NOLC1 / Nopp140 (Q14978) - a nucleolar and Cajal-body phosphoprotein in the pan-MLL-fusion core, and the first physical bridge to this graph's nucleolar convergence
also called NOLC1 · Nopp140 · p130 · NS5ATP13 · KIAA0035 · nucleolar and coiled-body phosphoprotein 1
NOLC1 (also called Nopp140) shuttles between the nucleolus - the cell's ribosome factory - and Cajal bodies, and it sits on the ribosomal DNA genes themselves. It co-purifies with every MLL fusion tested, which is the first physical link between the fusion protein and the nucleolar machinery this project has been circling for several cycles.
The same thing, for a scientist
NOLC1 (Q14978, 699 aa) is a highly phosphorylated chaperone that links the nucleolus to Cajal bodies, is recruited to nucleolar organiser region (NOR) chromatin in a UBF-dependent, transcription-independent manner, and provides the multivalent contacts with coilin that build Cajal bodies. In Skucha 2018 it co-purified with all seven MLL fusions; the MLL-AF4 (= KMT2A::AFF1) call is the weakest in this beat - p = 0.134 with spectral counts of **7|0**, meaning one replicate returned no spectra at all - while six other baits are strong, including MLL-AF1p at 4.03e-10 (20|20) and MLL-EEN at 1.47e-9 (49|45). This graph carries a standing unresolved convergence: KDM2B represses Pol I at rDNA, KMT2A and SETD1A bind whole rDNA loci, MLL-AF4 is predominantly nucleolar, and no publication contains two of the three. NOLC1 is a fourth line and the only one that is a physical association: a nucleolar, rDNA-associated protein recovered from an MLL-fusion purification. The MLL-AF4 measurement is too weak to carry that on its own, and the entry says so - but the pan-fusion pattern is not.
The Skucha row, and its weakness stated first
7 of 7 fusions. MLL-AF1p 4.03e-10 (20|20), MLL-AF4 0.134 (7|0), MLL-AF9 5.85e-7 (25|25), MLL-CBP 1.55e-4 (8|82), MLL-EEN 1.47e-9 (49|45), MLL-ENL 2.1e-8 (38|30), MLL-GAS7 0.0454 (6|10); negative control 0|0 1. The MLL-AF4 p-value of 0.134 is above any conventional threshold and one of its two replicates returned zero spectra. It is in the table only because the paper's rule keeps the top 300 per bait by rank. Read as an index-fusion measurement alone, this row supports nothing. Read as a pan-fusion pattern - six strong baits, two of them at 1e-9, in one isogenic system - it is one of the better-supported proteins in the whole 42-protein core.
Why this protein matters to a question this graph already has open
absence-kdm2b-and-the-kmt2a-fusion-are-both-nucleolar-and-nobody-has-put-them-together records three lines of evidence converging on rDNA - KDM2B repressing Pol I in the nucleolus, KMT2A and SETD1A binding entire rDNA loci, and MLL-AF4 being predominantly nucleolar and interfering with Pol I - with no publication containing two of them. All three are localisation or occupancy observations. NOLC1 adds a fourth line of a different kind: a physical co-purification. NOLC1 is recruited to NOR chromatin - the rDNA arrays themselves - UBF-dependently and independently of transcription 3, and it is nucleolar with an experimental UniProt code. So the fusion's purification contains a protein that sits on the locus the convergence is about. This entry does not claim the fusion binds rDNA through NOLC1; it records that the one piece of physical evidence that could bear on the convergence now exists and is weak.
What NOLC1 does
Nopp140 accumulates in the nucleolus and, after a lag, in coiled (Cajal) bodies, and dominant-negative partial constructs chase endogenous Nopp140 and shared antigens out of the nucleolus - the experiment that defined it as a molecular link between the two organelles 2. It is recruited with Treacle and the t-UTP pre-rRNA processing factors to NOR chromatin under UBF control 3. More recently, multivalent contacts between the coilin N-terminal domain and Nopp140 were shown to be required for Cajal body assembly, with Nopp140 itself having condensation capacity 4. So NOLC1 is a scaffolding component of two membraneless nuclear compartments and a resident of rDNA chromatin.
The counted absence
NOLC1[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR "MLL-AF4"[tiab] OR "MLL-AF9"[tiab]) returns 0, and the historical name Nopp140[tiab] AND (KMT2A[tiab] OR MLL[tiab]) also returns 0 - both querytranslations recorded in data, both against a positive control of 85 for MEN1 through the identical shape. NOLC1 and Nopp140 appear in zero node files in this graph before today. This is a protein with no KMT2A literature whatsoever, sitting in the core of the index fusion's own interactome.
| uniprot | Q14978 |
|---|---|
| length AA | 699 |
| accession resolution | Resolved live 2026-09-21: gene_exact:NOLC1 AND organism_id:9606 AND reviewed:true returns exactly one row, gene_primary NOLC1, Q14978, NOLC1_HUMAN, 699 aa, synonyms KIAA0035 and NS5ATP13. Matches Skucha's table. The common name Nopp140 does not appear in the gene-synonym field, which is why a symbol-only search misses the older literature - the historical name had to be searched separately. |
| localization | Nucleus, with a cytoplasmic pool (Nopp140 shuttles) |
| subnuclear localization | NUCLEOLUS (primary), and Cajal bodies; recruited to nucleolar organiser region (rDNA) chromatin. |
| localization evidence | UniProt Q14978, fetched 2026-09-21: 'Nucleus, nucleolus' with ECO:0000269 experimental evidence, and 'Cytoplasm' with ECO:0000269. The Cajal-body residence is established in the primary literature (E2, E4) rather than in the UniProt location list, which is an instance of the standing rule that the database's line is a pointer and not the best available source. |
| shown for fusion | KMT2A::AFF1 (MLL-AF4) by co-purification in Jurkat but at p = 0.134 with a zero-spectra replicate - not a usable index-fusion measurement on its own; strongly for MLL-AF1p, MLL-AF9, MLL-EEN, MLL-ENL and MLL-CBP in the same experiment. NO independent experiment ties NOLC1 to any KMT2A fusion. |
| graph context | NOLC1 and Nopp140 appear in ZERO node files in this graph before this entry (grep -rl over data/graph/nodes, 2026-09-21). The relevant existing entries are localization-nucleolus-kmt2a-fusion and absence-kdm2b-and-the-kmt2a-fusion-are-both-nucleolar-and-nobody-has-put-them-together; this entry adds a physical association to what were three localisation observations. |
| nucleolar convergence position | Fourth line, and the only physical one. The existing three are: KDM2B represses Pol I at rDNA; KMT2A and SETD1A bind whole rDNA loci; MLL-AF4 is predominantly nucleolar and interferes with Pol I. NOLC1 is nucleolar, rDNA-chromatin-recruited, and co-purifies with all seven MLL fusions. This entry deliberately does NOT assert that the convergence is now demonstrated - the index-fusion p-value is 0.134. |
skucha 2018
{
"bait": "MLL-AF4 (= KMT2A::AFF1)",
"p_value": 0.134,
"spectral_counts": "7|0",
"n_fusions_of_seven": 7,
"negative_control_counts": "0|0",
"per_bait": {
"MLL-AF1p": "4.03e-10 (20|20)",
"MLL-AF4": "0.134 (7|0)",
"MLL-AF9": "5.85e-07 (25|25)",
"MLL-CBP": "0.000155 (8|82)",
"MLL-EEN": "1.47e-09 (49|45)",
"MLL-ENL": "2.1e-08 (38|30)",
"MLL-GAS7": "0.0454 (6|10)"
},
"index_bait_warning": "p = 0.134 with one replicate at zero spectra. The index-fusion call is not significant by any conventional criterion and is included by the rank rule alone.",
"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", "cultured human cells - nucleolar/Cajal-body traffic, pseudo-NOR recruitment, coilin interaction", "no KMT2A-rearranged cell of any kind" ]
bounded literature
{
"query": "NOLC1[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab])",
"querytranslation": "\"NOLC1\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract])",
"count": 0,
"historical_name_query": "Nopp140[tiab] AND (KMT2A[tiab] OR MLL[tiab]) -> querytranslation \"Nopp140\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract]), count 0",
"names_tried": [
"NOLC1",
"Nopp140"
],
"date": "2026-09-21",
"tool": "NCBI esearch db=pubmed",
"positive_control": "the identical query shape with MEN1 returns 85",
"bound": "Titles and abstracts only; supporting figures not searched. Both the current symbol and the historical protein name were run, per the standing retired-symbol rule."
}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": "NOLC1",
"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"
}- Nucleolar and ribosome-biogenesis machinery is required by every proliferating cell. Any intervention aimed at this axis inherits the toxicity profile of a ribosomopathy, and NOLC1's partner TCOF1 causes Treacher Collins syndrome when haploinsufficient - a developmental phenotype in exactly the age group this disease affects.
- If the fusion's nucleolar pool is a sequestered, inactive reservoir rather than an active site, then drawing the fusion out of the nucleolus would increase rather than decrease the active pool.
- The index-fusion evidence here is a p-value of 0.134 with a zero-spectra replicate. Building an experiment on it is reasonable; building a therapeutic hypothesis on it is not.
- Does NOLC1 co-immunoprecipitate with the endogenous KMT2A::AFF1 fusion in a t(4;11) line, and does the fusion's nucleolar pool contain it?
- Is the MLL-AF4 7|0 spectral split a technical failure in one replicate or a genuinely bimodal association? The raw data at PXD009338 could answer this without new experiments.
- Do KMT2A::AFF1 and NOLC1 co-occupy rDNA/NOR chromatin? That single ChIP would turn a three-way coincidence into a mechanism or kill it.
- Are other nucleolar or Cajal-body proteins (coilin, treacle/TCOF1, UBF/UBTF, fibrillarin, the t-UTPs) present in the Skucha 960-protein network? A compartment-level signature would be much stronger than one protein.
- E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper
NOLC1 co-purified with all seven Strep-HA-tagged MLL fusions in isogenic Jurkat cells; the MLL-AF4 (= KMT2A::AFF1) call is p = 0.134 with 7|0 spectral counts, while six other baits are far stronger, reaching 4.03e-10 (20|20) for MLL-AF1p and 1.47e-09 (49|45) for MLL-EEN. 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. This is the weakest index-fusion call in this beat: p = 0.134, above any conventional threshold, with ZERO spectra in one of the two MLL-AF4 replicates. It is present only because the inclusion rule is a per-bait rank cutoff. The confidence of this item reflects the MLL-AF4 measurement, not the pan-fusion pattern; if the claim is narrowed to 'NOLC1 associates with MLL fusions as a class in this system' the evidence is considerably stronger. 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
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Nopp140 (NOLC1) functions as a molecular link between the nucleolus and coiled (Cajal) bodies: exogenous Nopp140 accumulates in the nucleolus rapidly and in coiled bodies after a lag, and partial constructs act as dominant negatives that chase endogenous Nopp140 and shared antigens out of the nucleolus.
Nopp140 functions as a molecular link between the nucleolus and the coiled bodies. · Isaac C, Yang Y, Meier UT · J Cell Biol 1998What this evidence cannot show
Transient transfection, mutational analysis and yeast two-hybrid in cultured cells, 1998; overexpression and dominant-negative constructs, so the stoichiometry is not endogenous. Not a haematopoietic or fusion system. Read from the abstract.
Evidence that argues against this (1)
- Dominant-negative relocalisation experiments can report a construct's aggregation behaviour rather than the endogenous protein's traffic; the later coilin work is the better-controlled version of the same claim. Courchaine E et al. 2022
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Nopp140 is recruited, with Treacle and the t-UTP pre-rRNA processing factors, to nucleolar organiser region chromatin - the rDNA arrays - in a UBF-dependent manner and independently of transcription, of the underlying DNA sequence and of position within the nucleolus.
Recruitment of factors linking transcription and processing of pre-rRNA to NOR chromatin is UBF-dependent and occurs independent of transcription in human cells. · Prieto JL, McStay B · Genes Dev 2007What this evidence cannot show
Human cells, using transcriptionally silent ectopic pseudo-NOR arrays as the assay - an artificial chromosomal array that mimics active NOR chromatin, so the recruitment is demonstrated onto a synthetic locus as well as endogenous NORs. Not a leukaemia system. Read from the abstract. This item is cited for NOLC1 being an rDNA-chromatin-associated protein, which is the fact that connects it to this graph's nucleolar convergence.
Evidence that argues against this (1)
- Recruitment to a pseudo-NOR shows what the chromatin structure is sufficient to attract; it does not establish that NOLC1 occupies endogenous rDNA in a leukaemic blast, which nobody has measured. Isaac C et al. 1998
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Multivalent interactions between the coilin N-terminal domain and Nopp140 are required to form and maintain Cajal bodies, and Nopp140 itself has condensation capacity.
The coilin N-terminus mediates multivalent interactions between coilin and Nopp140 to form and maintain Cajal bodies. · Courchaine E, Gelles-Watnick S, Machyna M, Straube K, Sauyet S, et al. · Nat Commun 2022What this evidence cannot show
Cultured cells with single-amino-acid mutational analysis; 'condensation capacity' is an in-cell observation and this project's standing rule applies - 1,6-hexanediol sensitivity and classical FRAP cannot distinguish phase separation from binding to clustered sites, so the condensate language should not be over-read. Not a haematopoietic or fusion system. Read from the abstract.
Evidence that argues against this (1)
- A punctate or condensate-like appearance is compatible with binding to spatially clustered sites; the discriminating assay (calibrated half-bleach measuring internal mixing) was not performed. Prieto JL et al. 2007
co-purified with MLL-AF4 at p=0.134 with a 7|0 spectral split - not significant for the index bait; strong for five other MLL fusions in the same experiment
- related to →The nucleolus — the one compartment with direct published images of a KMT2A fusion inside it
a nucleolar, rDNA-chromatin-recruited protein in the pan-MLL-fusion core - the first physical element of the nucleolar convergence
fourth line, and the only physical one: NOLC1 is nucleolar and NOR-chromatin-recruited and co-purifies with all seven MLL fusions
pan-fusion Skucha interactor with no gene entry before cycle 47
- ← co-occurs withGPATCH4 (Q5T3I0) - a nucleolar and Cajal-body helicase cofactor in the pan-MLL-fusion core, with no DHX15 and no G-patch relative beside it
two pan-fusion nucleolar/Cajal-body proteins in a thirteen-protein nucleolar block
two of thirteen nucleolar/ribosome-biogenesis proteins in the conserved interactome, both pan-fusion
both in the nucleolar block; NOLC1 is pan-fusion, PA2G4 is 6 of 7 but has the lower index-bait p
both in the index column above p = 0.05 (0.141 and 0.134) - the same caveat applies to both