ASB7 (Q9H672) - the brake on H3K9me3's own positive feedback loop, released by CDK1 in mitosis, and it reached this graph as the flattest dependency in the read queue

[]

{
  "positive_feedback": "HP1 recognises preexisting H3K9me3 and recruits SUV39H1, which methylates adjacent newly incorporated histones - self-reinforcing",
  "the_brake": "HP1 also recruits ASB7 to heterochromatin, and CUL5-ASB7 ubiquitinates SUV39H1 for degradation",
  "the_gate": "during mitosis CDK1 phosphorylates ASB7, preventing the ASB7-SUV39H1 interaction, so SUV39H1 is stabilised and H3K9me3 is restored",
  "purpose_as_stated_by_the_authors": "ensuring faithful epigenetic inheritance and preventing excessive heterochromatin formation",
  "how_it_was_found": "an unbiased genome-scale CRISPR-Cas9 screen",
  "note": "the same reader recruits both the writer and the writer's destroyer, which is what makes this a homeostatic circuit rather than a simple antagonism"
}

{
  "substrate": "DDA3 / PSRC1, a regulator of spindle dynamics",
  "mechanism": "ASB7 ubiquitinates DDA3 and targets it for proteasomal degradation; microtubules prevent the ASB7-DDA3 interaction and so stabilise DDA3",
  "phenotype": "ASB7 knockdown decreased microtubule polymerisation and increased the proportion of cells with unaligned chromosomes, rescued by deletion of DDA3",
  "citation": "PMID 27697924"
}

{
  "what_exists": "crystal structure of the ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron; ASB7 uses ANK3-6 to form an extended groove engaging an internal alpha-helix degron through side-chain electrostatic and hydrophobic interactions",
  "why_it_is_recorded": "the authors state the structure provides a basis for rational design of compounds targeting ASB7 by disrupting its interaction with its cognate degron - so this entry touches a potential intervention and carries bite_back",
  "citation": "PMID 39039081"
}

{
  "route": "recovered in this project's interactome census against one of the six core baits",
  "interaction_evidence": "1 bait, 2 publications, anti-tag co-IP, max IntAct MI-score 0.35 against IntAct's own 0.6 threshold",
  "dependency": "Chronos -0.0457, 0.5% of 1,258 lines below -0.5 - the second flattest in its read-queue set",
  "honest_statement": "the interaction evidence is weak and the dependency is flat. This entry is justified by the protein's curated and published FUNCTION, not by evidence that it binds the fusion."
}

{
  "mean_gene_effect": -0.0457,
  "frac_below_minus_0_5": 0.0048,
  "n_lines": 1258,
  "depmap_release": null,
  "rule_83": "the Open Targets depMapEssentiality payload carries no release identifier; figure measured in cycle 58 with all tissue blocks flattened and a payload guard at the panel maximum"
}

{
  "members": [
    "gene-asb7",
    "mark-h3k9me3",
    "gene-suv39h1",
    "gene-cbx5",
    "gene-cdk1",
    "gene-psrc1",
    "gene-cul5"
  ],
  "n_members": 7,
  "written": [
    "gene-asb7",
    "mark-h3k9me3",
    "gene-suv39h1",
    "gene-cbx5"
  ],
  "absent_from_this_graph": [
    "gene-cdk1",
    "gene-psrc1",
    "gene-cul5"
  ],
  "KING CORRECTION 2026-09-22": "This entry said \"one written member out of six\" in its summary while its own data block listed two written and five absent - seven members, not six. The summary and the data contradicted each other from the moment the entry was created, and a dispatch brief of mine inherited the summary figure and told an agent the circuit was one-sixth written. Found by Q110, which reported it as an error in an entry it did not own; recounted live against the node-id set rather than restated.",
  "and_the_count_moved_again_the_same_day": "gene-suv39h1 and gene-cbx5 were written by Q110 in cycle 60, so the circuit is now 4 of 7 written. The remaining absences are gene-cdk1, gene-psrc1, gene-cul5. gene-cdk1 was declined deliberately: its phosphosite is in a paper unreadable by all five routes this project uses (PMID 40440427, no PMCID, Europe PMC isOpenAccess N, publisher returns HTTP 403).",
  "the_notable_one_is_answered": "This entry asked \"Why does gene-suv39h1 not exist?\" as an open question. It exists now - O43463, 412 aa, KMT1A, X-linked at Xp11.23 - and the answer to the question the entry was really asking is that no published work places SUV39H1 at the KMT2A locus in any cell type, and ENCODE holds zero SUV39H1 ChIP-seq experiments in any cell type at all."
}