DNAJB13 (DnaJ homolog subfamily B member 13; also TSARG3/TSARG6) is an HSP40/J-domain protein that, despite belonging to the co-chaperone family, acts principally as a structural component of the axonemal radial spoke complex. It is a homodimer found in the radial spoke stalk together with RSPH14, DYDC1, ROPN1L and NME5, and is required for the proper formation and function of the ciliary and flagellar axoneme. It localizes to epithelial motile (respiratory) cilia and to the sperm flagellum, where in spermatids it is enriched at the head-tail coupling apparatus and in mature sperm is distributed along the flagellum. Expression is largely restricted to testis and trachea. DNAJB13 supports the motility of sperm and cilia; biallelic loss-of-function variants cause autosomal-recessive primary ciliary dyskinesia (CILD34) with central-complex defects and male infertility.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) transfer of generic HSP40 protein-folding activity from better-characterized DnaJ family members. DNAJB13's experimentally documented role is structural within the axonemal radial spoke, not autonomous folding. Reason: No direct evidence that DNAJB13 functions as a protein-folding chaperone in vivo; it is a J-domain protein so a residual co-chaperone/folding role is plausible, but it is downstream and non-core relative to its radial-spoke structural function. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia. |
| GO:0051087 protein-folding chaperone binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA transfer of chaperone-binding molecular function from the DnaJ family. DNAJB13 has a J domain that could engage HSP70, but no direct chaperone-binding data exist for this protein, whose established interactions are with radial-spoke partners. Reason: Plausible from the conserved J domain but not experimentally demonstrated for DNAJB13; retained as non-core because the documented function is axonemal-structural. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt DnaJ homolog subfamily B member 13 |
| GO:0005829 cytosol | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA cytosol localization transferred from family members. DNAJB13's documented site of action is the ciliary/flagellar axoneme (radial spoke), not the bulk cytosol. Reason: Conflicts with the experimentally established cilium/flagellum localization; cytosolic activity is a family-level inference unsupported for this axonemal protein. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt SUBCELLULAR LOCATION: Cell projection, cilium, flagellum |
| GO:0006457 protein folding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO electronic transfer of protein folding from the HSP40/DnaJ peptide-binding domain signature. Same caveat as the IBA folding term. Reason: Domain-based prediction; not demonstrated for DNAJB13 whose core role is structural in the radial spoke. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt HSP40/DnaJ peptide-binding domain |
| GO:0007017 microtubule-based process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Generic microtubule-based process, electronically assigned. Consistent with DNAJB13's role in the microtubule-based axoneme but uninformatively broad. Reason: Consistent with axonemal biology but too general to be a core annotation; more specific terms (cilium movement, flagellated sperm motility) capture the function. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia. |
| GO:0031514 motile cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic localization to motile cilium, redundant with and corroborated by the direct IDA evidence (PMID:27486783). Reason: Correct localization, independently supported by immunofluorescence in respiratory cilia. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Localizes both to epithelial motile cilium and the sperm flagellum |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: High-throughput binary yeast two-hybrid interactome (HuRI) capturing a set of partners (PLK4, TOM1L1, PIBF1, MSS51, ZC3H12A, SEPTIN1, LHX4, RAB3IP, MDFI, GORASP2, PICK1, ZRANB1). The bare protein binding term is uninformative and none of these partners map onto DNAJB13's radial-spoke biology. Reason: Records real but uninformative high-throughput binary interactions; bare protein binding is not elevated to core per curation guidelines and no specific informative MF is justified by these heterogeneous Y2H hits. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt P59910; O00444: PLK4; NbExp=3; IntAct=EBI-11514233, EBI-746202 |
| GO:0001534 radial spoke | IEA GO_REF:0000107 | ACCEPT | Summary: DNAJB13 is a component of the axonemal radial spoke stalk; this is its defining structural localization, supported by orthology, ComplexPortal curation and the Chlamydomonas radial-spoke ortholog. Reason: Radial spoke membership is the central, well-supported cellular component for DNAJB13. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Component of the axonemal radial |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad cytoplasm localization transferred from the mouse ortholog. Too general; the specific compartment is the ciliary/flagellar axoneme. Reason: Technically the axoneme is cytoplasmic, but the term is uninformatively broad relative to the documented cilium/flagellum localization. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt SUBCELLULAR LOCATION: Cell projection, cilium, flagellum |
| GO:0005930 axoneme | IEA GO_REF:0000107 | ACCEPT | Summary: Axoneme localization transferred from the mouse ortholog and consistent with radial-spoke membership; the radial spoke attaches to the axonemal doublet microtubules. Reason: Correct and specific localization for a radial-spoke component. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Component of the axonemal radial |
| GO:0036126 sperm flagellum | IEA GO_REF:0000120 | ACCEPT | Summary: Sperm flagellum localization, corroborated by the direct IDA evidence (PMID:27486783). Reason: Correct localization, independently demonstrated experimentally. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Localizes both to epithelial motile cilium and the sperm flagellum |
| GO:0120212 sperm head-tail coupling apparatus | IEA GO_REF:0000107 | ACCEPT | Summary: Localization to the sperm head-tail coupling apparatus, where DNAJB13 is rapidly enriched during spermatid elongation (By similarity to mouse). Reason: Supported by the UniProt subcellular-location note from the mouse ortholog; a genuine sperm sub-compartment localization. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt rapidly enriched in the coupling apparatus with the elongation of the spermatid |
| GO:0097225 sperm midpiece | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence localization to the sperm midpiece, consistent with distribution along the sperm flagellum. Reason: Direct antibody-based localization consistent with flagellar distribution. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt In mature spermatzoa evenly distributed along the flagellum |
| GO:0097228 sperm principal piece | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence localization to the sperm principal piece, consistent with flagellar distribution. Reason: Direct antibody-based localization consistent with flagellar distribution. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt In mature spermatzoa evenly distributed along the flagellum |
| GO:0097229 sperm end piece | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence localization to the sperm end piece, consistent with even distribution along the mature sperm flagellum. Reason: Direct antibody-based localization consistent with flagellar distribution. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt In mature spermatzoa evenly distributed along the flagellum |
| GO:0001534 radial spoke | NAS PMID:36417862 Differential requirements of IQUB for the assembly of radial... | ACCEPT | Summary: ComplexPortal/NAS assignment of DNAJB13 to the radial spoke, based on identification of RS1 components in mammalian sperm flagella. Reason: Reinforces the core radial-spoke membership with mammalian RS1 compositional data. Supporting Evidence: PMID:36417862 this study elucidates the RS1 components and function in mammalian flagella |
| GO:0030317 flagellated sperm motility | NAS PMID:36417862 Differential requirements of IQUB for the assembly of radial... | ACCEPT | Summary: DNAJB13, as a radial-spoke component, is required for sperm flagellar motility; loss causes male infertility from sperm motility defects. Reason: Well supported biological-process annotation; radial spoke (RS1) loss abolishes sperm motility and DNAJB13 mutation causes male infertility. Supporting Evidence: PMID:36417862 the absence of IQUB only resulted in male infertility, owing to the sperm motility defect |
| GO:0036126 sperm flagellum | NAS PMID:36417862 Differential requirements of IQUB for the assembly of radial... | ACCEPT | Summary: Sperm flagellum localization (NAS, ComplexPortal), redundant with the direct IDA evidence. Reason: Correct localization corroborated by experimental IDA. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Localizes both to epithelial motile cilium and the sperm flagellum |
| GO:0003341 cilium movement | NAS PMID:36417862 Differential requirements of IQUB for the assembly of radial... | ACCEPT | Summary: DNAJB13 participates in cilium movement as a radial-spoke component; radial spokes modulate beat frequency, amplitude and waveform. Reason: Supported by the radial-spoke role and by the CILD34 motile-cilia phenotype caused by DNAJB13 loss. Supporting Evidence: PMID:36417862 It modulates the beat frequency, amplitude, and waveform of the flagella and cilia |
| GO:0005929 cilium | NAS PMID:36417862 Differential requirements of IQUB for the assembly of radial... | ACCEPT | Summary: Cilium localization (NAS), a broader parent of the specific motile-cilium localization. Reason: Correct, though less specific than motile cilium; consistent with all evidence. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt SUBCELLULAR LOCATION: Cell projection, cilium, flagellum |
| GO:0005930 axoneme | NAS PMID:36417862 Differential requirements of IQUB for the assembly of radial... | ACCEPT | Summary: Axoneme localization (NAS), redundant with the IEA axoneme annotation and consistent with radial-spoke membership. Reason: Correct specific localization for a radial-spoke component. Supporting Evidence: PMID:36417862 The T-shaped radial spoke (RS) is a protein complex attached to the A microtubule of the outer doublet microtubules |
| GO:0097729 9+2 motile cilium | NAS PMID:36417862 Differential requirements of IQUB for the assembly of radial... | ACCEPT | Summary: Localization to the 9+2 motile cilium, the axonemal architecture bearing radial spokes and a central pair. Reason: Correct and specific; radial spokes are a defining feature of the 9+2 motile axoneme. Supporting Evidence: PMID:36417862 it extends toward the central pair |
| GO:0001534 radial spoke | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence/orthology-based assignment of DNAJB13 to the radial spoke (from mouse Q80Y75), consistent with all other radial-spoke evidence. Reason: Core localization, supported across multiple evidence lines. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Component of the axonemal radial |
| GO:0120212 sperm head-tail coupling apparatus | ISS GO_REF:0000024 | ACCEPT | Summary: ISS localization to the sperm head-tail coupling apparatus from the mouse ortholog, matching the UniProt note on spermatid enrichment. Reason: Consistent with the documented spermatid coupling-apparatus enrichment. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Tightly attached to the implantation fossa during the maturation of the spermatid |
| GO:0031514 motile cilium | IDA PMID:27486783 Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause... | ACCEPT | Summary: Direct immunofluorescence demonstration of DNAJB13 in epithelial motile (respiratory) cilia, lost in the CILD34 patient. Reason: Strongest evidence localization; directly observed in human respiratory cilia. Supporting Evidence: file:human/DNAJB13/DNAJB13-uniprot.txt Localizes both to epithelial motile cilium and the sperm flagellum |
| GO:0036126 sperm flagellum | IDA PMID:27486783 Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause... | ACCEPT | Summary: Direct immunofluorescence demonstration of DNAJB13 in the sperm flagellum, absent in the CILD34 patient with the Met278Arg variant. Reason: Strongest evidence localization; directly observed in human sperm flagella. Supporting Evidence: PMID:27486783 the absence of endogenous DNAJB13 in cilia and sperm from this individual |
| GO:1904158 axonemal central apparatus assembly | IMP PMID:27486783 Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause... | ACCEPT | Summary: Loss of DNAJB13 in PCD patients produces central-complex (central apparatus) defects of the axoneme with normal dynein arms, implicating DNAJB13 in central-apparatus assembly/function. Reason: Mutant-phenotype evidence; DNAJB13 deficiency causes axonemal central-complex defects, a core consequence of its radial-spoke role. Supporting Evidence: PMID:27486783 a PCD phenotype characterized by central complex (CC) defects but normal DA structure |
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Download this section (compressed HTML)Q: Does DNAJB13 retain any HSP70-stimulating co-chaperone activity within the radial spoke (e.g. chaperoning radial-spoke assembly), or is its J domain repurposed purely as a structural/dimerization module?
Q: Which radial-spoke partner interactions are direct, and does the Met278Arg instability act by disrupting incorporation into the assembled spoke?
Experiment: Cryo-EM of the mammalian radial spoke with and without DNAJB13 to define its structural position in the RS1 stalk and the effect of CILD34 variants on spoke architecture.
Experiment: In vitro J-domain functional assay (HSP70 ATPase stimulation) using recombinant DNAJB13 to test whether it has retained or lost canonical co-chaperone activity.
Experiment: Conditional Dnajb13 knockout in mouse multiciliated airway cells and spermatids with high-speed video microscopy to quantify the specific ciliary/flagellar beat defects.
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