DNAJB13

DNAJB13 is an HSP40/DnaJ-family co-chaperone that functions as a structural component of the radial spokes of the '9+2' axoneme in motile cilia and sperm flagella, where it is required for central complex stability and axonemal integrity (PMID:19919626, PMID:27486783). It is an axoneme-associated protein distributed along the entire sperm flagellum and present in motile cilia of trachea and oviduct, with constitutive (non-heat-shock-induced) expression (PMID:18247331, PMID:19919626). Loss-of-function mutations destabilize the protein and trigger its proteasomal degradation, producing absence of DNAJB13 from cilia and sperm axonemes, central complex defects, primary ciliary dyskinesia, and male infertility spanning asthenozoospermia and teratozoospermia (PMID:27486783, PMID:31342671, PMID:35166991). Within the axoneme it sits in a radial spoke head protein network: it physically interacts with DNAH12, an inner dynein arm component whose loss disrupts central pair stability in a manner involving DNAJB13 together with RSPH1 and RSPH9 [PMID:bio_10.1101_2024.06.20.599934]. The biochemical chaperone activity predicted from its conserved J domain has not been experimentally demonstrated in the available corpus, and its reported interaction with the glycolytic enzyme HK1 rests on a single pull-down (PMID:14970903, PMID:27998865).

1. 2004 Low

   Established the molecular identity of DNAJB13 by placing it in the HSP40/DnaJ family via a conserved J domain, framing it as a candidate HSP70 co-chaperone.

   Evidence Molecular cloning, sequence analysis, RT-PCR and Northern blot of TSARG6

   PMID:14970903

   Open questions at the time

   • Sequence-based inference only — no biochemical assay of J-domain function or HSP70 binding
   • No subcellular or tissue localization established
   • No functional phenotype linked
2. 2008 Medium

   Resolved where DNAJB13 acts by showing it is an axoneme-associated component of the sperm flagellum rather than a heat-inducible stress chaperone.

   Evidence Western blot, immunohistochemistry and fractionation of SDS-resistant sperm tail structures in mouse

   PMID:18247331

   Open questions at the time

   • Did not resolve the specific axonemal substructure
   • No mechanistic role demonstrated
   • Single lab
3. 2010 High

   Pinpointed DNAJB13 to the radial spokes of the '9+2' axoneme, defining its precise structural position in both flagella and motile cilia.

   Evidence Immunoelectron microscopy of mouse sperm flagella and immunohistochemistry of trachea and oviduct

   PMID:19919626

   Open questions at the time

   • Did not define radial spoke binding partners
   • No functional consequence of localization tested
   • Single lab
4. 2016 High

   Established DNAJB13 as causative for human disease by showing loss-of-function mutations destabilize the protein, drive its proteasomal degradation, and produce central complex defects and PCD.

   Evidence In vitro mutant expression and proteasome inhibition, whole-exome sequencing, transcript analysis, and immunofluorescence of patient cilia/sperm across two families

   PMID:27486783

   Open questions at the time

   • Molecular mechanism by which DNAJB13 loss causes central complex collapse not defined
   • Chaperone client proteins not identified
   • No structural model of DNAJB13 in the spoke
5. 2016 Low

   Probed a possible metabolic role by detecting an interaction between DNAJB13 and the glycolytic enzyme HK1 in testis.

   Evidence GST pull-down with recombinant DNAJB13 against mouse testis lysate, Western blot detection of HK1

   PMID:27998865

   Open questions at the time

   • Single pull-down without reciprocal Co-IP or in vivo validation
   • Functional consequence for motility untested
   • Whether interaction reflects chaperone-client relationship unknown
6. 2019 Medium

   Extended the disease spectrum and began mapping the sperm interactome, linking a missense allele to reduced DNAJB13 levels, tail ultrastructural defects, and immotile sperm in asthenozoospermia.

   Evidence Co-IP/mass spectrometry interactome, MRM protein quantification, TEM and immuno-EM of patient sperm

   PMID:31342671

   Open questions at the time

   • Interactome partners not individually validated
   • Genotype-phenotype mechanism for heterozygous allele not resolved
   • Single lab
7. 2022 Medium

   Confirmed loss of DNAJB13 expression as a cause of teratozoospermia with respiratory disease and clarified its developmental expression during spermiogenesis.

   Evidence Whole-exome sequencing, Western blot showing protein absence, immunofluorescence, and TEM in human and mouse

   PMID:35166991

   Open questions at the time

   • Does not explain variable phenotype across alleles
   • No molecular pathway from DNAJB13 loss to flagellar malformation
   • Single lab
8. 2024 Medium

   Positioned DNAJB13 within a radial spoke head network by showing it physically interacts with the inner dynein arm component DNAH12 and participates with RSPH1/RSPH9 in central pair stability.

   Evidence Co-IP, Dnah12 knockout and mutant mouse models, TEM and immunofluorescence (preprint)

   PMID:bio_10.1101_2024.06.20.599934

   Open questions at the time

   • Preprint, not yet peer-reviewed
   • Directness and stoichiometry of DNAJB13-DNAH12 interaction not resolved
   • Whether DNAJB13 acts as chaperone for these partners untested

• Whether DNAJB13 exerts a bona fide HSP40 chaperone activity — and what its client proteins are within the radial spoke — remains unresolved.
• No demonstrated HSP70 partnership or J-domain-dependent folding activity
• No identified chaperone clients among axonemal proteins
• No structural model of DNAJB13 within the radial spoke