ArticleJournal of cell science2012
ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+/K+ATPase.
Article in Journal of cell science, 2012. 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 17 papers.
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.
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.
Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.Cell communication and signaling : CCS · 2026Review
- Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications.Frontiers in cell and developmental biology · 2026Review
- ZNRF2 is essential for gliomagenesis through orchestrating glycolysis and acts as a promising therapeutic target in glioma.Journal of translational medicine · 2025Article
- Copper chelation redirects neutrophil function to enhance anti-GD2 antibody therapy in neuroblastoma.Nature communications · 2024Article
- The Drosophila ZNRF1/2 homologue, detour, interacts with HOPS complex and regulates autophagy.Communications biology · 2024Article
- A pancancer analysis of the oncogenic role of ZNRF2 in human tumours.Journal of cellular and molecular medicine · 2023Review
- ZNRF2 as an oncogene is transcriptionally regulated by CREB1 in breast cancer models.Human cell · 2023Article
- The phenotypic spectrum of pathogenic ATP1A1 variants expands: the novel p.P600R substitution causes demyelinating Charcot-Marie-Tooth disease.Journal of neurology · 2023Article
- Regulatory effect of insulin on the structure, function and metabolism of NaExperimental and therapeutic medicine · 2021Review
- Zika Infection Disrupts Proteins Involved in the Neurosensory System.Frontiers in cell and developmental biology · 2020Article
- Structural basis of generic versus specific E2-RING E3 interactions in protein ubiquitination.Protein science : a publication of the Protein Society · 2019Review
- Structural insights into the nanomolar affinity of RING E3 ligase ZNRF1 for Ube2N and its functional implications.The Biochemical journal · 2018Article
- Ubc13: the Lys63 ubiquitin chain building machine.Oncotarget · 2016Review
- The E3 ubiquitin ligase ZNRF2 is a substrate of mTORC1 and regulates its activation by amino acids.eLife · 2016Article
- Oxidative stress-dependent phosphorylation activates ZNRF1 to induce neuronal/axonal degeneration.The Journal of cell biology · 2015Article
- Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes.Diabetologia · 2015Article
- Identification of 2R-ohnologue gene families displaying the same mutation-load skew in multiple cancers.Open biology · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Here, we describe a phosphorylation-based reverse myristoyl switch for mammalian ZNRF2, and show that this E3 ubiquitin ligase and its sister protein ZNRF1 regulate the Na(+)/K(+) pump (Na(+)/K(+)ATPase). N-myristoylation localizes ZNRF1 and ZNRF2 to intracellular membranes and enhances their activity. However, when ZNRF2 is phosphorylated in response to agonists including insulin and growth factors, it binds to 14-3-3 and is released into the cytosol. On membranes, ZNRF1 and ZNRF2 interact with the Na(+)/K(+)ATPase α1 subunit via their UBZ domains, while their RING domains interact with E2 proteins, predominantly Ubc13 that, together with Uev1a, mediates formation of Lys63-ubiquitin linkages. ZNRF1 and ZNRF2 can ubiquitylate the cytoplasmic loop encompassing the nucleotide-binding and phosphorylation regions of the Na(+)/K(+)ATPase α1 subunit. Ouabain, a Na(+)/K(+)ATPase inhibitor and therapeutic cardiac glycoside, decreases ZNRF1 protein levels, whereas knockdown of ZNRF2 inhibits the ouabain-induced decrease of cell surface and total Na(+)/K(+)ATPase α1 levels. Thus, ZNRF1 and ZNRF2 are new players in regulation of the ubiquitous Na(+)/K(+)ATPase that is tuned to changing demands in many physiological contexts.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.