Evidence map›Paper›PMID 27199454›Full record

ArticlePhysiological genomics2016

Comprehensive database of human E3 ubiquitin ligases: application to aquaporin-2 regulation.

Barbara Medvar, Viswanathan Raghuram, Trairak Pisitkun, Abhijit Sarkar, Mark A Knepper

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Physiological genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

76 citing papers in PubMed, 109 citations in OpenAlex.

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  8. Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels.Proceedings of the National Academy of Sciences of the United States of America · 2026
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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 2 countries.

Barbara MedvarEpithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Vitreous State Laboratory, The Catholic University of America, Washington, District of Columbia; and.
Viswanathan RaghuramEpithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland;
Trairak PisitkunEpithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Systems Biology Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Abhijit SarkarVitreous State Laboratory, The Catholic University of America, Washington, District of Columbia; and.
Mark A KnepperEpithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; knepperm@nhlbi.nih.gov.
National Heart Lung and Blood Institute · USCatholic University of America · USChulalongkorn University · THNational Institutes of Health · US

Funding

Solute And Water Transport In Renal EpitheliaZIAHL001285 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KNEPPER, MARK · 2009 to 2025
$34.9M
Computational Tools for ProteomicsZIAHL006129 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KNEPPER, MARK · 2011 to 2025
$8.1M
SOLUTE AND WATER TRANSPORT IN RENAL EPITHELIAZ01HL001285 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KNEPPER, MARK A · 1998 to 2008
$3.8M
Intramural NIH HHS Z01 HL001285
6 · The paper itself

Abstract

Aquaporin-2 (AQP2) is regulated in part via vasopressin-mediated changes in protein half-life that are in turn dependent on AQP2 ubiquitination. Here we addressed the question, "What E3 ubiquitin ligase is most likely to be responsible for AQP2 ubiquitination?" using large-scale data integration based on Bayes' rule. The first step was to bioinformatically identify all E3 ligase genes coded by the human genome. The 377 E3 ubiquitin ligases identified in the human genome, consisting predominant of HECT, RING, and U-box proteins, have been used to create a publicly accessible and downloadable online database https://esbl.nhlbi.nih.gov/Databases/KSBP2/Targets/Lists/E3-ligases/). We also curated a second database of E3 ligase accessory proteins that included BTB domain proteins, cullins, SOCS-box proteins, and F-box proteins. Using Bayes' theorem to integrate information from multiple large-scale proteomic and transcriptomic datasets, we ranked these 377 E3 ligases with respect to their probability of interaction with AQP2. Application of Bayes' rule identified the E3 ligases most likely to interact with AQP2 as (in order of probability): NEDD4 and NEDD4L (tied for first), AMFR, STUB1, ITCH, ZFPL1. Significantly, the two E3 ligases tied for top rank have also been studied extensively in the reductionist literature as regulatory proteins in renal tubule epithelia. The concordance of conclusions from reductionist and systems-level data provides strong motivation for further studies of the roles of NEDD4 and NEDD4L in the regulation of AQP2 protein turnover.

Indexed as

Aquaporin 2Bayes TheoremGenome, HumanHumansNedd4 Ubiquitin Protein LigasesProtein BindingProteomeProteomicsTranscriptomeUbiquitinationUbiquitin-Protein LigasesVasopressinsAQP2 protein, humanAquaporin 2Nedd4 Ubiquitin Protein LigasesProteomeUbiquitin-Protein LigasesVasopressinsaquaporin-2collecting ductE3 ubiquitin ligaseskidney

Identifiers

PMID27199454
PMCPMC4967219
OpenAlexW2392974489

What OpenQuestion holds

Textmetadata
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.