CSNK2B / CK2beta (P67870) - the regulatory subunit of casein kinase 2, in the pan-MLL-fusion core, with no CSNK2B-and-KMT2A literature at all
also called CSNK2B · CK2beta · CK2B · CK2N · G5A · casein kinase II subunit beta · phosvitin
CK2 is a always-on kinase that tags other proteins with phosphate; CSNK2B is its regulatory half, which decides which proteins the kinase will find. It co-purifies with every MLL fusion tested, which matters here because this project already suspects CK2 of switching a key contact on the surviving half of the fusion protein on and off.
The same thing, for a scientist
CSNK2B (P67870, 215 aa) is the beta regulatory subunit of protein kinase CK2, which assembles as an alpha2-beta2 holoenzyme and whose beta subunit governs substrate selection and stability rather than catalysis. In Skucha 2018 it co-purified with all seven MLL fusions, MLL-AF4 (= KMT2A::AFF1) at p = 0.0119 with 3|3 spectra and a clean 0|0 negative control. It is a low-abundance call - three spectra in each replicate - but it is pan-fusion and it lands directly on an existing beat in this graph: mechanism-ck2-t2724-s2726-licenses-taspase1-cleavage and hyp-ck2-is-the-second-handle-on-the-retained-fragment both argue that CK2 acts on the retained KMT2A fragment. Those entries are built on the catalytic subunits (this graph holds gene-csnk2a1 and gene-csnk2a2); the regulatory subunit had no entry, and the Skucha row is the first direct physical evidence that any CK2 subunit is in a KMT2A-fusion purification. Independent function comes from two conditional knockouts in haematopoiesis: CK2beta is required for normal HSC biology and erythropoiesis in mouse, and B-cell-specific CK2beta deletion shifts B cells toward the marginal zone through de-repressed NOTCH2 signalling - a B-lineage phenotype, which is rare among this beat's proteins.
The Skucha row
7 of 7 fusions. MLL-AF1p 0.00881 (3|3), MLL-AF4 0.0119 (3|3), MLL-AF9 0.0125 (8|6), MLL-CBP 0.0959 (1|9), MLL-EEN 0.00432 (9|14), MLL-ENL 0.00133 (8|12), MLL-GAS7 0.00759 (9|11); negative control 0|0 1. Note the MLL-CBP value, p = 0.0959 with 1|9 spectra, is above any conventional threshold and is counted as an interaction only because the paper's rule is a rank cutoff - a concrete instance of why the '7 of 7' label must be read as 'in the top 300 for each of seven baits', not as 'significant seven times'.
Why this row is worth more than three spectra usually are
This graph already contains a CK2 beat: mechanism-ck2-t2724-s2726-licenses-taspase1-cleavage and hyp-ck2-is-the-second-handle-on-the-retained-fragment, plus exp-ck2-inhibitor-two-route-separation and the LEDGF phospho-switch entries. Those were built from kinase-substrate and phospho-site evidence, not from a physical interaction with a fusion. The Skucha row supplies, for the first time in this graph, a CK2 subunit recovered from an MLL-fusion affinity purification - and it is the regulatory subunit, the one that determines which substrates CK2 sees. It does not establish a direct contact, and CK2 is an abundant, promiscuous nuclear kinase whose subunits are common in interaction datasets.
Independent function, and unusually for this beat it is in B cells
Conditional deletion of CK2beta in mouse haematopoiesis increases fetal-liver HSC numbers and proliferation, alters quiescence and lineage-commitment transcription factors, and cripples HSPC function in transplantation 2. A B-cell-specific CK2beta knockout expands marginal-zone B cells at the expense of follicular B cells through increased NOTCH2 signalling, and impairs class-switched germinal-centre output 3. This graph's disease begins in a fetal-liver or pro-B compartment, so both systems are closer to the index disease than most evidence in this beat - though both are mouse and neither involves a fusion.
The counted absence
CSNK2B[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR "MLL-AF4"[tiab] OR "MLL-AF9"[tiab]) returns 0 records (querytranslation recorded in data; positive control through the identical shape with MEN1 returns 85). Widening to the pathway name, CK2[tiab] AND (KMT2A[tiab] OR MLL[tiab]) returns 2, and title-checking leaves 0 about CK2 acting on a KMT2A fusion: PMID 42378254 is about phosphorylated DEK and PBX3, PMID 39940843 measures CK2 transcript levels across paediatric ALL subgroups (reporting CK2 above healthy donors in B-ALL, with MYC rather than CK2 singled out in the MLL-rearranged subgroup). Per this project's standing rule, the zero is bounded by titles and abstracts only - a CK2 measurement sitting in a supporting figure of a KMT2A paper would be invisible to it.
| uniprot | P67870 |
|---|---|
| length AA | 215 |
| accession resolution | Resolved live 2026-09-21: gene_exact:CSNK2B AND organism_id:9606 AND reviewed:true returns exactly one row, gene_primary CSNK2B, P67870, CSK2B_HUMAN, 215 aa, synonyms CK2N and G5A. Note the related trap already in this graph's rule set: CSNK2A1 is an ALIAS SYMBOL of CSNK2A2, so the catalytic subunits can be swapped by an alias-matching lookup. CSNK2B is not affected by that collision - it is a different gene product of a different length (215 aa against 391 and 350). |
| localization | Nucleus (and cytoplasm; CK2 is not compartment-restricted) |
| subnuclear localization | Not assigned. No published experiment places CK2beta in a named subnuclear compartment in any KMT2A-rearranged cell. |
| localization evidence | UniProt P67870 records a single subcellular location, Nucleus, with one ECO:0000269 experimental citation. Fetched 2026-09-21. The absence of a cytoplasmic annotation on the UniProt record should not be read as absence of a cytoplasmic pool - CK2 holoenzyme is well described in both compartments. |
| shown for fusion | KMT2A::AFF1 (MLL-AF4) plus all six other Skucha baits, by co-purification only. NO independent experiment ties CSNK2B to a KMT2A fusion in any system. |
| graph context | This graph holds gene-csnk2a1 and gene-csnk2a2 (catalytic subunits) and a CK2 mechanism beat - mechanism-ck2-t2724-s2726-licenses-taspase1-cleavage, hyp-ck2-is-the-second-handle-on-the-retained-fragment, exp-ck2-inhibitor-two-route-separation - but held no entry for the regulatory subunit before this one. CSNK2B appeared in exactly one node file before today (grep -rl, 2026-09-21). |
skucha 2018
{
"bait": "MLL-AF4 (= KMT2A::AFF1)",
"p_value": 0.0119,
"spectral_counts": "3|3",
"n_fusions_of_seven": 7,
"negative_control_counts": "0|0",
"per_bait": {
"MLL-AF1p": "0.00881 (3|3)",
"MLL-AF4": "0.0119 (3|3)",
"MLL-AF9": "0.0125 (8|6)",
"MLL-CBP": "0.0959 (1|9)",
"MLL-EEN": "0.00432 (9|14)",
"MLL-ENL": "0.00133 (8|12)",
"MLL-GAS7": "0.00759 (9|11)"
},
"source": "analyses/skucha-mll-fusion-interactome/results.json, re-derived from the cached MOESM4 xlsx on 2026-09-21"
}cell types and states
[ "Jurkat (human T-ALL) - AP-MS host, nuclear lysate", "mouse fetal-liver HSC and HSPC, conditional CK2beta knockout - increased HSC number, impaired transplantation", "mouse B cells, B-cell-specific CK2beta knockout - marginal-zone expansion via NOTCH2, impaired class switching", "no KMT2A-rearranged cell of any kind" ]
bounded literature
{
"query": "CSNK2B[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab])",
"querytranslation": "\"CSNK2B\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract])",
"count": 0,
"date": "2026-09-21",
"tool": "NCBI esearch db=pubmed",
"positive_control": "the identical query shape with MEN1 in place of CSNK2B returns 85, so the instrument can return a one",
"pathway_name_query": "CK2[tiab] AND (KMT2A[tiab] OR MLL[tiab]) returns 2, querytranslation \"CK2\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract]); title-checked to 0 on topic (PMID 42378254 phospho-DEK/PBX3; PMID 39940843 CK2 transcript levels across paediatric ALL subgroups)",
"names_tried": [
"CSNK2B",
"CK2"
],
"bound": "Titles and abstracts only. A CK2 measurement inside a supporting figure of a KMT2A paper is unreachable by this query."
}functionally screened in the source paper
{
"_added": "king, cycle 48, 2026-09-21, after Q86 flagged that cycle-47 entries understate the record. Verified by me directly from the supplementary file, not from the paper's prose.",
"screened": true,
"library_symbol": "CSNK2B",
"shrnas_for_this_gene": 6,
"design": "Supplementary Table 6 / MOESM5 is 768 data rows, 128 unique gene symbols, EXACTLY 6 shRNAs each -- counted with openpyxl on 2026-09-21. Negative-selection RNAi screen in MLL-AF9-expressing MOLM-13.",
"what_this_DOES_establish": "Every one of the 128 conserved MLL-fusion interactors, this protein included, was functionally tested against an MLL fusion. An entry saying 'nothing in the paper validates this prey' is true of BINDING and understates the record.",
"what_this_does_NOT_establish": "A per-gene result. Scores are presented as heatmaps (Fig. 2c/2d) and no per-gene depletion value is tabulated, so for any individual gene the outcome is measured-not-reported. It is also MLL-AF9 MOLM-13, a myeloid line, not the index fusion and not B-lineage.",
"absence_class_for_the_per_gene_score": "measured-not-reported"
}- CK2beta is required for normal HSC function and for normal B-cell development in mouse. Any CK2-directed therapy in an infant is acting on a subunit whose loss impairs the very compartment that has to reconstitute.
- Published CK2 chemistry - CX-4945, TBB, DMAT - is pan-catalytic-subunit and does not distinguish CSNK2A1 from CSNK2A2, let alone deliver a beta-subunit-selective effect. A hypothesis about the regulatory subunit cannot currently be tested with the available drugs.
- CK2 is one of the most promiscuous kinases in the cell; an interactome row of three spectra is a weak basis for an intervention and should be replaced by a targeted co-IP before anything is designed around it.
- Are CSNK2A1 or CSNK2A2 also in the Skucha 960-protein network? If the holoenzyme is present rather than the beta subunit alone, the row becomes a complex-level observation and much harder to dismiss as background.
- Does CK2 holoenzyme co-immunoprecipitate with the endogenous KMT2A::AFF1 fusion in a t(4;11) line, and does CX-4945 change the fusion's interactome?
- The existing hypothesis is that CK2 phosphorylates the retained KMT2A fragment. Does the fusion's association with CK2beta depend on that phosphosite, or is it upstream of it?
- Is CK2beta's marginal-zone/NOTCH2 phenotype relevant at the pro-B stage at all, given that stage precedes a surface B-cell receptor?
- E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper
CSNK2B co-purified with all seven Strep-HA-tagged MLL fusions in isogenic Jurkat cells, with MLL-AF4 (= KMT2A::AFF1) at combined p = 0.0119, 3|3 spectral counts, negative control 0|0.
MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. · Skucha A, Ebner J, Schmoellerl J, Roth M, Eder T, Cesar-Razquin A, Stukalov A, Vittori S, Muhar M, Lu B, Aichinger M, Jude J, Mueller AC, Gyorffy B, Vakoc CR, Valent P, Bennett KL, Zuber J, Superti-Furga G, Grebien F · Nature Communications 2018What this evidence cannot show
SYSTEM: the AP-MS host is JURKAT, a T-ALL line, whereas KMT2A::AFF1 disease is B-lineage infant leukaemia, so a partner that needs a B-cell or infant proteome cannot appear here and a T-lineage partner can appear spuriously. The bait is a Strep-HA-tagged, SINGLE-COPY, doxycycline-INDUCED transgene, not the endogenous fusion. Prey was recovered from bulk nuclear lysate, so co-purification is not evidence of a direct contact. INCLUSION RULE: the paper kept the top 300 interactions per bait by combined p-value rather than applying a p threshold (Methods, verbatim: "The 300 most significant interactions per bait were retained"). Measured by this beat by reading the cached Supplementary Table 5 xlsx directly on 2026-09-21: 545 of the 2,049 per-bait p-values in the table (26.6%) exceed 0.05, to a maximum of 0.175. This graph's own king analysis ana-the-index-fusion-interactome-is-not-distinctive-and-two-earlier-answers-were-artifacts found the MLL-AF4 column reaches deepest into the weak tail of the seven, so an MLL-AF4 p-value is systematically weaker than the same protein's p-value under another bait and should not be read as a weaker interaction. Three spectra in each replicate is a low-abundance identification, and CK2 subunits are abundant and promiscuous. The MLL-CBP call for this protein (p = 0.0959, 1|9) is above any conventional significance threshold and is included only by the rank rule, so '7 of 7' overstates the consistency for this particular protein. Values re-read from the cached xlsx on 2026-09-21.
Evidence that argues against this (1)
- IntAct has never curated this dataset (pubid:29777171 returns 0 rows against a working positive control), so no independent curator has re-examined these calls, and the raw data at ProteomeXchange PXD009338 have not been reanalysed here. Nothing in the paper validates this particular prey by an orthogonal assay: of the twelve proteins in this beat, only SETD2 is mentioned anywhere in the paper's body text (counted by regex over the PMC full text, 2026-09-21; SF3A3 appears once, as a named non-selective control). ProteomeXchange/PRIDE 2018
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
CK2beta is required for normal haematopoiesis in mouse: conditional CK2beta-knockout fetal livers show increased HSC numbers with higher proliferation, altered expression of quiescence, self-renewal and lineage-commitment transcription factors, and HSPCs that fail to support haematopoiesis in transplantation.
CK2beta Regulates Hematopoietic Stem Cell Biology and Erythropoiesis. · Quotti Tubi L, Canovas Nunes S, Mandato E, Pizzi M, Vitulo N, et al. · HemaSphere 2023What this evidence cannot show
Mouse conditional knockout, normal haematopoiesis, no fusion and no leukaemia. Fetal-liver HSCs are the compartment this graph proposes as the cell of origin for infant KMT2A::AFF1, which is why this system is worth recording, but a knockout phenotype in normal cells says nothing about a fusion interaction. Read from the abstract.
Evidence that argues against this (1)
- A requirement in normal HSCs is an argument AGAINST CK2beta as a therapeutic target in an infant, not for it. Quotti Tubi L et al. 2022
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
B-cell-specific deletion of CK2beta in mouse increases marginal-zone and reduces follicular B cells through increased NOTCH2 pathway activation, and limits the generation of class-switched germinal-centre B cells and immunoglobulins.
CK2beta-regulated signaling controls B cell differentiation and function. · Quotti Tubi L, Mandato E, Canovas Nunes S, Arjomand A, Zaffino F, et al. · Front Immunol 2022What this evidence cannot show
Mouse, mature B-cell compartments (marginal zone, follicular, germinal centre) - not the pro-B or fetal-liver progenitor stage where infant KMT2A::AFF1 arises, and not a leukaemia. Read from the abstract. It is cited here because B-lineage CK2beta biology exists at all, which is more than can be said for most proteins in this beat.
Evidence that argues against this (1)
- Mature-B phenotypes may not transfer to a pro-B blast; a BCR-dependent phenotype in particular cannot, because the pro-B stage precedes a surface BCR. Quotti Tubi L et al. 2023
co-purified with MLL-AF4 in Jurkat AP-MS, p=0.0119, 3|3 spectra - low abundance, no orthogonal validation
- part of →CSNK2A1 (casein kinase 2 alpha) - the one kinase that turns up three separate times in KMT2A biology
beta regulatory subunit of the CK2 alpha2-beta2 holoenzyme
beta regulatory subunit of the CK2 alpha2-beta2 holoenzyme (CK2alpha' catalytic subunit)
first physical recovery of any CK2 subunit from an MLL-fusion affinity purification - the regulatory one
pan-fusion Skucha interactor with no gene entry before cycle 47
Both subunits' compartments are recorded as 'nucleus and cytoplasm; CK2 is not compartment-restricted', and for alpha-prime that string is a mouse inference. If the functional unit is the alpha2-beta2 holoenzyme, the address of a free catalytic subunit is a fact about a species that may barely exist - nobody has localised an alpha-prime-containing holoenzyme in any cell (Q93 2026-09-21)