LMNA - LEDGF is a prey of the nuclear-envelope MARKER bait, so this row is a statement about address, not about complex membership
also called lamin A/C · Prelamin-A/C · LMN1 · HGPS · CMD1A · LGMD1B
Lamin A/C is the mesh that lines the inside of the nuclear membrane and anchors silent stretches of DNA against it. A 2018 methods paper used lamin A/C as a reference marker for 'this is the nuclear envelope', and LEDGF - the protein that tethers the leukaemia fusion to chromatin - turned up in its neighbourhood, which tells you where LEDGF sometimes is rather than what it is attached to.
The same thing, for a scientist
LMNA (HGNC:6636, ENSG00000160789, UniProt P02545, 664 aa, 1q22) encodes lamin A and lamin C, the type-V intermediate filaments that form the nuclear lamina [E3]. It enters this project's core-complex interactome through two IntAct rows in which **LMNA is the bait and PSIP1/LEDGF is the prey**: IM-26301, MI:1314 BioID, MI:2364 proximity, MI:1060 spoke expansion, MI-score 0.27, host HEK293 Flp-In [E2]. **The provenance of that bait is what makes this entry worth writing.** The source is the MAC-tag paper, which systematically applied an AP-MS/BioID-compatible tag to **18 subcellular and 3 sub-organelle localization markers** to build a molecular-context database [E1], and its own text names LMNA explicitly as the **nuclear envelope marker**: *'nuclear envelope marker (Prelamin-A/C, LMNA)'* [E4]. A prey of a localization-marker bait is, by the experiment's own design, a **statement about molecular context** - where the prey is - and not a claim that the two proteins are in a complex. This graph has repeatedly been bitten by reading a database row as the claim its row-type does not make; here the row's true meaning is unusually well documented and unusually useful, because subnuclear address is one of the PI's named saturation axes.
What the interaction record actually is, and what the experiment was for
Two IntAct rows, IM-26301, from Liu et al. 2018. Detection MI:1314 proximity-dependent biotin identification; interaction type MI:2364 proximity; expansion MI:1060 spoke; experimental roles MI:0496 bait (LMNA) / MI:0498 prey (PSIP1); host taxid:9606(Homo sapiens HEK293flp-in embryonic kidney cell); curator annotation figure legend: Supplementary table 1c; MI-score 0.27 2.
The paper designed the MAC-tag to combine AP-MS and BioID in one construct and then applied it to 18 subcellular and 3 sub-organelle localization markers, generating a molecular context database, which can be used to define a protein's molecular location 1. In the full text, LMNA appears in the marker list alongside GOLGA2 (cis-Golgi), H3.1 (chromatin), LAMP1 (lysosome), PSMA1 (proteasome), RAB11A and RAB9A (endosomes), TUBA1A and TUBG1 4. The authors also report that LMNA's BioID neighbourhood contains nuclear pore components and importins that AP-MS does not recover, and interpret this as LMNA transiting the pore 4 - a direct demonstration that this bait's BioID list contains route and residence, not complex membership.
So the honest reading of the PSIP1 row is: in HEK293 Flp-In cells, a fraction of LEDGF is within BioID labelling distance of the nuclear envelope / lamina. It is not evidence that LEDGF binds lamin A/C.
Why this matters to the lab: the lamina is the anti-chromatin compartment
Lamin-associated domains are the classic repressive, late-replicating, gene-poor compartment. LEDGF's characterised role is the opposite: a PWWP reader of H3K36me2/3 over the bodies of actively transcribed genes, tethering MLL and MLL fusions there. A LEDGF pool near the lamina is therefore either (i) a transiting or unengaged pool, (ii) a genuine second address nobody has characterised, or (iii) a proximity-labelling artefact of an abundant nuclear protein in an over-expressing cell.
This graph already holds localization-nuclear-lamina-lads-kmt2a-r and localization-nuclear-envelope-proximity-kmt2a-amino-terminus, so the lamina is an axis already open here, and this row is a second, independent-bait datum on it. It is not a strong datum. It is one bait, one paper, one method, in kidney cells, and it should be used to motivate a measurement rather than to support a claim.
Localization of LMNA itself
UniProt P02545 assigns, all experimentally, nucleus lamina, nucleus envelope, nucleoplasm, nucleus matrix and - notably - nucleus speckle 3. The nucleoplasmic and speckle pools are real and are frequently forgotten when lamin A/C is treated as a pure envelope protein; anyone reading the PSIP1 proximity as 'LEDGF is at the periphery' has to exclude the nucleoplasmic lamin pool first. That is a genuine confounder of this row and it is recorded here rather than left to a reader.
Cell type, cell state, other fusion families
Cell type of the observation: HEK293 Flp-In embryonic kidney. Not haematopoietic, not leukaemic, not KMT2A-rearranged. Cell state: none specified; asynchronous culture. Lamina organisation is cell-cycle dependent and the lamina disassembles in mitosis, which the row cannot resolve.
Other fusion families: nobody has looked. This entry asserts nothing about lamin association in NUP98, CBFA2T3::GLIS2 or any other family. Note that NUP98 fusions are the obvious place such a question would matter, since NUP98 is a nuclear pore protein - but that is a reason to ask, not an answer.
| hgnc ID | HGNC:6636 |
|---|---|
| symbol | LMNA |
| ensembl gene ID | ENSG00000160789 |
| uniprot | P02545 |
| length AA | 664 |
| chromosomal location | 1q22 |
| identifier provenance | HGNC REST fetch/symbol/LMNA and UniProtKB P02545 retrieved live 2026-09-23. |
| subnuclear location | nuclear lamina and envelope, plus documented nucleoplasmic, matrix and speckle pools |
| cell type of the observation | HEK293 Flp-In embryonic kidney - not haematopoietic, not KMT2A-rearranged |
| epigenetic role | Structural. The lamina defines lamin-associated domains, the repressive gene-poor compartment - the opposite of the H3K36me2/3 gene bodies LEDGF reads. |
| shown for fusion | NO - nobody has looked in any fusion. The row is wild-type PSIP1 in HEK293 Flp-In. |
| evidence class | single publication, single method, spoke-expanded BioID from a LOCALIZATION-MARKER bait; read as address, not as complex membership |
prev and alias symbols
[ "LMN1", "CMD1A", "LGMD1B", "PRO1", "LMNL1", "HGPS", "MADA" ]
interaction with project baits
[
{
"bait": "PSIP1",
"bait_uniprot": "O75475",
"partner_experimental_role": "bait",
"scaffold_experimental_role": "prey",
"method": "MI:1314 proximity-dependent biotin identification",
"interaction_type": "MI:2364 proximity",
"expansion": "MI:1060 spoke",
"mi_score": 0.27,
"imex": "IM-26301",
"pmid": "29568061",
"host_cell": "HEK293 Flp-In embryonic kidney",
"n_rows": 2,
"n_publications": 1,
"bait_provenance": "LMNA is one of 18 SUBCELLULAR LOCALIZATION MARKER baits in this study - the nuclear envelope marker - so the row is a molecular-context statement by the experiment's own design"
}
]subcellular location uniprot
[ "Nucleus lamina (ECO:0000269, ECO:0000305)", "Nucleus envelope (ECO:0000269)", "Nucleus, nucleoplasm (ECO:0000269)", "Nucleus matrix (ECO:0000269)", "Nucleus speckle (ECO:0000269)" ]
- If LEDGF has a lamina-associated pool, an intervention against the LEDGF-MLL interface may displace the fusion into, rather than off, a repressive compartment - and repositioning is not the same as inactivation.
- Lamin A/C is mutated in a dozen human laminopathies and is structural; nothing here is a target proposal, and an entry about a localization-marker bait should not be read as nominating one.
- Does LEDGF have a genuine lamina-proximal pool in a KMT2A-rearranged human B-ALL cell, or is the HEK293 row an over-expression artefact? Lamin B1 DamID plus LEDGF CUT&RUN in SEM answers it directly.
- If a LEDGF pool is lamina-proximal, is KMT2A::AFF1 there with it, or does the fusion only engage the H3K36me2/3 gene-body pool? This is the question that decides whether the row matters at all.
- Which lamin pool produced the proximity - the peripheral lamina or the nucleoplasmic lamin A/C? UniProt documents both and BioID cannot separate them.
- Does the LEDGF signal in this bait's list behave like the pore components the authors attribute to transit, i.e. present in BioID and absent from AP-MS? The paper's own AP-MS arm could settle this and was not examined by this beat.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Liu et al. designed the MAC-tag combining AP-MS and BioID in a single construct and systematically applied it to 18 subcellular and 3 sub-organelle localization markers, generating a molecular context database that can be used to define a protein's molecular location, and showed that combining the AP-MS and BioID results makes it possible to obtain interaction distances within a protein complex.
An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. · Liu X, Salokas K, Tamene F, et al. · Nat Commun 2018What this evidence cannot show
Abstract read and the full text retrieved from Europe PMC PMC5864832 (161,537 characters) and searched for LMNA. The supplementary table containing the PSIP1 row itself was not opened; that pair was read from the IMEx deposition. All work is in HEK293 Flp-In cells with tetracycline-inducible tagged bait over-expression.
Evidence that argues against this (1)
- This is a methods paper. Its purpose is to demonstrate a tag, and its localization-marker baits were chosen to define compartments, not to discover biology. A prey list from such a bait is a compartment census with the usual proximity-labelling false-positive rate, and the paper reports no validation of the LMNA-PSIP1 pair. source 2026
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
IntAct serves two curated human LMNA-PSIP1 rows: MI:1314 proximity-dependent biotin identification, MI:2364 proximity, MI:1060 spoke expansion, LMNA experimental role MI:0496 bait and PSIP1 MI:0498 prey, MI-score 0.27, host taxid:9606 Homo sapiens HEK293flp-in embryonic kidney cell, IMEx IM-26301, publication PMID 29568061, curator annotation 'Supplementary table 1c'.
IntAct molecular interaction database (EMBL-EBI), PSICQUIC tab27 record for id:O75475 AND id:P02545 2026What this evidence cannot show
Retrieved live 2026-09-23. Two rows from ONE publication are not two independent observations. Rule 93: PSICQUIC is a floor relative to IntAct REST.
Evidence that argues against this (1)
- Two rows from one publication are one observation, not a replication - IntAct deposits a row per experiment within a paper. Separately, rule 93: PSICQUIC is a floor relative to IntAct REST, so this is a minimum row count and a REST query for P02545/O75475 was not run. source 2026
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProt P02545 is 664 aa and describes lamins as intermediate filament proteins assembling into the nuclear lamina on the nucleoplasmic side of the inner nuclear membrane, with experimental (ECO:0000269) subcellular locations nucleus lamina, nucleus envelope, nucleoplasm, nucleus matrix and nucleus speckle.
What this evidence cannot show
Fetched live 2026-09-23. Rule 91 applies to the ECO codes. The nucleus-lamina call carries both ECO:0000269 and ECO:0000305, i.e. part of it is curator inference.
Evidence that argues against this (1)
- The nucleus-lamina call carries ECO:0000305 as well as ECO:0000269, i.e. part of it is curator inference rather than a read experiment. More importantly for this entry, UniProt also documents nucleoplasmic, matrix and SPECKLE pools of lamin A/C, which means 'LMNA bait' does not equal 'nuclear periphery' and the proximity row cannot be attributed to the lamina without excluding the internal pools. source 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The MAC-tag paper's own text names LMNA as its nuclear envelope localization marker - 'nuclear envelope marker (Prelamin-A/C, LMNA)' in the marker list alongside GOLGA2, histone H3.1, LAMP1, PSMA1, RAB11A, RAB9A, TUBA1A and TUBG1 - and reports that LMNA's BioID but not AP-MS neighbourhood contains nuclear pore components and importins, which the authors interpret as transient interaction and in vivo biotinylation during transit through the pore.
An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations - full text, Europe PMC PMC5864832 · Liu X, Salokas K, Tamene F, et al. · Nat Commun 2018What this evidence cannot show
Full text retrieved from Europe PMC fullTextXML for PMC5864832 on 2026-09-23 and the LMNA occurrences read directly; 161,537 characters. The quoted marker-list sentence and the pore-transit interpretation are verbatim from that text. This item is separated from [E1] precisely because it rests on the body text rather than the abstract, and the distinction changes how much weight the 'marker bait' reading can carry.
Evidence that argues against this (1)
- That LMNA was used as a compartment marker does not prove every prey in its list is merely co-located: a marker bait can still have real binding partners, and lamin A/C has many. The row cannot distinguish the two readings, which is why this entry claims address rather than complex membership and claims neither strongly. source 2026
- co-occurs with →PSIP1 / LEDGF p75 — the tether with the best therapeutic index in the whole interactome
LMNA bait / PSIP1 prey, two spoke-expanded BioID rows, IntAct IM-26301 - and LMNA is the study's nuclear-envelope MARKER bait, so this is address, not complex membership
a second, independent bait placing a LEDGF pool near the lamina in HEK293 Flp-In
same compartment, different scaffold protein