Affinage

CAMK2D

Calcium/calmodulin-dependent protein kinase type II subunit delta · UniProt Q13557

Round 2 corrected
Length
499 aa
Mass
56.4 kDa
Annotated
2026-04-28
49 papers in source corpus 16 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CAMK2D encodes the δ subunit of the dodecameric calcium/calmodulin-dependent protein kinase II (CaMKII), a multifunctional serine/threonine kinase activated by Ca²⁺/calmodulin binding and sustained by autophosphorylation at Thr287 or by oxidation of Met281/282, each generating autonomous kinase activity (PMID:12045104, PMID:24030498). In cardiomyocytes, the cytoplasmic splice variant (δC) phosphorylates ryanodine receptors and phospholamban to increase SR Ca²⁺ leak and L-type Ca²⁺ current, and its chronic overactivation causes dilated cardiomyopathy, while the nuclear variant (δB) modulates cardiomyocyte Ca²⁺ transients depending on its NLS-phosphorylation-regulated subcellular localization (PMID:12676814, PMID:12676813, PMID:41487088). CaMKIIδ selectively phosphorylates HDAC4 via a unique docking site to drive nuclear export and hypertrophic gene reprogramming, and oxidative activation of CaMKIIδ at Met281/282 is required for atrial fibrillation susceptibility (PMID:16767219, PMID:24030498). Heterozygous gain-of-function CAMK2D variants cause dilated cardiomyopathy with neurodevelopmental features in humans, while loss-of-function variants produce isolated neurological phenotypes (PMID:38272033).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1999 High

    Establishing that multiple CAMK2D splice isoforms exist in human heart and that the cardiac-enriched δ3 isoform is upregulated in failing myocardium resolved which CaMKII gene is relevant to human heart failure.

    Evidence RT-PCR isoform profiling and semi-quantitative expression analysis in failing vs. non-failing human ventricular tissue

    PMID:10189359

    Open questions at the time
    • Functional consequences of individual splice variants not tested
    • Cause versus consequence of upregulation in heart failure undetermined
  2. 2001 High

    Reconstitution of the autophosphorylation mechanism at Thr286/287 and demonstration of autonomous activity, CaM trapping, and molecular memory established the core enzymology shared by all CaMKII isoforms including δ.

    Evidence Biochemical reconstitution, in vitro kinase assays, autoregulatory domain mutagenesis, calmodulin-binding studies

    PMID:12045104

    Open questions at the time
    • Isoform-specific regulation of the δ subunit not distinguished from α/β/γ
    • Structural basis of holoenzyme assembly at atomic resolution not yet available
  3. 2003 High

    Transgenic overexpression of CaMKIIδC proved that this cytoplasmic splice variant is sufficient to cause dilated cardiomyopathy and identified its direct substrates—ryanodine receptor and phospholamban—linking CaMKIIδ to pathological SR Ca²⁺ leak, reduced SR Ca²⁺ load, and spontaneous Ca²⁺ sparks.

    Evidence Transgenic mouse overexpression of δC, co-immunoprecipitation with RyR, site-specific phosphorylation assays, confocal Ca²⁺ imaging, patch-clamp, pharmacological CaMKII inhibition

    PMID:12676813 PMID:12676814

    Open questions at the time
    • Whether endogenous CaMKIIδC activation at physiological levels drives the same phenotype was unclear
    • Relative contributions of RyR leak vs. phospholamban phosphorylation vs. NCX upregulation not fully delineated
  4. 2006 High

    Discovery that CaMKIIδ selectively docks on and phosphorylates HDAC4 (but not HDAC5/7/9) to drive nuclear export established a mechanism linking CaMKII activation to hypertrophic transcriptional reprogramming.

    Evidence In vitro kinase assays with HDAC4 docking-site mutants, co-immunoprecipitation, subcellular localization imaging, cardiomyocyte hypertrophy rescue with signal-resistant HDAC4 mutant

    PMID:16767219

    Open questions at the time
    • Full set of HDAC4 phosphorylation sites and their individual contributions not mapped
    • Whether CaMKIIδ-HDAC4 axis operates in non-cardiac tissues not addressed
  5. 2013 High

    Demonstrating that oxidation of Met281/282 on CaMKIIδ generates autonomous kinase activity and is required for atrial fibrillation established a Ca²⁺-independent, redox-dependent activation mode with direct arrhythmogenic consequences.

    Evidence Knock-in oxidation-resistant (MM-VV) mice, transgenic MsrA overexpression, angiotensin II–induced AF model, programmed electrical stimulation, oxidized CaMKII immunoblotting in human atrial tissue

    PMID:24030498

    Open questions at the time
    • Relative contribution of oxidative vs. autophosphorylation-mediated activation in vivo not quantified
    • Downstream arrhythmogenic substrates beyond RyR not fully identified
  6. 2023 Medium

    Identification of CaMKIIδ as a scaffold that concentrates the RNF8–MAD2 mitotic checkpoint complex via phospho-Thr287/RNF8-FHA interaction revealed an unexpected non-cardiac, cell-cycle-related function for CAMK2D in glioma stem cells.

    Evidence BioID proximity proteomics, co-immunoprecipitation, FHA- and RING-domain mutant analysis, mitotic progression and tumorigenicity assays in glioma stem cells

    PMID:37468549

    Open questions at the time
    • Whether this scaffolding role extends to non-glioma dividing cells is unknown
    • Stoichiometry and structural basis of the CAMK2D–RNF8–MAD2 complex not resolved
    • Independent replication needed
  7. 2023 Medium

    Identification of CAMK2D gain-of-function variants causing dilated cardiomyopathy with neurodevelopmental features and loss-of-function variants causing isolated neurological phenotypes established CAMK2D as a Mendelian disease gene affecting both heart and brain.

    Evidence Whole-exome/genome sequencing of eight patients, kinase activity assays on recombinant variants, clinical phenotyping, mouse neurodevelopment studies

    PMID:38272033

    Open questions at the time
    • Precise neuronal substrates mediating intellectual disability not identified
    • Small cohort size limits genotype–phenotype delineation
  8. 2023 Medium

    BBLN was identified as a direct activator of CAMK2D that promotes necroptosis and cardiac fibrosis; a BBLN mutant unable to bind CAMK2D was inert, positioning CAMK2D as a critical effector of hypoxia-driven cardiac injury.

    Evidence BBLN overexpression mouse model, binding-deficient BBLN mutant, CAMK2D siRNA rescue, cardiac function and necroptosis marker measurements

    PMID:38666071

    Open questions at the time
    • Binding interface and stoichiometry of BBLN–CAMK2D interaction not structurally characterized
    • Whether BBLN activates other CaMKII isoforms not tested
  9. 2024 Medium

    CAMK2D phosphorylates Tau at Ser324 within a circRNA/14-3-3/CAMK2D complex, promoting Tau aggregation and lipid-peroxide-dependent ferroptosis, revealing a kinase-substrate relationship outside the cardiac field.

    Evidence Co-immunoprecipitation of complex components, site-specific Tau phosphorylation, Tau aggregation assays, in vivo ferroptosis rescue with ferrostatin-1 and TRx0237

    PMID:38634567

    Open questions at the time
    • Whether CAMK2D-Tau interaction occurs in neurons (where both are abundant) not examined
    • Independence of the ferroptosis phenotype from GPX4 pathway requires deeper validation
  10. 2026 High

    Multi-omic analysis of human myocardium pre/post LVAD support showed that the δB nuclear splice variant's subcellular localization is regulated by NLS-proximal hyperphosphorylation, and cytoplasm-restricted δB uniquely remodels the cardiomyocyte phosphoproteome and blunts calcium transients, establishing that splice-variant-specific localization dictates functional output.

    Evidence Paired pre/post-LVAD human tissue RNA-seq and phosphoproteomics, primary rat cardiomyocyte nuclear localization assays, engineered human heart tissue calcium transient measurements

    PMID:41487088

    Open questions at the time
    • Identity of the kinase(s) phosphorylating the δB NLS region not determined
    • Whether restoring δB nuclear targeting reverses pathological remodeling in vivo not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full phosphoproteome of CaMKIIδ substrates in cardiomyocytes, the structural basis of holoenzyme isoform-specific assembly and splice-variant targeting, and the therapeutic window for CaMKIIδ inhibition given its emerging roles in brain development, mitotic checkpoint, and neuroprotection.
  • Comprehensive substrate map for CaMKIIδ in cardiac and neuronal cells lacking
  • High-resolution structure of full-length δ holoenzyme not available
  • Isoform-selective pharmacological inhibitors not yet developed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0140657 ATP-dependent activity 1
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-397014 Muscle contraction 3 R-HSA-5357801 Programmed Cell Death 2
Partners
BBLNHDAC4MAD2L1MAPTPLNRNF8RYR2YWHAZ
Complex memberships
CaMKII holoenzyme (dodecamer)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 The CaMKIIδC splice variant (cytoplasmic isoform of CAMK2D) is selectively upregulated and its phosphorylation elevated after cardiac pressure overload. Transgenic overexpression of CaMKIIδC in mice caused dilated cardiomyopathy with reduced fractional shortening and premature death. CaMKII was found associated with the ryanodine receptor (RyR) by co-immunoprecipitation, and phosphorylation of RyR at a CaMKII site and phospholamban at the CaMKII-specific site were increased, establishing that CaMKIIδC directly phosphorylates Ca2+ regulatory proteins in vivo. Transgenic mouse overexpression, immunocytochemistry for subcellular localization, co-immunoprecipitation with RyR, phosphorylation site-specific Western blotting, isolated myocyte Ca2+ measurements Circulation research High 12676814
2003 Transgenic overexpression of CaMKIIδC uniquely alters cardiomyocyte Ca2+ handling: SR Ca2+ content is reduced >50%, fractional SR Ca2+ release is increased, and spontaneous Ca2+ spark frequency is doubled. Acute CaMKII inhibition normalized Ca2+ spark frequency and ICa, confirming direct CaMKII activation of ryanodine receptors and L-type Ca2+ current. Enhanced diastolic SR Ca2+ leak, reduced SR Ca2+-ATPase expression, and increased Na+-Ca2+ exchanger function collectively explain the reduced SR Ca2+ load. Transgenic mouse model, confocal Ca2+ spark imaging, patch-clamp (ICa), caffeine-exposure [Ca2+]i decline kinetics, CaMKII inhibitor (KN-93) acute application, protein expression measurements Circulation research High 12676813
2001 CaMKII (including the δ isoform encoded by CAMK2D) is a dodecameric holoenzyme where Ca2+/calmodulin binding to the autoregulatory domain disinhibits kinase activity, enabling autophosphorylation at Thr286 (Thr287 in δ) that generates Ca2+/CaM-independent (autonomous) activity, CaM trapping, and CaM capping, conferring molecular memory to the enzyme. Biochemical reconstitution, in vitro kinase assays, autoregulatory domain mutagenesis, calmodulin-binding studies (reviewed with primary experimental data) Annual review of biochemistry High 12045104
1999 Multiple δ-isoforms of CaMKII (δ2, δ3, δ4, δ8, δ9, δ11) are differentially expressed in human cardiac and skeletal muscle; isoform δ3 is characteristically expressed in cardiac muscle and its transcript and protein levels are significantly increased in failing human myocardium with dilated cardiomyopathy, establishing CAMK2D upregulation as a feature of human heart failure. RT-PCR isoform profiling, complete cDNA sequencing of human δ2, semi-quantitative RT-PCR on left ventricular tissue from failing vs. non-failing hearts, Western blotting with subclass-specific antibody Circulation research High 10189359
2006 CaMKII (the δ isoform, CAMK2D) selectively signals to HDAC4 but not other class IIa HDACs via a unique docking site on HDAC4 absent in HDAC5/7/9. CaMKII phosphorylation of HDAC4 promotes nuclear export and prevents nuclear import, derepressing HDAC target genes. In cardiomyocytes, CaMKII phosphorylation of HDAC4 drives hypertrophic growth, which is blocked by a signal-resistant HDAC4 mutant. Co-immunoprecipitation, in vitro kinase assays with HDAC4 docking-site mutants, subcellular localization imaging (nuclear export assays), cardiomyocyte hypertrophy assays with signal-resistant mutant The Journal of clinical investigation High 16767219
2013 Oxidative modification of CaMKIIδ (CAMK2D) at methionine residues (Met281/282) activates the kinase and triggers atrial fibrillation. Knock-in mice with the critical oxidation sites mutated (MM-VV) and mice overexpressing methionine sulfoxide reductase A (which reduces oxidized CaMKII) were resistant to angiotensin II-induced AF, demonstrating that reactive oxygen species activate CaMKIIδ through oxidation to promote arrhythmia. Knock-in mouse model (MM-VV oxidation-site mutants), transgenic methionine sulfoxide reductase A overexpression, angiotensin II infusion AF model, AF susceptibility testing by programmed electrical stimulation, oxidized CaMKII immunoblotting in patient atria Circulation High 24030498
2017 miR-146a directly targets and suppresses Camk2d expression in chondrocytes, and miR-146a knockout mice show alleviated articular cartilage degeneration in OA models. Camk2d is identified as an essential target of miR-146a in regulating cartilage homeostasis, and treatment with miR-146a inhibitor alleviated OA-induced cartilage destruction via restoring Camk2d expression. miR-146a knockout mouse models (spontaneous and surgically induced OA), miR-146a inhibitor treatment, luciferase reporter assays for direct miR-146a/Camk2d targeting, cartilage matrix gene expression assays Cell death & disease Medium 28383548
2023 CAMK2D serves as a molecular scaffold that concentrates the RNF8-MAD2 mitotic checkpoint complex via transient interactions between phospho-Thr287 of CAMK2D and the FHA domain of RNF8. RNF8 competes with p31comet for binding to closed-conformation MAD2 via its RING domain. This CAMK2D-RNF8-MAD2 complex generates the mitotic checkpoint signal; RNF8 overexpression impairs glioma stem cell mitotic progression in an FHA- and RING-dependent manner. RNF8 proximity proteomics (BioID), co-immunoprecipitation, domain-specific mutant analysis (FHA-domain and RING-domain mutants), mitotic progression assays in glioma stem cells, GSC tumorigenicity assays Cell death and differentiation Medium 37468549
2023 CAMK2D gain-of-function (GoF) variants cause both dilated cardiomyopathy and neurodevelopmental symptoms (intellectual disability, delayed speech, behavioral problems), whereas loss-of-function (LoF) variants induce only neurological symptoms. Eight individuals with heterozygous CAMK2D variants were identified, and functional testing of variants confirmed GoF or LoF activity, establishing that CAMK2D plays essential roles in both human heart and brain development. Whole-exome/genome sequencing of patient cohort, functional variant classification (kinase activity assays for GoF/LoF), clinical phenotyping including cardiac evaluation, mouse neurodevelopment studies American journal of human genetics Medium 38272033
2023 BBLN (bublin coiled-coil protein) directly binds and activates CAMK2D to promote cardiac inflammation, fibrosis, and necroptosis. A BBLN mutant with impaired CAMK2D binding was inert. siRNA-mediated knockdown of CAMK2D retarded BBLN-induced heart failure symptoms. BBLN is induced by hypoxia (a major feature of tetralogy of Fallot) and its downregulation decreased CAMK2D hyperactivity and cardiovascular dysfunction. BBLN overexpression mouse model, BBLN CAMK2D-binding mutant, siRNA knockdown of CAMK2D, protein interaction assays, cardiac function measurements (mortality, fibrosis, necroptosis markers), hypoxia induction experiments Nature cardiovascular research Medium 38666071
2023 CAMK2D is highly expressed in 70% of malignant mesothelioma tissues and is upregulated in BAP1-knockout human mesothelial cells. The CaMKII inhibitor KN-93 shows selective antiproliferative activity against BAP1-deficient cells and suppresses tumor growth in BAP1-deficient xenograft models, establishing CAMK2D as a therapeutic target downstream of BAP1 loss. BAP1 knockout cell line generation, cDNA microarray and qRT-PCR, IHC of 80 MMe tissue samples, KN-93 inhibitor treatment, xenograft mouse tumor growth assays Cell death discovery Medium 37479714
2024 CAMK2D phosphorylates Tau at Ser324, and within the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex this phosphorylation changes the phosphorylation status of Tau bound to 14-3-3, promoting Tau aggregation. The resulting Tau aggregation induces accumulation of lipid peroxides (LPOs) causing LPO-dependent (GPX4-independent) ferroptosis, which inhibits epithelial ovarian cancer peritoneal metastasis. Co-immunoprecipitation to identify complex components, site-specific phosphorylation analysis (Ser324), Tau aggregation assays, ferroptosis rescue with ferrostatin-1 and TRx0237 in vivo, RNA pull-down for circRNA-protein interactions Advanced science Medium 38634567
2025 CAMK2D (and mammalian TANK binding kinase 1) phosphorylates TIR domain proteins at a conserved serine residue spatially close to the catalytic glutamate, blocking TIR NADase activity and suppressing SARM1 TIR signaling in animals. This phosphorylation mechanism maintains growth by preventing TIR-mediated cell death/axon degeneration. In vitro kinase assays with CAMK2D phosphorylating TIR domains, site-directed mutagenesis of the conserved serine, NADase activity assays, SARM1 signaling functional assays bioRxiv (preprint)preprint Medium
2025 In RBM20-deficient mouse hearts, CAMK2D is misspliced and overactivated, with increased phosphorylation of multiple CAMK2D substrates. Camk2d knockout in Rbm20-deficient mice (double KO) rescued heart failure and sudden cardiac death. AAV9-mediated re-expression of single CAMK2D splice variants in DKO hearts reintroduced cardiac dysfunction irrespective of splice variant, demonstrating that CAMK2D overactivation—not missplicing per se—underlies the pathological phenotype. Pharmacological inhibition with hesperadin rescued cardiac function in Rbm20-R636Q knock-in mice. Double knockout mouse genetics (Camk2d/Rbm20), phosphoproteomic analysis of CAMK2D targets, AAV9 splice variant re-expression, hesperadin (CAMK2 inhibitor) pharmacological treatment, cardiac function measurements (echocardiography, survival) bioRxiv (preprint)preprint Medium
2026 Alternative splicing of CAMK2D, specifically increased inclusion of exon 14 encoding the nuclear splice variant CAMK2D-B, is inversely correlated with myocardial functional recovery after LVAD support. Hyperphosphorylation near the nuclear localization signal in CAMK2D-B prevents adrenergic stress-dependent nuclear targeting of this isoform. A cytoplasm-restricted CAMK2D-B uniquely remodeled the phosphoproteome of primary rat cardiomyocytes compared with a nuclear-competent version, and blunted calcium transients in engineered heart tissues, establishing that subcellular localization of CAMK2D-B determines its functional impact on cardiomyocyte calcium handling. Bulk RNA-seq, tandem mass tag proteomics and phosphoproteomics of paired pre/post-LVAD human myocardium, subcellular fractionation, primary rat cardiomyocyte nuclear localization assays, engineered human heart tissue calcium transient measurements Circulation High 41487088
2025 CAMK2 (cardiomyocyte-specific Camk2d/Camk2g double knockout) is an upstream regulator that triggers pathological metabolic substrate switching in heart failure: pressure-overloaded cDKO hearts showed no increase in myocardial glucose uptake (by [18F]FDG-PET) and retained lipid reserves, while control hearts showed a six-fold increase in glucose uptake. Transcriptomics revealed CAMK2-dependent induction of Nr4a1 and repression of fatty acid genes preceding upregulation of glucose utilization genes. NR4A1 directly bound and repressed the FATP1 promoter, defining a CAMK2–NR4A1 axis driving lipid depletion and HFrEF. Cardiomyocyte-specific Camk2d/Camk2g double knockout mice, dynamic [18F]FDG-PET imaging, transcriptomics, cardiomyocyte-specific Nr4a1 knockout, NR4A1 overexpression in iPSC-derived cardiomyocytes, FATP1 promoter binding assays bioRxiv (preprint)preprint Medium
2025 CAMK2D overexpression in retinal pigment epithelial cells attenuates sodium iodate-induced apoptosis and retinal degeneration, and knockdown exacerbates degeneration. CAMK2D regulates complement factor I (CFI) expression, and the protective effect of CAMK2D operates through CFI: CFI knockdown increases apoptosis, but CAMK2D overexpression in CFI-knockdown cells partially restores protection. Western blot confirmed CAMK2D regulates CFI protein levels in vivo. Lentiviral and AAV-mediated CAMK2D knockdown/overexpression in ARPE-19 cells and mouse RPE, flow cytometry apoptosis assay, OCT/ERG retinal function, TUNEL staining, RNA-seq, Western blot for CFI Investigative ophthalmology & visual science Medium 39873650
2022 Silencing CAMK2D in spermatogonia from varicocele rat testes significantly promoted spermatogonial proliferation, accompanied by downregulation of CAMKII, FOXO1, and β-catenin, identifying a CAMK2D–FOXO1/β-catenin axis that restrains spermatogonial proliferation. CAMK2D siRNA knockdown in spermatogonia, CCK-8 proliferation assay, qRT-PCR and Western blotting for CAMKII, FOXO1, and β-catenin, immunofluorescence for c-kit Evidence-based complementary and alternative medicine Low 35911132
2020 CDR1as (a circular RNA) acts as a sponge for miR-7-5p, thereby de-repressing CAMK2D and CNN3 expression. This CDR1as/miR-7-5p/CAMK2D axis mediates hypoxia-induced osteoblastic differentiation and calcification of human pulmonary artery smooth muscle cells. Dual-luciferase reporter and RNA antisense purification assays validated direct miR-7-5p targeting of CAMK2D. Dual-luciferase reporter assay, RNA antisense purification, miR-7-5p mimic/inhibitor transfection, CAMK2D overexpression/knockdown, alizarin red S staining, alkaline phosphatase activity, calcium deposition quantification Molecular therapy. Nucleic acids Low 33230455

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2001 Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function. Annual review of biochemistry 549 12045104
2003 The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circulation research 477 12676814
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2006 CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. The Journal of clinical investigation 430 16767219
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2001 Ca(2+)/CaM-dependent kinases: from activation to function. Annual review of pharmacology and toxicology 411 11264466
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2003 Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release. Circulation research 391 12676813
2003 The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron 372 14622581
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2004 Phosphoproteomic analysis of the developing mouse brain. Molecular & cellular proteomics : MCP 291 15345747
2020 Phosphorylated tau interactome in the human Alzheimer's disease brain. Brain : a journal of neurology 290 32812023
1999 Identification and expression of delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium. Circulation research 276 10189359
2013 Oxidized Ca(2+)/calmodulin-dependent protein kinase II triggers atrial fibrillation. Circulation 268 24030498
2017 miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2. Cell death & disease 85 28383548
2020 circRNA CDR1as Promotes Pulmonary Artery Smooth Muscle Cell Calcification by Upregulating CAMK2D and CNN3 via Sponging miR-7-5p. Molecular therapy. Nucleic acids 49 33230455
2024 Role of CAMK2D in neurodevelopment and associated conditions. American journal of human genetics 24 38272033
2021 MicroRNA-135b/CAMK2D Axis Contribute to Malignant Progression of Gastric Cancer through EMT Process Remodeling. International journal of biological sciences 18 34131397
2018 Overexpression of SMARCA2 or CAMK2D is associated with cisplatin resistance in human epithelial ovarian cancer. Oncology letters 18 30127991
2024 Tau Aggregation-Dependent Lipid Peroxide Accumulation Driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau Complex Inhibits Epithelial Ovarian Cancer Peritoneal Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 38634567
2010 Polymorphisms in CACNA1E and Camk2d are associated with seizure susceptibility of Sprague-Dawley rats. Epilepsy research 10 20638246
2023 CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma. Cell death and differentiation 9 37468549
2025 CAMK2D and Complement Factor I-Involved Calcium/Calmodulin Signaling Modulates Sodium Iodate-Induced Mouse Retinal Degeneration. Investigative ophthalmology & visual science 8 39873650
2024 Construction of a molecular inflammatory predictive model with histone modification-related genes and identification of CAMK2D as a potential response signature to infliximab in ulcerative colitis. Frontiers in immunology 5 38274809
2023 CAMK2D: a novel molecular target for BAP1-deficient malignant mesothelioma. Cell death discovery 4 37479714
2023 BBLN triggers CAMK2D pathology in mice under cardiac pressure overload and potentially in unrepaired hearts with tetralogy of Fallot. Nature cardiovascular research 4 38666071
2023 Sequencing of the Pituitary Transcriptome after GnRH Treatment Uncovers the Involvement of lncRNA-m23b/miR-23b-3p/CAMK2D in FSH Synthesis and Secretion. Genes 3 37107604
2023 CAMK2D De Novo Missense Variant in Patient with Syndromic Neurodevelopmental Disorder: A Case Report. Genes 3 37372357
2022 Silencing CAMK2D Promotes the Proliferation of Spermatogonia in the Testis of Experimental Varicocele Rats. Evidence-based complementary and alternative medicine : eCAM 1 35911132
2026 Myocardial Recovery With Mechanical Circulatory Support Is Linked to Alternative Splicing and Subcellular Localization of CAMK2D. Circulation 0 41487088
2025 Ethyl acetate extract of Knoxia roxburghii (Rubiaceae) down-regulates ECHDC1, CAMK2D, DDB1, UBA6, BIRC6, and HK1 proteins and ameliorates the symptoms of diabetes mellitus. Frontiers in pharmacology 0 40766763
2025 Intron polymorphism in Camk2d is associated with ventricular arrhythmias in normal adult Sprague-Dawley rats. Experimental animals 0 41183881
2025 RAW 264.7-derived exosomal miR-494-3p regulates inflammation and osteogenic differentiation of human periodontal ligament stem cells through regulating CAMK2D. Archives of oral biology 0 41240683