ArticleMolecular cell2016
Identification of PGAM5 as a Mammalian Protein Histidine Phosphatase that Plays a Central Role to Negatively Regulate CD4(+) T Cells.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 96 citations in OpenAlex.
- A phosphohistidine phosphatase promotes starvation survival by dephosphorylating nucleoside diphosphate kinase.Cell reports · 2026Article
- The function of phosphoglycerate mutase 1 (PGAM1) and its role in diseases.Frontiers in molecular biosciences · 2026Review
- Using phage display for rational engineering of a higher-affinity humanized 3' phosphohistidine-specific antibody.Communications chemistry · 2025Article
- Decoding protein N-phosphorylation functionality and sequence patterns.Briefings in bioinformatics · 2025Article
- Nucleoside diphosphate kinase A (NME1) catalyses its own oligophosphorylation.Nature chemistry · 2025Article
- Are you having a LaPh? Diverse roles of Labile Phosphorylation in mammalian cells.Biochemical Society transactions · 2025Review
- A multi-omics and mediation-based genetic screening approach identifies STX4 as a key link between epigenetic regulation, immune cells, and childhood asthma.Clinical epigenetics · 2025Article
- Review
- Cryo-EM Detection of AMPylated Histidine Implies Covalent Catalysis in AMPylation Mediated by a Bacterial Effector.Journal of molecular biology · 2025Article
- The dual role of PGAM5 in inflammation.Experimental & molecular medicine · 2025Review
- LHPP Attenuates Lipid Dysfunction of Uveal Melanoma by Relieving the Histidine Phosphorylation of ACO2.Research (Washington, D.C.) · 2025Article
- Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024Review
- [Progress in enrichment methods for proteinSe pu = Chinese journal of chromatography · 2024Review
- A salt bridge of the C-terminal carboxyl group regulates PHPT1 substrate affinity and catalytic activity.Protein science : a publication of the Protein Society · 2024Article
- Mitochondrial phosphoproteomes are functionally specialized across tissues.Life science alliance · 2024Article
- PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation.Acta biochimica et biophysica Sinica · 2023Article
- Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells.Biomedicines · 2023Article
- Mitochondrial PGAM5-Drp1 signaling regulates the metabolic reprogramming of macrophages and regulates the induction of inflammatory responses.Frontiers in immunology · 2023Article
- Histidine dephosphorylation of the Gβ protein GPB-1 promotes axon regeneration in C. elegans.EMBO reports · 2022Article
- E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.Hepatology (Baltimore, Md.) · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Whereas phosphorylation of serine, threonine, and tyrosine is exceedingly well characterized, the role of histidine phosphorylation in mammalian signaling is largely unexplored. Here we show that phosphoglycerate mutase family 5 (PGAM5) functions as a phosphohistidine phosphatase that specifically associates with and dephosphorylates the catalytic histidine on nucleoside diphosphate kinase B (NDPK-B). By dephosphorylating NDPK-B, PGAM5 negatively regulates CD4(+) T cells by inhibiting NDPK-B-mediated histidine phosphorylation and activation of the K(+) channel KCa3.1, which is required for TCR-stimulated Ca(2+) influx and cytokine production. Using recently developed monoclonal antibodies that specifically recognize phosphorylation of nitrogens at the N1 (1-pHis) or N3 (3-pHis) positions of the imidazole ring, we detect for the first time phosphoisoform-specific regulation of histidine-phosphorylated proteins in vivo, and we link these modifications to TCR signaling. These results represent an important step forward in studying the role of histidine phosphorylation in mammalian biology and disease.
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