Affinage

CMPK2

UMP-CMP kinase 2, mitochondrial · UniProt Q5EBM0

Length
449 aa
Mass
49.4 kDa
Annotated
2026-06-09
85 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CMPK2 (cytidine/uridine monophosphate kinase 2) is a mitochondrially localized nucleotide kinase that is rate-limiting for de novo synthesis of mitochondrial DNA and the generation of oxidized mtDNA, coupling mitochondrial nucleotide metabolism to innate immune signaling (PMID:34142025, PMID:38701781, PMID:36443312). Its kinase activity depends on conserved catalytic residues, including a TMK-domain aspartate and a covalently targetable lysine (Lys265), and produces newly synthesized mtDNA whose oxidized form drives NLRP3 inflammasome activation across diverse tissues and disease settings, including cerebral ischemia, hepatic injury, MASH, atherosclerosis, and allergic rhinitis (PMID:38701781, PMID:37859535, PMID:39855350, PMID:39799434, PMID:37339559). The same mtDNA output feeds the cGAS-STING axis: CMPK2 binds cGAS and amplifies STING-dependent neuroinflammation and inflammasome signaling (PMID:40189684, PMID:38481810, PMID:39799434). Beyond mtDNA, CMPK2 acts as a type I interferon-stimulated antiviral effector with both kinase-dependent and kinase-independent activities — its N-terminal cysteine-rich domain alone restricts flavivirus translation, while the catalytic domain works together with Viperin-produced ddhCTP to suppress coronavirus RNA-dependent RNA polymerase, with mitochondrial localization required for antiviral function (PMID:37075076, PMID:36930652). In mitochondria CMPK2 physically associates with TK2 to compartmentalize two-step thymidine phosphorylation through substrate channeling (PMID:40967432), and its mitochondrial retention is controlled by ZDHHC20-catalyzed palmitoylation at Cys137/153, reversed by PPT1, which also promotes ddhCTP production and MAVS stabilization for antiviral IFN-I (PMID:42011944). CMPK2 also has a kinase-independent pro-inflammatory arm: it interacts with IKKα/β through its C-terminal domain to activate NF-κB and NLRP3 (PMID:42208328). Transcription is driven by JAK/STAT2, IRF1/IRF3, GATA6, and RUNX1, and protein levels are negatively regulated by the E3 ligase TRIM7 (PMID:41351988, PMID:42174715, PMID:37339559, PMID:40252934, PMID:41723894). Biallelic loss-of-function CMPK2 variants cause a mitochondrial deficiency with reduced mtDNA copy number, impaired ATP production, and abnormal cristae leading to brain calcification (PMID:36443312).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2021 High

    Establishing that CMPK2 is mitochondrial and rate-limiting for newly synthesized and oxidized mtDNA answered how a nucleotide kinase could control inflammasome activation, placing it upstream of NLRP3 via Ox-mtDNA.

    Evidence siRNA/CRISPR knockout, subcellular fractionation, and in vivo AAV knockdown in microglia/macrophages

    PMID:34142025 PMID:38701781

    Open questions at the time
    • Did not define the enzymatic step or substrate specificity in vitro
    • Mechanism of mtDNA oxidation not resolved
  2. 2021 High

    Demonstrating that CMPK2 also resides in cytosolic fractions and that its IFN-α induction is JAK/Tyk2-dependent connected interferon signaling to CMPK2-driven mtROS, scavenger receptor expression, and foam cell formation.

    Evidence Subcellular fractionation, reciprocal KD/KO, JAK inhibitors, and foam cell assays in macrophages

    PMID:33874983

    Open questions at the time
    • Functional role of the cytosolic pool versus mitochondrial pool not separated
    • Direct STAT effector at the promoter not identified here
  3. 2022 High

    Patient genetics combined with knockout/knock-in mice established CMPK2 as a Mendelian disease gene, showing loss-of-function causes mtDNA depletion, bioenergetic failure, and brain calcification.

    Evidence Cmpk2 KO and patient-mutation knock-in mice, patient PBMC transcriptomics, EM of neuronal mitochondria

    PMID:36443312

    Open questions at the time
    • Tissue selectivity of the calcification phenotype unexplained
    • Link between elevated inorganic phosphate and calcification not mechanistically closed
  4. 2023 High

    Domain mapping revealed CMPK2's antiviral activity is partly kinase-independent — the N-terminal cysteine-rich domain alone restricts flavivirus translation — distinguishing its enzymatic from non-enzymatic functions.

    Evidence Domain deletion and cysteine mutagenesis with Zika replication assays and mitochondrial targeting deletion

    PMID:37075076

    Open questions at the time
    • Molecular target of NTD-mediated translation block unknown
    • How mitochondrial localization enables a translation-targeting effect unresolved
  5. 2023 High

    Showing CMPK2 cooperates with Viperin/ddhCTP to inhibit coronavirus RdRp clarified how its catalytic domain and a separate antiviral domain jointly enable broad antiviral restriction.

    Evidence Domain mutants, ddhCTP production and RdRp activity assays across multiple CoV genera; IFN/IRF1-dependent transcription

    PMID:36930652

    Open questions at the time
    • Exact biochemical product of CMPK2 feeding ddhCTP synthesis not fully defined
    • Stoichiometry of CMPK2-Viperin cooperation unresolved
  6. 2023 High

    Identification of a covalent inhibitor binding Lys265 with a confirmed in vitro kinase assay pinned a catalytically essential residue and validated CMPK2 as a druggable anti-inflammatory target.

    Evidence Affinity MS, lysine reactivity profiling, recombinant kinase assay, MST, myeloid-specific Cmpk2-KO mice

    PMID:37859535

    Open questions at the time
    • Full active-site architecture and substrate-binding mode not structurally resolved
  7. 2025 High

    Proximity labeling and functional channeling assays established a physical CMPK2-TK2 association that compartmentalizes thymidine phosphorylation, defining a concrete enzymatic partnership in the mitochondrial matrix.

    Evidence Proximity labeling, immunofluorescence, fractionation, and AZT-block assays in isolated mitochondria from multiple rat tissues

    PMID:40967432

    Open questions at the time
    • Whether channeling extends to cytidine/uridine substrates not addressed
    • Structural basis of the TK2-CMPK2 interface unknown
  8. 2025 Medium

    Multiple disease-specific studies converged on a CMPK2 → mtDNA → cGAS-STING/NLRP3 inflammatory axis, including a direct CMPK2-cGAS binding model and STING-dependent epistasis in allergic and neutrophil contexts.

    Evidence Genetic KO of CMPK2 and STING, mtDNA depletion, STING inhibitors, molecular docking, and phagocytosis assays across AR, neuroinflammation, and bacterial infection models

    PMID:38481810 PMID:39799434 PMID:40189684 PMID:40616692

    Open questions at the time
    • CMPK2-cGAS interaction rests on docking, not biochemical pulldown
    • Whether CMPK2 binds cGAS directly or acts solely through mtDNA not separated
  9. 2025 Medium

    A glycolysis-lactylation branch was uncovered in which CMPK2-driven lactate lactylates and deactivates STING to suppress IFN-I, revealing context-dependent dual output that can both activate and dampen innate immunity.

    Evidence Cmpk2 deficiency/overexpression, glycolysis flux, STING lactylation assays, and RUNX1 promoter analysis in microglia

    PMID:40252934

    Open questions at the time
    • How CMPK2 enhances glycolytic flux mechanistically unresolved
    • Tissue/context determinants of pro- versus anti-IFN outcome unclear
  10. 2025 Medium

    Transcription factor mapping (STAT2, IRF3, GATA6, RUNX1) defined the regulatory network that places CMPK2 downstream of interferon and stress signaling, including a feed-forward loop amplifying mtDNA synthesis.

    Evidence ChIP, SPR, knockdown/overexpression of STAT2/IRF3, GATA6 endothelial KO, and RUNX1 promoter analysis

    PMID:37339559 PMID:40252934 PMID:41351988 PMID:42174715

    Open questions at the time
    • Relative hierarchy of these transcription factors across cell types not established
    • Combinatorial promoter regulation unresolved
  11. 2026 High

    Palmitoylation control resolved how CMPK2's mitochondrial retention and antiviral output are dynamically regulated, identifying ZDHHC20 as writer, PPT1 as eraser, and MAVS stabilization plus ddhCTP as downstream effects.

    Evidence Palmitoylation assay, Cys137/153 mutagenesis, ZDHHC20/PPT1 manipulation, MAVS co-IP, ddhCTP and viral assays

    PMID:42011944

    Open questions at the time
    • How palmitoylation status couples to kinase activity not defined
    • Physiological signals driving dynamic depalmitoylation in vivo unclear
  12. 2026 High

    A C-terminal-dependent CMPK2-IKKα/β interaction and LPS-induced nuclear translocation established a kinase- and mitochondria-independent pro-inflammatory arm driving NF-κB/NLRP3.

    Evidence Co-IP, luciferase reporters, domain deletion mutants, NF-κB inhibitor rescue, confocal localization, CMPK2 KO mice

    PMID:42208328

    Open questions at the time
    • Nuclear function of CMPK2 not characterized beyond translocation
    • Direct IKK substrate/CMPK2 binding interface not mapped
  13. 2026 Medium

    Identifying TRIM7 as an E3 ligase that interacts with and negatively regulates CMPK2 added post-translational turnover as a control point limiting CMPK2-driven inflammation.

    Evidence Co-IP, TRIM7 overexpression/knockout, CMPK2 inhibition rescue in renal IRI

    PMID:41723894

    Open questions at the time
    • Direct ubiquitination of CMPK2 by TRIM7 and target residues not demonstrated
    • Single Co-IP-based interaction without reciprocal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CMPK2's distinct functional arms — mitochondrial nucleotide channeling, kinase-independent antiviral restriction, cytosolic/nuclear NF-κB activation, and glycolysis-driven STING lactylation — are coordinated within a single cell remains unresolved.
  • No structural model integrating catalytic and non-catalytic domains
  • Switch governing pro-inflammatory versus IFN-suppressive output undefined
  • Direct substrate spectrum (CMP/UMP versus thymidine pathway) not biochemically delineated in human enzyme

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140098 catalytic activity, acting on RNA 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005739 mitochondrion 4 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-1430728 Metabolism 2 R-HSA-8953854 Metabolism of RNA 2
Partners
CGASIKKΑ/ΒMAVSPPT1RSAD2TK2TRIM7ZDHHC20

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 CMPK2 is localized to mitochondria and is required for mitochondrial DNA synthesis; its knockdown reduces newly synthesized mtDNA and oxidized mtDNA (Ox-mtDNA) formation, thereby blocking NLRP3 inflammasome activation in microglia/macrophages. siRNA knockdown, CRISPR-Cas9 knockout, subcellular fractionation, AAV-mediated knockdown in CX3CR1Cre/ERT2 mice iScience High 34142025 38701781
2024 Microglial CMPK2 knockdown in ischemic mice suppresses NLRP3 inflammasome activation by limiting newly synthesized mtDNA and Ox-mtDNA formation, reducing infarct size and improving neurological outcomes. Cre recombination-dependent AAV knockdown in CX3CR1Cre/ERT2 mice, measurement of mtDNA/Ox-mtDNA, NLRP3 inflammasome activation assays Cell reports. Medicine High 38701781
2022 Loss-of-function biallelic variants in CMPK2 cause mitochondrial deficiency: Cmpk2-knockout mouse neurons have fewer mtDNA copies, down-regulated mitochondrial proteins, reduced ATP production, elevated intracellular inorganic phosphate, and impaired cristae architecture, leading to brain calcification. Cmpk2 knockout mice, knock-in mice bearing patient mutation, transcriptome analysis of patient PBMCs, in situ hybridization, single-cell RNA sequencing, electron microscopy of neuronal mitochondria Cell discovery High 36443312
2023 CMPK2 restricts Zika virus replication by specifically inhibiting viral translation; the N-terminal domain (NTD) lacking kinase activity is sufficient for antiviral activity, and seven conserved cysteine residues within the NTD are critical. Mitochondrial localization of CMPK2 is required for its antiviral effects. CMPK2 overexpression, domain deletion/mutagenesis (NTD constructs, cysteine mutants), viral replication assays, mitochondrial targeting sequence deletion PLoS pathogens High 37075076
2023 CMPK2 acts as a host restriction factor against multiple coronaviruses; its antiviral activity requires both the classical catalytic domain and a newly identified antiviral key domain. CMPK2, together with Viperin and ddhCTP, suppresses RNA-dependent RNA polymerase activity of CoVs. CMPK2 transcription is regulated by IFN-dependent and IRF1-dependent pathways post-infection. Transcriptomic analysis, overexpression and knockdown in multiple cell types, domain mutant analysis, ddhCTP production assay, RNA polymerase activity assay PLoS biology High 36930652
2018 CMPK2 is associated with type I IFN-induced HIV restriction in humans; RNAi knockdown of CMPK2 attenuated the antiviral effect of IFN on HIV restriction in CD4+ T cell culture. In vivo IFN-α2b injection in HIV-infected patients, RNA sequencing of activated CD4+ T cells, in vitro RNAi knockdown, HIV replication assay Science advances Medium 30083606
2021 CMPK2 is present in both mitochondrial and cytosolic fractions in macrophages; IFN-α-induced CMPK2 expression is inhibited by JAK1/2 and Tyk2 inhibitors. Both knockdown and knockout of CMPK2 attenuate IFN-α-mediated foam cell formation by reducing scavenger receptor class A (SR-A) expression and mtROS production, and blocking inflammasome activation. Subcellular fractionation, siRNA knockdown, CRISPR/Cas9 knockout, JAK inhibitor treatment, SR-A expression assay, foam cell quantification by Oil Red O/Dil-oxLDL Arthritis research & therapy High 33874983
2022 Bidirectional alteration of CMPK2 expression (both silencing and constitutive overexpression) in macrophages disrupts mitochondrial physiology, causing membrane potential depolarization, elevated ROS, disturbed architecture, and increased glycolytic flux, resulting in pro-inflammatory gene expression (IL-1β, TNF-α, IL-8). siRNA knockdown, stable overexpression, mitochondrial membrane potential assay, ROS measurement, metabolic flux analysis, cytokine gene expression Frontiers in immunology Medium 36451821
2021 CBD decreases CMPK2 expression, which subsequently inhibits generation of oxidized mitochondrial DNA and suppresses NLRP3 inflammasome activation and pyroptosis; these effects are mediated mostly by PPARγ and partially by CB1 receptor. In vivo oral ulcer mouse model, gene expression analysis, CBD treatment, GSDMD and pyroptosis quantification, PPARγ and CB1 antagonist treatment Journal of dental research Medium 34269108
2021 CMPK2 knockdown reduces NLRP3 inflammasome activation and related cytokines (IL-18, IL-1β, cleaved-caspase-1) in hepatic I/R injury; functional analysis shows CMPK2 is dispensable for AIM2 inflammasome but is required specifically for NLRP3 inflammasome activation in this context. CMPK2 knockdown in RAW264.7 cells, H/R model, AIM2 and NLRP3 inhibition, in vivo mouse hepatic I/R model, serum cytokine assay, ALT/AST measurement Experimental and therapeutic medicine Medium 34659504
2023 GATA6 directly targets CMPK2 as a transcriptional target gene; endothelial CMPK2 mediates monocyte adherence and migration, and pro-inflammatory macrophage foam cell formation through regulation of the CMPK2-NLRP3 pathway in atherosclerosis. Endothelial cell-specific Gata6 knockout mouse model, ChIP/target gene identification, AAV9-Icam2-driven Cmpk2-shRNA endothelial delivery, in vivo atherosclerosis lesion quantification Redox biology High 37339559
2024 FTO regulates CMPK2 expression in fibroblast-like synoviocytes; the FTO-CMPK2 pathway controls synovial inflammation through the mtDNA-mediated cGAS/STING pathway, affecting chondrocyte homeostasis in rheumatoid arthritis. FTO inhibition, gene knockdown, in vitro and in vivo RA models, cGAS/STING pathway analysis International journal of biological sciences Medium 38481810
2025 CMPK2 promotes microglial activation and neuroinflammation through the cGAS-STING signaling pathway; molecular docking experiments show CMPK2 stably binds to cGAS at the protein level, and cGAS knockdown mitigated CMPK2 overexpression-induced neuroinflammatory responses. LPS-treated BV2 and primary microglial cells, CMPK2 overexpression, cGAS knockdown, cytokine measurement, molecular docking Scientific reports Medium 40189684
2025 CMPK2 facilitates neuropathic pain by enhancing glycolysis in microglia, leading to increased lactate production that induces lactylation and deactivation of STING, thereby suppressing IFN-I production. RUNX1 was identified as a transcription factor that promotes CMPK2 upregulation in microglia. Cmpk2 deficiency (in vivo/in vitro), microglial overexpression, glycolysis flux assay, lactate measurement, STING lactylation assay, RUNX1 ChIP/promoter analysis Brain, behavior, and immunity Medium 40252934
2025 CMPK2 interacts with TK2 in mitochondria; proximity labeling and immunofluorescence microscopy show TK2-CMPK2 co-localization, and their association prevents TMP from diffusing away, enabling compartmentalized two-step phosphorylation of thymidine to TDP within the mitochondrial matrix. Proximity labeling (BioID/equivalent), immunofluorescence microscopy, differential centrifugation fractionation, AZT-block assays in isolated mitochondria from rat heart, liver, kidney, brain The Journal of biological chemistry High 40967432
2026 TRIM7, an E3 ubiquitin ligase, interacts with CMPK2 and negatively regulates its expression; TRIM7 overexpression mitigates inflammation and apoptosis in renal ischemia-reperfusion injury, and CMPK2 inhibition reverses the enhanced inflammation seen upon TRIM7 knockout. Co-immunoprecipitation, TRIM7 overexpression and knockout (in vivo and in vitro), CMPK2 inhibition rescue experiment, renal IRI model International immunopharmacology Medium 41723894
2026 Palmitic acid (PA) induces CMPK2 palmitoylation, which maintains its mitochondrial localization. ZDHHC20 catalyzes CMPK2 palmitoylation at cysteines 137 and 153; the thioesterase PPT1 removes this modification. Palmitoylated CMPK2 promotes production of ddhCTP and stabilizes MAVS, enhancing IFN-I production against RNA viruses. PPT1 deficiency restores CMPK2 palmitoylation and antiviral immunity. Palmitoylation assay, site-directed mutagenesis (Cys137/Cys153), ZDHHC20 and PPT1 knockdown/overexpression, mitochondrial localization imaging, MAVS co-IP, ddhCTP production assay, viral replication assay Advanced science High 42011944
2026 CMPK2 interacts with IKKα/β via its C-terminal domain, enhancing NF-κB phosphorylation and NLRP3 inflammasome activation. LPS induces CMPK2 translocation from cytoplasm to nucleus. The C-terminal domain is essential for pro-inflammatory NF-κB activity, whereas deletion of the N-terminal mitochondrial targeting sequence does not abolish this activity. Co-immunoprecipitation, dual-luciferase reporter assay, confocal microscopy (localization), domain deletion mutants, NF-κB pathway inhibitor (BAY11-7082) rescue, CMPK2 KO mice International immunopharmacology High 42208328
2025 STAT2 directly binds to the CMPK2 promoter and regulates its transcription; DSG interacts with STAT2 at Pro630 and Lys689 residues, inhibiting STAT2 phosphorylation and downstream CMPK2 expression, thereby suppressing mtDNA synthesis in macrophages. Chromatin immunoprecipitation (ChIP), Stat2 knockdown/overexpression, surface plasmon resonance, Western blotting, mtDNA synthesis assay Phytomedicine Medium 41351988
2025 IRF3 associates with the CMPK2 promoter and regulates CMPK2 transcription following mitochondrial DNA release and cGAS-STING pathway activation in the context of neuropathic pain, suggesting a feedback loop where CMPK2 upregulation further enhances mtDNA synthesis and innate immune activation. ChIP-seq/promoter analysis, single-cell RNA sequencing, AAV-mediated CMPK2 silencing, pharmacological inhibition with NDGA, in vivo nerve injury model, BV2 and primary microglia experiments Journal of translational medicine Medium 42174715
2023 Dracorhodin (DP) covalently targets CMPK2 at lysine 265, inhibiting its kinase activity; this inhibition suppresses NLRP3 inflammasome activation via the LPS-induced CMPK2 pathway, and the anti-sepsis effect of DP is weakened in myeloid-specific Cmpk2-ablated mice. Affinity MS, quantitative lysine reactivity profiling, mutant binding tests, recombinant CMPK2 kinase assay (ADP-GLO), microscale thermophoresis (Kd measurement), myeloid-specific Cmpk2-KO mouse model Clinical and translational medicine High 37859535
2025 Cmpk2 deficiency in neutrophils impairs bacterial phagocytosis and reduces host survival during bacterial infection; the phagocytosis deficit is STING-dependent, as differences between WT and Cmpk2 KO neutrophils are eliminated by a STING inhibitor. Cmpk2 global KO mice, flow cytometry phagocytosis assay, STING inhibitor (C176) rescue, zebrafish embryo infection model, scRNA-seq analysis Lung Medium 40616692
2022 In chicken cells, Asp135 in the TMK (thymidylate kinase) catalytic domain of CMPK2 is critical for antiviral activity against AIV and NDV; CMPK2 expression is regulated by the MDA5/IFN-β pathway. Site-directed mutagenesis (Asp135), overexpression, MDA5 and IFN-β knockdown, viral replication assay in DF-1 cells Frontiers in microbiology Medium 35633731
2023 miR-202-5p (from BMSC-derived exosomes) directly targets CMPK2 mRNA; validated by dual-luciferase reporter assay and RNA immunoprecipitation. CMPK2 knockdown reverses the pro-pyroptosis effect of exosomal miR-202-5p inhibition in lung ischemia-reperfusion injury. Dual-luciferase reporter assay, RNA immunoprecipitation, CMPK2 knockdown, H/R cell model, pyroptosis marker quantification The Kaohsiung journal of medical sciences Medium 37092308
2025 CMPK2 promotes NLRP3 inflammasome activation via the mtDNA-cGAS-STING pathway in allergic rhinitis; depletion of mtDNA or inhibition of STING signaling reduces HDM-induced NLRP3 activation, and genetic knockout of CMPK2 or STING alleviates AR symptoms in mice. CMPK2 overexpression in HNEPCs, CMPK2 and STING genetic knockout mice, mtDNA depletion, STING inhibition, NLRP3/ASC/CASP1/IL-1β measurement Clinical and translational medicine Medium 39799434
2025 Hepatocyte-specific Cmpk2 deletion mitigates liver injury, inflammation, and fibrosis in MASH mice by suppressing NLRP3 inflammasome activation and hepatic pyroptosis; nordihydroguaiaretic acid (NDGA) was identified as a pharmacological CMPK2 inhibitor via surface plasmon resonance imaging coupled with enzyme activity detection. Hepatocyte-specific conditional Cmpk2 knockout mice, multiple murine MASH models, surface plasmon resonance imaging, NLRP3 inflammasome assays, pyroptosis quantification Journal of hepatology High 39855350
2026 RSAD2 (Viperin) and CMPK2 coordinately regulate EBV reactivation; depletion of CMPK2 led to reactivation of EBV lytic gene expression during latency. RSAD2 and CMPK2 have overlapping functions in regulating IFN-signaling pathways, oxidative phosphorylation, protein translation, and unfolded protein response. Both converge on control of GSDMD-associated pyroptosis and ATF-4-associated UPR despite distinct subcellular localizations (ER vs. mitochondria). RSAD2 and CMPK2 depletion in B-lymphocytes, transcriptomic analysis, ddhCTP production assay (RSAD2-dependent), metabolomics bioRxivpreprint Medium 41676616

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Spontaneous mutations in the env gene of the human immunodeficiency virus type 1 NDK isolate are associated with a CD4-independent entry phenotype. Journal of virology 147 9420253
2024 Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke. Cell reports. Medicine 108 38701781
2002 Escherichia coli strains (ndk) lacking nucleoside diphosphate kinase are powerful mutators for base substitutions and frameshifts in mismatch-repair-deficient strains. Genetics 65 12242219
2021 CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome. Journal of dental research 57 34269108
2018 CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans. Science advances 57 30083606
2021 Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways. iScience 56 34142025
2017 Nucleoside diphosphate kinase (Ndk): A pleiotropic effector manipulating bacterial virulence and adaptive responses. Microbiological research 55 28942838
2022 Loss of function of CMPK2 causes mitochondria deficiency and brain calcification. Cell discovery 51 36443312
2020 Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3-c-Myc axis. Oncogene 47 32203166
1991 Production of scatter factor by ndk, a strain of epithelial cells, and inhibition of scatter factor activity by suramin. Journal of cell science 44 1829089
2022 Electroacupuncture Inhibits NLRP3 Activation by Regulating CMPK2 After Spinal Cord Injury. Frontiers in immunology 34 35401582
2014 Pseudomonas aeruginosa injects NDK into host cells through a type III secretion system. Microbiology (Reading, England) 33 24699069
2013 The NM23-H1/H2 homolog NDK-1 is required for full activation of Ras signaling in C. elegans. Development (Cambridge, England) 31 23900546
2021 Mitochondrial protein CMPK2 regulates IFN alpha-enhanced foam cell formation, potentially contributing to premature atherosclerosis in SLE. Arthritis research & therapy 30 33874983
2023 Endothelial Gata6 deletion reduces monocyte recruitment and proinflammatory macrophage formation and attenuates atherosclerosis through Cmpk2-Nlrp3 pathways. Redox biology 29 37339559
2024 The FTO-CMPK2 Pathway in Fibroblast-like Synoviocytes Modulates Rheumatoid Arthritis Synovial Inflammation and Cartilage Homeostasis via mtDNA Regulation. International journal of biological sciences 28 38481810
2023 CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. PLoS biology 26 36930652
2019 Identification of fish CMPK2 as an interferon stimulated gene against SVCV infection. Fish & shellfish immunology 25 31125665
2016 Ndk, a novel host-responsive regulator, negatively regulates bacterial virulence through quorum sensing in Pseudomonas aeruginosa. Scientific reports 25 27345215
2014 NDK-1, the homolog of NM23-H1/H2 regulates cell migration and apoptotic engulfment in C. elegans. PloS one 23 24658123
2023 Bone marrow mesenchymal stem cell-derived exosomes miR-202-5p inhibited pyroptosis to alleviate lung ischemic-reperfusion injury by targeting CMPK2. The Kaohsiung journal of medical sciences 22 37092308
2021 CMPK2 accelerates liver ischemia/reperfusion injury via the NLRP3 signaling pathway. Experimental and therapeutic medicine 21 34659504
2017 Discovery of novel inhibitors for Leishmania nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization. Journal of computer-aided molecular design 21 28551817
2023 CMPK2 restricts Zika virus replication by inhibiting viral translation. PLoS pathogens 20 37075076
2023 Dracorhodin targeting CMPK2 attenuates inflammation: A novel approach to sepsis therapy. Clinical and translational medicine 20 37859535
2022 The mitochondrial gene-CMPK2 functions as a rheostat for macrophage homeostasis. Frontiers in immunology 20 36451821
2020 CMPK2 of triploid crucian carp is involved in immune defense against bacterial infection. Developmental and comparative immunology 20 33186560
2025 CMPK2 promotes NLRP3 inflammasome activation via mtDNA-STING pathway in house dust mite-induced allergic rhinitis. Clinical and translational medicine 18 39799434
2025 Hepatocellular CMPK2 promotes the development of metabolic dysfunction-associated steatohepatitis. Journal of hepatology 18 39855350
2023 ASIC1a-CMPK2-mediated M1 macrophage polarization exacerbates chondrocyte senescence in osteoarthritis through IL-18. International immunopharmacology 18 37660594
1999 Isolation and characterization of Neurospora crassa nucleoside diphosphate kinase NDK-1. European journal of biochemistry 18 10583364
2018 Immunization of BALB/c mice with a combination of four recombinant Brucella abortus proteins, AspC, Dps, InpB and Ndk, confers a marked protection against a virulent strain of Brucella abortus. Vaccine 17 29678458
2024 Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses. Journal of medical virology 16 38695269
2015 Immunogenicity and protective effect of recombinant Brucella abortus Ndk (rNdk) against a virulent strain B. abortus 544 infection in BALB/c mice. FEMS microbiology letters 16 25724777
2012 T cells induced by recombinant chimpanzee adenovirus alone and in prime-boost regimens decrease chimeric EcoHIV/NDK challenge virus load. European journal of immunology 16 22930183
2007 Catalase-1 (CAT-1) and nucleoside diphosphate kinase-1 (NDK-1) play an important role in protecting conidial viability under light stress in Neurospora crassa. Molecular genetics and genomics : MGG 16 17636331
2005 Photomorphogenetic characteristics are severely affected in nucleoside diphosphate kinase-1 (ndk-1)-disrupted mutants in Neurospora crassa. Molecular genetics and genomics : MGG 16 16307287
2021 MiR-494-3p alleviates acute lung injury through regulating NLRP3 activation by targeting CMPK2. Biochemistry and cell biology = Biochimie et biologie cellulaire 15 34037470
1992 The human immunodeficiency virus (HIV) gag gene product p18 is responsible for enhanced fusogenicity and host range tropism of the highly cytopathic HIV-1-NDK strain. Journal of virology 15 1357191
2018 An insect nucleoside diphosphate kinase (NDK) functions as an effector protein in wheat - Hessian fly interactions. Insect biochemistry and molecular biology 13 29913225
2023 Cmpk2 regulates mitochondrial function in glucocorticoid-induced osteoblast senescence and affects glucocorticoid-inhibited osteoblast differentiation. Archives of gerontology and geriatrics 11 37269696
2015 Extreme dNTP pool changes and hypermutability in dcd ndk strains. Mutation research 11 26789486
2011 Selection of putative colorectal cancer markers by applying PCA on the soluble proteome of tumors: NDK A as a promising candidate. Journal of proteomics 11 21385632
1998 Primary intestinal epithelial cells can be infected with laboratory-adapted strain HIV type 1 NDK but not with clinical primary isolates. AIDS research and human retroviruses 11 9764906
2025 CMPK2 promotes microglial activation through the cGAS-STING pathway in the neuroinflammatory mechanism. Scientific reports 10 40189684
2022 A Role for the Chicken Interferon-Stimulated Gene CMPK2 in the Host Response Against Virus Infection. Frontiers in microbiology 10 35633731
2025 CMPK2 facilitates pain sensitization by promoting the lactylation and deactivation of cGAS-STING pathway in neuropathic pain. Brain, behavior, and immunity 9 40252934
2020 Nucleoside Diphosphate Kinases (ndk) reveals a key role in adhesion and virulence of Aeromonas veronii. Microbial pathogenesis 9 33122048
1995 Fusogenic determinants of highly cytopathic subtype D Zairian isolate HIV-1 NDK. Virology 9 7778297
1983 Location on the Salmonella typhimurium chromosome of the gene encoding nucleoside diphosphokinase (ndk). Journal of bacteriology 9 6296042
2023 Naringin from Coffee Inhibits Foodborne Aspergillus fumigatus via the NDK Pathway: Evidence from an In Silico Study. Molecules (Basel, Switzerland) 8 37446851
2024 CMPK2 Promotes CD4+ T Cell Activation and Apoptosis through Modulation of Mitochondrial Dysfunction in Systemic Lupus Erythematosus. Cell biochemistry and biophysics 7 39078538
2021 NDK/NME proteins: a host-pathogen interface perspective towards therapeutics. Current genetics 7 34480234
2019 The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/Dynamin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 7 31242766
2015 NDK Interacts with FtsZ and Converts GDP to GTP to Trigger FtsZ Polymerisation--A Novel Role for NDK. PloS one 7 26630542
2005 Acanthamoeba polyphaga mimivirus NDK: preliminary crystallographic analysis of the first viral nucleoside diphosphate kinase. Acta crystallographica. Section F, Structural biology and crystallization communications 7 16511098
2002 Adaptation of a CXCR4-using human immunodeficiency type 1 NDK virus in intestinal cells is associated with CD4-independent replication. Virology 7 12504579
1999 Mutations in the env gene of human immunodeficiency virus type 1 NDK isolates and the use of African green monkey CXCR4 as a co-receptor in COS-7 cells. The Journal of general virology 6 10466793
2017 The dosage-dependent effect exerted by the NM23-H1/H2 homolog NDK-1 on distal tip cell migration in C. elegans. Laboratory investigation; a journal of technical methods and pathology 5 28920944
1998 Analysis of a Streptomyces coelicolor A3(2) locus containing the nucleoside diphosphate kinase (ndk) and folylpolyglutamate synthetase (folC) genes. FEMS microbiology letters 5 9503623
2023 Molecular docking and simulation studies against nucleoside diphosphate kinase (NDK) of Pseudomonas aeruginosa with secondary metabolite identified by genome mining from paenibacillusehimensis. Journal of biomolecular structure & dynamics 4 36651083
2025 Biological functions and clinical implications of the CMPK2 across multisystemic diseases. Cell & bioscience 3 40867000
2023 The selected genes NR6A1, RSAD2-CMPK2, and COL3A1 contribute to body size variation in Meishan pigs through different patterns. Journal of animal science 3 37703114
2022 Functional Variants Associated With CMPK2 and in ASB16 Influence Bovine Digital Dermatitis. Frontiers in genetics 3 35832195
1995 Neutralizing antibodies against highly cytopathic Zairian human immunodeficiency type-1 virus (HIV-1) NDK are present in sera outside Africa. Vaccine 3 7631521
1994 Sequence and characterization of the Escherichia coli genome between the ndk and gcpE genes. FEMS microbiology letters 3 7926684
2025 Developmentally endothelial locus-1 facilitates intestinal inflammation resolution by suppressing the Cmpk2-cGAS-STING pathway and promoting reparatory macrophage transition. Journal of advanced research 2 40288675
2025 Diosgenin ameliorates colitis by inhibiting mitochondrial DNA synthesis in macrophages via STAT2-CMPK2 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 2 41351988
2024 LincRNA-p21/AIF-1/CMPK2/NLRP3 pathway promoted inflammation, autophagy and apoptosis of human tubular epithelial cell induced by urate via exosomes. Scientific reports 2 39103417
2016 Data of the interacting protein networks and nucleotide metabolism pathways related to NDK and NT5. Data in brief 2 27921077
2013 Heat and SDS insensitive NDK dimers are largely stabilised by hydrophobic interaction to form functional hexamer in Mycobacterium smegmatis. Acta biochimica Polonica 2 23789118
2025 Porphyromonas gingivalis promotes oral carcinogenesis through the NDK-ATP-P2X7 signal axis: An in vitro experimental study. Archives of oral biology 1 40513260
2026 Endothelial TET2 deficiency exacerbates diabetic coronary microvascular dysfunction via CMPK2-mediated mitochondrial impairment. Clinical science (London, England : 1979) 0 41657223
2026 RSAD2/VIPERIN and CMPK2 Coordinate an Immunometabolic Response to Epstein-Barr Virus. bioRxiv : the preprint server for biology 0 41676616
2026 TRIM7 negatively regulates CMPK2 suppressing inflammation and apoptosis in renal ischemia-reperfusion injury. International immunopharmacology 0 41723894
2026 Mechanism of Portulaca oleracea acidic polysaccharide in ameliorating renal injury in hyperuricemia mice by regulating the CMPK2/NLRP3 pathway. International journal of biological macromolecules 0 41786169
2026 MSC-derived exosomes ameliorate systemic lupus erythematosus by reprogramming macrophage mitochondrial homeostasis via the CMPK2-cGAS-STING axis. Journal of nanobiotechnology 0 41888792
2026 Mitochondrial kinase CMPK2 in immune homeostasis and disease: from metabolic regulation to inflammatory signaling. International immunopharmacology 0 41915996
2026 Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20-Mediated CMPK2 Palmitoylation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42011944
2026 Mitochondrial DNA release contributes to neuropathic pain via a cGAS-STING-IRF3-CMPK2-associated immunometabolic feedback mechanism. Journal of translational medicine 0 42174715
2026 CMPK2 promotes M1 macrophage polarization in sepsis-induced acute lung injury via NLRP3/NF-κB signalling. International immunopharmacology 0 42208328
2026 Electroacupuncture alleviates spinal cord injury by regulating M2-like polarization of myeloid cells through CMPK2/NLRP3 inflammasome inhibition. International immunopharmacology 0 42251832
2025 Cmpk2 Protects Against Acute Lung Injury in Mice. Lung 0 40616692
2025 Compartmentalized thymidine phosphorylation by mitochondrial nucleotide kinases TK2 and CMPK2. The Journal of biological chemistry 0 40967432
2001 [Fragile X mental retardation protein interacts with human NDK/Nm23-H2]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 0 12901102

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