id: P59910
gene_symbol: DNAJB13
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
alternative_products:
- name: '1'
  id: P59910-1
- name: 2 (TSARG5)
  id: P59910-2
  sequence_note: VSP_008519, VSP_008520
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Plausible from the conserved J domain but not experimentally demonstrated for DNAJB13; retained as non-core because the documented function is axonemal-structural.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: DnaJ homolog subfamily B member 13
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Conflicts with the experimentally established cilium/flagellum localization; cytosolic activity is a family-level inference unsupported for this axonemal protein.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cell projection, cilium, flagellum'
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO electronic transfer of protein folding from the HSP40/DnaJ peptide-binding domain signature. Same caveat as the IBA folding term.
    action: KEEP_AS_NON_CORE
    reason: Domain-based prediction; not demonstrated for DNAJB13 whose core role is structural in the radial spoke.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: HSP40/DnaJ peptide-binding domain
- term:
    id: GO:0007017
    label: microtubule-based process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Generic microtubule-based process, electronically assigned. Consistent with DNAJB13's role in the microtubule-based axoneme but uninformatively broad.
    action: KEEP_AS_NON_CORE
    reason: Consistent with axonemal biology but too general to be a core annotation; more specific terms (cilium movement, flagellated sperm motility) capture the function.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic localization to motile cilium, redundant with and corroborated by the direct IDA evidence (PMID:27486783).
    action: ACCEPT
    reason: Correct localization, independently supported by immunofluorescence in respiratory cilia.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Localizes both to epithelial motile cilium and the sperm flagellum
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: 'P59910; O00444: PLK4; NbExp=3; IntAct=EBI-11514233, EBI-746202'
- term:
    id: GO:0001534
    label: radial spoke
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    reason: Radial spoke membership is the central, well-supported cellular component for DNAJB13.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Component of the axonemal radial
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Broad cytoplasm localization transferred from the mouse ortholog. Too general; the specific compartment is the ciliary/flagellar axoneme.
    action: KEEP_AS_NON_CORE
    reason: Technically the axoneme is cytoplasmic, but the term is uninformatively broad relative to the documented cilium/flagellum localization.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cell projection, cilium, flagellum'
- term:
    id: GO:0005930
    label: axoneme
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Axoneme localization transferred from the mouse ortholog and consistent with radial-spoke membership; the radial spoke attaches to the axonemal doublet microtubules.
    action: ACCEPT
    reason: Correct and specific localization for a radial-spoke component.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Component of the axonemal radial
- term:
    id: GO:0036126
    label: sperm flagellum
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Sperm flagellum localization, corroborated by the direct IDA evidence (PMID:27486783).
    action: ACCEPT
    reason: Correct localization, independently demonstrated experimentally.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Localizes both to epithelial motile cilium and the sperm flagellum
- term:
    id: GO:0120212
    label: sperm head-tail coupling apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Localization to the sperm head-tail coupling apparatus, where DNAJB13 is rapidly enriched during spermatid elongation (By similarity to mouse).
    action: ACCEPT
    reason: Supported by the UniProt subcellular-location note from the mouse ortholog; a genuine sperm sub-compartment localization.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: rapidly enriched in the coupling apparatus with the elongation of the spermatid
- term:
    id: GO:0097225
    label: sperm midpiece
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localization to the sperm midpiece, consistent with distribution along the sperm flagellum.
    action: ACCEPT
    reason: Direct antibody-based localization consistent with flagellar distribution.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: In mature spermatzoa evenly distributed along the flagellum
- term:
    id: GO:0097228
    label: sperm principal piece
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localization to the sperm principal piece, consistent with flagellar distribution.
    action: ACCEPT
    reason: Direct antibody-based localization consistent with flagellar distribution.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: In mature spermatzoa evenly distributed along the flagellum
- term:
    id: GO:0097229
    label: sperm end piece
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localization to the sperm end piece, consistent with even distribution along the mature sperm flagellum.
    action: ACCEPT
    reason: Direct antibody-based localization consistent with flagellar distribution.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: In mature spermatzoa evenly distributed along the flagellum
- term:
    id: GO:0001534
    label: radial spoke
  evidence_type: NAS
  original_reference_id: PMID:36417862
  qualifier: part_of
  review:
    summary: ComplexPortal/NAS assignment of DNAJB13 to the radial spoke, based on identification of RS1 components in mammalian sperm flagella.
    action: ACCEPT
    reason: Reinforces the core radial-spoke membership with mammalian RS1 compositional data.
    supported_by:
    - reference_id: PMID:36417862
      supporting_text: this study elucidates the RS1 components and function in mammalian flagella
- term:
    id: GO:0030317
    label: flagellated sperm motility
  evidence_type: NAS
  original_reference_id: PMID:36417862
  qualifier: involved_in
  review:
    summary: DNAJB13, as a radial-spoke component, is required for sperm flagellar motility; loss causes male infertility from sperm motility defects.
    action: ACCEPT
    reason: Well supported biological-process annotation; radial spoke (RS1) loss abolishes sperm motility and DNAJB13 mutation causes male infertility.
    supported_by:
    - reference_id: PMID:36417862
      supporting_text: the absence of IQUB only resulted in male infertility, owing to the sperm motility defect
- term:
    id: GO:0036126
    label: sperm flagellum
  evidence_type: NAS
  original_reference_id: PMID:36417862
  qualifier: located_in
  review:
    summary: Sperm flagellum localization (NAS, ComplexPortal), redundant with the direct IDA evidence.
    action: ACCEPT
    reason: Correct localization corroborated by experimental IDA.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Localizes both to epithelial motile cilium and the sperm flagellum
- term:
    id: GO:0003341
    label: cilium movement
  evidence_type: NAS
  original_reference_id: PMID:36417862
  qualifier: involved_in
  review:
    summary: DNAJB13 participates in cilium movement as a radial-spoke component; radial spokes modulate beat frequency, amplitude and waveform.
    action: ACCEPT
    reason: Supported by the radial-spoke role and by the CILD34 motile-cilia phenotype caused by DNAJB13 loss.
    supported_by:
    - reference_id: PMID:36417862
      supporting_text: It modulates the beat frequency, amplitude, and waveform of the flagella and cilia
- term:
    id: GO:0005929
    label: cilium
  evidence_type: NAS
  original_reference_id: PMID:36417862
  qualifier: located_in
  review:
    summary: Cilium localization (NAS), a broader parent of the specific motile-cilium localization.
    action: ACCEPT
    reason: Correct, though less specific than motile cilium; consistent with all evidence.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cell projection, cilium, flagellum'
- term:
    id: GO:0005930
    label: axoneme
  evidence_type: NAS
  original_reference_id: PMID:36417862
  qualifier: located_in
  review:
    summary: Axoneme localization (NAS), redundant with the IEA axoneme annotation and consistent with radial-spoke membership.
    action: ACCEPT
    reason: Correct specific localization for a radial-spoke component.
    supported_by:
    - reference_id: PMID:36417862
      supporting_text: The T-shaped radial spoke (RS) is a protein complex attached to the A microtubule of the outer doublet microtubules
- term:
    id: GO:0097729
    label: 9+2 motile cilium
  evidence_type: NAS
  original_reference_id: PMID:36417862
  qualifier: located_in
  review:
    summary: Localization to the 9+2 motile cilium, the axonemal architecture bearing radial spokes and a central pair.
    action: ACCEPT
    reason: Correct and specific; radial spokes are a defining feature of the 9+2 motile axoneme.
    supported_by:
    - reference_id: PMID:36417862
      supporting_text: it extends toward the central pair
- term:
    id: GO:0001534
    label: radial spoke
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    summary: Sequence/orthology-based assignment of DNAJB13 to the radial spoke (from mouse Q80Y75), consistent with all other radial-spoke evidence.
    action: ACCEPT
    reason: Core localization, supported across multiple evidence lines.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Component of the axonemal radial
- term:
    id: GO:0120212
    label: sperm head-tail coupling apparatus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: ISS localization to the sperm head-tail coupling apparatus from the mouse ortholog, matching the UniProt note on spermatid enrichment.
    action: ACCEPT
    reason: Consistent with the documented spermatid coupling-apparatus enrichment.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Tightly attached to the implantation fossa during the maturation of the spermatid
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IDA
  original_reference_id: PMID:27486783
  qualifier: located_in
  review:
    summary: Direct immunofluorescence demonstration of DNAJB13 in epithelial motile (respiratory) cilia, lost in the CILD34 patient.
    action: ACCEPT
    reason: Strongest evidence localization; directly observed in human respiratory cilia.
    supported_by:
    - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
      supporting_text: Localizes both to epithelial motile cilium and the sperm flagellum
- term:
    id: GO:0036126
    label: sperm flagellum
  evidence_type: IDA
  original_reference_id: PMID:27486783
  qualifier: located_in
  review:
    summary: Direct immunofluorescence demonstration of DNAJB13 in the sperm flagellum, absent in the CILD34 patient with the Met278Arg variant.
    action: ACCEPT
    reason: Strongest evidence localization; directly observed in human sperm flagella.
    supported_by:
    - reference_id: PMID:27486783
      supporting_text: the absence of endogenous DNAJB13 in cilia and sperm from this individual
- term:
    id: GO:1904158
    label: axonemal central apparatus assembly
  evidence_type: IMP
  original_reference_id: PMID:27486783
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Mutant-phenotype evidence; DNAJB13 deficiency causes axonemal central-complex defects, a core consequence of its radial-spoke role.
    supported_by:
    - reference_id: PMID:27486783
      supporting_text: a PCD phenotype characterized by central complex (CC) defects but normal DA structure
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:27486783
  title: Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; body confirms biallelic
      DNAJB13 mutations cause PCD and male infertility via axonemal/radial-spoke and
      sperm flagellar defects, and GOA anchors this PMID to GO:0031514/GO:0036126/GO:1904158
      (IDA/IMP), supporting DNAJB13's core cilium/flagellum axoneme role.
  findings:
  - statement: Biallelic DNAJB13 mutations cause primary ciliary dyskinesia (CILD34) with central-complex defects but normal dynein arms, and male infertility from sperm flagellar dysfunction; DNAJB13 is required for proper formation and function of ciliary and flagellar axonemes.
    reference_section_type: ABSTRACT
  - statement: The Chlamydomonas ortholog of DNAJB13 localizes to the radial spokes; the p.Met278Arg variant causes protein instability and proteasomal degradation, with loss of endogenous DNAJB13 from cilia and sperm.
    reference_section_type: ABSTRACT
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:36417862
  title: Differential requirements of IQUB for the assembly of radial spoke 1 and the motility of mouse cilia and flagella.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; body confirms DNAJB13 is
      a radial-spoke-1 stalk component in mammalian sperm flagella. Corroborates the
      RS1/cilium-motility role (GOA anchors this PMID as NAS for radial spoke and
      sperm flagellum); supporting rather than primary functional evidence.
  findings:
  - statement: The radial spoke modulates beat frequency, amplitude and waveform of flagella and cilia; RS1 components (including DNAJB13) were identified in mammalian sperm flagella, and loss of RS1 (via Iqub deletion) causes male infertility from sperm motility defects.
    reference_section_type: ABSTRACT
- id: file:human/DNAJB13/DNAJB13-uniprot.txt
  title: UniProt entry P59910 (DJB13_HUMAN), DnaJ homolog subfamily B member 13
  findings:
  - statement: Functions as part of axonemal radial spoke complexes important for sperm and cilia motility; homodimer; component of radial spoke complex 1 (RS1) spoke stalk; localizes to motile cilium and sperm flagellum.
    reference_section_type: OTHER
core_functions:
- description: Structural component of the axonemal radial spoke (RS1 stalk) required for assembly and function of the ciliary/flagellar central apparatus and thereby for motility of sperm flagella and respiratory motile cilia.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  in_complex:
    id: GO:0001534
    label: radial spoke
  locations:
  - id: GO:0005930
    label: axoneme
  supported_by:
  - reference_id: file:human/DNAJB13/DNAJB13-uniprot.txt
    supporting_text: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
  - reference_id: PMID:27486783
    supporting_text: a PCD phenotype characterized by central complex (CC) defects but normal DA structure
- description: Participates in cilium and flagellated sperm movement as part of the radial-spoke mechanochemical signal-transduction apparatus that regulates axonemal beat.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  locations:
  - id: GO:0097729
    label: 9+2 motile cilium
  supported_by:
  - reference_id: PMID:36417862
    supporting_text: It modulates the beat frequency, amplitude, and waveform of the flagella and cilia
  directly_involved_in:
  - id: GO:0003341
    label: cilium movement
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: Which radial-spoke partner interactions are direct, and does the Met278Arg instability act by disrupting incorporation into the assembled spoke?
suggested_experiments:
- description: 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.
- description: In vitro J-domain functional assay (HSP70 ATPase stimulation) using recombinant DNAJB13 to test whether it has retained or lost canonical co-chaperone activity.
- description: Conditional Dnajb13 knockout in mouse multiciliated airway cells and spermatids with high-speed video microscopy to quantify the specific ciliary/flagellar beat defects.