Evidence map›Paper›PMID 26588485›Full record

ArticlePloS one2015

Evolutionary Loss of Activity in De-Ubiquitylating Enzymes of the OTU Family.

Marcell Louis, Kay Hofmann, Meike Broemer

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.3field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Bourbon and Mycbp function with Otu to promote Sxl protein expression in theProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Review
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  11. Bam-dependent deubiquitinase complex can disrupt germ-line stem cell maintenance by targeting cyclin A.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Marcell LouisGerman Center for Neurodegenerative Diseases (DZNE), Bonn, c/o LiMeS, Carl-Troll-Str. 31, 53115, Bonn, Germany.
Kay HofmannUniversity of Cologne, Institute for Genetics, Zülpicher Str. 47a, 50674, Cologne, Germany.
Meike BroemerGerman Center for Neurodegenerative Diseases (DZNE), Bonn, c/o LiMeS, Carl-Troll-Str. 31, 53115, Bonn, Germany.
German Center for Neurodegenerative Diseases · DEUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding function and specificity of de-ubiquitylating enzymes (DUBs) is a major goal of current research, since DUBs are key regulators of ubiquitylation events and have been shown to be mutated in human diseases. Most DUBs are cysteine proteases, relying on a catalytic triad of cysteine, histidine and aspartate to cleave the isopeptide bond between two ubiquitin units in a poly-ubiquitin chain. We have discovered that the two Drosophila melanogaster homologues of human OTUD4, CG3251 and Otu, contain a serine instead of a cysteine in the catalytic OTU (ovarian tumor) domain. DUBs that are serine proteases instead of cysteine- or metallo-proteases have not been described. In line with this, neither CG3251 nor Otu protein were active to cleave ubiquitin chains. Re-introduction of a cysteine in the catalytic center did not render the enzymes active, indicating that further critical features for ubiquitin binding or cleavage have been lost in these proteins. Sequence analysis of OTUD4 homologues from various other species showed that within this OTU subfamily, loss of the catalytic cysteine has occurred frequently in presumably independent events, as well as gene duplications or triplications, suggesting DUB-independent functions of OTUD4 proteins. Using an in vivo RNAi approach, we show that CG3251 might function in the regulation of Inhibitor of Apoptosis (IAP)-antagonist-induced apoptosis, presumably in a DUB-independent manner.

Indexed as

Amino Acid SequenceAmino Acid SubstitutionAnimalsApoptosisBinding SitesCatalytic DomainConserved SequenceCysteineDrosophila melanogasterDrosophila ProteinsEvolution, MolecularGene Expression RegulationHumansInhibitor of Apoptosis ProteinsMolecular Sequence DataProtein BindingCysteineDrosophila ProteinsInhibitor of Apoptosis ProteinsOTUD4 protein, humanotu protein, DrosophilaRNA, Small InterferingSerineUbiquitinUbiquitin-Specific Proteases

Identifiers

PMID26588485
PMCPMC4654579
OpenAlexW2286402846

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.