Affinage

CSNK2A1

Casein kinase II subunit alpha · UniProt P68400

Round 2 corrected
Length
391 aa
Mass
45.1 kDa
Annotated
2026-04-28
78 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSNK2A1 encodes the catalytic α subunit of casein kinase II (CK2), a constitutively active, ubiquitous serine/threonine kinase that assembles into an α2β2 tetrameric holoenzyme and phosphorylates more than 100 substrates to regulate cell division, signal transduction, protein stability, autophagy, and DNA damage repair (PMID:7896000, PMID:22017874, PMID:34359939). CK2α is essential for viability—demonstrated by lethality of dual catalytic-subunit deletion in yeast—and functions in cell polarity and actin cytoskeleton organization; in mouse skeletal muscle, conditional loss causes neuromuscular junction fragmentation, impaired oxidative metabolism, and stimulated autophagy (PMID:2196445, PMID:9488724, PMID:36552726). Key substrates include PTEN (C-terminal phosphorylation stabilizing the protein against proteasomal degradation), α-synuclein (Ser129), p62/SQSTM1 (Ser403, enhancing autophagic clearance), SIRT6 (Ser338, activating DNA damage repair), AKT1, MAX, and IGF2R (Ser2484), with CK2α activity itself modulated by cholesterol binding and OGT-mediated O-GlcNAcylation (PMID:11035045, PMID:10617630, PMID:22017874, PMID:27746184, PMID:39547439, PMID:38289573). Germline loss-of-function mutations in CSNK2A1 cause Okur-Chung neurodevelopmental syndrome (PMID:27048600).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1988 High

    Identification of the yeast CKA1 gene as encoding the CK2 catalytic α subunit established genetic access to CK2 and revealed functional redundancy with CKA2.

    Evidence Gene isolation, sequencing, and gene disruption in S. cerevisiae

    PMID:3062376

    Open questions at the time
    • Functional specialization between α and α′ not yet resolved
    • No mammalian ortholog characterization
  2. 1990 High

    Demonstrating that simultaneous loss of both catalytic subunits is lethal—rescued by Drosophila CK2α—established CK2 as an essential, evolutionarily conserved kinase.

    Evidence Double gene disruption and cross-species complementation in yeast

    PMID:2196445

    Open questions at the time
    • Essential substrates not identified
    • Requirement for β subunit in vivo unclear
  3. 1992 High

    Purification of catalytically active free CK2α monomer from rescued yeast showed that the β subunit is dispensable for basal catalytic activity, defining CK2α as an autonomous kinase.

    Evidence Biochemical purification and in vitro kinase assays from genetically rescued strains

    PMID:1527008

    Open questions at the time
    • Substrate specificity differences between free α and holoenzyme not resolved
    • In vivo relevance of monomeric activity uncertain
  4. 1998 High

    Temperature-sensitive CKA1 alleles revealed a specific role in cell polarity maintenance, with actin delocalization and multinucleate arrest, distinguishing CKA1 from CKA2 function.

    Evidence Conditional allele with fluorescence microscopy and cell cycle analysis in yeast

    PMID:9488724

    Open questions at the time
    • Direct polarity substrates not identified
    • Mechanism linking CK2α to actin organization unknown
  5. 2000 High

    Identification of α-synuclein Ser129 as a constitutive CK2 phosphorylation site in vivo provided the first link between CK2 and neurodegeneration-associated substrates.

    Evidence Site-directed mutagenesis, in vitro kinase assay, 2D phosphopeptide mapping, and CK2 inhibitor treatment in cells

    PMID:10617630

    Open questions at the time
    • Functional consequence of Ser129 phosphorylation on α-synuclein aggregation not determined in this study
    • Whether CK2 is the sole Ser129 kinase in vivo unclear
  6. 2001 High

    Demonstrating that CK2-mediated C-terminal phosphorylation of PTEN protects it from proteasomal degradation established CK2 as a regulator of tumor suppressor stability.

    Evidence In vitro kinase assay, phosphorylation-defective PTEN mutants, proteasome inhibitor and stability assays

    PMID:11035045

    Open questions at the time
    • Identity of the E3 ligase targeting unphosphorylated PTEN not identified
    • In vivo relevance in tumor models not tested
  7. 2011 High

    CK2 phosphorylation of p62/SQSTM1 at Ser403 enhanced UBA domain affinity for polyubiquitin chains and autophagic clearance, directly linking CK2 to selective autophagy.

    Evidence In vitro kinase assay, mutagenesis, autophagy flux assays, and polyglutamine inclusion body assay

    PMID:22017874

    Open questions at the time
    • Whether CK2 regulates autophagy through additional substrates beyond p62 not addressed
    • Tissue-specific relevance not tested
  8. 2016 High

    Discovery that de novo CSNK2A1 mutations cause Okur-Chung neurodevelopmental syndrome established the first Mendelian disease link and confirmed the gene's essential role in human brain development.

    Evidence Whole exome sequencing of 4102 intellectual disability cases with identification of multiple independent de novo variants

    PMID:27048600

    Open questions at the time
    • Pathogenic mechanism (loss of kinase activity vs. dominant-negative vs. haploinsufficiency) not resolved
    • No functional assays on patient variants reported in this study
  9. 2016 High

    CK2α was shown to phosphorylate SIRT6 at Ser338, with downstream effects on β-catenin and NF-κB signaling in breast cancer, establishing SIRT6 as a functionally consequential CK2 substrate.

    Evidence Co-IP, GST pull-down, in vitro kinase assay, and site-directed mutagenesis with proliferation and invasion readouts

    PMID:27746184

    Open questions at the time
    • Whether SIRT6 phosphorylation affects its deacetylase activity directly not measured
    • Generalizability beyond breast cancer not established
  10. 2021 High

    Extending the SIRT6 axis, CK2α-mediated Ser338 phosphorylation was shown to activate DNA damage repair and confer doxorubicin resistance in osteosarcoma, broadening CK2's role to chemoresistance.

    Evidence Site-directed mutagenesis, in vivo xenograft model, pharmacological inhibition with emodin

    PMID:34359939

    Open questions at the time
    • Which specific DNA repair pathway is activated not delineated
    • Whether other CK2 substrates contribute to chemoresistance in parallel not tested
  11. 2022 High

    Muscle-specific Csnk2a1 knockout mice revealed age-dependent neuromuscular junction fragmentation, impaired oxidative metabolism, and stimulated autophagy, establishing CK2α as essential for mammalian skeletal muscle homeostasis.

    Evidence Conditional knockout (HSA-Cre), grip strength, electrophysiology, immunohistochemistry, and enzyme activity assays

    PMID:36552726

    Open questions at the time
    • Direct phosphorylation substrates mediating NMJ maintenance not identified
    • Whether neuronal CK2α contributes to the phenotype not distinguished
  12. 2023 Medium

    CK2α phosphorylation of MAX was shown to shift MAX from homodimers to C-MYC–MAX and β-catenin–MAX heterodimers, activating HMGB1/IL-6 transcription, revealing a mechanism by which CK2 modulates MYC-dependent gene expression.

    Evidence Co-IP, promoter activity assays, CX-4945 inhibition, in vivo mouse model

    PMID:37347224

    Open questions at the time
    • Specific phosphorylation site(s) on MAX not mapped in this study
    • Whether this mechanism operates in non-malignant contexts unknown
  13. 2024 High

    Cholesterol was identified as a direct CK2α-binding ligand that augments kinase activity and drives phosphorylation of IGF2R at Ser2484, creating a metabolic feedback loop coupling lipid sensing to mitochondrial oxidative phosphorylation.

    Evidence Cholesterol-binding assay, in vitro kinase assay, phosphoproteomics, patient-derived organoids and xenografts

    PMID:39547439

    Open questions at the time
    • Structural basis of cholesterol–CK2α binding not resolved
    • Whether other lipids also modulate CK2 activity not tested
  14. 2024 Medium

    OGT-mediated O-GlcNAcylation of CK2α was shown to enhance its protein stability, identifying a post-translational mechanism that tunes CK2 abundance in colorectal cancer.

    Evidence Immunoprecipitation for O-GlcNAc modification, knockdown rescue, tumor-bearing mouse model

    PMID:38289573

    Open questions at the time
    • Specific O-GlcNAcylation sites on CK2α not mapped
    • Whether O-GlcNAcylation affects kinase activity independently of stability not tested
  15. 2025 Medium

    A pathogenic frameshift variant in CSNK2A1 was shown to reduce protein abundance through elevated ubiquitination-dependent degradation rather than impairing catalytic activity, clarifying a loss-of-function mechanism in Okur-Chung syndrome.

    Evidence In vitro kinase assay, quantitative mRNA/protein analysis, ubiquitination assay

    PMID:41216289

    Open questions at the time
    • Single variant studied; generalizability to other OCNDS variants unknown
    • No neuronal or brain-relevant model used
  16. 2025 Medium

    AP-MS of fission yeast Cka1 revealed interactions with RSC chromatin remodeling, monopolin, and spliceosomal complexes, with direct phosphorylation of monopolin subunits Pcs1 and Mde4 expanding CK2's role to chromosome segregation.

    Evidence RNase-free tandem affinity purification with mass spectrometry, in vitro kinase assay

    PMID:40700808

    Open questions at the time
    • Functional consequence of monopolin phosphorylation on chromosome segregation fidelity not tested
    • Validation in mammalian systems absent

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for allosteric activation of CK2α by cholesterol and other ligands, the complete inventory of CK2α substrates that mediate neurodevelopmental pathology in Okur-Chung syndrome, and whether monomeric versus holoenzyme CK2α pools have distinct substrate selectivity in vivo.
  • No structural model of cholesterol–CK2α complex
  • Neuronal substrates relevant to OCNDS not identified
  • In vivo partitioning between monomeric and holoenzyme CK2α activity not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 12 GO:0140096 catalytic activity, acting on a protein 9
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1643685 Disease 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-1640170 Cell Cycle 3 R-HSA-9612973 Autophagy 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
AKT1CSNK2BDDX3XHMGA2MAXPTENSIRT6SQSTM1
Complex memberships
CK2 holoenzyme (α2β2 tetramer)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The CKA1 gene of S. cerevisiae encodes the 42 kDa alpha catalytic subunit of casein kinase II, which is 67% identical to the Drosophila CK2α. Null mutations in CKA1 alone are phenotypically wild type, indicating functional redundancy with the alpha' subunit encoded by CKA2. Gene isolation, sequencing, gene replacement/disruption Molecular and cellular biology High 3062376
1990 CK2 catalytic activity (encoded by CKA1 and CKA2) is essential for viability in S. cerevisiae; simultaneous disruption of both catalytic subunit genes is lethal. Cells depleted of CK2 activity arrest with increased cell size and a pseudomycelial morphology. Yeast lacking both endogenous catalytic subunits are rescued by expression of Drosophila CK2α alone (free monomeric catalytic subunit) or α+β, demonstrating evolutionary conservation of function. Double gene disruption, complementation with Drosophila subunits, genetic rescue assay Molecular and cellular biology High 2196445
1992 The free monomeric CK2α catalytic subunit is not toxic in vivo and is sufficient to rescue lethality of cka1/cka2 double disruption. CK2 purified from rescued strains shows that free alpha monomer is catalytically active; overexpression of total CK2 activity 6–18 fold has no overt phenotypic consequence. Purification and biochemical characterization of CK2 from genetically rescued yeast strains, in vitro kinase assays The Journal of biological chemistry High 1527008
1994 The human CSNK2A1 gene is located on chromosome 20p13. The gene contains tandemly arranged Alu repeats within introns and consists of at least 8 exons (bases 102–824 of coding region characterized). Exon/intron boundaries conform to the gt/ag rule. Genomic cloning, sequencing, FISH chromosomal localization Genomics Medium 8188256
1995 CK2 is a ubiquitous eukaryotic serine/threonine kinase that phosphorylates more than 100 substrates involved in cell division and signal transduction. The α subunit is the catalytic subunit and the β subunit is regulatory; they form an α2β2 tetrameric holoenzyme. CK2 activity is constitutive and is present in both nucleus and cytoplasm. Biochemical characterization, review of in vitro kinase assays across multiple studies FASEB journal High 7896000
1998 The complete human CSNK2A1 gene spans 70 kb and consists of 13 exons. The promoter lacks a TATA box, contains a CpG island and GC boxes, characteristic of a housekeeping gene. Promoter activity was confirmed by reporter gene assay within the region from position −256 to +144. Two transcription start sites were identified by primer extension. Genomic cloning, sequencing, reporter gene assay, primer extension Genomics Medium 9503018
1998 Temperature-sensitive mutations in yeast CKA1 reveal a specific role for CK2α in maintenance of cell polarity. cka1(ts) strains arrest with nonpolarized actin cytoskeleton, delocalized chitin deposition, and multinucleate cell bodies, demonstrating functional specialization of CKA1 versus CKA2 catalytic subunits. Temperature-sensitive allele generation, fluorescence microscopy, cell cycle analysis The Journal of biological chemistry High 9488724
2000 CK2 phosphorylates α-synuclein constitutively at serine 129 in vivo. This phosphorylation site was mapped by site-directed mutagenesis and confirmed by in vitro kinase assay and two-dimensional phosphopeptide mapping. Inhibition of CK2 in vivo reduces phosphorylation at Ser129. Site-directed mutagenesis, in vitro kinase assay, 2D phosphopeptide mapping, CK2 inhibitor treatment The Journal of biological chemistry High 10617630
2001 CK2 phosphorylates the tumor suppressor PTEN at a cluster of Ser/Thr residues in its C-terminal regulatory domain in a constitutive manner. Phosphorylation-defective PTEN mutants showed decreased stability and accelerated proteasomal degradation, indicating that CK2-mediated phosphorylation stabilizes PTEN against proteasomal degradation. In vitro kinase assay, site-directed mutagenesis, proteasome inhibitor studies, protein stability assays The Journal of biological chemistry High 11035045
2011 CK2 directly phosphorylates p62/SQSTM1 at serine 403 within its ubiquitin-associated (UBA) domain. This phosphorylation increases the affinity of UBA for polyubiquitin chains, enhancing autophagic clearance of polyubiquitinated proteins. CK2 overexpression reduces formation of polyglutamine-expanded huntingtin inclusion bodies in a p62-dependent manner. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, autophagy flux assays, cellular inclusion body formation assay Molecular cell High 22017874
2011 Yeast Cka2 kinase phosphorylates C-terminal serines of the E2 ubiquitin-conjugating enzyme Cdc34 (tmCdc34 mutant), and this phosphorylation prevents the synthesis of free polyubiquitin chains, likely by promoting their attachment to substrate. This reveals a regulatory role for CK2α in the ubiquitin-proteasome pathway. In vitro kinase assay, polyubiquitination assay, genetic epistasis with Ubp14 Cell division Medium 21453497
2015 Yeast CKA2 regulates nitric oxide (NO) accumulation by controlling NOS-like activity, and thereby functions in H2O2-induced apoptosis and high-temperature stress tolerance. Δcka2 mutants show reduced NO accumulation, decreased NOS-like activity, reduced apoptosis after H2O2, and hypersensitivity to high temperature. Gene deletion, NO measurement, NOS-like activity assay, survival assay with NO donor rescue FEMS yeast research Medium 26100262
2016 CSNK2A1 (CK2α) physically binds to and phosphorylates SIRT6. Evidence includes co-immunoprecipitation, GST pull-down assay, in vitro kinase assay, and transfection of kinase-dead CSNK2A1. CSNK2A1-mediated phosphorylation of SIRT6 at Ser338 promotes breast cancer cell proliferation and invasion; mutation of Ser338 inhibits MCF7 proliferation and decreases expression of MMP9, β-catenin, cyclin D1, and NF-κB. Co-immunoprecipitation, GST pull-down, in vitro kinase assay, site-directed mutagenesis, knockdown/overexpression with proliferation/invasion readouts The American journal of pathology High 27746184
2016 De novo missense and canonical splice site mutations in CSNK2A1 cause a human neurodevelopmental syndrome (Okur-Chung syndrome) characterized by intellectual disability, developmental delay, hypotonia, speech problems, microcephaly, and dysmorphic features. This is the first report of germline CSNK2A1 mutations causing human disease. Whole exome sequencing of 4102 intellectual disability/developmental delay cases, identification of de novo variants Human genetics High 27048600
2019 CSNK2A1 promotes gastric cancer invasion through the PI3K-Akt-mTOR signaling pathway and facilitates epithelial-mesenchymal transition (EMT). Overexpression of CSNK2A1 increases proliferation, invasion, and migration; silencing inhibits these processes. Western blot confirmed modulation of PI3K-Akt-mTOR pathway components. Stable overexpression and knockdown cell lines, invasion/migration assays, Western blot for pathway components Cancer management and research Medium 31819646
2019 The crystal structures of Cryptococcus neoformans CK2α ortholog (Cka1) in complex with AMPPNP-Mg2+ (2.40 Å) and CX-4945 inhibitor (2.09 Å) were solved. Structural comparison reveals dynamic architecture of the N-lobe across species. In vitro kinase assay demonstrated that CX-4945 inhibits human CK2α more efficiently than Cka1, explaining differences in binding affinity. X-ray crystallography, in vitro kinase inhibition assay Scientific reports High 31591414
2020 miR-1184 directly targets CSNK2A1 mRNA as validated by RNA immunoprecipitation and luciferase reporter assay. Overexpression of miR-1184 suppresses colon cancer cell proliferation and promotes apoptosis, effects reversed by CSNK2A1 overexpression, placing CSNK2A1 downstream of miR-1184 in this pathway. Luciferase reporter assay, RNA immunoprecipitation, overexpression/knockdown with functional rescue Molecular and cellular probes Medium 32619668
2020 A novel chromosomal fusion gene CSNK2A1-PDGFRB was identified in myeloid neoplasm with eosinophilia. The fusion retains the entire kinase domain of PDGFRB and responds to imatinib at low concentration, resulting in sustained complete remission. RNA sequencing, RT-PCR, Sanger sequencing, clinical imatinib treatment response Cancer research and treatment Medium 33421986
2021 CSNK2A1-mediated phosphorylation of SIRT6 at Ser338 activates the DNA damage repair pathway, conferring resistance to doxorubicin in osteosarcoma cells. Overexpression of CSNK2A1 induces resistance; knockdown potentiates cytotoxicity. In vivo, mutation of SIRT6 Ser338 attenuates CSNK2A1-mediated resistance. The CK2 inhibitor emodin potentiated doxorubicin cytotoxicity. Overexpression/knockdown, site-directed mutagenesis of phosphorylation site, in vivo xenograft model, pharmacological inhibition Cells High 34359939
2021 CSNK2A1 binds to and phosphorylates HMGA2. LC-MS/MS identified high-potential HMGA2-CSNK2A1 interaction; immunoprecipitation confirmed binding; immunofluorescence showed co-localization in the nucleus. Cisplatin induces CSNK2A1-HMGA2 interaction and promotes HMGA2 phosphorylation; CX-4945 (CSNK2A1 inhibitor) blocks HMGA2 phosphorylation and sensitizes tumor cells to cisplatin. LC-MS/MS, co-immunoprecipitation, immunofluorescence, pharmacological inhibition with CX-4945 FEBS open bio Medium 34115920
2022 The fission yeast CK2 catalytic subunit Cka1 phosphorylates the transcriptional coactivator PC4 at two serine residues, downregulating its RNA polymerase II coactivator function. The regulatory β-subunit (Ckb1) downregulates PC4 phosphorylation by Cka1. Mutation of both serine residues abolishes CK2 phosphorylation and the phosphorylation-insensitive mutant retains transcriptional coactivator activity even after Cka1 treatment. In vitro kinase assay, site-directed mutagenesis, in vitro transcription assay International journal of molecular sciences High 36012759
2022 Skeletal muscle-specific conditional knockout of CSNK2A1 in mice causes age-dependent reduced grip strength, impaired neuromuscular transmission, fragmented neuromuscular junctions (NMJs) with increased synaptic gene expression, increased central nuclei (muscle regeneration marker), impaired oxidative metabolism, and stimulated autophagy. Loss of CSNK2A1 also alters protein abundance of other CK2 subunits. Conditional knockout mouse (HSA-Cre), grip strength testing, electrophysiology, immunohistochemistry, enzyme activity assays, Western blot Cells High 36552726
2022 CircNDST1 binds CSNK2A1 protein directly (RNA pull-down and RIP validated) and promotes interaction between CSNK2A1 and AKT, leading to activation of the PI3K-Akt pathway and EMT in papillary thyroid cancer. Acting as a scaffold, circNDST1 enhances CSNK2A1-AKT physical association. RNA pull-down, RNA immunoprecipitation, Western blot for pathway activation, knockdown studies Journal of endocrinological investigation Medium 36306106
2023 CSNK2A1-mediated phosphorylation of MAX shifts MAX from MAX-MAX homodimers to C-MYC-MAX and β-catenin-MAX heterodimers, increasing HMGB1 and IL-6 promoter activities. Overexpression of phosphorylated MAX promotes cell proliferation, migration, invasion, and cholangiocarcinogenesis; CX-4945 (CK2 inhibitor) reverses these effects. Co-immunoprecipitation, promoter activity assays, overexpression/knockdown, CX-4945 pharmacological inhibition, in vivo mouse model Hepatology communications Medium 37347224
2023 DUSP2 competes with AKT1 to bind CSNK2A1, thereby inhibiting CSNK2A1-mediated phosphorylation of AKT1 and promoting apoptosis in pancreatic cancer. Aberrant AKT1 activation leads to TRIM21-mediated ubiquitination and proteasomal degradation of DUSP2, forming a positive feedback loop. Co-immunoprecipitation, competitive binding assay, phosphorylation analysis, in vitro and in vivo apoptosis assays Cancer letters High 37390887
2023 TMPO-AS1L lncRNA acts as a scaffold that strengthens the interaction between CSNK2A1 and DDX3X, activating Wnt/β-catenin signaling to promote prostate cancer bone metastasis. Co-immunoprecipitation, RNA pulldown, in vitro and in vivo functional assays Cell death discovery Medium 37542040
2024 CSNK2A1 confers gemcitabine resistance in pancreatic ductal adenocarcinoma by activating autophagy. CSNK2A1 transcription is regulated by H3K27 acetylation. Silmitasertib (CSNK2A1 inhibitor) effectively inhibits autophagy and, in combination with gemcitabine, shows remarkable efficacy in PDAC patient-derived xenograft models. Bioinformatics, PDX model, siRNA knockdown, Silmitasertib pharmacological inhibition, autophagy assays Cancer letters Medium 38290659
2024 OGT promotes O-GlcNAc glycosylation of CSNK2A1, enhancing its protein stability. OGT-mediated glycosylation of CSNK2A1 reverses tumor suppression caused by CSNK2A1 knockdown, and CSNK2A1 promotes colorectal cancer progression via the PI3K/AKT pathway. Immunoprecipitation, Western blot, immunofluorescence for O-GlcNAc modification, knockdown rescue assay, tumor-bearing mouse model Molecular biotechnology Medium 38289573
2024 Cholesterol directly binds CSNK2A1 and augments its kinase activity, leading to phosphorylation of IGF2R at Ser2484. This cascade rewires lipid-driven mitochondrial oxidative phosphorylation and creates a positive feedback loop for cholesterol biosynthesis in hepatocellular carcinoma. Initial transcriptional activation of CSNK2A1 is driven by RAD21 upregulation. Proteomics, phosphoproteomics, cholesterol-binding assay, in vitro kinase assay, patient-derived organoids and xenografts Journal of advanced research High 39547439
2025 SOX4 transcription factor upregulates CSNK2A1 expression by binding to its promoter (confirmed by ChIP and dual-luciferase reporter). Elevated CSNK2A1 phosphorylates TOP2A, promoting breast cancer cell proliferation, migration, invasion, and tumor growth in vivo. Silencing SOX4 reduces CSNK2A1-TOP2A phosphorylation and suppresses tumor growth. ChIP, dual-luciferase reporter assay, RT-qPCR, Western blot, CCK-8, colony formation, Transwell assay, mouse xenograft model FASEB journal Medium 39931818
2025 S. pombe Cka1 (CK2α ortholog) interacts with components of the RSC chromatin remodeling complex, DNA packaging complexes, the Pcs1/Mde4 monopolin complex, and snoRNA-containing ribonucleoproteins and spliceosomal machinery. In vitro kinase assays confirmed that Cka1 directly phosphorylates Pcs1 and Mde4, monopolin subunits involved in mitotic division. RNase-free tandem affinity purification coupled with mass spectrometry, in vitro kinase assay Biochemical and biophysical research communications Medium 40700808
2025 A frameshift mutation in CSNK2A1 (c.1020_1021delAG, p.Gly342Glnfs*57) significantly reduces protein expression through elevated ubiquitination-dependent proteasomal degradation, despite elevated mutant mRNA levels. In vitro kinase assay showed the variant did not impair intrinsic kinase activity, indicating the pathogenic mechanism is reduced protein abundance rather than catalytic dysfunction. In vitro kinase assay, quantitative mRNA/protein analysis, ubiquitination assay, bioinformatic structural prediction Frontiers in genetics Medium 41216289
2025 CSNK2A1 modulates dermal fibroblast senescence; ellagic acid upregulates CSNK2A1 expression, activates Nrf2, reduces ROS and inflammatory cytokines (IL-6, TNF-α, IL-1β) via NF-κB p65 inhibition. Silmitasertib (CSNK2A1 inhibitor) negates these anti-senescence effects, demonstrating CSNK2A1's role in oxidative stress and inflammation signaling. MTT assay, Western blot, fluorescence ROS staining, SA-β-gal staining, flow cytometry, TUNEL assay, pharmacological inhibition Clinical, cosmetic and investigational dermatology Medium 40860313
2025 CK2 inhibitor CX-4945 decreases EWS-FLI1 oncoprotein abundance in Ewing sarcoma cells through increased ubiquitination and proteasomal degradation. Genetic inhibition of CK2 recapitulates this effect, demonstrating CSNK2A1-dependent stabilization of EWS-FLI1. CX-4945 shows anti-tumor activity in metastatic xenograft models and synergistic cytotoxicity with temozolomide and irinotecan. Genetic knockdown, pharmacological inhibition (CX-4945), ubiquitination assay, tumor organoids, patient-derived xenograft cells, in vivo xenograft model bioRxivpreprint Medium bio_10.1101_2025.09.24.677357

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. The Journal of biological chemistry 3823 17580304
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
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
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
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
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2001 ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Molecular and cellular biology 909 11390642
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Molecular cell 698 22325352
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1995 Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 577 7896000
2011 Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Molecular cell 571 22017874
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2001 The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. The Journal of biological chemistry 555 11035045
2000 Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. The Journal of biological chemistry 444 10617630
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1995 Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function. The Journal of cell biology 427 7790358
2018 Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation. Cell research 424 29507397
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1990 Isolation, sequencing, and disruption of the yeast CKA2 gene: casein kinase II is essential for viability in Saccharomyces cerevisiae. Molecular and cellular biology 331 2196445
1988 Isolation, sequencing, and disruption of the CKA1 gene encoding the alpha subunit of yeast casein kinase II. Molecular and cellular biology 115 3062376
2016 De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features. Human genetics 73 27048600
2016 CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients. The American journal of pathology 73 27746184
2019 Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures. Journal of human genetics 64 30655572
1998 Temperature-sensitive mutations of the CKA1 gene reveal a role for casein kinase II in maintenance of cell polarity in Saccharomyces cerevisiae. The Journal of biological chemistry 61 9488724
1992 Purification and characterization of casein kinase II (CKII) from delta cka1 delta cka2 Saccharomyces cerevisiae rescued by Drosophila CKII subunits. The free catalytic subunit of casein kinase II is not toxic in vivo. The Journal of biological chemistry 44 1527008
1994 The human gene (CSNK2A1) coding for the casein kinase II subunit alpha is located on chromosome 20 and contains tandemly arranged Alu repeats. Genomics 43 8188256
2018 Extending the phenotype associated with the CSNK2A1-related Okur-Chung syndrome-A clinical study of 11 individuals. American journal of medical genetics. Part A 35 29383814
1998 Genomic organization and promoter identification of the human protein kinase CK2 catalytic subunit alpha (CSNK2A1). Genomics 31 9503018
2019 CSNK2A1 Promotes Gastric Cancer Invasion Through the PI3K-Akt-mTOR Signaling Pathway. Cancer management and research 27 31819646
2021 Identification of novel CSNK2A1 variants and the genotype-phenotype relationship in patients with Okur-Chung neurodevelopmental syndrome: a case report and systematic literature review. The Journal of international medical research 24 34038195
2023 DUSP2 recruits CSNK2A1 to suppress AKT1-mediated apoptosis resistance under hypoxic microenvironment in pancreatic cancer. Cancer letters 22 37390887
2022 In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia. Scientific reports 21 36271116
2020 miR-1184 regulates the proliferation and apoptosis of colon cancer cells via targeting CSNK2A1. Molecular and cellular probes 18 32619668
2024 CSNK2A1 confers gemcitabine resistance to pancreatic ductal adenocarcinoma via inducing autophagy. Cancer letters 16 38290659
2023 The long transcript of lncRNA TMPO-AS1 promotes bone metastases of prostate cancer by regulating the CSNK2A1/DDX3X complex in Wnt/β-catenin signaling. Cell death discovery 16 37542040
2021 CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway. Cells 16 34359939
2022 Fusogenic peptide delivery of bioactive siRNAs targeting CSNK2A1 for treatment of ovarian cancer. Molecular therapy. Nucleic acids 15 36213692
2022 Predictive functional, statistical and structural analysis of CSNK2A1 and CSNK2B variants linked to neurodevelopmental diseases. Frontiers in molecular biosciences 14 36310603
2022 CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K-Akt pathway and epithelial-mesenchymal transition. Journal of endocrinological investigation 13 36306106
2023 P300 increases CSNK2A1 expression which accelerates colorectal cancer progression through activation of the PI3K-AKT-mTOR axis. Experimental cell research 11 37391010
2019 [A case of Okur-Chung syndrome caused by CSNK2A1 gene variation and review of literature]. Zhonghua er ke za zhi = Chinese journal of pediatrics 11 31060130
2020 [Identification of a novel de novo variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 9 32472542
2015 CKA2 functions in H2O2-induced apoptosis and high-temperature stress tolerance by regulating NO accumulation in yeast. FEMS yeast research 9 26100262
2021 CSNK2A1-mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer. FEBS open bio 8 34115920
2011 The loop-less tmCdc34 E2 mutant defective in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2. Cell division 8 21453497
2024 O-GlcNAcylation of CSNK2A1 by OGT is Involved in the Progression of Colorectal Cancer. Molecular biotechnology 7 38289573
2023 CSNK2A1-mediated MAX phosphorylation upregulates HMGB1 and IL-6 expression in cholangiocarcinoma progression. Hepatology communications 7 37347224
2023 Inherited CSNK2A1 variants in families with Okur-Chung neurodevelopmental syndrome. Clinical genetics 7 37491870
2020 Identification of a Novel CSNK2A1-PDGFRB Fusion Gene in a Patient with Myeloid Neoplasm with Eosinophilia. Cancer research and treatment 7 33421986
2021 Long non-coding RNA B3GALT5-AS1 contributes to the progression of gastric cancer via interacting with CSNK2A1. Experimental and therapeutic medicine 6 34306196
2024 Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis. Journal of advanced research 5 39547439
2023 A Case of Okur-Chung Neurodevelopmental Syndrome with a Novel, de novo Variant on the CSNK2A1 Gene in a Turkish Patient. Molecular syndromology 4 38357263
2024 Comprehensive landscape of gastric cancer-targeted therapy and identification of CSNK2A1 as a potential target. Heliyon 3 39253198
2024 Expanding the phenotypic spectrum of CSNK2A1-associated Okur-Chung neurodevelopmental syndrome. HGG advances 3 39497417
2019 Structural analysis of fungal pathogenicity-related casein kinase α subunit, Cka1, in the human fungal pathogen Cryptococcus neoformans. Scientific reports 3 31591414
1994 PstI identifies biallelic DNA polymorphism of the human casein kinase 2 alpha gene (CSNK2A1). Human genetics 3 7909530
2025 Novel role of the SOX4/CSNK2A1 axis in regulating TOP2A phosphorylation in breast cancer progression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 39931818
2025 Clinical and molecular results in 15 Turkish patients with Wiedemann-Steiner syndrome: identification of eight novel KMT2A variants and a case of dual molecular diagnosis in the CSNK2A1. European journal of pediatrics 2 40742416
2025 Ellagic Acid Mediates the Delay of Dermal Fibroblast Senescence via CSNK2A1. Clinical, cosmetic and investigational dermatology 2 40860313
2024 Patient with a heterozygous pathogenic variant in CSNK2A1 gene: A new case to update the Okur-Chung neurodevelopmental syndrome. American journal of medical genetics. Part A 2 38711237
2022 The Catalytic Subunit of Schizosaccharomyces pombe CK2 (Cka1) Negatively Regulates RNA Polymerase II Transcription through Phosphorylation of Positive Cofactor 4 (PC4). International journal of molecular sciences 2 36012759
2022 In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions. Cells 2 36552726
2025 Exploring the Cka1 kinase interactome: unveiling novel potential regulatory roles of CKII kinase in S. pombe. Biochemical and biophysical research communications 1 40700808
2024 A guide to selecting high-performing antibodies for CSNK2A1 (UniProt ID: P68400) for use in western blot, immunoprecipitation and immunofluorescence. F1000Research 1 39403680
2025 Identification and functional analysis of a novel CSNK2A1 frameshift variant in stillbirth. Frontiers in genetics 0 41216289
2025 A Case of CSNK2A1 Gene Variant Causing Okur-Chung Syndrome and Analysis of the Clinical Phenotypic Spectrum. Molecular genetics & genomic medicine 0 41395761