ArticleThe Journal of biological chemistry2012
Membrane topology and intracellular processing of cyclin M2 (CNNM2).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 102 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Article
- Distinct Mg²⁺ responses and species-specific transcriptional regulation of the magnesium transporter MGR2 in Saccharum officinarum and Saccharum spontaneum.BMC plant biology · 2026Article
- Magnesium Supplementation Improves Cortical Stratification and Neuronal Differentiation in Blood-Brain Barrier-Integrated Human Brain Organoids.Biomedicines · 2026Article
- Molecular Basis of Rare Inherited Tubulopathies of the Kidney: A Primer for Clinicians.International journal of molecular sciences · 2026Review
- Genome-Wide Identification, Phylogeny and Expression Analysis of the Magnesium Release Gene Family in Wheat (Current issues in molecular biology · 2025Article
- microRNAs Regulate Cellular Magnesium by Tuning Expression of the Plasma Membrane Protein CNNM4.ACS chemical biology · 2025Article
- Multiple independent MGR5 alleles contribute to a clinal pattern in leaf magnesium across the distribution of Arabidopsis thaliana.The New phytologist · 2025Article
- A distal convoluted tubule-specific isoform of murine SLC41A3 extrudes magnesium.Acta physiologica (Oxford, England) · 2025Article
- The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease.International journal of molecular sciences · 2025Review
- Two novel variants inFrontiers in genetics · 2025Article
- Unlocking TRPM7 interactions: A database-driven quest.Computational and structural biotechnology journal · 2025Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Conserved Genes in Highly Regenerative Metazoans Are Associated with Planarian Regeneration.Genome biology and evolution · 2024Article
- Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants.Scientific reports · 2024Article
- Dimerization of the CNNM extracellular domain.Protein science : a publication of the Protein Society · 2024Article
- Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.eLife · 2023Article
- PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural insights into regulation of TRPM7 divalent cation uptake by the small GTPase ARL15.bioRxiv : the preprint server for biology · 2023Article
- Structural and functional comparison of magnesium transporters throughout evolution.Cellular and molecular life sciences : CMLS · 2022Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, mutations in the cyclin M2 (CNNM2) gene were identified to be causative for severe hypomagnesemia. In kidney, CNNM2 is a basolaterally expressed protein with predominant expression in the distal convoluted tubule. Transcellular magnesium (Mg(2+)) reabsorption in the distal convoluted tubule represents the final step before Mg(2+) is excreted into the urine, thus fine-tuning its final excretion via a tightly regulated mechanism. The present study aims to get insight in the structure of CNNM2 and to characterize its post-translational modifications. Here, membrane topology studies using intramolecular epitopes and immunocytochemistry showed that CNNM2 has an extracellular N terminus and an intracellular C terminus. This suggests that one of the predicted transmembrane regions might be re-entrant. By homology modeling, we demonstrated that the loss-of-function mutation as found in patients disturbs the potential ATP binding by the intracellular cystathionine β-synthase domains. In addition, the cellular processing pathway of CNNM2 was exposed in detail. In the endoplasmic reticulum, the signal peptidase complex cleaves off a large N-terminal signal peptide of about 64 amino acids. Mutagenesis screening showed that CNNM2 is glycosylated at residue Asn-112, stabilizing CNNM2 on the plasma membrane. Interestingly, co-immunoprecipitation studies evidenced that CNNM2a forms heterodimers with the smaller isoform CNNM2b. These new findings on CNNM2 structure and processing may aid to elucidate the physiological role of CNNM2 in Mg(2+) reabsorption in the kidney.
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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.