DNAJC21 (Q5F1R6) research notes

J-domain (HSP40) co-chaperone of the HSP70 system acting in ribosome biogenesis,
specifically maturation of the large (60S) ribosomal subunit. Also named DNAJA5.

Architecture

• N-terminal J-domain (HPD motif) that recruits/stimulates HSP70 ATPases.
• Two C2H2 zinc fingers within an otherwise disordered C-terminal region.
• Human counterpart of the yeast 60S-maturation J-protein Jjj1.

Function / localization

• Localizes to cytoplasm, nucleus and especially the nucleolus; associates with
  precursor 45S rRNA. [UniProt Q5F1R6 subcellular location]
• Works with the HSP70 chaperone HSPA8 and cofactors PA2G4 (60S nuclear-export
  factor) and ZNF622 to drive late nucleolar rRNA processing and cytoplasmic
  maturation/recycling of the 60S subunit. PMID:27346687

Disease

• Biallelic loss-of-function variants cause a cancer-prone bone marrow failure
  syndrome (BMFS3), Shwachman–Diamond-like — establishing DNAJC21 as a ribosomopathy
  gene. PMID:27346687

Curation calls

• Core MFs: HSP70 (HSPA8) co-chaperone binding (GO:0051087) driving 60S maturation;
  RNA binding (GO:0003723) to precursor rRNA.
• Bare high-throughput protein binding to HTT/MTERF1 and domain-only nucleic-acid
  binding marked over-annotated; folding terms kept non-core (co-chaperone, not foldase).