DNAJB13 research notes

Identity

• UniProt P59910 (DJB13_HUMAN), 316 aa. HGNC:30718. Synonyms TSARG3, TSARG6 (testis/spermatogenesis).
• DnaJ homolog subfamily B member 13; HSP40/J-domain co-chaperone family. J domain at residues 4-68.

Core function

• Structural/co-chaperone component of the axonemal radial spoke complex (radial spoke stalk),
  essential for motility of sperm flagella and motile (respiratory) cilia.
  [PMID:27486783 "Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia." (UniProt FUNCTION)]
• The Chlamydomonas ortholog localizes to radial spokes PMID:27486783.
• Homodimer; component of radial spoke complex 1 (RS1) spoke stalk together with RSPH14, DYDC1, ROPN1L, NME5 (UniProt SUBUNIT).
• RS1 composition / function in mammalian flagella confirmed by Iqub mouse model PMID:36417862.

Localization

• Cell projection: cilium, flagellum. Epithelial motile cilium and sperm flagellum [PMID:27486783 IDA].
• In spermatids enriched at the head-tail coupling apparatus; in mature sperm distributed along flagellum (By similarity to mouse Q80Y75).
• Tissue: testis and trachea.

Disease

• Biallelic mutations cause primary ciliary dyskinesia type 34 (CILD34, MIM:617091), autosomal recessive, with central-complex (CC) defects but normal dynein arms; male infertility from sperm flagellar dysfunction.
  PMID:27486783
• p.Met278Arg (CILD34 variant): protein instability, proteasomal degradation; loss of endogenous DNAJB13 in cilia/sperm. No effect on homodimerization.

Chaperone activity

• Despite J-domain (HSP40), the established in vivo role is structural within the radial spoke, not a classic
  cytosolic HSP70-stimulating chaperone. IBA terms "protein-folding chaperone binding", "unfolded protein binding",
  "protein folding", and "cytosol" are transferred from family/PANTHER and are weakly supported for THIS protein's
  documented axonemal function. No direct demonstration of HSP70 ATPase stimulation for DNAJB13.

Interactome (PMID:32296183, "A reference map of the human binary protein interactome" — HuRI Y2H)

• IPI partners: PLK4 (O00444), TOM1L1 (O75674-2), PIBF1 (Q4G0R1), MSS51 (Q4VC12), ZC3H12A (Q5D1E8),
  SEPTIN1 (Q8WYJ6), LHX4 (Q969G2), RAB3IP (Q96QF0-7), MDFI (Q99750), GORASP2 (Q9H8Y8), PICK1 (Q9NRD5), ZRANB1 (Q9UGI0).
• These are high-throughput binary Y2H hits, none of which map onto the radial-spoke biology; bare "protein binding", uninformative.

GO annotation review reasoning

• Strong/accept: motile cilium, sperm flagellum (IDA, PMID:27486783); radial spoke (ISS/NAS/ComplexPortal); axoneme; axonemal central apparatus assembly (IMP, PMID:27486783); flagellated sperm motility / cilium movement (NAS).
• HPA sperm sub-compartments (midpiece/principal piece/end piece, IDA) — consistent with flagellar localization, keep.
• microtubule-based process (IEA/ARBA) — generic but consistent with axonemal role; keep as non-core.
• protein folding / chaperone binding / unfolded protein binding (IBA/IEA) — family-transferred, not demonstrated for this protein's documented function; mark as over-annotated or non-core.