mod (Modulo, CG2050, FBgn0002780; UniProt P13469) - manual literature synthesis

No deep-research API was available; this synthesis was assembled by hand from PubMed
searches (query modulo[Title] AND Drosophila, 12 hits) and the cached publications in
publications/. Full text was read for PMID:11854460, PMID:23028777, PMID:39700092 and
PMID:39848495; the others are abstract-only in the cache.

Identity and domain architecture

• 542 aa nuclear protein; N-terminal acidic/disordered region (1-166), four RRM domains
  (175-251, 258-331, 340-429, 420-489), basic C-terminal tail (UniProt P13469 FT lines).
• Described as the Drosophila homologue of nucleolin PMID:16877538. Note it lacks the GAR/RGG domain typical
  of vertebrate nucleolin; the architecture (acidic N-terminus + tandem RRMs + basic tail) is
  nucleolin-like.
• PANTHER places it in the very large PTHR24012 "RNA BINDING PROTEIN" family together with SR
  proteins and hnRNPs; this is the origin of the splicing and nuclear-speck IBA rows.

Nucleic acid binding

• Direct DNA binding PMID:1425581.
• Structure/function: basic terminal domains bind DNA without sequence specificity; the central
  RRM domain recognises a specific RNA motif class; phosphorylation down-regulates DNA binding
  PMID:10037720.
• Nucleolar Mod is phosphorylated and in an RNP particle; chromatin-bound Mod is not
  PMID:10037720.
• Sdic promoter-binding protein purified from testis was identified as Modulo
  PMID:16877538. This specific-binding
  claim sits uneasily with the 1999 in vitro finding of non-specific DNA binding.
• RIP-seq in larval brain identified bound mRNAs, including proneural and ribosomal-protein
  transcripts PMID:39700092.

Localization

• Nucleolus (major) and chromatin/heterochromatin (minor) PMID:9718368; DNA targets are repetitive elements, not rDNA PMID:9718368.
• Embryonic nuclei, mostly nucleolar; polytene chromosome bands and heterochromatin shared
  with dCBP [PMID:11854460, full text].
• S2 cells: nucleolar in interphase, perichromosomal in metaphase, not at centromeres
  [PMID:23028777 "In interphase, we confirmed that Modulo accumulates at the nucleolus and has
  a weaker staining on DNA"; "Metaphase spreads showed localization of Modulo around the
  periphery of chromosomes"].
• Neuroblasts: nucleolar (Fibrillarin overlap) in interphase; perichromosomal and cytoplasmic
  in mitosis PMID:39700092.

Interactions

• dCBP (nejire): yeast two-hybrid, GST pulldown, co-IP from Kc cells; Mod 219-493 suffices
  PMID:11854460.
• CAL1 (CENP-A loading factor): reciprocal co-IP from S2 nuclear extracts PMID:23028777.
• Piwi: reciprocal co-IP in ovaries PMID:39848495.

Biological roles (mostly genetic)

• Dominant suppressor of position-effect variegation; null is recessive lethal with melanotic
  tumours PMID:1425581.
• Required downstream of patterning genes for morphogenesis of several embryonic tissues
  PMID:7813788.
• Direct dMyc target required for growth of proliferative (not endoreplicating) cells
  PMID:12834864; null clones have a Minute-like phenotype, consistent with a role in
  ribosome biogenesis PMID:9718368.
• Male germline: required for transcription of spermatid differentiation genes
  PMID:16877538.
• Centromere integrity: RNAi reduces nucleolar CAL1, new CAL1 recruitment and centromeric CID;
  causes chromosome missegregation PMID:23028777.
• Neuroblast maintenance PMID:39700092; piRNA-directed transposon silencing / H3K9me3 at TEs
  in ovaries PMID:39848495.

All biological-process roles above rest on loss-of-function phenotypes; the molecular step
Modulo performs in each is not established.