6769a-3p decreases the amount of OTUB2. 1 / 1
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Hsa-miR-5687 decreases the amount of OTUB2. 1 / 1
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Hsa-miR-4773 decreases the amount of OTUB2. 1 / 1
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Hsa-miR-4682 decreases the amount of OTUB2. 1 / 1
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Hsa-miR-4424 decreases the amount of OTUB2. 1 / 1
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Hsa-miR-4420 decreases the amount of OTUB2. 1 / 1
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Hsa-miR-4313 decreases the amount of OTUB2. 1 / 1
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Hsa-miR-3943 decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-3680-5p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-335-5p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-3186-5p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-215-5p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-192-5p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-181b-3p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-181b-2-3p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-1304-3p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-125a-5p decreases the amount of OTUB2. 1 / 1
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biopax:mirtarbase
No evidence text available
Hexabromocyclododecane decreases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Genistein affects OTUB2
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Genistein increases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
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Ethylene glycol increases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
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Dorsomorphin decreases the amount of OTUB2. 1 / 1
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ctd
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Dibutyl phthalate decreases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
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Dexamethasone increases the amount of OTUB2. 1 / 1
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ctd
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Cypermethrin increases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Crocidolite asbestos increases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Cisplatin affects OTUB2
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Cisplatin increases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Casticin affects OTUB2
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Casticin decreases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Bisphenol F affects OTUB2
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Bisphenol F increases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Bisphenol A affects OTUB2
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Bisphenol A increases the amount of OTUB2. 1 / 1
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ctd
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Aluminium atom decreases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Acetamide affects OTUB2
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Acetamide decreases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
U2AF2 affects OTUB2
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U2AF2 inhibits OTUB2. 1 / 1
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Importantly, knockdown of U2AF2 rescued the promoting effect of OTUB2 on H292 cell migration and invasion.
Soot affects OTUB2
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Soot decreases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
Soman affects OTUB2
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Soman decreases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
SAX affects OTUB2
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SAX activates OTUB2. 1 / 1
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FOS increased Ruminococcus2 OTU3 and Lactobacillus OTU37, SAX increased Bacteroides OTU2, and CAX increased Bacteroides OTU11.
Palm Oil affects OTUB2
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Palm Oil increases the amount of OTUB2. 1 / 1
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ctd
No evidence text available
PAX4 affects OTUB2
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PAX4 decreases the amount of OTUB2. 1 / 1
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biopax:msigdb
No evidence text available
OTUB2 affects translation
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These results suggest that the deletion of Otu2 does not cause abortive translation.

eidos
OTUB2 Promotes Homologous Recombination Repair Through Stimulating Rad51 Expression in Endometrial Cancer .

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Consistent with this possibility, in depth taxonomic analysis of the 16S rDNA dataset revealed that OTU2, OTU6, and OTU24 decreased in their relative abundance with co-housing, indicating that these bacterial species might have promoted skin inflammation in ft/ft mice.

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Here we demonstrate that OTUB2, an OTU deubiquitinase, is upregulated in colorectal cancer (CRC) and exacerbates the progression of CRC through modulating the aerobic glycolysis.

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We also confirmed that OTUB2 enhanced the proliferation, migration, and invasion abilities of NSCLC cells In vitro.
OTUB2 affects cell cycle
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A more detailed in silico gene analysis within this pathway disclosed that PAX4 induced the expression of both cell cycle activators such as CYCLIN A2, B2, D1 and D3, CMYC, HDAC and PCNA as well cell cycle inhibitors such as P21, P53, OTUB2 and ERRFI1 (XREF_TABLE).
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Mechanistically , OTUB2 directly interacts with pyruvate kinase M2 ( PKM2 ) and inhibits its ubiquitination by blocking the interaction between PKM2 and its ubiquitin E3 ligase Parkin , thereby enhancing PKM2 activity and promoting glycolysis .
OTUB2 affects Ubiquitin
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These data, combined with the observation that NCS induced formation of RAP80 foci was inhibited by OTUB2 overexpression and accelerated by OTUB2 depletion, indicate that OTUB2 negatively regulates DN[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
OTUB2 affects TBK1
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OTUB2 inhibits TBK1. 1 / 1
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[172] Because various components are involved in virus induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS mediated but not TBK1- and IRF3 mediated signaling.
OTUB2 affects RNF168
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OTUB2 inhibits RNF168. 1 / 1
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On the other hand, we also found 13 DUBs that were recruited to DNA damage sites but gave only marginal DSB repair defects upon siRNA depletion, including OTUB1, a negative regulator of the UBE2N (UBC13) ubiquitin E2 enzyme 24, USP44 that is reported to antagonize RNF168 dependent ubiquitylation 25, and OTUB2 that functions in repair-pathway choice 26 (XREF_FIG, XREF_FIG, and XREF_FIG), suggesting that some of the additional DUBs we identified might be negative DDR regulators and/or be involved in repair-pathway choice.
OTUB2 affects PGK1
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Modified OTUB2 increases the amount of PGK1. 1 / 1
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Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells.
OTUB2 affects PGAM1
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Modified OTUB2 increases the amount of PGAM1. 1 / 1
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Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells.
OTUB2 affects PFKL
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Modified OTUB2 increases the amount of PFKL. 1 / 1
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Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells.
OTUB2 affects Neoplasms
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Furthermore, in vivo assays show that knockout of OTUB2 inhibits tumor growth in mice.

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OTUB2 Promotes Cancer Metastasis via Hippo Independent Activation of YAP and TAZ.
OTUB2 affects Mice
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OTUB2 activates Mice. 1 / 1
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Furthermore, in vivo assays show that knockout of OTUB2 inhibits tumor growth in mice.
OTUB2 affects MTOR
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OTUB2 activates MTOR. 1 / 1
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The phosphorylation levels of mTOR and AKT were increased, indicating that the mTOR pathway may be activated by OTUB2.
OTUB2 affects MAVS
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OTUB2 inhibits MAVS. 1 / 1
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[172] Because various components are involved in virus induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS mediated but not TBK1- and IRF3 mediated signaling.
OTUB2 affects MAP3K7
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OTUB2 inhibits MAP3K7. 1 / 1
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Furthermore, the DUBs OTUB1 and OTUB2 also negatively regulate TAK1 signaling by removing K63 chains from TRAF6 after viral infection (Figs.
OTUB2 affects L3MBTL1
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OTUB2 decreases the amount of ubiquitinated L3MBTL1. 1 / 1
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When in vivo ubiquitinated L3MBTL1 was incubated with recombinant OTUB2 proteins, recombinant OTUB2 decreased the amount of ubiquitinated L3MBTL1 and generated ubiquitin monomers.
OTUB2 affects KDM1A
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OTUB2 increases the amount of KDM1A. 1 / 1
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Notably, we demonstrated that OTUB2 increased lysine-specific histone demethylase 1A (KDM1A) expression through deubiquitination.
OTUB2 affects Interferon
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These findings suggest that OTUB1 and OTUB2 negatively regulate virus triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6.
OTUB2 affects INS
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OTUB2 activates INS. 1 / 1
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OTUB2 knockdown increased caspase-3/7 activity in MIN6 cells and primary human islets and inhibited insulin secretion and increased nuclear factor-kappaB (NF-kappaB) activity both under basal conditions and following cytokine treatment.
OTUB2 affects HK2
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Modified OTUB2 increases the amount of HK2. 1 / 1
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Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells.
OTUB2 affects ESR2
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OTUB2 activates ESR2. 1 / 1
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Clearly, the RTP values of compounds 2a and 2c are far greater for the ERbeta mediated response (OTUB2 activation in ERalpha + ERbeta cells) than the ERalpha mediated response (PR activation in ERalpha only cells).
OTUB2 affects ESR1
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OTUB2 activates ESR1. 1 / 1
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Clearly, the RTP values of compounds 2a and 2c are far greater for the ERbeta mediated response (OTUB2 activation in ERalpha + ERbeta cells) than the ERalpha mediated response (PR activation in ERalpha only cells).
OTUB2 affects DNA Damage
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OTUB2 was recently reported to suppress DNA damage responses through suppression of deubiquitylation of ubiquitylated proteins with RNF8 XREF_BIBR.
OTUB2 affects DDX58
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OTUB2 inhibits DDX58. 1 / 1
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Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63-linked polyubiquitin chains. [172] Because various components are involved in virusinduced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS-mediated but not TBK1-and IRF3-mediated signaling.
OTUB2 affects Caspase_3_7