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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: CK2beta is predominantly nuclear (and cytoplasmic); nuclear localization is well supported experimentally. Accept as a correct, if general, localization. Reason: Nucleus is a documented subcellular location of CSNK2B (UniProt SUBCELLULAR LOCATION; experimental nucleus annotations from PMID:31341047 and PMID:21282530). |
| GO:0005956 protein kinase CK2 complex | IEA GO_REF:0000002 | ACCEPT | 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. Reason: Direct structural and biochemical evidence places CSNK2B as the regulatory subunit bridging the two catalytic subunits in the CK2 holoenzyme. Supporting Evidence: PMID:11574463 In the CK2 complex the regulatory subunits form a stable dimer linking the two catalytic subunits, which make no direct contact with one another. |
| GO:0019887 protein kinase regulator activity | IEA GO_REF:0000002 | ACCEPT | 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. Reason: CSNK2B is the prototypical protein kinase regulatory subunit; this term captures its central non-catalytic function within the holoenzyme. Supporting Evidence: PMID:19324893 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. |
| GO:0005515 protein binding | IPI PMID:10094392 Interactions of protein kinase CK2beta subunit within the ho... | MARK AS OVER ANNOTATED | 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. Reason: Bare GO:0005515 conveys no specific molecular function; the biologically meaningful relationships (CK2 holoenzyme assembly) are captured by more specific terms. |
| GO:0005515 protein binding | IPI PMID:11574463 Crystal structure of human protein kinase CK2: insights into... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (interaction with CSNK2A1 from the holoenzyme crystal structure). The specific, informative content is the CK2 complex membership. Reason: Bare protein binding is uninformative; holoenzyme assembly is captured by GO:0005956 and GO:0019887. |
| GO:0005515 protein binding | IPI PMID:12769847 Phosphorylation of the WASP-VCA domain increases its affinit... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:14667819 Analysis of a high-throughput yeast two-hybrid system and it... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a high-throughput MHC class III Y2H study (CSNK2A1/CSNK2A2). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:16977309 A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking. | MARK AS OVER ANNOTATED | Summary: Generic protein binding (PACS1) from the PACS-1/GGA3/CK2 trafficking complex study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:19011756 KIF5C: a new binding partner for protein kinase CK2 with a p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (KIF5C/CK2 interaction; CSNK2A subunits). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:20664522 Phosphorylation of CLIP-170 by Plk1 and CK2 promotes timely ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CLIP-170/CLIP1). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:21078624 Comparison of an expanded ataxia interactome with patient me... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CACNA1A) from an expanded ataxia interactome. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:21282530 Interaction proteomics analysis of polycomb proteins defines... | MARK AS OVER ANNOTATED | 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. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (NMT2, CENPB) from a directed signal-transduction interaction network. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:21968188 p53 deacetylation by SIRT1 decreases during protein kinase C... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (SIRT1, CSNK2A1) from a CK2/SIRT1/p53 senescence study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a large-scale human liver interactome (CSNK2A1/CSNK2A2, RSK2/RPS6KA3, MSK1/RPS6KA5, PHRF1). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A2) from a standardized AP-MS reproducibility study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:23555304 Dynamic circadian protein-protein interaction networks predi... | MARK AS OVER ANNOTATED | 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. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:24535599 Phosphorylation of Grb14 BPS domain by GSK-3 correlates with... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) from a Grb14/insulin receptor study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) from the AUTS2-Polycomb study. Uninformative function term; the substantive finding (CK2 in PRC1-AUTS2) is captured elsewhere. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) from a TRAIL-apoptosis kinase network. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A2) from a quantitative human interactome. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:26562092 CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Cont... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CRY1, BMAL1) from the CRY/CK2/BMAL1 circadian study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:26711270 A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) from an ECD/RUVBL1/R2TP study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A2, RNF2, CSNK2A1) from a Polycomb complexome map. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) from the LuTHy two-hybrid technology paper. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (RSK2/RPS6KA3) from an EGFR-network rewiring study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a binary interactome reference map (many partners). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a kinase interaction network (CSNK2A1/A2, RSK2, MSK1). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) from a neurodegenerative-disease interactome. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a proteome-scale cell-specific interactome (CSNK2A1/A2, RSK2, MSK1, RNF2, PHRF1). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from OpenCell endogenous-tagging interactome (CSNK2A1/A2, RSK2, NMT2, CENPB, RNF2, RBM39). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:36833176 Haploinsufficiency as a Foreground Pathomechanism of Poirer-... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) reported alongside POBINDS disease modeling. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:36876296 Analyzing the interactome of human CK2Ξ² in prostate carcinom... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a CK2beta prostate-carcinoma interactome (CSNK2A2, HSP70-1, ARHGEF12). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:38225382 Systematic discovery of protein interaction interfaces using... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CSNK2A1) from an AlphaFold-guided interface-discovery study. Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a multimodal cell-map interactome (many partners including CSNK2A1/A2, RNF2, PHRF1). Uninformative function term. Reason: Bare protein binding conveys no specific molecular function. |
| GO:0042802 identical protein binding | IPI PMID:10094392 Interactions of protein kinase CK2beta subunit within the ho... | ACCEPT | 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. Reason: CSNK2B homodimerization (beta dimer) is well established structurally and is required for holoenzyme assembly. Supporting Evidence: PMID:11574463 the regulatory subunits form a stable dimer linking the two catalytic subunits |
| GO:0042802 identical protein binding | IPI PMID:14667819 Analysis of a high-throughput yeast two-hybrid system and it... | ACCEPT | Summary: CSNK2B homodimerization (beta dimer), recovered in a Y2H screen. Supported. Reason: CSNK2B self-association into the beta dimer is structurally established. |
| GO:0042802 identical protein binding | IPI PMID:21282530 Interaction proteomics analysis of polycomb proteins defines... | ACCEPT | Summary: CSNK2B homodimerization recovered in PRC1 interaction proteomics. Supported. Reason: CSNK2B self-association into the beta dimer is structurally established. |
| GO:0042802 identical protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | ACCEPT | Summary: CSNK2B homodimerization recovered in a liver interactome. Supported. Reason: CSNK2B self-association into the beta dimer is structurally established. |
| GO:0042802 identical protein binding | IPI PMID:23555304 Dynamic circadian protein-protein interaction networks predi... | ACCEPT | Summary: CSNK2B homodimerization recovered in a circadian PPI network. Supported. Reason: CSNK2B self-association into the beta dimer is structurally established. |
| GO:0042802 identical protein binding | IPI PMID:36876296 Analyzing the interactome of human CK2Ξ² in prostate carcinom... | ACCEPT | Summary: CSNK2B homodimerization recovered in a CK2beta prostate-carcinoma interactome. Supported. Reason: CSNK2B self-association into the beta dimer is structurally established. |
| GO:0005956 protein kinase CK2 complex | IPI PMID:22506723 Structural determinants of protein kinase CK2 regulation by ... | ACCEPT | Summary: CSNK2B as part of the CK2 complex, from a structural study of CK2 autoinhibitory polymerization (ComplexPortal). Core CC annotation. Reason: CSNK2B is a constitutive subunit of the CK2 holoenzyme. |
| GO:0001650 fibrillar center | IDA GO_REF:0000052 | KEEP AS NON CORE | 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. Reason: A specific nuclear sublocalization from HPA imaging; consistent with the broadly nuclear distribution of CK2 but not a defining location. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence localizes CSNK2B to the nucleoplasm, consistent with its well-documented nuclear distribution. Reason: Nucleoplasmic/nuclear localization of CK2beta is well supported. |
| GO:0005634 nucleus | EXP PMID:31341047 Identification of ARKL1 as a Negative Regulator of Epstein-B... | ACCEPT | Summary: Experimental nuclear localization of CSNK2B (acting at the EBV Z promoter with ARKL1/Jun). Core localization. Reason: Direct experimental evidence for nuclear localization. Supporting Evidence: PMID:31341047 ARKL1 was associated with Zp in reporter assays and this was increased by additional CK2Ξ² |
| GO:0000785 chromatin | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | KEEP AS NON CORE | 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. Reason: Chromatin association is plausible (CK2 in PRC1-AUTS2 and at promoters) but is a context-specific, complex-driven localization, not the core CC. |
| GO:0031507 heterochromatin formation | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | MARK AS OVER ANNOTATED | 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. 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. |
| GO:0035102 PRC1 complex | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:25519132 the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of P300 leads to gene activation |
| GO:0045893 positive regulation of DNA-templated transcription | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | KEEP AS NON CORE | 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. Reason: Process driven by the broader PRC1-AUTS2 complex; CSNK2B's direct contribution is kinase-regulatory (phosphorylation of RING1B by embedded CK2). Supporting Evidence: PMID:25519132 the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of P300 leads to gene activation |
| GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process | IDA PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:28031292 the phosphorylation of HSJ1 by CK2 reduced its ability to bind ubiquitylated clients |
| GO:0060391 positive regulation of SMAD protein signal transduction | IDA PMID:19592636 Casein kinase 2beta as a novel enhancer of activin-like rece... | KEEP AS NON CORE | 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. Reason: Well-supported but specialized signaling role (one of many CK2-modulated pathways); non-core for the regulatory subunit. Supporting Evidence: PMID:19592636 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. |
| GO:0000785 chromatin | IDA PMID:31341047 Identification of ARKL1 as a Negative Regulator of Epstein-B... | KEEP AS NON CORE | 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. Reason: Experimentally supported but context-specific (EBV Zp); chromatin is not the defining location of the CK2 regulatory subunit. Supporting Evidence: PMID:31341047 ARKL1 was associated with Zp in reporter assays and this was increased by additional CK2Ξ² |
| GO:0016605 PML body | IDA PMID:20719947 Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase... | KEEP AS NON CORE | 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. Reason: Experimentally supported but infection-context-specific; not the core CK2beta location. Supporting Evidence: PMID:20719947 protein interactions with CK2Ξ² can redirect CK2 to increase CK2 activity toward specific substrates |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:31341047 Identification of ARKL1 as a Negative Regulator of Epstein-B... | ACCEPT | 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. 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. Supporting Evidence: PMID:31341047 silencing of CK2Ξ², but not the CK2Ξ± catalytic subunit, abrogated the ARKL1-Jun interaction and phenocopied ARKL1 silencing in promoting EBV reactivation |
| GO:0075342 symbiont-mediated disruption of host cell PML body | IDA PMID:20719947 Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase... | KEEP AS NON CORE | 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. Reason: Experimentally supported microbial-infection process; a hijacked, context-specific role rather than a core CSNK2B function. Supporting Evidence: PMID:20719947 protein interactions with CK2Ξ² can redirect CK2 to increase CK2 activity toward specific substrates |
| GO:1903901 negative regulation of viral life cycle | IDA PMID:31341047 Identification of ARKL1 as a Negative Regulator of Epstein-B... | KEEP AS NON CORE | 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. Reason: Experimentally supported but context-specific (EBV reactivation); not a core CSNK2B function. Supporting Evidence: PMID:31341047 silencing of CK2Ξ², but not the CK2Ξ± catalytic subunit, abrogated the ARKL1-Jun interaction and phenocopied ARKL1 silencing in promoting EBV reactivation |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:19324893 CK2 phosphorylation of the PRH/Hex homeodomain functions as ... | KEEP AS NON CORE | 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. Reason: A genuine, specific TF interaction (PRH/HHEX), but it represents substrate/partner docking rather than a core, broadly defining molecular function. Supporting Evidence: PMID:19324893 PRH interacts with the beta subunit of CK2 in vitro and in cells |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | ACCEPT | 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. 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. Supporting Evidence: PMID:28031292 CK2 is a highly pleiotropic and constitutively active enzyme mainly present in cells as a tetramer, composed of two catalytic (Ξ± and/or Ξ±') and two regulatory (Ξ²) subunits. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:15723517 Interactions of the HIV-1 Tat and RAP74 proteins with the RN... | MODIFY | 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. 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 replacements: protein kinase regulator activity |
| GO:0005956 protein kinase CK2 complex | IDA PMID:15723517 Interactions of the HIV-1 Tat and RAP74 proteins with the RN... | ACCEPT | Summary: CSNK2B as part of the CK2 complex (in the context of FCP1 phosphorylation). Core CC annotation. Reason: CSNK2B is a constitutive subunit of the CK2 holoenzyme. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | 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. Reason: Reactome bulk-secretome transfer; not a biologically informative location for an intracellular kinase regulatory subunit. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Extracellular region via ficolin-rich granule exocytosis (Reactome neutrophil degranulation). Bulk-secretome transfer, not core. Reason: Reactome bulk-secretome transfer; not a biologically informative location. |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Secretory granule lumen from neutrophil-degranulation Reactome transfer. Not a core localization of an intracellular kinase subunit. Reason: Reactome neutrophil-degranulation bulk transfer; not biologically informative for CSNK2B. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Ficolin-1-rich granule lumen from neutrophil-degranulation Reactome transfer. Not core. Reason: Reactome neutrophil-degranulation bulk transfer; not biologically informative for CSNK2B. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805059 | ACCEPT | Summary: Nucleoplasm from Reactome (CK2:FACT phosphorylates TP53). Consistent with the documented nuclear localization of CK2beta. Reason: Nucleoplasmic localization is consistent with experimental nuclear localization of CSNK2B. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805061 | ACCEPT | Summary: Nucleoplasm from Reactome (CK2 binds FACT). Consistent with nuclear localization. Reason: Nucleoplasmic localization is consistent with experimental nuclear localization of CSNK2B. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9831712 | ACCEPT | Summary: Nucleoplasm from Reactome (M dimer phosphorylation pathway). Consistent with nuclear localization. Reason: Nucleoplasmic localization is consistent with experimental nuclear localization of CSNK2B. |
| GO:0003682 chromatin binding | IDA PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | KEEP AS NON CORE | 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. Reason: Chromatin binding via PRC1-AUTS2 complex membership; context-specific rather than a core molecular function of the kinase regulatory subunit. Supporting Evidence: PMID:25519132 the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive activity |
| GO:0032927 positive regulation of activin receptor signaling pathway | IMP PMID:19592636 Casein kinase 2beta as a novel enhancer of activin-like rece... | KEEP AS NON CORE | 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. Reason: Well-supported but specialized signaling role; non-core for the regulatory subunit. Supporting Evidence: PMID:19592636 siRNA-mediated silencing of endogenous CK2beta inhibited TGF-beta1 and BMP-9-stimulated Smad1/5/8 phosphorylation and ALK-1-mediated reporter activation |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: Nucleus from high-throughput proteomic characterization of the sperm nucleus. Consistent with the well-documented nuclear localization of CSNK2B. Reason: Nuclear localization is well supported; this HDA annotation is concordant. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | 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. Reason: High-throughput proteomic detection in exosomes; not a biologically informative core localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201717 | ACCEPT | Summary: Cytosol from Reactome (CSNK2-mediated phosphorylation of DVL, Wnt signaling). CK2 is broadly cytosolic; cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2529020 | ACCEPT | Summary: Cytosol from Reactome (CK2 phosphorylates condensin I subunits). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392752 | ACCEPT | Summary: Cytosol from Reactome (phosphorylation of L1 by CK-II). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814409 | ACCEPT | Summary: Cytosol from Reactome (CK2 phosphorylates PDCL). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850945 | ACCEPT | Summary: Cytosol from Reactome (CK2 phosphorylates PTEN). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8873929 | ACCEPT | Summary: Cytosol from Reactome (CK2 phosphorylates STARD10). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948039 | ACCEPT | Summary: Cytosol from Reactome (FUNDC1 phosphorylation by CK2, mitophagy). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9831514 | ACCEPT | Summary: Cytosol from Reactome (CK2 phosphorylates nascent viral P protein). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9931418 | ACCEPT | Summary: Cytosol from Reactome (CK2 phosphorylates CD274/PD-L1). Cytosolic localization is accurate. Reason: Cytosolic localization of the CK2 holoenzyme is well established. |
| GO:0005102 signaling receptor binding | IPI PMID:19592636 Casein kinase 2beta as a novel enhancer of activin-like rece... | KEEP AS NON CORE | Summary: CK2beta binds the cytoplasmic domain of the signaling receptor ALK-1/ACVRL1 (P37023). A specific, experimentally mapped receptor interaction. Reason: A genuine specific receptor interaction (ALK-1), but partner/substrate docking rather than a core broadly defining molecular function. Supporting Evidence: PMID:19592636 The cytoplasmic domain of ALK-1 specifically binds to CK2beta in vitro and in vivo. |
| GO:0043537 negative regulation of blood vessel endothelial cell migration | IDA PMID:19592636 Casein kinase 2beta as a novel enhancer of activin-like rece... | KEEP AS NON CORE | Summary: CK2beta with ALK-1 inhibits endothelial cell migration. A specific, experimentally supported endothelial role downstream of ALK-1 signaling; non-core. Reason: Specialized, context-specific vascular role; non-core for the kinase regulatory subunit. Supporting Evidence: PMID:19592636 CK2beta enhanced the ability of activated or ligand-stimulated ALK-1 to inhibit endothelial cell migration |
| GO:0061154 endothelial tube morphogenesis | IMP PMID:19592636 Casein kinase 2beta as a novel enhancer of activin-like rece... | KEEP AS NON CORE | Summary: ALK-1 and CK2beta antagonize endothelial tubule formation in Matrigel. A specific, experimentally supported endothelial role; non-core. Reason: Specialized, context-specific vascular role; non-core. Supporting Evidence: PMID:19592636 ALK-1 and CK2beta antagonized endothelial tubule formation in Matrigel |
| GO:0005634 nucleus | IDA PMID:21282530 Interaction proteomics analysis of polycomb proteins defines... | ACCEPT | Summary: Experimental nuclear localization of CSNK2B from PRC1 interaction proteomics / imaging. Core localization. Reason: Direct evidence for nuclear localization, consistent with other experimental nucleus annotations. |
| GO:0031519 PcG protein complex | IDA PMID:21282530 Interaction proteomics analysis of polycomb proteins defines... | KEEP AS NON CORE | 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. Reason: Genuine but specialized association with Polycomb complexes; not the core CK2-holoenzyme identity. |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:1856204 Structure of the gene encoding human casein kinase II subuni... | ACCEPT | 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. Reason: contributes_to is the correct qualifier for a regulatory subunit of an active kinase complex. |
| GO:0008285 negative regulation of cell population proliferation | TAS PMID:19324893 CK2 phosphorylation of the PRH/Hex homeodomain functions as ... | KEEP AS NON CORE | 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. Reason: A reported (and somewhat context-dependent) role; non-core relative to the kinase-regulatory and complex annotations. Supporting Evidence: PMID:19324893 CK2beta also has roles that are independent of CK2 enzymatic activity and these include the negative regulation of cell proliferation |
| GO:0065003 protein-containing complex assembly | NAS PMID:19324893 CK2 phosphorylation of the PRH/Hex homeodomain functions as ... | KEEP AS NON CORE | 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. Reason: Reflects CK2beta's role in holoenzyme assembly; accurate but general, and overlaps the more specific kinase-regulator/adaptor annotations. Supporting Evidence: PMID:19324893 The CK2beta subunit is important in the assembly of CK2, enzyme stability and enzyme activity. |
| GO:0005102 signaling receptor binding | IPI PMID:19233263 Protein kinase CK2 interacts with adiponectin receptor 1 and... | KEEP AS NON CORE | Summary: CK2 (regulatory subunit) interacts with adiponectin receptor 1 (AdipoR1, Q96A54) and participates in adiponectin signaling. A specific receptor interaction. Reason: Genuine specific receptor interaction (AdipoR1), but partner docking rather than a core defining molecular function. Supporting Evidence: PMID:19233263 Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signaling |
| GO:0005737 cytoplasm | IDA PMID:19233263 Protein kinase CK2 interacts with adiponectin receptor 1 and... | ACCEPT | Summary: Cytoplasmic localization observed in the adiponectin-signaling study. Consistent with the broadly cytoplasmic distribution of CK2. Reason: Cytoplasmic localization of CK2beta is well supported. |
| GO:0005886 plasma membrane | IDA PMID:19233263 Protein kinase CK2 interacts with adiponectin receptor 1 and... | KEEP AS NON CORE | Summary: CK2 colocalizes with the plasma membrane in the AdipoR1 context (receptor-associated). A context-specific colocalization, not a defining location. Reason: Context-specific colocalization with a membrane receptor; non-core. Supporting Evidence: PMID:19233263 interacts with adiponectin receptor 1 |
| GO:0033211 adiponectin-activated signaling pathway | IDA PMID:19233263 Protein kinase CK2 interacts with adiponectin receptor 1 and... | KEEP AS NON CORE | Summary: CK2 participates in adiponectin (AdipoR1) signaling; the CK2 inhibitor DMAT modulates the pathway. A specific, experimentally supported signaling role; non-core. Reason: Specialized, context-specific signaling role; non-core for the regulatory subunit. Supporting Evidence: PMID:19233263 participates in adiponectin signaling |
| GO:0019887 protein kinase regulator activity | NAS PMID:2666134 Human phosvitin/casein kinase type II. Molecular cloning and... | ACCEPT | Summary: Protein kinase regulator activity, the core molecular function of CSNK2B, asserted from the original cDNA cloning paper. Core MF. Reason: Core molecular function of the CK2 regulatory subunit. |
| GO:0019904 protein domain specific binding | IPI PMID:11984006 The Chediak-Higashi protein interacts with SNARE complex and... | KEEP AS NON CORE | 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. Reason: Specific interaction reported in a single Y2H/interaction study; partner docking, non-core. |
| GO:0007165 signal transduction | TAS PMID:2513884 Cloning and characterization of a cDNA encoding the beta sub... | MARK AS OVER ANNOTATED | Summary: Very general 'signal transduction' assertion from the original cDNA characterization. CK2 does participate broadly in signaling, but this term is uninformatively general. Reason: Overly general process term; the specific CK2-modulated pathways are better captured by the dedicated signaling annotations. |
| GO:0005956 protein kinase CK2 complex | NAS PMID:2666134 Human phosvitin/casein kinase type II. Molecular cloning and... | ACCEPT | Summary: CSNK2B as part of the CK2 complex, asserted in the original cDNA cloning paper. Core CC annotation. Reason: CSNK2B is a constitutive subunit of the CK2 holoenzyme. |
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Download this section (compressed HTML)Q: Which biological functions of CSNK2B are genuinely independent of the CK2 catalytic subunits (e.g. monomeric/free CK2beta roles) versus mediated through the holoenzyme?
Q: Does POBINDS pathology arise primarily from reduced CK2 holoenzyme activity (haploinsufficiency) or from loss of specific CK2beta adaptor/substrate-recruitment functions?
Q: How does the KSSR protein-interaction pocket shape the spectrum of CK2beta-dependent substrates and partners across tissues?
Experiment: 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.
Experiment: 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.
Experiment: Modeling POBINDS variants (truncating and missense) in neuronal systems to test holoenzyme assembly, stability, basal CK2 activity, and effects on specific substrate phosphorylation.
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