Oncofusion

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Geneweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q20-proximity-interactome

PPIL4 - a spliceosomal cyclophilin whose BioID neighbourhood is the widest overlap with this graph's subject matter of any bait

also called peptidylprolyl isomerase like 4 · CypL4 · HDCME13P

PPIL4 is a folding enzyme that rides along with the spliceosome. Its list of neighbours inside a leukaemia cell contains more of the proteins this project studies than any other tagged protein.

The same thing, for a scientist

PPIL4 (Q8WUA2, 492 aa) is one of the fifty RNA-binding proteins used as a BioID2 bait in K562. Its curated neighbourhood contains **671 preys**, among them **AFF4**, **ELL**, **MLLT1**, **CDK9**, **CCNT1**, **KMT2A**, **PSIP1**, **WDR5** and 24 others [E1]. Nothing here is a binding claim: proximity labelling reports that two proteins came within roughly 10 nm during a multi-hour labelling window, recovery is abundance-weighted, and the pairs are spoke-expanded from a bait-centric pulldown [E2]. PPIL4 reaches **thirty-two** of the proteins this graph holds entries for, including AFF4, all of ELL/ENL/CDK9/CCNT1, KMT2A, LEDGF/PSIP1, WDR5, ASH2L, KAT7, BRD4 and both SETD1 paralogues. It does **not** reach AFF1 and does **not** reach MEN1. That breadth is a property of a 671-prey pulldown and is reported here as the limiting case: if a bait this broad still misses menin, absence of menin from other neighbourhoods carries even less information than assumed.

Go deeper
What this bait reaches in this graph's subject matter

PPIL4 reaches thirty-two of the proteins this graph holds entries for, including AFF4, all of ELL/ENL/CDK9/CCNT1, KMT2A, LEDGF/PSIP1, WDR5, ASH2L, KAT7, BRD4 and both SETD1 paralogues. It does not reach AFF1 and does not reach MEN1. That breadth is a property of a 671-prey pulldown and is reported here as the limiting case: if a bait this broad still misses menin, absence of menin from other neighbourhoods carries even less information than assumed.

Full list of recovered proteins that have entries or canonical ids in this graph: AFF4, ELL, MLLT1, CDK9, CCNT1, KMT2A, PSIP1, WDR5, KAT7, ICE1, ICE2, PAF1, BRD4, NELFE, ASH2L, ELOA, CDC73, RTF1, KMT2D, SETD1A, SETD1B, HCFC1, SIRT1, HDAC1, HDAC2, CHD8, ARID1A, RUNX1, IGF2BP2, HNRNPA2B1, YTHDC1, RBM15 1.

Why the deflating reading is the default

A bait with 671 preys recovers roughly a quarter of the dataset's entire prey space. Co-occurrence inside a list that long is weak evidence about any individual pair, and the compartment effect - splicing is co-transcriptional, so a spliceosomal bait sits where the elongation machinery is - explains the pattern without any direct contact 2.

This entry exists so the observation is on record with its limits attached, not because a target has been found.

Retained region

Retained region: not determinable from this data. The SEC proteins here were preys, never baits, so what was labelled is the endogenous full-length wild-type protein. Biotinylation happens at accessible lysines anywhere on the prey and no site-level biotinylation was reported, so nothing distinguishes a contact with the AFF1 N-terminus that KMT2A::AFF1 discards from one with the C-terminal half it keeps.

Facts and figures
uniprotQ8WUA2
gene symbolPPIL4
length AA492
uniprot resolution noteAccession taken from the IntAct MITAB bait column; primary gene name and sequence length read back from the UniProt REST API on 2026-09-19 as PPIL4, 492 aa.
roleBioID2 bait
n preys total671
methodBioID2 in K562 (PSI-MI MI:1314), spoke-expanded
subnuclear localizationNONE - AND IT IS A BOUNDED ABSENCE OF THE STRONGEST KIND IN THIS TRANCHE, BECAUSE THE WHOLE LITERATURE IS NINE RECORDS AND NOT ONE CONTAINS AN IMAGE. PPIL4[tiab] returns 9 records in total; PPIL4[tiab] against nuclear, speckle, spliceosome and localization returns 2, and both were read: the 2001 cloning paper whose nuclear claim is the NLS prediction above, and a 2023 cryo-EM structure of the human spliceosome in which PPIL4 appears as a structural component rather than a localised protein [E_q91_ppil4_loc3]. NOBODY HAS EVER LOOKED AT THIS PROTEIN IN A CELL. Given that a spliceosomal cyclophilin would be expected in nuclear speckles - where every other splicing factor in this graph is recorded - the absence is a genuinely cheap experiment rather than a hard one, which is why it is filed as never-measured rather than never-measurable.
localization shown for fusionNO - nobody has looked, in any fusion, in any lineage, and nobody has looked in any cell at all. PPIL4[tiab] AND MLL[tiab] = 0 and PPIL4[tiab] AND KMT2A[tiab] = 0 against an operand of nine [E_q91_ppil4_loc3]. The BioID2 neighbourhood that connects PPIL4 to this graph reaches KMT2A itself, so the specific unasked question is sharp: does PPIL4 occupy the same compartment as the elongation machinery it labels, or is a 671-prey neighbourhood reporting abundance?
proximity preys of interest
[
  "AFF4",
  "ELL",
  "MLLT1",
  "CDK9",
  "CCNT1",
  "KMT2A",
  "PSIP1",
  "WDR5",
  "KAT7",
  "ICE1",
  "ICE2",
  "PAF1",
  "BRD4",
  "NELFE",
  "ASH2L",
  "ELOA",
  "CDC73",
  "RTF1",
  "KMT2D",
  "SETD1A",
  "SETD1B",
  "HCFC1",
  "SIRT1",
  "HDAC1",
  "HDAC2",
  "CHD8",
  "ARID1A",
  "RUNX1",
  "IGF2BP2",
  "HNRNPA2B1",
  "YTHDC1",
  "RBM15"
]
depmap kmt2a selectivity
{
  "chronos_mean_kmt2a_rearranged": -0.8597,
  "chronos_mean_other_leukaemia": -0.9369,
  "difference": 0.0772,
  "pan_essentiality_all_lines": -0.9391,
  "selectivity_rank": 16264,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}
localization
{
  "CONSTITUTIVE": "NUCLEUS, PREDICTED - AND THIS PROTEIN HAS NEVER BEEN IMAGED. UniProt Q8WUA2 (fetched live 2026-09-21) carries ONE subcellular location value, 'Nucleus', on a bare ECO:0000305 - CURATOR INFERENCE, with no experimental attribution of any kind, no location note and no annotated NLS in the retrieved feature table [E_q91_ppil4_loc1]. This is the weakest evidence tier in the whole tranche: not an over-reaching ECO:0000269 (SMARCD1), not a transfer from an orthologue (SGF29, SMC3), not an empty evidence list on a well-studied protein (SMARCB1, SIAH1), but an explicit curator inference on a protein with a nine-record literature.",
  "WHERE_THE_INFERENCE_CAME_FROM": "Almost certainly from the sole primary source. The cloning paper reports that besides the PPIase motif, PPIL4 has an RNA RECOGNITION MOTIF (RRM), A PAIR OF BIPARTITE NUCLEAR TARGETING SEQUENCES, and a lysine-rich domain - and it calls PPIL4 a 'novel NUCLEAR RNA-binding cyclophilin-like gene' IN ITS TITLE on that basis. The nuclear claim is a SEQUENCE PREDICTION from bipartite NLS motifs in a cDNA isolated from a human fetal brain library, not a measurement [E_q91_ppil4_loc2]."
}
cell type
{
  "measured_in": "NOTHING. The cDNA came from a human FETAL BRAIN library and the expression evidence is RT-PCR across tissues [E_q91_ppil4_loc2]; the structural work is in vitro on purified spliceosomes [E_q91_ppil4_loc3]. There is no cell-biological experiment on PPIL4 anywhere.",
  "the_only_cell_type_connection_this_entry_has": "K562, and it is as a BAIT rather than as a subject: PPIL4 is one of fifty RNA-binding proteins used as a BioID2 bait in K562, and its 671-prey neighbourhood reaches thirty-two proteins this graph holds entries for, including AFF4, ELL, MLLT1, CDK9, CCNT1, KMT2A, PSIP1 and WDR5 - while reaching NEITHER AFF1 NOR MEN1 (this entry's E1). Proximity labelling in a leukaemia line is the only experiment that has ever put this protein in a named cell.",
  "never": "No localisation in any cell type, let alone a KMT2A-rearranged one."
}
cell state
{
  "none_recorded": "No cell-cycle, stress, damage or differentiation behaviour of PPIL4 is reported anywhere retrieved. For a protein with nine records this is unsurprising and it should be recorded as an absence of effort rather than an absence of phenomena.",
  "the_state_it_implies": "PPIL4 is the PPIase that rides with the spliceosome through catalytic activation, a stage driven by the helicases PRP2/DHX16 and Aquarius [E_q91_ppil4_loc3]. Its 'state' is a step in the splicing cycle rather than a cellular state - which is a reason its distribution might be uninformative even if measured, and a reason to measure it once rather than repeatedly."
}
localization bounded absence
{
  "date": "2026-09-22",
  "tool": "NCBI esearch db=pubmed",
  "run_by": "Q91",
  "queries": [
    {
      "query": "PPIL4[tiab]",
      "querytranslation": "\"PPIL4\"[Title/Abstract]",
      "count": 9,
      "role": "operand control - AND the total literature. Nine records."
    },
    {
      "query": "PPIL4[tiab] AND (nuclear[tiab] OR speckle[tiab] OR spliceosome[tiab] OR localization[tiab])",
      "querytranslation": "\"PPIL4\"[Title/Abstract] AND (\"nuclear\"[Title/Abstract] OR \"speckle\"[Title/Abstract] OR \"spliceosome\"[Title/Abstract] OR \"localization\"[Title/Abstract])",
      "count": 2,
      "both_read": true,
      "containing_an_image_of_the_protein_in_a_cell": 0
    },
    {
      "query": "PPIL4[tiab] AND MLL[tiab]",
      "querytranslation": "\"PPIL4\"[Title/Abstract] AND \"MLL\"[Title/Abstract]",
      "count": 0
    },
    {
      "query": "PPIL4[tiab] AND KMT2A[tiab]",
      "querytranslation": "\"PPIL4\"[Title/Abstract] AND \"KMT2A\"[Title/Abstract]",
      "count": 0
    }
  ],
  "reading": "With a nine-record total literature, a title-and-abstract bound is very nearly a bound on the papers themselves - the usual rule-80 escape hatch (the measurement is in a supporting figure) has only nine papers to hide in, and two of them were read. This is the most defensible bounded absence in the tranche. The aliases CypL4 and HDCME13P were not run as separate operands.",
  "absence_class": "never-measured"
}
How this could bite us back
  • This is a bait's neighbourhood, not a partner list. Promoting anything in it to a target would be the error this beat exists to prevent.
  • PPIL4 is broadly expressed and, on the evidence here, has no leukaemia-specific role. Any intervention aimed at it would hit splicing in every cell.
Still open
  1. Does PPIL4 co-immunoprecipitate with any of the elongation proteins in its neighbourhood, in any cell type? No such experiment was found.
  2. Is PPIL4 required in KMT2A-rearranged cells? It was absent from this project's 79-gene RNA-layer DepMap panel and should be added to any repeat.
  3. Would the same neighbourhood be recovered with a nucleus-restricted or endogenously tagged construct rather than an overexpressed one?
Every source behind this entry (6)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    As a BioID2 bait in K562 in the IMEx IM-30059 deposition, PPIL4 (Q8WUA2) recovers 671 distinct curated preys, including AFF4, ELL, MLLT1, CDK9, CCNT1, KMT2A, PSIP1, WDR5, KAT7, ICE1, ICE2, PAF1, BRD4, NELFE, ASH2L, ELOA, CDC73, RTF1, KMT2D, SETD1A, SETD1B, HCFC1, SIRT1, HDAC1, HDAC2, CHD8, ARID1A, RUNX1, IGF2BP2, HNRNPA2B1, YTHDC1, RBM15.

    What this evidence cannot show

    Retrieved from IntAct 2026-09-19 over the authors' curated bona fide pair list. A neighbourhood of this size contains a slice of most nuclear processes, so co-occurrence is weak evidence about any pair. The bait is an overexpressed BioID2 fusion in K562, which carries BCR::ABL1 and no KMT2A rearrangement; no fusion protein is present anywhere in the experiment.

    Evidence that argues against this (2)
    • In the largest human BioID survey (192 baits, HEK293) a prey's bait profile is dominated by subcellular compartment rather than by binding, so a splicing bait recovering co-transcriptional machinery is the expected background of the method. Go CD et al. 2021
    • The founding BioID report describes the reagent as labelling proteins near the bait without binding it; promiscuous labelling of the vicinity is designed behaviour. Roux KJ et al. 2012
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Every row in this deposition is proximity-dependent biotin identification (PSI-MI MI:1314), spoke-expanded (MI:1060) from a bait-centric streptavidin pulldown, with the RBP in bait role MI:0496 and the recovered protein in prey role MI:0498, and carries an IntAct MI-score of 0.27.

    What this evidence cannot show

    Spoke expansion means each deposited pair is a bait-to-prey assignment rather than an observed binary contact, and the uniform MI-score carries no information about individual pairs.

    Evidence that argues against this (1)
    • BioID and affinity purification of chromatin-associated complexes recover few shared partners and enrich for different processes, so a proximity hit list is not a complex roster. Lambert JP et al. 2015
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Peptidyl-prolyl isomerases of the cyclophilin family are components of the activated human spliceosome, resolved structurally in the Bact-to-B* catalytic activation transition.

    Structural basis of catalytic activation in human splicing. · Schmitzová J, et al. · Nature 2023
    What this evidence cannot show

    A cryo-EM structural paper on human spliceosome catalytic activation; abstract read, full text not read. It establishes the family's spliceosomal context, not PPIL4's specific role, and has no connection to leukaemia.

    Evidence that argues against this (1)
    • Background biology of a bait explains why its neighbourhood looks the way it does and is therefore an argument against, not for, reading the neighbourhood as a list of partners. A co-transcriptional protein is near transcription because it is co-transcriptional. Go CD et al. 2021
  4. E_q91_ppil4_loc1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    UniProtKB Q8WUA2 (PPIL4_HUMAN, primary gene PPIL4, 492 aa, read back live 2026-09-21) carries exactly ONE subcellular location value, 'Nucleus', attributed to a bare ECO:0000305 - CURATOR INFERENCE - with NO experimental attribution, no source accession, no location note, and no nuclear localisation signal in the retrieved feature table despite the primary literature describing a pair of bipartite nuclear targeting sequences.

    What this evidence cannot show

    Brief rule 91 item 4 instructs beats to distinguish ECO:0000269 from ECO:0000305 and flags SMARCD2's ECO:0000305-only nuclear call as unusual for a BAF subunit. This is the same form, with less behind it: SMARCD2 at least sits in a complex purified from nuclei.

    Evidence that argues against this (1)
    • The inference is probably correct and that is precisely why it is worth flagging. A spliceosomal PPIase with an RRM is nuclear; nobody would bet against it. But the annotation's confidence is doing work it did not earn, and this graph has a live use for the distinction - PPIL4's entry exists because its BioID2 neighbourhood reaches thirty-two entries in this corpus including KMT2A, and the deflationary reading of that neighbourhood turns on whether PPIL4 is genuinely resident where the elongation machinery is. An unmeasured compartment cannot adjudicate that, and a confident-looking database row invites a reader to think it can. Zeng L et al. 2001
  5. E_q91_ppil4_loc2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The sole primary source for PPIL4's nuclear localisation is a sequence prediction in a cDNA-cloning paper. PPIL4 was cloned from a HUMAN FETAL BRAIN cDNA library during large-scale sequencing; the encoded protein shares 96% amino-acid identity with a mouse early-embryo protein; bioinformatics placed the gene at chromosome 6q24-q25; and BESIDES THE PPIase MOTIF, PPIL4 HAS AN RNA RECOGNITION MOTIF (RRM), A PAIR OF BIPARTITE NUCLEAR TARGETING SEQUENCES, AND A LYSINE-RICH DOMAIN. Expression was assessed by RT-PCR. The paper's title calls PPIL4 a 'novel NUCLEAR RNA-binding cyclophilin-like gene' on this basis.

    What this evidence cannot show

    2001, read from the abstract. A bipartite NLS prediction is a motif match, and motif-based NLS prediction has a well-known false-positive rate in lysine-rich proteins - and this protein has a lysine-rich domain, which is exactly the sequence context that generates spurious bipartite NLS calls.

    Evidence that argues against this (1)
    • The word 'nuclear' in this paper's TITLE is the mechanism by which an unmeasured property became an established-looking fact, and the chain is short enough to see end to end: a motif predictor fires on a lysine-rich region, the prediction goes in the title, a curator reads the title and records 'Nucleus', the ECO code correctly says inference - and every downstream reader sees a UniProt compartment. This graph has a named comparator for the pattern in localization-meis1-nucleus-is-a-sequence-prediction-and-one-isoform-is-cytoplasmic, where the same shape was found for a far more important protein and where a second isoform turned out to be cytoplasmic. Nobody has looked for PPIL4 isoforms. UniProt Consortium 2026
  6. E_q91_ppil4_loc3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    Counted absence over an entire literature, 2026-09-22, querytranslation read back on every line. PPIL4[tiab] = 9 records IN TOTAL. PPIL4[tiab] against nuclear, speckle, spliceosome and localization = 2, both read: the 2001 cloning paper above, and a 2023 cryo-EM study of catalytic activation in human splicing which resolves the BAQR spliceosome intermediate and shows how PRP2/DHX16 and Aquarius remodel it - a structural paper in which PPIL4 is a component of a purified particle, with no cellular localisation. PPIL4[tiab] AND MLL[tiab] = 0 and PPIL4[tiab] AND KMT2A[tiab] = 0.

    What this evidence cannot show

    Confidence is 'strong' rather than 'moderate' here, against this beat's practice for counted absences, for a specific reason: rule 80 says a PubMed zero is bounded by abstracts rather than papers, and that escape hatch is nine papers wide for PPIL4. The aliases CypL4 and HDCME13P were not run and should be before anyone treats this as final.

    Evidence that argues against this (1)
    • The honest objection is that a nine-record literature makes this absence cheap rather than strong - nobody has looked at PPIL4 for any purpose, so of course nobody has localised it, and the absence carries almost no information about whether PPIL4 matters. What makes it worth recording is the asymmetry with the reason this entry exists: PPIL4's BioID2 neighbourhood is the WIDEST overlap with this graph's subject matter of any bait in that dataset, thirty-two entries including KMT2A and the entire SEC. The protein with the broadest proximity to this project's machinery is also the least studied protein in this tranche by a factor of forty. That is either a large gap or a large artefact, and one immunofluorescence would start to tell them apart. Schmitzová J et al. 2023
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