id: P67870
gene_symbol: CSNK2B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: CSNK2B (casein kinase II subunit beta, CK2beta) is the non-catalytic
  regulatory subunit of protein kinase CK2 (casein kinase 2), a constitutively active,
  highly pleiotropic acidophilic serine/threonine kinase. The CK2 holoenzyme is a
  heterotetramer in which a CSNK2B beta dimer bridges two catalytic alpha subunits
  (CSNK2A1 and/or CSNK2A2); the beta subunits form a stable zinc-finger-mediated dimer
  that links the two catalytic subunits, which make no direct contact with each other.
  CSNK2B has no catalytic activity of its own. Within the holoenzyme it docks and stabilizes
  the catalytic subunits, raises basal catalytic activity, modulates substrate specificity
  and selectivity, and can recruit specific substrates and partners (e.g. via its C-terminal
  region and its KSSR protein-interaction pocket). CK2 phosphorylates hundreds of substrates
  bearing acidic residues C-terminal to the phosphoacceptor (consensus S/T-X-X-D/E),
  influencing transcription, translation, cell cycle, DNA repair, Wnt and other signaling,
  circadian rhythm, and apoptosis (its major recognized role being to counteract apoptosis).
  CSNK2B also has activities reported to be partly independent of CK2 catalysis, including
  negative regulation of cell proliferation and adaptor/scaffolding roles. It localizes
  predominantly to the nucleus and cytoplasm. In humans, de novo loss-of-function and
  missense variants cause Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), an
  autosomal dominant disorder of seizures and intellectual disability, consistent with
  haploinsufficiency.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: PMID:10094392
  title: Interactions of protein kinase CK2beta subunit within the holoenzyme and
    with other proteins.
  findings: []
- id: PMID:11574463
  title: 'Crystal structure of human protein kinase CK2: insights into basic properties
    of the CK2 holoenzyme.'
  findings:
  - statement: The CK2 holoenzyme is a tetramer in which the two regulatory (beta)
      subunits form a stable dimer that links the two catalytic subunits, which make
      no direct contact with one another; the structure is consistent with constitutive
      activity and a flexible docking role for the regulatory subunit.
    reference_section_type: ABSTRACT
- id: PMID:11984006
  title: The Chediak-Higashi protein interacts with SNARE complex and signal transduction
    proteins.
  findings: []
- id: PMID:12769847
  title: Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3
    complex and enhances actin polymerization by WASP.
  findings: []
- id: PMID:14667819
  title: Analysis of a high-throughput yeast two-hybrid system and its use to predict
    the function of intracellular proteins encoded within the human MHC class III
    region.
  findings: []
- id: PMID:15723517
  title: Interactions of the HIV-1 Tat and RAP74 proteins with the RNA polymerase
    II CTD phosphatase FCP1.
  findings: []
- id: PMID:16977309
  title: A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking.
  findings: []
- id: PMID:1856204
  title: Structure of the gene encoding human casein kinase II subunit beta.
  findings: []
- id: PMID:19011756
  title: 'KIF5C: a new binding partner for protein kinase CK2 with a preference for
    the CK2alpha'' subunit.'
  findings: []
- id: PMID:19233263
  title: Protein kinase CK2 interacts with adiponectin receptor 1 and participates
    in adiponectin signaling.
  findings: []
- id: PMID:19324893
  title: CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible
    switch for DNA binding.
  findings:
  - statement: PRH/HHEX interacts with the CK2 beta subunit in vitro and in cells;
      CK2 phosphorylates the PRH homeodomain (S163, S177), inhibiting its DNA binding
      and transcriptional activity. CK2beta is important in CK2 assembly, stability
      and activity, can interact with substrates and modulators, and has roles independent
      of CK2 catalysis including negative regulation of cell proliferation.
    reference_section_type: RESULTS
- id: PMID:19592636
  title: Casein kinase 2beta as a novel enhancer of activin-like receptor-1 signaling.
  findings:
  - statement: CK2beta binds the cytoplasmic domain of ALK-1/ACVRL1 (CK2beta residues
      181-199), enhancing ligand-stimulated Smad1/5/8 phosphorylation and ALK-1 reporter
      activity; CK2beta silencing reduces this signaling, and CK2beta with ALK-1 antagonizes
      endothelial cell migration and tubule formation.
    reference_section_type: ABSTRACT
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
- id: PMID:20664522
  title: Phosphorylation of CLIP-170 by Plk1 and CK2 promotes timely formation of
    kinetochore-microtubule attachments.
  findings: []
- id: PMID:20719947
  title: Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to disrupt
    PML nuclear bodies.
  findings:
  - statement: EBV EBNA1 binds CK2 via CK2beta, increasing association of CK2 with
      PML and PML phosphorylation, which triggers PML polyubiquitylation and degradation;
      CK2beta enhances catalytic activity/stability and can mediate interactions with
      CK2 substrates, redirecting CK2 toward specific substrates.
    reference_section_type: RESULTS
- id: PMID:21078624
  title: Comparison of an expanded ataxia interactome with patient medical records
    reveals a relationship between macular degeneration and ataxia.
  findings: []
- id: PMID:21282530
  title: Interaction proteomics analysis of polycomb proteins defines distinct PRC1
    complexes in mammalian cells.
  findings: []
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
- id: PMID:21900206
  title: A directed protein interaction network for investigating intracellular signal
    transduction.
  findings: []
- id: PMID:21968188
  title: p53 deacetylation by SIRT1 decreases during protein kinase CKII downregulation-mediated
    cellular senescence.
  findings: []
- id: PMID:21988832
  title: Toward an understanding of the protein interaction network of the human liver.
  findings: []
- id: PMID:22325352
  title: PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family
    complexes.
  findings: []
- id: PMID:22506723
  title: Structural determinants of protein kinase CK2 regulation by autoinhibitory
    polymerization.
  findings: []
- id: PMID:23455922
  title: Interlaboratory reproducibility of large-scale human protein-complex analysis
    by standardized AP-MS.
  findings: []
- id: PMID:23555304
  title: Dynamic circadian protein-protein interaction networks predict temporal organization
    of cellular functions.
  findings: []
- id: PMID:24535599
  title: Phosphorylation of Grb14 BPS domain by GSK-3 correlates with complex forming
    of Grb14 and insulin receptor.
  findings: []
- id: PMID:2513884
  title: Cloning and characterization of a cDNA encoding the beta subunit of human
    casein kinase II.
  findings: []
- id: PMID:25519132
  title: An AUTS2-Polycomb complex activates gene expression in the CNS.
  findings:
  - statement: CK2 (CSNK2A/B) is a component of a non-canonical PRC1-AUTS2 complex;
      the CK2 component phosphorylates RING1B and neutralizes PRC1 repressive activity,
      while AUTS2-mediated recruitment of P300 leads to gene activation.
    reference_section_type: ABSTRACT
- id: PMID:25852190
  title: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides
    a source of potential targets for combination therapy.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries
    and abundances.
  findings: []
- id: PMID:26562092
  title: CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian
    Circadian Clock.
  findings: []
- id: PMID:2666134
  title: Human phosvitin/casein kinase type II. Molecular cloning and sequencing of
    full-length cDNA encoding subunit beta.
  findings: []
- id: PMID:26711270
  title: A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component
    RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.
  findings: []
- id: PMID:27705803
  title: A High-Density Map for Navigating the Human Polycomb Complexome.
  findings: []
- id: PMID:28031292
  title: Protein kinase CK2 modulates HSJ1 function through phosphorylation of the
    UIM2 domain.
  findings:
  - statement: CK2 (a tetramer of two catalytic and two regulatory beta subunits)
      phosphorylates HSJ1/DNAJB2 within its UIM2 (Ser250 dominant, Ser247 hierarchical),
      reducing HSJ1 binding to ubiquitylated clients and chaperone activity; CK2 inhibition
      enhances client binding, i.e. CK2 negatively regulates proteasomal degradation
      of HSJ1 clients. CK2 is highly pleiotropic and constitutively active and its
      major recognized function is counteracting apoptosis.
    reference_section_type: RESULTS
- id: PMID:29997244
  title: 'LuTHy: a double-readout bioluminescence-based two-hybrid technology for
    quantitative mapping of protein-protein interactions in mammalian cells.'
  findings: []
- id: PMID:31341047
  title: Identification of ARKL1 as a Negative Regulator of Epstein-Barr Virus Reactivation.
  findings:
  - statement: CK2beta mediates the interaction between ARKL1/ARK2N and c-Jun at the
      EBV Z promoter; silencing CK2beta (but not CK2alpha) phenocopies ARKL1 loss
      and promotes EBV reactivation, so CK2beta acts as an adaptor required for ARKL1-mediated
      repression of BZLF1/Zp and negative regulation of the viral life cycle. CSNK2B
      localizes to the nucleus and is active on chromatin.
    reference_section_type: RESULTS
- id: PMID:31784560
  title: Germline de novo variants in CSNK2B in Chinese patients with epilepsy.
  findings:
  - statement: De novo CSNK2B variants (including missense and truncating variants)
      cause Poirier-Bienvenu neurodevelopmental syndrome with epilepsy and intellectual
      disability, consistent with a haploinsufficiency mechanism.
    reference_section_type: ABSTRACT
- id: PMID:28585349
  title: CSNK2B splice site mutations in patients cause intellectual disability with
    or without myoclonic epilepsy.
  findings:
  - statement: CSNK2B splice-site mutations cause intellectual disability with or without
      myoclonic epilepsy (POBINDS).
    reference_section_type: ABSTRACT
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing
    transforming levels of KRAS(G13D).
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human
    Kinases.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36833176
  title: Haploinsufficiency as a Foreground Pathomechanism of Poirer-Bienvenu Syndrome
    and Novel Insights Underlying the Phenotypic Continuum of CSNK2B-Associated Disorders.
  findings: []
- id: PMID:36876296
  title: Analyzing the interactome of human CK2β in prostate carcinoma cells reveals
    HSP70-1 and Rho guanin nucleotide exchange factor 12 as novel interaction partners.
  findings: []
- id: PMID:38225382
  title: Systematic discovery of protein interaction interfaces using AlphaFold and
    experimental validation.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: file:human/CSNK2B/CSNK2B-uniprot.txt
  title: UniProt entry P67870 (CSK2B_HUMAN)
  findings: []
- id: Reactome:R-HSA-201717
  title: CSNK2-mediated phosphorylation of DVL
  findings: []
- id: Reactome:R-HSA-2529020
  title: CK2 phosphorylates condensin I subunits
  findings: []
- id: Reactome:R-HSA-392752
  title: Phosphorylation of L1 by CK-II
  findings: []
- id: Reactome:R-HSA-6798748
  title: Exocytosis of secretory granule lumen proteins
  findings: []
- id: Reactome:R-HSA-6800434
  title: Exocytosis of ficolin-rich granule lumen proteins
  findings: []
- id: Reactome:R-HSA-6805059
  title: CK2:FACT phosphorylates TP53
  findings: []
- id: Reactome:R-HSA-6805061
  title: CK2 binds FACT
  findings: []
- id: Reactome:R-HSA-6814409
  title: CK2 phosphorylates PDCL
  findings: []
- id: Reactome:R-HSA-8850945
  title: Casein kinase II phosphorylates PTEN
  findings: []
- id: Reactome:R-HSA-8873929
  title: Casein kinase II phosphorylates STARD10
  findings: []
- id: Reactome:R-HSA-8948039
  title: FUNDC1 is phosphorylated by CK2
  findings: []
- id: Reactome:R-HSA-9831514
  title: CK2 phosphorylates nascent P
  findings: []
- id: Reactome:R-HSA-9831712
  title: M dimer is phosphorylated
  findings: []
- id: Reactome:R-HSA-9931418
  title: CK2 phosphorylates CD274
  findings: []
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: CK2beta is predominantly nuclear (and cytoplasmic); nuclear localization
      is well supported experimentally. Accept as a correct, if general, localization.
    action: ACCEPT
    reason: Nucleus is a documented subcellular location of CSNK2B (UniProt SUBCELLULAR
      LOCATION; experimental nucleus annotations from PMID:31341047 and PMID:21282530).
- term:
    id: GO:0005956
    label: protein kinase CK2 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: CSNK2B is, by definition, a subunit of the CK2 holoenzyme (protein kinase
      CK2 complex). This is the core cellular-component annotation for this gene.
    action: ACCEPT
    reason: Direct structural and biochemical evidence places CSNK2B as the regulatory
      subunit bridging the two catalytic subunits in the CK2 holoenzyme.
    supported_by:
    - reference_id: PMID:11574463
      supporting_text: In the CK2 complex the regulatory subunits form a stable dimer
        linking the two catalytic subunits, which make no direct contact with one
        another.
- term:
    id: GO:0019887
    label: protein kinase regulator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Protein kinase regulator activity is the core molecular function of CSNK2B
      - as the regulatory subunit it modulates the basal activity, stability and substrate
      selectivity of the CK2 catalytic subunits.
    action: ACCEPT
    reason: CSNK2B is the prototypical protein kinase regulatory subunit; this term
      captures its central non-catalytic function within the holoenzyme.
    supported_by:
    - reference_id: PMID:19324893
      supporting_text: The CK2beta subunit is important in the assembly of CK2, enzyme
        stability and enzyme activity. It can interact with modulators of CK2 activity
        as well as with CK2 substrates and is thought to be required for the selection
        of substrates.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10094392
  qualifier: enables
  review:
    summary: Generic protein binding annotation (interactions with CK2 catalytic subunits
      CSNK2A1/CSNK2A2 and RSK2). 'protein binding' is uninformative as a function
      term; the underlying interactions are better captured by the CK2 complex and
      kinase-regulator annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare GO:0005515 conveys no specific molecular function; the biologically
      meaningful relationships (CK2 holoenzyme assembly) are captured by more specific
      terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11574463
  qualifier: enables
  review:
    summary: Generic protein binding (interaction with CSNK2A1 from the holoenzyme
      crystal structure). The specific, informative content is the CK2 complex membership.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative; holoenzyme assembly is captured
      by GO:0005956 and GO:0019887.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12769847
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14667819
  qualifier: enables
  review:
    summary: Generic protein binding from a high-throughput MHC class III Y2H study
      (CSNK2A1/CSNK2A2). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16977309
  qualifier: enables
  review:
    summary: Generic protein binding (PACS1) from the PACS-1/GGA3/CK2 trafficking
      complex study. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19011756
  qualifier: enables
  review:
    summary: Generic protein binding (KIF5C/CK2 interaction; CSNK2A subunits). Uninformative
      function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20664522
  qualifier: enables
  review:
    summary: Generic protein binding (CLIP-170/CLIP1). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21078624
  qualifier: enables
  review:
    summary: Generic protein binding (CACNA1A) from an expanded ataxia interactome.
      Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21282530
  qualifier: enables
  review:
    summary: Generic protein binding (Polycomb proteins CBX4, RNF2, CSNK2A1) from
      PRC1 interaction proteomics. Uninformative function term; PRC1/Polycomb associations
      are captured by complex-membership annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21900206
  qualifier: enables
  review:
    summary: Generic protein binding (NMT2, CENPB) from a directed signal-transduction
      interaction network. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21968188
  qualifier: enables
  review:
    summary: Generic protein binding (SIRT1, CSNK2A1) from a CK2/SIRT1/p53 senescence
      study. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  qualifier: enables
  review:
    summary: Generic protein binding from a large-scale human liver interactome (CSNK2A1/CSNK2A2,
      RSK2/RPS6KA3, MSK1/RPS6KA5, PHRF1). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23455922
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A2) from a standardized AP-MS reproducibility
      study. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23555304
  qualifier: enables
  review:
    summary: Generic protein binding from a circadian PPI network (CSNK2A1/A2, CLOCK,
      CRY1, BMAL1). Uninformative function term; circadian roles are substrate-driven
      pleiotropy of CK2.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24535599
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) from a Grb14/insulin receptor study.
      Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25519132
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) from the AUTS2-Polycomb study. Uninformative
      function term; the substantive finding (CK2 in PRC1-AUTS2) is captured elsewhere.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25852190
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) from a TRAIL-apoptosis kinase network.
      Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A2) from a quantitative human interactome.
      Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26562092
  qualifier: enables
  review:
    summary: Generic protein binding (CRY1, BMAL1) from the CRY/CK2/BMAL1 circadian
      study. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26711270
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) from an ECD/RUVBL1/R2TP study. Uninformative
      function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27705803
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A2, RNF2, CSNK2A1) from a Polycomb complexome
      map. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29997244
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) from the LuTHy two-hybrid technology
      paper. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31980649
  qualifier: enables
  review:
    summary: Generic protein binding (RSK2/RPS6KA3) from an EGFR-network rewiring study.
      Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic protein binding from a binary interactome reference map (many
      partners). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  qualifier: enables
  review:
    summary: Generic protein binding from a kinase interaction network (CSNK2A1/A2,
      RSK2, MSK1). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) from a neurodegenerative-disease interactome.
      Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding from a proteome-scale cell-specific interactome
      (CSNK2A1/A2, RSK2, MSK1, RNF2, PHRF1). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Generic protein binding from OpenCell endogenous-tagging interactome
      (CSNK2A1/A2, RSK2, NMT2, CENPB, RNF2, RBM39). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36833176
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) reported alongside POBINDS disease modeling.
      Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36876296
  qualifier: enables
  review:
    summary: Generic protein binding from a CK2beta prostate-carcinoma interactome
      (CSNK2A2, HSP70-1, ARHGEF12). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:38225382
  qualifier: enables
  review:
    summary: Generic protein binding (CSNK2A1) from an AlphaFold-guided interface-discovery
      study. Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Generic protein binding from a multimodal cell-map interactome (many partners
      including CSNK2A1/A2, RNF2, PHRF1). Uninformative function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding conveys no specific molecular function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:10094392
  qualifier: enables
  review:
    summary: CSNK2B forms a zinc-finger-mediated homodimer (the beta dimer that bridges
      the two catalytic subunits). Self-association is genuine and structurally central,
      so identical protein binding is supported.
    action: ACCEPT
    reason: CSNK2B homodimerization (beta dimer) is well established structurally and
      is required for holoenzyme assembly.
    supported_by:
    - reference_id: PMID:11574463
      supporting_text: the regulatory subunits form a stable dimer linking the two
        catalytic subunits
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:14667819
  qualifier: enables
  review:
    summary: CSNK2B homodimerization (beta dimer), recovered in a Y2H screen. Supported.
    action: ACCEPT
    reason: CSNK2B self-association into the beta dimer is structurally established.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:21282530
  qualifier: enables
  review:
    summary: CSNK2B homodimerization recovered in PRC1 interaction proteomics. Supported.
    action: ACCEPT
    reason: CSNK2B self-association into the beta dimer is structurally established.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  qualifier: enables
  review:
    summary: CSNK2B homodimerization recovered in a liver interactome. Supported.
    action: ACCEPT
    reason: CSNK2B self-association into the beta dimer is structurally established.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:23555304
  qualifier: enables
  review:
    summary: CSNK2B homodimerization recovered in a circadian PPI network. Supported.
    action: ACCEPT
    reason: CSNK2B self-association into the beta dimer is structurally established.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:36876296
  qualifier: enables
  review:
    summary: CSNK2B homodimerization recovered in a CK2beta prostate-carcinoma interactome.
      Supported.
    action: ACCEPT
    reason: CSNK2B self-association into the beta dimer is structurally established.
- term:
    id: GO:0005956
    label: protein kinase CK2 complex
  evidence_type: IPI
  original_reference_id: PMID:22506723
  qualifier: part_of
  review:
    summary: CSNK2B as part of the CK2 complex, from a structural study of CK2 autoinhibitory
      polymerization (ComplexPortal). Core CC annotation.
    action: ACCEPT
    reason: CSNK2B is a constitutive subunit of the CK2 holoenzyme.
- term:
    id: GO:0001650
    label: fibrillar center
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence places CSNK2B in the nucleolar fibrillar center.
      CK2 is known to be nucleolar/nuclear; plausible but a fine-grained sublocalization
      from a single imaging source.
    action: KEEP_AS_NON_CORE
    reason: A specific nuclear sublocalization from HPA imaging; consistent with the
      broadly nuclear distribution of CK2 but not a defining location.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localizes CSNK2B to the nucleoplasm, consistent
      with its well-documented nuclear distribution.
    action: ACCEPT
    reason: Nucleoplasmic/nuclear localization of CK2beta is well supported.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:31341047
  qualifier: located_in
  review:
    summary: Experimental nuclear localization of CSNK2B (acting at the EBV Z promoter
      with ARKL1/Jun). Core localization.
    action: ACCEPT
    reason: Direct experimental evidence for nuclear localization.
    supported_by:
    - reference_id: PMID:31341047
      supporting_text: ARKL1 was associated with Zp in reporter assays and this was
        increased by additional CK2β
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: NAS
  original_reference_id: PMID:22325352
  qualifier: located_in
  review:
    summary: Chromatin localization asserted via CSNK2B membership in PRC1-family complexes.
      This is a complex-membership-driven transfer; CSNK2B's presence on chromatin
      reflects the embedded CK2 within Polycomb complexes rather than a defining CK2beta
      location.
    action: KEEP_AS_NON_CORE
    reason: Chromatin association is plausible (CK2 in PRC1-AUTS2 and at promoters)
      but is a context-specific, complex-driven localization, not the core CC.
- term:
    id: GO:0031507
    label: heterochromatin formation
  evidence_type: NAS
  original_reference_id: PMID:22325352
  qualifier: involved_in
  review:
    summary: Heterochromatin formation assigned via CSNK2B co-membership in PRC1-family
      complexes. This is a process transfer from the broader Polycomb complex; CSNK2B's
      direct contribution is its kinase-regulatory role within embedded CK2, not chromatin
      compaction per se.
    action: MARK_AS_OVER_ANNOTATED
    reason: Process transferred from the PRC1 complex; CSNK2B does not itself drive
      heterochromatin formation, and the AUTS2-PRC1 CK2 component is reported to neutralize
      (not enhance) PRC1 repression.
- term:
    id: GO:0035102
    label: PRC1 complex
  evidence_type: NAS
  original_reference_id: PMID:22325352
  qualifier: part_of
  review:
    summary: CSNK2B/CK2 co-purifies as a component of a subset of non-canonical PRC1
      (PCGF/AUTS2) complexes. Membership is reported in multiple proteomic studies.
    action: KEEP_AS_NON_CORE
    reason: CK2 is a bona fide component of certain non-canonical PRC1 complexes, but
      this is a specialized context rather than CSNK2B's core CK2-holoenzyme identity.
    supported_by:
    - reference_id: PMID:25519132
      supporting_text: the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive
        activity, whereas AUTS2-mediated recruitment of P300 leads to gene activation
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: NAS
  original_reference_id: PMID:22325352
  qualifier: involved_in
  review:
    summary: Positive regulation of transcription assigned via the PRC1-AUTS2 activating
      complex, where the CK2 component neutralizes PRC1 repression and AUTS2 recruits
      P300. This is a complex-driven, context-specific process and not a core CSNK2B
      function.
    action: KEEP_AS_NON_CORE
    reason: Process driven by the broader PRC1-AUTS2 complex; CSNK2B's direct contribution
      is kinase-regulatory (phosphorylation of RING1B by embedded CK2).
    supported_by:
    - reference_id: PMID:25519132
      supporting_text: the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive
        activity, whereas AUTS2-mediated recruitment of P300 leads to gene activation
- term:
    id: GO:0032435
    label: negative regulation of proteasomal ubiquitin-dependent protein catabolic
      process
  evidence_type: IDA
  original_reference_id: PMID:28031292
  qualifier: involved_in
  review:
    summary: CK2 phosphorylates HSJ1/DNAJB2 in its UIM2, reducing binding to ubiquitylated
      clients and slowing their proteasomal degradation; CK2 inhibition enhances client
      binding and degradation. This is a substrate-specific downstream effect of CK2
      catalytic activity rather than a direct CSNK2B molecular function.
    action: KEEP_AS_NON_CORE
    reason: A genuine, well-demonstrated CK2-dependent effect, but it is one of hundreds
      of substrate-driven downstream processes; non-core for the regulatory subunit.
    supported_by:
    - reference_id: PMID:28031292
      supporting_text: the phosphorylation of HSJ1 by CK2 reduced its ability to bind
        ubiquitylated clients
- term:
    id: GO:0060391
    label: positive regulation of SMAD protein signal transduction
  evidence_type: IDA
  original_reference_id: PMID:19592636
  qualifier: involved_in
  review:
    summary: CK2beta binds the ALK-1/ACVRL1 cytoplasmic domain and enhances ligand-stimulated
      Smad1/5/8 phosphorylation; CK2beta silencing reduces this. A specific, experimentally
      supported signaling role, but a context-specific downstream process rather than
      CSNK2B's core function.
    action: KEEP_AS_NON_CORE
    reason: Well-supported but specialized signaling role (one of many CK2-modulated
      pathways); non-core for the regulatory subunit.
    supported_by:
    - reference_id: PMID:19592636
      supporting_text: The ALK-1/CK2beta interaction specifically enhanced Smad1/5/8
        phosphorylation and ALK-1-mediated reporter activation in response to TGF-beta1
        and BMP-9 treatment.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:31341047
  qualifier: is_active_in
  review:
    summary: CSNK2B is active on chromatin at the EBV Z promoter, mediating ARKL1/Jun-dependent
      repression. Direct experimental support for chromatin activity in this viral
      context.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but context-specific (EBV Zp); chromatin is not
      the defining location of the CK2 regulatory subunit.
    supported_by:
    - reference_id: PMID:31341047
      supporting_text: ARKL1 was associated with Zp in reporter assays and this was
        increased by additional CK2β
- term:
    id: GO:0016605
    label: PML body
  evidence_type: IDA
  original_reference_id: PMID:20719947
  qualifier: is_active_in
  review:
    summary: Upon EBV infection, EBNA1 increases CK2 (via CK2beta) association with
      PML bodies, promoting PML phosphorylation and degradation. CSNK2B is active at
      PML bodies in this viral context.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but infection-context-specific; not the core CK2beta
      location.
    supported_by:
    - reference_id: PMID:20719947
      supporting_text: protein interactions with CK2β can redirect CK2 to increase
        CK2 activity toward specific substrates
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:31341047
  qualifier: enables
  review:
    summary: CSNK2B bridges ARK2N/ARKL1 and c-Jun (mediating their interaction via
      its KSSR pocket), functioning as a molecular adaptor/scaffold. This adaptor/scaffold
      activity is a genuine core molecular function of CSNK2B beyond its kinase-regulatory
      role.
    action: ACCEPT
    reason: Direct experimental evidence that CSNK2B mediates the ARK2N-Jun interaction,
      a bona fide adaptor function; consistent with the holoenzyme's documented docking/scaffolding
      role.
    supported_by:
    - reference_id: PMID:31341047
      supporting_text: silencing of CK2β, but not the CK2α catalytic subunit, abrogated the ARKL1-Jun interaction and phenocopied ARKL1 silencing in promoting EBV reactivation
- term:
    id: GO:0075342
    label: symbiont-mediated disruption of host cell PML body
  evidence_type: IDA
  original_reference_id: PMID:20719947
  qualifier: involved_in
  review:
    summary: Via EBNA1-directed recruitment of CK2 to PML, CSNK2B contributes to EBV-mediated
      disruption of host PML nuclear bodies (PML phosphorylation and degradation).
      A virus-hijacking process, non-core.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported microbial-infection process; a hijacked, context-specific
      role rather than a core CSNK2B function.
    supported_by:
    - reference_id: PMID:20719947
      supporting_text: protein interactions with CK2β can redirect CK2 to increase
        CK2 activity toward specific substrates
- term:
    id: GO:1903901
    label: negative regulation of viral life cycle
  evidence_type: IDA
  original_reference_id: PMID:31341047
  qualifier: involved_in
  review:
    summary: CSNK2B is required for ARKL1-mediated repression of the EBV BZLF1/Z promoter;
      silencing CK2beta promotes EBV reactivation. A virus-restriction process, non-core
      for the kinase regulatory subunit.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but context-specific (EBV reactivation); not a
      core CSNK2B function.
    supported_by:
    - reference_id: PMID:31341047
      supporting_text: silencing of CK2β, but not the CK2α catalytic subunit, abrogated
        the ARKL1-Jun interaction and phenocopied ARKL1 silencing in promoting EBV
        reactivation
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:19324893
  qualifier: enables
  review:
    summary: CSNK2B binds the transcription factor PRH/HHEX in vitro and in cells.
      This is a specific protein-protein interaction with a Pol II transcription factor;
      more informative than bare protein binding but reflects a substrate/partner-recruitment
      interaction.
    action: KEEP_AS_NON_CORE
    reason: A genuine, specific TF interaction (PRH/HHEX), but it represents substrate/partner
      docking rather than a core, broadly defining molecular function.
    supported_by:
    - reference_id: PMID:19324893
      supporting_text: PRH interacts with the beta subunit of CK2 in vitro and in
        cells
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: PMID:28031292
  qualifier: contributes_to
  review:
    summary: With the contributes_to qualifier, this captures that CSNK2B, as a non-catalytic
      subunit, contributes to the serine/threonine kinase activity of the CK2 holoenzyme
      (e.g. toward HSJ1). This is the accepted way to annotate a regulatory subunit
      of an active kinase complex.
    action: ACCEPT
    reason: contributes_to is appropriate for a non-catalytic subunit that is part
      of an active kinase complex; CSNK2B contributes to CK2 holoenzyme S/T kinase
      activity.
    supported_by:
    - reference_id: PMID:28031292
      supporting_text: CK2 is a highly pleiotropic and constitutively active enzyme
        mainly present in cells as a tetramer, composed of two catalytic (α and/or
        α') and two regulatory (β) subunits.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:15723517
  qualifier: enables
  review:
    summary: CSNK2B does not itself enable serine/threonine kinase activity - it is
      the non-catalytic regulatory subunit. The 'enables' qualifier here is misleading;
      it should be contributes_to (as a subunit of the active holoenzyme), or better
      captured by protein kinase regulator activity.
    action: MODIFY
    reason: CSNK2B has no intrinsic catalytic activity; an 'enables' kinase-activity
      annotation is incorrect for the beta subunit. The kinase-regulator role (GO:0019887)
      is the accurate molecular function; the holoenzyme contribution is captured by
      the contributes_to annotation.
    proposed_replacement_terms:
    - id: GO:0019887
      label: protein kinase regulator activity
- term:
    id: GO:0005956
    label: protein kinase CK2 complex
  evidence_type: IDA
  original_reference_id: PMID:15723517
  qualifier: part_of
  review:
    summary: CSNK2B as part of the CK2 complex (in the context of FCP1 phosphorylation).
      Core CC annotation.
    action: ACCEPT
    reason: CSNK2B is a constitutive subunit of the CK2 holoenzyme.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  qualifier: located_in
  review:
    summary: Extracellular localization is a bulk neutrophil-degranulation/secretome
      transfer from Reactome (exocytosis of secretory granule lumen proteins). CK2beta
      is an intracellular kinase subunit; extracellular region is not a meaningful
      core localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Reactome bulk-secretome transfer; not a biologically informative location
      for an intracellular kinase regulatory subunit.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  qualifier: located_in
  review:
    summary: Extracellular region via ficolin-rich granule exocytosis (Reactome neutrophil
      degranulation). Bulk-secretome transfer, not core.
    action: MARK_AS_OVER_ANNOTATED
    reason: Reactome bulk-secretome transfer; not a biologically informative location.
- term:
    id: GO:0034774
    label: secretory granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  qualifier: located_in
  review:
    summary: Secretory granule lumen from neutrophil-degranulation Reactome transfer.
      Not a core localization of an intracellular kinase subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: Reactome neutrophil-degranulation bulk transfer; not biologically informative
      for CSNK2B.
- term:
    id: GO:1904813
    label: ficolin-1-rich granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  qualifier: located_in
  review:
    summary: Ficolin-1-rich granule lumen from neutrophil-degranulation Reactome transfer.
      Not core.
    action: MARK_AS_OVER_ANNOTATED
    reason: Reactome neutrophil-degranulation bulk transfer; not biologically informative
      for CSNK2B.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6805059
  qualifier: located_in
  review:
    summary: Nucleoplasm from Reactome (CK2:FACT phosphorylates TP53). Consistent with
      the documented nuclear localization of CK2beta.
    action: ACCEPT
    reason: Nucleoplasmic localization is consistent with experimental nuclear localization
      of CSNK2B.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6805061
  qualifier: located_in
  review:
    summary: Nucleoplasm from Reactome (CK2 binds FACT). Consistent with nuclear localization.
    action: ACCEPT
    reason: Nucleoplasmic localization is consistent with experimental nuclear localization
      of CSNK2B.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9831712
  qualifier: located_in
  review:
    summary: Nucleoplasm from Reactome (M dimer phosphorylation pathway). Consistent
      with nuclear localization.
    action: ACCEPT
    reason: Nucleoplasmic localization is consistent with experimental nuclear localization
      of CSNK2B.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:25519132
  qualifier: enables
  review:
    summary: Chromatin binding assigned in the AUTS2-Polycomb context (CK2 as a PRC1-AUTS2
      component). Plausible given CK2 association with Polycomb/promoter chromatin,
      but reflects complex context rather than a defining CSNK2B function.
    action: KEEP_AS_NON_CORE
    reason: Chromatin binding via PRC1-AUTS2 complex membership; context-specific rather
      than a core molecular function of the kinase regulatory subunit.
    supported_by:
    - reference_id: PMID:25519132
      supporting_text: the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive
        activity
- term:
    id: GO:0032927
    label: positive regulation of activin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19592636
  qualifier: involved_in
  review:
    summary: CK2beta enhances ALK-1/ACVRL1 (an activin-receptor-like kinase) signaling;
      siRNA knockdown reduces Smad1/5/8 signaling and reporter activity. A specific,
      experimentally supported signaling role, non-core.
    action: KEEP_AS_NON_CORE
    reason: Well-supported but specialized signaling role; non-core for the regulatory
      subunit.
    supported_by:
    - reference_id: PMID:19592636
      supporting_text: siRNA-mediated silencing of endogenous CK2beta inhibited TGF-beta1
        and BMP-9-stimulated Smad1/5/8 phosphorylation and ALK-1-mediated reporter
        activation
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  qualifier: located_in
  review:
    summary: Nucleus from high-throughput proteomic characterization of the sperm nucleus.
      Consistent with the well-documented nuclear localization of CSNK2B.
    action: ACCEPT
    reason: Nuclear localization is well supported; this HDA annotation is concordant.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: Extracellular exosome from a high-throughput exosome proteomics study.
      CK2 is frequently detected in exosome proteomes, but this is not a core localization
      for an intracellular kinase regulatory subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput proteomic detection in exosomes; not a biologically informative
      core localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-201717
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (CSNK2-mediated phosphorylation of DVL, Wnt signaling).
      CK2 is broadly cytosolic; cytosolic localization is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2529020
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (CK2 phosphorylates condensin I subunits). Cytosolic
      localization is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-392752
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (phosphorylation of L1 by CK-II). Cytosolic localization
      is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814409
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (CK2 phosphorylates PDCL). Cytosolic localization
      is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8850945
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (CK2 phosphorylates PTEN). Cytosolic localization
      is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8873929
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (CK2 phosphorylates STARD10). Cytosolic localization
      is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8948039
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (FUNDC1 phosphorylation by CK2, mitophagy). Cytosolic
      localization is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9831514
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (CK2 phosphorylates nascent viral P protein). Cytosolic
      localization is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9931418
  qualifier: located_in
  review:
    summary: Cytosol from Reactome (CK2 phosphorylates CD274/PD-L1). Cytosolic localization
      is accurate.
    action: ACCEPT
    reason: Cytosolic localization of the CK2 holoenzyme is well established.
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IPI
  original_reference_id: PMID:19592636
  qualifier: enables
  review:
    summary: CK2beta binds the cytoplasmic domain of the signaling receptor ALK-1/ACVRL1
      (P37023). A specific, experimentally mapped receptor interaction.
    action: KEEP_AS_NON_CORE
    reason: A genuine specific receptor interaction (ALK-1), but partner/substrate
      docking rather than a core broadly defining molecular function.
    supported_by:
    - reference_id: PMID:19592636
      supporting_text: The cytoplasmic domain of ALK-1 specifically binds to CK2beta
        in vitro and in vivo.
- term:
    id: GO:0043537
    label: negative regulation of blood vessel endothelial cell migration
  evidence_type: IDA
  original_reference_id: PMID:19592636
  qualifier: involved_in
  review:
    summary: CK2beta with ALK-1 inhibits endothelial cell migration. A specific, experimentally
      supported endothelial role downstream of ALK-1 signaling; non-core.
    action: KEEP_AS_NON_CORE
    reason: Specialized, context-specific vascular role; non-core for the kinase regulatory
      subunit.
    supported_by:
    - reference_id: PMID:19592636
      supporting_text: CK2beta enhanced the ability of activated or ligand-stimulated
        ALK-1 to inhibit endothelial cell migration
- term:
    id: GO:0061154
    label: endothelial tube morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:19592636
  qualifier: involved_in
  review:
    summary: ALK-1 and CK2beta antagonize endothelial tubule formation in Matrigel.
      A specific, experimentally supported endothelial role; non-core.
    action: KEEP_AS_NON_CORE
    reason: Specialized, context-specific vascular role; non-core.
    supported_by:
    - reference_id: PMID:19592636
      supporting_text: ALK-1 and CK2beta antagonized endothelial tubule formation in
        Matrigel
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21282530
  qualifier: located_in
  review:
    summary: Experimental nuclear localization of CSNK2B from PRC1 interaction proteomics
      / imaging. Core localization.
    action: ACCEPT
    reason: Direct evidence for nuclear localization, consistent with other experimental
      nucleus annotations.
- term:
    id: GO:0031519
    label: PcG protein complex
  evidence_type: IDA
  original_reference_id: PMID:21282530
  qualifier: colocalizes_with
  review:
    summary: CSNK2B colocalizes with the Polycomb group (PcG) protein complex. Consistent
      with CK2 being a component of non-canonical PRC1 complexes; a colocalization
      in a specialized context.
    action: KEEP_AS_NON_CORE
    reason: Genuine but specialized association with Polycomb complexes; not the core
      CK2-holoenzyme identity.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: PMID:1856204
  qualifier: contributes_to
  review:
    summary: With contributes_to, this captures that CSNK2B contributes to the CK2
      holoenzyme's serine/threonine kinase activity as a non-catalytic subunit. Appropriate
      annotation.
    action: ACCEPT
    reason: contributes_to is the correct qualifier for a regulatory subunit of an
      active kinase complex.
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: TAS
  original_reference_id: PMID:19324893
  qualifier: involved_in
  review:
    summary: CK2beta has roles, reported to be partly independent of CK2 catalysis,
      including negative regulation of cell proliferation. Literature-supported but
      a broad downstream process.
    action: KEEP_AS_NON_CORE
    reason: A reported (and somewhat context-dependent) role; non-core relative to
      the kinase-regulatory and complex annotations.
    supported_by:
    - reference_id: PMID:19324893
      supporting_text: CK2beta also has roles that are independent of CK2 enzymatic
        activity and these include the negative regulation of cell proliferation
- term:
    id: GO:0065003
    label: protein-containing complex assembly
  evidence_type: NAS
  original_reference_id: PMID:19324893
  qualifier: involved_in
  review:
    summary: CK2beta is important in the assembly of the CK2 holoenzyme (beta-dimer-mediated
      self-assembly bridging the catalytic subunits). Supported, and closely tied
      to its core scaffolding role, though the term is general.
    action: KEEP_AS_NON_CORE
    reason: Reflects CK2beta's role in holoenzyme assembly; accurate but general, and
      overlaps the more specific kinase-regulator/adaptor annotations.
    supported_by:
    - reference_id: PMID:19324893
      supporting_text: The CK2beta subunit is important in the assembly of CK2, enzyme
        stability and enzyme activity.
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IPI
  original_reference_id: PMID:19233263
  qualifier: enables
  review:
    summary: CK2 (regulatory subunit) interacts with adiponectin receptor 1 (AdipoR1,
      Q96A54) and participates in adiponectin signaling. A specific receptor interaction.
    action: KEEP_AS_NON_CORE
    reason: Genuine specific receptor interaction (AdipoR1), but partner docking rather
      than a core defining molecular function.
    supported_by:
    - reference_id: PMID:19233263
      supporting_text: Protein kinase CK2 interacts with adiponectin receptor 1 and
        participates in adiponectin signaling
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19233263
  qualifier: located_in
  review:
    summary: Cytoplasmic localization observed in the adiponectin-signaling study.
      Consistent with the broadly cytoplasmic distribution of CK2.
    action: ACCEPT
    reason: Cytoplasmic localization of CK2beta is well supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:19233263
  qualifier: colocalizes_with
  review:
    summary: CK2 colocalizes with the plasma membrane in the AdipoR1 context (receptor-associated).
      A context-specific colocalization, not a defining location.
    action: KEEP_AS_NON_CORE
    reason: Context-specific colocalization with a membrane receptor; non-core.
    supported_by:
    - reference_id: PMID:19233263
      supporting_text: interacts with adiponectin receptor 1
- term:
    id: GO:0033211
    label: adiponectin-activated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:19233263
  qualifier: involved_in
  review:
    summary: CK2 participates in adiponectin (AdipoR1) signaling; the CK2 inhibitor
      DMAT modulates the pathway. A specific, experimentally supported signaling role;
      non-core.
    action: KEEP_AS_NON_CORE
    reason: Specialized, context-specific signaling role; non-core for the regulatory
      subunit.
    supported_by:
    - reference_id: PMID:19233263
      supporting_text: participates in adiponectin signaling
- term:
    id: GO:0019887
    label: protein kinase regulator activity
  evidence_type: NAS
  original_reference_id: PMID:2666134
  qualifier: enables
  review:
    summary: Protein kinase regulator activity, the core molecular function of CSNK2B,
      asserted from the original cDNA cloning paper. Core MF.
    action: ACCEPT
    reason: Core molecular function of the CK2 regulatory subunit.
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IPI
  original_reference_id: PMID:11984006
  qualifier: enables
  review:
    summary: CSNK2B binds the Chediak-Higashi protein (LYST, Q99698) as a signal-transduction-associated
      interactor. A specific domain interaction, but partner-binding rather than a
      core defining function.
    action: KEEP_AS_NON_CORE
    reason: Specific interaction reported in a single Y2H/interaction study; partner
      docking, non-core.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: TAS
  original_reference_id: PMID:2513884
  qualifier: involved_in
  review:
    summary: Very general 'signal transduction' assertion from the original cDNA characterization.
      CK2 does participate broadly in signaling, but this term is uninformatively general.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly general process term; the specific CK2-modulated pathways are better
      captured by the dedicated signaling annotations.
- term:
    id: GO:0005956
    label: protein kinase CK2 complex
  evidence_type: NAS
  original_reference_id: PMID:2666134
  qualifier: part_of
  review:
    summary: CSNK2B as part of the CK2 complex, asserted in the original cDNA cloning
      paper. Core CC annotation.
    action: ACCEPT
    reason: CSNK2B is a constitutive subunit of the CK2 holoenzyme.
core_functions:
- description: Regulatory (beta) subunit of the protein kinase CK2 holoenzyme - a non-catalytic
    protein kinase regulatory subunit that dimerizes and bridges the two catalytic
    subunits (CSNK2A1/CSNK2A2), stabilizing the holoenzyme and modulating its basal
    activity and substrate selectivity.
  molecular_function:
    id: GO:0019887
    label: protein kinase regulator activity
  in_complex:
    id: GO:0005956
    label: protein kinase CK2 complex
  supported_by:
  - reference_id: PMID:11574463
    supporting_text: the regulatory subunits form a stable dimer linking the two catalytic
      subunits, which make no direct contact with one another
  - reference_id: PMID:19324893
    supporting_text: The CK2beta subunit is important in the assembly of CK2, enzyme
      stability and enzyme activity.
- description: Molecular adaptor/scaffold that recruits specific substrates and partner
    proteins to the CK2 holoenzyme (e.g. via its C-terminal region and the KSSR protein-interaction
    pocket), redirecting CK2 activity toward selected substrates and bridging interactions
    such as ARK2N-Jun.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  supported_by:
  - reference_id: PMID:31341047
    supporting_text: silencing of CK2β, but not the CK2α catalytic subunit, abrogated the ARKL1-Jun interaction and phenocopied ARKL1 silencing in promoting EBV reactivation
  - reference_id: PMID:20719947
    supporting_text: protein interactions with CK2β can redirect CK2 to increase
      CK2 activity toward specific substrates
- description: As part of the constitutively active CK2 holoenzyme, contributes to serine/threonine
    protein phosphorylation of acidic-motif substrates (consensus S/T-X-X-D/E), the
    biochemical activity underlying CK2's pleiotropic downstream roles.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  in_complex:
    id: GO:0005956
    label: protein kinase CK2 complex
  supported_by:
  - reference_id: PMID:28031292
    supporting_text: CK2 is a highly pleiotropic and constitutively active enzyme mainly
      present in cells as a tetramer, composed of two catalytic (α and/or α') and
      two regulatory (β) subunits.
proposed_new_terms: []
suggested_questions:
- question: Which biological functions of CSNK2B are genuinely independent of the CK2 catalytic subunits (e.g. monomeric/free CK2beta roles) versus mediated through the holoenzyme?
- question: Does POBINDS pathology arise primarily from reduced CK2 holoenzyme activity (haploinsufficiency) or from loss of specific CK2beta adaptor/substrate-recruitment functions?
- question: How does the KSSR protein-interaction pocket shape the spectrum of CK2beta-dependent substrates and partners across tissues?
suggested_experiments:
- description: Quantitative phosphoproteomics comparing CSNK2B-null/knockdown versus wild-type cells to define the CK2beta-dependent substrate landscape and distinguish holoenzyme-dependent from beta-independent effects.
- description: Structure-guided separation-of-function mutants (e.g. KSSR pocket, C-terminal alpha-contact region, zinc-finger dimerization) to dissect adaptor/substrate-recruitment roles from holoenzyme assembly and basal-activity regulation.
- description: Modeling POBINDS variants (truncating and missense) in neuronal systems to test holoenzyme assembly, stability, basal CK2 activity, and effects on specific substrate phosphorylation.