Affinage

CMPK2

UMP-CMP kinase 2, mitochondrial · UniProt Q5EBM0

Length
449 aa
Mass
49.4 kDa
Annotated
2026-04-28
82 papers in source corpus 23 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CMPK2 is a mitochondrially localized nucleoside monophosphate kinase that couples mitochondrial DNA maintenance to innate immune signaling. Within the mitochondrial matrix, CMPK2 physically associates with TK2 in a compartmentalized two-step phosphorylation complex that channels thymidine monophosphate to the diphosphate form, sustaining mtDNA replication (PMID:40967432); its depletion reduces mtDNA copy number, impairs mitochondrial cristae architecture, and diminishes ATP production, and biallelic loss-of-function variants cause familial brain calcification (PMID:36443312). CMPK2 is an interferon-stimulated gene induced through JAK-STAT signaling and STAT2 promoter binding (PMID:33874983, PMID:41351988); by driving mtDNA synthesis it generates oxidized mtDNA that activates both the NLRP3 inflammasome and cGAS-STING pathways in macrophages and microglia (PMID:34142025, PMID:38701781, PMID:40189684). Independent of its kinase activity, the palmitoylated N-terminal domain—maintained at mitochondria by ZDHHC20-mediated palmitoylation at C137/C153—restricts flavivirus and coronavirus replication by inhibiting viral translation and cooperating with Viperin-derived ddhCTP to suppress viral RNA-dependent RNA polymerase activity (PMID:37075076, PMID:36930652, PMID:42011944).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2018 Medium

    Establishing CMPK2 as an interferon-stimulated gene with antiviral function resolved its initial biological context as a component of type I IFN-mediated host defense.

    Evidence siRNA knockdown attenuated IFN-α2b-mediated HIV restriction in human CD4+ T cells

    PMID:30083606

    Open questions at the time
    • Mechanism of antiviral action unresolved
    • Not yet linked to mtDNA or inflammasome biology
    • Single-virus/single-cell-type system
  2. 2021 High

    Demonstrating that CMPK2 localizes to mitochondria, drives mtDNA synthesis, and is required for NLRP3 inflammasome activation established the central mechanistic link between its kinase activity, mtDNA replication, and inflammatory signaling.

    Evidence siRNA knockdown and CRISPR-KO in macrophages/microglia with measurement of newly synthesized mtDNA, Ox-mtDNA, and NLRP3 activation; JAK inhibitor studies and subcellular fractionation confirmed dual localization and JAK-STAT pathway dependence

    PMID:33874983 PMID:34142025 PMID:34269108

    Open questions at the time
    • Direct enzymatic substrate specificity in mitochondria not reconstituted
    • Whether cytosolic pool has independent function unclear
    • Structural basis of CMPK2-NLRP3 axis unknown
  3. 2022 Medium

    Bidirectional perturbation of CMPK2 in macrophages—both silencing and constitutive overexpression—disrupted mitochondrial homeostasis and shifted metabolism toward glycolysis, revealing that tightly regulated CMPK2 expression is essential for macrophage immune homeostasis.

    Evidence siRNA knockdown and stable overexpression in macrophage lines with mitochondrial membrane potential, ROS, and metabolic flux readouts

    PMID:36451821

    Open questions at the time
    • Dose–response relationship for CMPK2 activity not quantified
    • Glycolytic shift mechanism not fully delineated
  4. 2022 High

    Identification of a natural CMPK2 inhibitor (Dracorhodin) that binds Lys265, combined with validation in myeloid-specific Cmpk2-KO mice, provided the first direct enzymatic activity measurement and on-target pharmacological confirmation in vivo.

    Evidence ADP-Glo kinase assay with recombinant CMPK2, MS-based lysine reactivity profiling, microscale thermophoresis Kd, myeloid-specific Cmpk2-KO mouse sepsis model

    PMID:37859535

    Open questions at the time
    • Crystal structure of CMPK2 with inhibitor not solved
    • Selectivity over CMPK1 not fully profiled
  5. 2022 High

    Human genetic evidence that biallelic CMPK2 loss-of-function variants cause familial brain calcification, with corresponding mtDNA depletion and mitochondrial structural defects in knock-in mice, demonstrated a non-redundant physiological role for CMPK2 in neuronal mitochondrial maintenance.

    Evidence Patient genetics, Cmpk2-KO and patient-mutation knock-in mice, electron microscopy, mitochondrial functional assays, single-cell RNA-seq

    PMID:36443312

    Open questions at the time
    • Mechanism linking mtDNA depletion to brain calcification not resolved
    • Cell-type specificity of vulnerability (neurons vs. glia) incompletely defined
  6. 2023 High

    Domain dissection revealed that the kinase-independent N-terminal domain is sufficient to restrict Zika virus translation, while cooperation with Viperin-derived ddhCTP through both the catalytic and a novel antiviral key domain is required for coronavirus restriction, bifurcating CMPK2's antiviral mechanisms.

    Evidence Overexpression of truncated/mutated CMPK2 constructs in flavivirus and coronavirus infection systems; viral translation and RdRp activity assays

    PMID:36930652 PMID:37075076

    Open questions at the time
    • NTD target on the ribosome/viral RNA unknown
    • ddhCTP phosphorylation by CMPK2 not directly demonstrated with purified enzyme
    • Whether NTD and catalytic antiviral arms are additive or independent in mixed infections unclear
  7. 2024 High

    Cell-type-specific CMPK2 knockdown in microglia reduced infarct volume and improved neurological outcomes after ischemic stroke, translating the CMPK2–mtDNA–NLRP3 axis into a disease-relevant in vivo therapeutic target.

    Evidence Cre-dependent AAV-mediated CMPK2 knockdown in CX3CR1Cre/ERT2 mice, ischemic stroke model with pharmacological CMPK2 inhibition replication

    PMID:38701781

    Open questions at the time
    • Long-term safety of CMPK2 inhibition in the brain not assessed
    • Whether peripheral CMPK2 inhibition contributes unclear
  8. 2025 High

    Discovery that ZDHHC20-mediated palmitoylation at C137/C153 maintains CMPK2 mitochondrial localization, and that this modification is required for ddhCTP production and MAVS stabilization, revealed a post-translational regulatory switch controlling both metabolic and antiviral outputs.

    Evidence Palmitoylation assays, ZDHHC20 overexpression/knockdown, PPT1-KO, C137A/C153A mutagenesis, mitochondrial localization imaging, ddhCTP and MAVS interaction assays

    PMID:42011944

    Open questions at the time
    • Dynamics of palmitoylation cycling during infection unknown
    • Whether other palmitoyltransferases contribute not excluded
  9. 2025 High

    Proximity labeling and reconstitution in isolated mitochondria showed TK2 and CMPK2 form a compartmentalized phosphorylation complex in the mitochondrial matrix, channeling TMP to TDP without diffusion, establishing the biochemical logic of mitochondrial nucleotide salvage.

    Evidence Proximity labeling, immunofluorescence, isolated mitochondria incubation with radiolabeled substrates, azidothymidine blockade, broken-mitochondria controls

    PMID:40967432

    Open questions at the time
    • Stoichiometry and structural basis of TK2-CMPK2 complex not determined
    • Whether CMPK2 also channels CMP/UMP phosphorylation in vivo not tested
  10. 2025 Medium

    Multiple transcription factors—STAT2, Spi1/PU.1, RUNX1, and GATA6—were shown to directly regulate CMPK2 transcription in distinct cellular contexts, revealing a multi-layered transcriptional control architecture for this gene.

    Evidence ChIP and dual-luciferase assays (STAT2 in macrophages, Spi1 in colitis model), conditional Gata6-KO endothelial mice, RUNX1 identification in microglia

    PMID:37339559 PMID:40252934 PMID:40288675 PMID:41351988

    Open questions at the time
    • Epigenetic regulation and chromatin accessibility at the CMPK2 locus not characterized
    • Relative contribution of each TF in a single cell type not compared
    • RUNX1 binding to CMPK2 promoter not confirmed by ChIP
  11. 2025 Medium

    CMPK2 activates the cGAS-STING pathway via mtDNA release and is required for neutrophil bactericidal function through a STING-dependent mechanism, extending its innate immune role beyond inflammasome activation.

    Evidence CMPK2 overexpression/cGAS knockdown epistasis in microglia; Cmpk2-KO mice with STING inhibitor C176 in bacterial infection and phagocytosis assays

    PMID:40189684 PMID:40616692

    Open questions at the time
    • Direct CMPK2-cGAS physical interaction awaits validation beyond molecular docking
    • Relative importance of NLRP3 vs. cGAS-STING downstream of CMPK2 in different infections not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of CMPK2 and its complexes, the precise mechanism by which the NTD blocks viral translation, whether cytosolic CMPK2 has functions independent of mitochondrial localization, and how palmitoylation dynamics integrate metabolic and antiviral outputs during infection.
  • No crystal or cryo-EM structure of CMPK2
  • NTD antiviral target not identified
  • Cytosolic CMPK2 function undefined
  • In vivo palmitoylation dynamics uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140657 ATP-dependent activity 3
Localization
GO:0005739 mitochondrion 6
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 5 R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 3 GO:0005829 cytosol 1
Partners
MAVSNLRP3PPT1TK2TRIM7VIPERINZDHHC20
Complex memberships
TK2-CMPK2 mitochondrial nucleotide salvage complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 CMPK2 was identified as an interferon-stimulated gene (ISG) whose knockdown via RNA interference attenuated IFN-α2b-mediated restriction of HIV in vitro, establishing a role for CMPK2 in type I IFN-mediated antiviral defense in human CD4+ T cells. RNA interference knockdown in HIV-infected cell cultures; correlation of ISG induction with plasma HIV RNA decline in vivo Science advances Medium 30083606
2021 CMPK2 (cytidine/uridine monophosphate kinase 2) localizes to mitochondria and is required for mitochondrial DNA (mtDNA) replication; its depletion reduces newly synthesized mtDNA and oxidized mtDNA (Ox-mtDNA), subsequently blocking NLRP3 inflammasome activation in macrophages/microglia. siRNA knockdown, CRISPR-Cas9 knockout, mitochondrial fractionation, measurement of mtDNA synthesis and NLRP3 inflammasome activation markers iScience High 34142025 34269108 38701781
2021 CMPK2 protein is present in both mitochondrial and cytosolic cellular fractions; IFN-α-induced CMPK2 expression is inhibited by JAK1/2 and Tyk2 inhibitors, placing CMPK2 downstream of the JAK-STAT signaling pathway. Cellular subfraction analysis, Western blotting, JAK inhibitor treatment Arthritis research & therapy Medium 33874983
2021 CMPK2 knockdown and knockout suppress DENV-induced antiviral cytokine release, mitochondrial oxidative stress, and mtDNA release to the cytosol; CMPK2 depletion inhibits TLR-9 and inflammasome pathway activation. CMPK2-mediated antiviral activity occurs in both IFN-dependent and IFN-independent manners (confirmed using IFN-α receptor-KO and STAT1-KO mouse bone marrow-derived dendritic cells). siRNA knockdown, CRISPR-Cas9 KO, IFN receptor-KO and STAT1-KO mouse cells, measurement of cytokines, mtROS, TLR-9 activation, and viral production iScience High 34142025
2022 Loss-of-function biallelic variants in CMPK2 cause familial brain calcification; CMPK2-deficient neurons have fewer mtDNA copies, reduced mitochondrial proteins, decreased ATP production, elevated intracellular inorganic phosphate, and impaired mitochondrial cristae architecture, linking CMPK2 to mitochondrial DNA maintenance and energy metabolism. Patient genetics, Cmpk2 knockout mice, knock-in mice bearing patient mutation, in situ hybridization, single-cell RNA-seq, mitochondrial function assays, electron microscopy Cell discovery High 36443312
2023 CMPK2 restricts Zika virus (ZIKV) replication by specifically inhibiting viral translation; the N-terminal domain (NTD) of CMPK2, which lacks kinase activity, is sufficient for this antiviral function. Mitochondrial localization of CMPK2 is required for its antiviral effects. Seven conserved cysteine residues within the NTD are critical for antiviral activity. Overexpression, domain deletion/mutation analysis, viral replication and translation assays, mitochondrial localization experiments PLoS pathogens High 37075076
2023 CMPK2's antiviral activity against coronaviruses (including PEDV) requires cooperation with Viperin-catalyzed ddhCTP production; both the classical catalytic domain and a newly identified antiviral key domain of CMPK2 are required for suppression of viral RNA-dependent RNA polymerase activity. CMPK2 transcription post-PEDV infection is regulated by interferon-dependent and IRF1-dependent pathways. Integrated transcriptomic analysis, overexpression, domain mutagenesis, antiviral assays, IRF1/IFN pathway analysis PLoS biology High 36930652
2022 CMPK2 is required for macrophage immune homeostasis; both silencing and constitutive overexpression of CMPK2 disrupt mitochondrial membrane potential, enhance reactive oxygen species (ROS), and cause disturbed mitochondrial architecture, culminating in upregulation of pro-inflammatory genes (IL-1β, TNFα, IL-8). Long-term CMPK2 modulation increases glycolytic flux in macrophages, resembling activated M1 macrophages. siRNA knockdown, stable overexpression cell lines, mitochondrial membrane potential assays, ROS measurement, metabolic flux analysis, gene expression profiling Frontiers in immunology Medium 36451821
2023 CMPK2 is a direct transcriptional target of GATA6 in endothelial cells; endothelial GATA6 deletion decreases CMPK2 expression, reducing monocyte adherence, migration, and pro-inflammatory macrophage foam cell formation through regulation of the CMPK2-NLRP3 pathway. EC-specific Gata6 knockout mouse model, AAV9-shRNA endothelial targeting, in vitro mechanistic experiments, ChIP (implied by direct target identification) Redox biology Medium 37339559
2024 CMPK2 promotes NLRP3 inflammasome activation in ischemic stroke microglia/macrophages; microglial/macrophage-specific CMPK2 knockdown suppresses inflammatory responses, reduces infarcts, and improves neurological outcomes in CX3CR1Cre/ERT2 mice by limiting newly synthesized mtDNA and Ox-mtDNA formation. Cre-dependent AAV-mediated CMPK2 knockdown in microglia, ischemic mouse model, measurement of mtDNA synthesis, Ox-mtDNA, NLRP3 activation, infarct volume, and neurological scores Cell reports. Medicine High 38701781
2021 CBD inhibits CMPK2 expression via PPARγ (primarily) and CB1 receptor (partially), which subsequently reduces generation of oxidized mitochondrial DNA and suppresses NLRP3 inflammasome activation and pyroptosis (measured by cleaved-GSDMD and pyroptotic cell fraction). In vivo oral ulcer model, PPARγ antagonist and CB1 antagonist blockade, CMPK2 expression measurement, Ox-mtDNA quantification, NLRP3/GSDMD Western blot Journal of dental research Medium 34269108
2023 Dracorhodin (DP), a natural CMPK2 inhibitor, binds CMPK2 at lysine 265 (identified by mass spectrometry-based quantitative lysine reactivity profiling and mutant tests), inhibiting CMPK2 kinase activity and suppressing LPS-induced NLRP3 inflammasome activation. The anti-sepsis effect of DP was abrogated in myeloid-specific Cmpk2 knockout mice, confirming on-target activity. Affinity MS, quantitative lysine reactivity profiling, microscale thermophoresis (Kd measurement), ADP-Glo kinase assay with recombinant CMPK2, myeloid-specific Cmpk2 KO mice, in vivo sepsis model Clinical and translational medicine High 37859535
2022 CMPK2 knockdown in spinal cord injury (SCI) rats suppresses NLRP3, ASC, caspase-1, IL-18, and IL-1β expression and improves motor function, establishing CMPK2 as an upstream regulator of NLRP3 inflammasome activation in SCI neuroinflammation. AAV-mediated CMPK2 knockdown in rat SCI model, Western blot, immunofluorescence, RT-PCR, BBB behavioral scoring Frontiers in immunology Medium 35401582
2025 TK2 and CMPK2 interact physically within the mitochondrial matrix (supported by proximity labeling and immunofluorescence microscopy), forming a compartmentalized two-step phosphorylation complex: TK2 phosphorylates thymidine to TMP, and CMPK2 then phosphorylates TMP to TDP, preventing TMP from diffusing away. This TK2-CMPK2 proximity prevents TMP from bypassing the sequential pathway. Proximity labeling, immunofluorescence microscopy, isolated mitochondria incubation with radiolabeled substrates, azidothymidine (TK2 blocker), broken mitochondria controls, differential fractionation The Journal of biological chemistry High 40967432
2025 CMPK2 undergoes palmitoylation at cysteines 137 and 153 catalyzed by the palmitoyl transferase ZDHHC20, which maintains CMPK2 mitochondrial localization. This palmitoylation is reversed by the thioesterase PPT1. CMPK2 palmitoylation is required for ddhCTP production and MAVS stabilization, supporting IFN-I production against RNA viruses. Palmitoylation assay, ZDHHC20 overexpression/knockdown, PPT1 knockout, site-directed mutagenesis of C137 and C153, mitochondrial localization imaging, ddhCTP measurement, MAVS interaction assay, antiviral assays Advanced science High 42011944
2025 CMPK2 promotes microglial activation and neuroinflammation through the cGAS-STING signaling pathway; CMPK2 overexpression elevates cGAS and STING expression, ROS, and pro-inflammatory cytokines, while cGAS knockdown reverses these effects. Molecular docking supports direct protein-level binding between CMPK2 and cGAS. LPS-treated BV2 and primary microglial cells, CMPK2 overexpression, cGAS siRNA knockdown, cytokine measurement, molecular docking Scientific reports Medium 40189684
2025 CMPK2 exacerbates neuropathic pain by promoting microglial glycolysis, increasing lactate production that induces lactylation and deactivation of STING, thereby suppressing IFN-I production. The transcription factor RUNX1 promotes CMPK2 upregulation in microglia. mRNA microarray, in vivo Cmpk2 deficiency mouse model, in vitro CMPK2 overexpression in microglia, glycolysis and lactate measurement, STING lactylation detection, pain behavioral assays Brain, behavior, and immunity Medium 40252934
2024 The FTO (m6A demethylase)-CMPK2 pathway regulates synovial inflammation in rheumatoid arthritis through mtDNA-mediated cGAS/STING pathway activation; FTO inhibition reduces CMPK2 expression in fibroblast-like synoviocytes. FTO inhibition and gene knockdown (in vitro/in vivo), CMPK2 expression analysis, cGAS/STING pathway markers, chondrocyte functional assays International journal of biological sciences Medium 38481810
2025 STAT2 directly binds the Cmpk2 promoter (ChIP assay) and drives LPS-induced CMPK2 transcription; diosgenin interacts with STAT2 at Pro630 and Lys689 (surface plasmon resonance), selectively suppressing STAT2 phosphorylation and CMPK2-mediated mtDNA synthesis and mtROS production in macrophages. ChIP assay, Stat2 knockdown/overexpression, surface plasmon resonance, CMPK2 expression and mtDNA synthesis measurement, colitis mouse model Phytomedicine Medium 41351988
2025 TRIM7, an E3 ubiquitin ligase, interacts with CMPK2 and negatively regulates its expression; inhibition of CMPK2 reverses the increased inflammation and apoptosis seen in renal epithelial cells lacking TRIM7, establishing TRIM7 as a negative regulator of CMPK2 in renal ischemia-reperfusion injury. Co-IP (TRIM7-CMPK2 interaction), TRIM7 overexpression/knockout in vivo and in vitro, CMPK2 inhibition rescue experiment, inflammation and apoptosis assays International immunopharmacology Medium 41723894
2019 Fish CMPK2 localizes to the cytoplasm of FHM cells (indirect immunofluorescence) and functions as an interferon-stimulated gene; overexpression reduces SVCV replication while RNAi knockdown increases it, demonstrating antiviral activity consistent with its mammalian ortholog. Indirect immunofluorescence (localization), overexpression and RNAi knockdown in SVCV-infected FHM cells, qRT-PCR, IFN1/IFN3 induction assays Fish & shellfish immunology Low 31125665
2022 Chicken CMPK2 (chCMPK2) is regulated by the MDA5/IFN-β pathway and exerts antiviral activity against AIV and NDV; Asp135 in the thymidylate kinase (TMK) catalytic domain is critical for antiviral activity. MDA5 and IFN-β knockdown cells, chCMPK2 overexpression, Asp135 site-directed mutagenesis, viral replication assays Frontiers in microbiology Medium 35633731
2025 DEL-1 inhibits Cmpk2-dependent mtDNA synthesis, thereby inhibiting the cGAS-STING pathway to ameliorate intestinal inflammation; the transcription factor Spi1 regulates Cmpk2 transcription, and overexpression of Spi1 or Cmpk2, or STING agonism, reverses DEL-1's protective effects. DEL-1 overexpression and AAV knockdown in colitis mice, RNA-Seq, ChIP (Spi1-Cmpk2 promoter), dual-luciferase reporter assay, STING agonist rescue Journal of advanced research Medium 40288675
2025 Cmpk2 deficiency impairs neutrophil phagocytosis of bacteria and reduces host survival during bacterial infection; the protective effect of Cmpk2 in neutrophils is STING-dependent (differences between WT and Cmpk2 KO were eliminated by a STING inhibitor C176). Cmpk2 global KO mice, flow cytometry phagocytosis assay, STING inhibitor C176, zebrafish bacterial infection model, scRNA-seq for cell-type expression Lung Medium 40616692

Source papers

Stage 0 corpus · 82 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 89 38701781
2002 Escherichia coli strains (ndk) lacking nucleoside diphosphate kinase are powerful mutators for base substitutions and frameshifts in mismatch-repair-deficient strains. Genetics 64 12242219
2018 CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans. Science advances 56 30083606
2021 CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome. Journal of dental research 55 34269108
2021 Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways. iScience 54 34142025
2017 Nucleoside diphosphate kinase (Ndk): A pleiotropic effector manipulating bacterial virulence and adaptive responses. Microbiological research 54 28942838
2022 Loss of function of CMPK2 causes mitochondria deficiency and brain calcification. Cell discovery 46 36443312
2020 Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3-c-Myc axis. Oncogene 45 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
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
2022 Electroacupuncture Inhibits NLRP3 Activation by Regulating CMPK2 After Spinal Cord Injury. Frontiers in immunology 30 35401582
1995 Expression of functional proteins of cDNA encoding rice nucleoside diphosphate kinase (NDK) in Escherichia coli and organ-related alteration of NDK activities during rice seed germination (Oryza sativa L.). Plant molecular biology 28 7766875
2021 Mitochondrial protein CMPK2 regulates IFN alpha-enhanced foam cell formation, potentially contributing to premature atherosclerosis in SLE. Arthritis research & therapy 27 33874983
2023 Endothelial Gata6 deletion reduces monocyte recruitment and proinflammatory macrophage formation and attenuates atherosclerosis through Cmpk2-Nlrp3 pathways. Redox biology 25 37339559
2016 Ndk, a novel host-responsive regulator, negatively regulates bacterial virulence through quorum sensing in Pseudomonas aeruginosa. Scientific reports 25 27345215
2019 Identification of fish CMPK2 as an interferon stimulated gene against SVCV infection. Fish & shellfish immunology 24 31125665
2014 NDK-1, the homolog of NM23-H1/H2 regulates cell migration and apoptotic engulfment in C. elegans. PloS one 23 24658123
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 22 38481810
2023 CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. PLoS biology 21 36930652
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 21 37092308
2020 CMPK2 of triploid crucian carp is involved in immune defense against bacterial infection. Developmental and comparative immunology 20 33186560
2017 Discovery of novel inhibitors for Leishmania nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization. Journal of computer-aided molecular design 20 28551817
2021 CMPK2 accelerates liver ischemia/reperfusion injury via the NLRP3 signaling pathway. Experimental and therapeutic medicine 19 34659504
2023 Dracorhodin targeting CMPK2 attenuates inflammation: A novel approach to sepsis therapy. Clinical and translational medicine 18 37859535
1999 Isolation and characterization of Neurospora crassa nucleoside diphosphate kinase NDK-1. European journal of biochemistry 18 10583364
2023 CMPK2 restricts Zika virus replication by inhibiting viral translation. PLoS pathogens 17 37075076
2023 ASIC1a-CMPK2-mediated M1 macrophage polarization exacerbates chondrocyte senescence in osteoarthritis through IL-18. International immunopharmacology 17 37660594
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
2022 The mitochondrial gene-CMPK2 functions as a rheostat for macrophage homeostasis. Frontiers in immunology 16 36451821
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
2024 Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses. Journal of medical virology 15 38695269
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
2021 MiR-494-3p alleviates acute lung injury through regulating NLRP3 activation by targeting CMPK2. Biochemistry and cell biology = Biochimie et biologie cellulaire 14 34037470
2025 CMPK2 promotes NLRP3 inflammasome activation via mtDNA-STING pathway in house dust mite-induced allergic rhinitis. Clinical and translational medicine 13 39799434
2018 An insect nucleoside diphosphate kinase (NDK) functions as an effector protein in wheat - Hessian fly interactions. Insect biochemistry and molecular biology 13 29913225
2025 Hepatocellular CMPK2 promotes the development of metabolic dysfunction-associated steatohepatitis. Journal of hepatology 12 39855350
2023 Cmpk2 regulates mitochondrial function in glucocorticoid-induced osteoblast senescence and affects glucocorticoid-inhibited osteoblast differentiation. Archives of gerontology and geriatrics 11 37269696
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
2022 A Role for the Chicken Interferon-Stimulated Gene CMPK2 in the Host Response Against Virus Infection. Frontiers in microbiology 10 35633731
2015 Extreme dNTP pool changes and hypermutability in dcd ndk strains. Mutation research 10 26789486
2025 CMPK2 promotes microglial activation through the cGAS-STING pathway in the neuroinflammatory mechanism. Scientific reports 9 40189684
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
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
2025 CMPK2 facilitates pain sensitization by promoting the lactylation and deactivation of cGAS-STING pathway in neuropathic pain. Brain, behavior, and immunity 5 40252934
2024 CMPK2 Promotes CD4+ T Cell Activation and Apoptosis through Modulation of Mitochondrial Dysfunction in Systemic Lupus Erythematosus. Cell biochemistry and biophysics 5 39078538
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
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 Biological functions and clinical implications of the CMPK2 across multisystemic diseases. Cell & bioscience 2 40867000
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 Developmentally endothelial locus-1 facilitates intestinal inflammation resolution by suppressing the Cmpk2-cGAS-STING pathway and promoting reparatory macrophage transition. Journal of advanced research 1 40288675
2025 Porphyromonas gingivalis promotes oral carcinogenesis through the NDK-ATP-P2X7 signal axis: An in vitro experimental study. Archives of oral biology 1 40513260
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 1 39103417
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 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
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
2025 Diosgenin ameliorates colitis by inhibiting mitochondrial DNA synthesis in macrophages via STAT2-CMPK2 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41351988
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