Affinage

DNAJA1

DnaJ homolog subfamily A member 1 · UniProt P31689

Length
397 aa
Mass
44.9 kDa
Annotated
2026-06-09
54 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAJA1 (Hdj-2/HSDJ) is a farnesylated Hsp40/DnaJ co-chaperone that partners with Hsc70/Hsp70 to govern protein quality control across folding, assembly, and stability decisions (PMID:10075921, PMID:9839446). Through its J-domain it recruits and is regulated at the Hsp70 interface, a surface defined structurally by NMR that overlaps a predicted inhibitory site (PMID:24512202, PMID:36291603), while its zinc-binding architecture is required for structural integrity and aggregation-suppressing chaperone activity, with copper able to partially substitute for zinc (PMID:37244380). Acting with Hsc70, DNAJA1 suppresses aggregation of folding-challenged clients such as nascent CFTR NBD1 and polyglutamine-expanded androgen receptor, and can refold mislocalized nuclear receptors (PMID:10075921, PMID:10196362, PMID:9168467). A central, recurring activity is the stabilization of specific client proteins against proteasomal degradation: it selectively binds conformational (not DNA-contact or wild-type) mutant p53 to block CHIP-mediated ubiquitylation and degradation, sustaining oncogenic migration, filopodia formation, and metastasis via CDC42/RAC1 (PMID:27775703, PMID:33208462, PMID:34183772), and it likewise stabilizes activation-induced deaminase (AID) to support antibody isotype switching (PMID:22085931), PIWI proteins including PIWIL1 (PMID:31076507), and E2F1-induced CDC45 to drive cell-cycle progression (PMID:31477839). Stabilization of mutant p53 and AID requires DNAJA1 farnesylation at its C-terminal CAAX motif, linking its function to the mevalonate pathway and rendering it sensitive to statins and farnesyltransferase inhibitors (PMID:27775703, PMID:31397499, PMID:22085931). DNAJA1 abundance and activity are themselves controlled post-translationally by HDAC6-mediated deacetylation that tunes Hsc70 binding (PMID:25311840), CRBN-mediated ubiquitin-dependent degradation (PMID:33972400), and YOD1-mediated deubiquitination (PMID:42103167). Its handling of aggregation-prone neuronal substrates is context-dependent — it promotes ubiquitin-dependent tau clearance (PMID:22343013, PMID:33972400) yet can favor aggregation of polyglutamine huntingtin and amyloid-beta (PMID:32424160, PMID:36448030). DNAJA1 relocalizes from the cytoplasm to the nucleus, nucleolus, or Golgi upon heat shock, irradiation, or influenza infection, where it independently binds the PB2/PA polymerase subunits to enhance viral RNA synthesis through its C-terminal substrate-binding domain rather than its J-domain (PMID:9839446, PMID:16818651, PMID:25253355). At the organismal level DNAJA1 supports radioresistance (PMID:16818651), spermatogenesis and male fertility (PMID:39208916), and mitochondrial homeostasis, including activation of the mitochondrial unfolded protein response (PMID:40412052, PMID:42103167).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1997 Medium

    Established that the Hsp70/DnaJ system can act in the nucleus, not just cytoplasm, by showing DNAJA1 overexpression rescues a misfolded glucocorticoid receptor mutant's trafficking and transcriptional function.

    Evidence Overexpression rescue with immunofluorescence and reporter assays in COS-1 cells

    PMID:9168467

    Open questions at the time
    • Direct binding to the receptor not demonstrated
    • Endogenous-level relevance not tested
  2. 1998 Medium

    Defined DNAJA1's basal physical properties and stress behavior — it is farnesylated, ubiquitously expressed, and redistributes to Golgi/nucleolus/nuclear membrane on heat shock — framing localization as a regulated feature.

    Evidence Metabolic labeling for farnesylation plus immunostaining and blotting

    PMID:9839446

    Open questions at the time
    • Functional role of farnesylation not yet defined
    • Mechanism of stress relocalization unknown
  3. 1999 High

    Showed DNAJA1 works synergistically with Hsc70 on a physiological folding client (nascent CFTR), suppressing NBD1 aggregation during co-translational assembly, establishing its general aggregation-suppression activity.

    Evidence Co-IP of CFTR translation intermediates plus in vitro aggregation assay with purified components

    PMID:10075921

    Open questions at the time
    • ATPase stimulation kinetics not quantified
    • In vivo CFTR maturation consequence not measured
  4. 1999 Medium

    Extended chaperone activity to disease-relevant aggregates, showing DNAJA1 suppresses polyglutamine androgen receptor aggregation and is sequestered into inclusions with Hsp70/Hsp90 and proteasome caps.

    Evidence Transfection, immunofluorescence, and EM co-localization in HeLa cells

    PMID:10196362

    Open questions at the time
    • Direct vs indirect suppression not distinguished
    • Single overexpression system
  5. 2000 Low

    Revealed that DNAJA1's effect on aggregation is substrate- and cell-type-dependent, sometimes promoting rather than suppressing polyglutamine huntingtin inclusions.

    Evidence Transfection and inclusion counting across COS-7, PC12, SH-SY5Y cells

    PMID:10717003

    Open questions at the time
    • Single method without mechanistic explanation
    • Cell-type variability unexplained
  6. 2003 Medium

    Linked alternative splicing to subcellular targeting, showing an NLS-containing isoform localizes to the nucleus while the shorter isoform distributes diffusely.

    Evidence GFP-fusion imaging in HeLa cells

    PMID:12974469

    Open questions at the time
    • Functional differences between isoforms not characterized
    • Endogenous isoform abundance unknown
  7. 2006 Medium

    Connected stress-induced nuclear migration to a phenotype, showing irradiation drives farnesylation-dependent nuclear translocation of DNAJA1 and that DNAJA1 levels set radiosensitivity.

    Evidence Immunofluorescence, FTase inhibitor, siRNA/overexpression with clonogenic survival in glioblastoma cells

    PMID:16818651

    Open questions at the time
    • Nuclear DNAJA1 substrates after irradiation unknown
    • Mechanism linking DNAJA1 to DNA damage response undefined
  8. 2011 High

    Identified the first endogenous client whose stability depends on DNAJA1 — AID — establishing paralog-specific, farnesylation-dependent client stabilization with an immune phenotype.

    Evidence Knockdown/overexpression, knockout mice, FTase inhibitor, isotype-switching assays

    PMID:22085931

    Open questions at the time
    • Whether stabilization is Hsp70-dependent not resolved
    • Direct AID-binding interface not mapped
  9. 2012 Medium

    Showed DNAJA1 promotes ubiquitin-dependent clearance of tau, positioning it in neurodegenerative proteostasis.

    Evidence Overexpression/knockdown, ubiquitination-site mutants, in vivo correlation

    PMID:22343013

    Open questions at the time
    • E3 ligase mediating tau clearance not identified
    • Relationship to Hsp70 co-induction antagonism unexplained
  10. 2014 Medium

    Defined post-translational and structural regulation of DNAJA1 — HDAC6 deacetylation tunes Hsc70 binding, and NMR mapped a J-domain Hsp70/inhibitory interface — and linked DNAJA1 to JNK signaling.

    Evidence Acetylome proteomics and co-IP (HDAC6); NMR structure and JNK readouts in cancer cells

    PMID:24512202 PMID:25311840

    Open questions at the time
    • Acetylation sites controlling activity not pinpointed
    • Mechanism of JNK suppression undefined
  11. 2014 High

    Established a J-domain-independent function, showing DNAJA1 binds influenza PB2/PA, translocates to the nucleus on infection, and enhances viral RNA synthesis via its C-terminal substrate-binding domain.

    Evidence Co-IP, in vitro RNA synthesis assay, domain mutagenesis, immunofluorescence

    PMID:25253355

    Open questions at the time
    • Whether enhancement reflects chaperoning of polymerase folding vs direct effect unclear
    • Hsp70 involvement not tested
  12. 2016 High

    Defined DNAJA1's most-studied oncogenic client: it directly binds and stabilizes conformational mutant p53 by blocking CHIP-mediated degradation, a function dependent on the mevalonate pathway.

    Evidence Reciprocal co-IP, knockdown/rescue, statin screen in cancer lines

    PMID:27775703

    Open questions at the time
    • Precise binding interface not yet mapped at this stage
    • Generality across mutp53 alleles untested here
  13. 2016 High

    Identified DNAJA1 as an interactor, regulator, and glutamine-donor substrate of transglutaminase 2, coupling it to TG2 conformational/activity control.

    Evidence GST pull-down, MS, ELISA, SPR, transamidation assays

    PMID:27551108

    Open questions at the time
    • Cellular consequence of TG2 modification of DNAJA1 unknown
    • Physiological context of this interaction undefined
  14. 2019 High

    Mechanistically tied DNAJA1's client-stabilizing function to its lipid modification, showing CAAX-motif farnesylation is required to bind and protect mutant p53.

    Evidence CAAX mutagenesis, co-IP, FTase inhibitor and knockdown, mouse model

    PMID:31397499

    Open questions at the time
    • How farnesylation enables client binding mechanistically unclear
    • Membrane vs soluble pool contributions unresolved
  15. 2019 Medium

    Expanded the client repertoire to germline and cell-cycle proteins — DNAJA1 stabilizes conserved PIWI proteins (PIWIL1) and E2F1-induced CDC45 to drive proliferation.

    Evidence Yeast two-hybrid, co-IP, knockdown, stability assays in planarian/human cells (PIWI); ChIP/reporter and stability assays in colorectal cells (CDC45)

    PMID:31076507 PMID:31477839

    Open questions at the time
    • Whether stabilization is direct chaperoning or indirect not fully resolved
    • Hsp70 dependence not established for these clients
  16. 2020 Medium

    Demonstrated opposing aggregation control among DnaJ family members — DNAJA1 knockout reduces polyQ-huntingtin aggregation whereas DNAJB6 knockout increases it.

    Evidence CRISPR knockout, microscopy, filter trap in HEK293

    PMID:32424160

    Open questions at the time
    • Mechanism by which DNAJA1 promotes polyQ aggregation unknown
    • Relevance to neuronal cells untested
  17. 2020 Medium

    Mapped a druggable mutant-p53 interaction pocket in the glycine/phenylalanine-rich region, validating it by mutagenesis that disrupts binding and destabilizes mutp53.

    Evidence Homology modeling, mutagenesis, co-IP, virtual screening, in vivo growth assays

    PMID:33208462

    Open questions at the time
    • Experimental structure of the pocket lacking
    • Selectivity over other clients unknown
  18. 2021 High

    Established client selectivity and downstream consequence: DNAJA1 binds conformational but not DNA-contact or wild-type p53, and its loss reduces CDC42/RAC1 activity, migration, and metastasis.

    Evidence Co-IP selectivity, knockdown, Rho-GTPase and migration assays, xenograft metastasis models in HNSCC

    PMID:34183772

    Open questions at the time
    • Structural basis of conformational-mutant selectivity not defined
    • Mechanistic link to GTPase activation indirect
  19. 2021 Medium

    Identified ubiquitin-mediated control of DNAJA1 abundance by cereblon, with CRBN loss enhancing DNAJA1 chaperone capacity to reduce pathologic tau.

    Evidence Co-IP, CRBN knockout mice, tau aggregation/kinase assays

    PMID:33972400

    Open questions at the time
    • DNAJA1 ubiquitination sites not mapped
    • Whether Hsp70 is co-degraded in cells unresolved
  20. 2022 Medium

    Provided high-resolution structural and chemical-biology tools — an NMR J-domain/linker structure with binding sites and small molecules (A11) that bind J-domain residues Y7/K44/Q47 to deplete DNAJA1 and mutp53.

    Evidence NMR, ITC, pull-down/MS, virtual screening, mutagenesis and cell-based depletion/migration assays

    PMID:36291603 PMID:36316326

    Open questions at the time
    • Full-length structure including substrate-binding domain lacking
    • On-target selectivity of compounds in vivo unproven
  21. 2022 Medium

    Showed conserved pro-aggregation behavior toward amyloid-beta — the ortholog Ydj1 binds Abeta, drives oligomerization, and routes it to mitochondria, with deletion protective.

    Evidence Yeast genetic screen, interaction assays, Drosophila AD model, mitochondrial fractionation

    PMID:36448030

    Open questions at the time
    • Direct evidence in mammalian neurons absent
    • Distinction from tau-clearance role unexplained
  22. 2023 Medium

    Established that zinc binding is essential for DNAJA1 structural integrity and chaperone activity, with copper partly substituting.

    Evidence In vitro aggregation assays, metal chelation/reconstitution, yeast complementation, biophysics

    PMID:37244380

    Open questions at the time
    • Physiological metal occupancy in cells unknown
    • Link between metal loss and client release undefined
  23. 2024 Medium

    Defined an organismal proteostasis requirement — DNAJA1 knockout reduces testis polyubiquitination and causes complete male infertility with spermatogenesis defects.

    Evidence Knockout mice, Western blot, immunofluorescence, fertility assays

    PMID:39208916

    Open questions at the time
    • Specific spermatogenic clients unidentified
    • Mechanism connecting DNAJA1 to ubiquitination not resolved
  24. 2024 Medium

    Linked DNAJA1 to endothelial barrier control, showing its knockout suppresses heat-stroke-induced MLCK-MLC signaling and preserves junctional proteins.

    Evidence Knockout cells/mice, TEER, permeability, proteomics, heat-stroke model

    PMID:38551163

    Open questions at the time
    • Direct DNAJA1 target in the MLCK pathway unknown
    • Whether effect is chaperone-dependent untested
  25. 2025 Medium

    Connected DNAJA1 to mitochondrial regulation via a direct PSMD9 interaction through an EXKK motif, with proteasome inhibition enhancing binding and DNAJA1 stability.

    Evidence MS, in vitro binding with purified proteins, mutagenesis, co-IP, mitochondrial membrane potential in MCF7

    PMID:40412052

    Open questions at the time
    • Functional consequence of the interaction for proteostasis unclear
    • How PSMD9 binding affects mitochondrial potential mechanistically unknown
  26. 2026 Medium

    Identified YOD1 deubiquitination as a stabilizing input enabling DNAJA1-HSP70 activation of the mitochondrial UPR to limit neuronal apoptosis after subarachnoid hemorrhage.

    Evidence Docking, co-IP, stability assays, YOD1 overexpression in SAH models, mitochondrial assays

    PMID:42103167

    Open questions at the time
    • DNAJA1 ubiquitination/deubiquitination sites not mapped
    • Direct role in UPRmt induction vs correlation unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how DNAJA1 achieves client selectivity (e.g., conformational mutant p53 vs others) and how farnesylation, zinc binding, and the J-domain versus C-terminal substrate-binding domain are coordinated to switch between Hsp70-dependent folding and Hsp70-independent functions.
  • No full-length structure with bound client
  • No reconstitution dissecting farnesylation/zinc/J-domain contributions to a single client
  • Substrate-recognition code undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 3 GO:0005829 cytosol 2 GO:0005635 nuclear envelope 1 GO:0005730 nucleolus 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1
Partners
AICDACDC45CRBNHSPA8PIWIL1PSMD9TGM2TP53

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Hdj-2 (DNAJA1) and Hsc70 form complexes with nascent CFTR at the ER, with complex formation initiated when NBD1 emerges in the cytosol and diminishing after R-domain expression. In experiments with purified components, Hdj-2 and Hsc70 acted synergistically to suppress NBD1 aggregation, suggesting Hdj-2/Hsc70 facilitate early CFTR assembly including formation of an intramolecular NBD1-R-domain complex. Co-immunoprecipitation of CFTR translation intermediates with Hdj-2/Hsc70; in vitro aggregation suppression assay with purified components The EMBO journal High 10075921
1999 HDJ-2/HSDJ co-expression significantly suppresses polyglutamine-expanded androgen receptor (ARQ48) aggregate formation in HeLa cells; ARQ48 aggregates co-localize with and sequester HDJ-2/HSDJ, Hsp70, Hsp90, and proteasome PA700 caps but not 20S core particles. Transient transfection in HeLa cells, immunofluorescence, electron microscopy, co-localization studies Human molecular genetics Medium 10196362
1997 HDJ-2/HSDJ overexpression corrects aberrant subnuclear trafficking of a glucocorticoid receptor zinc finger mutant (R496) and restores its transactivation and transrepression activity, demonstrating that the Hsp70/DnaJ chaperone system can act in the nucleus to refold mislocalized/misfolded receptors. Transient transfection in COS-1 cells, immunofluorescence co-localization, transactivation/transrepression reporter assays Molecular biology of the cell Medium 9168467
1998 HDJ-2 (DNAJA1) is farnesylated but not glycosylated, is ubiquitously expressed, localizes throughout the cytoplasm and around the nuclear membrane under basal conditions, and migrates to the Golgi, nucleolus, and nuclear membrane upon heat shock. Immunohistochemistry with polyclonal and monoclonal antibodies, metabolic labeling to determine farnesylation, Western and Northern blot analysis The international journal of biochemistry & cell biology Medium 9839446
2006 Irradiation causes HDJ-2 to migrate from the cytoplasm to the nucleus; this migration is inhibited by farnesyltransferase inhibitor R115777 pre-treatment. Genetic inhibition of HDJ-2 increases radiosensitivity, while overexpression confers radioresistance in glioblastoma cells. Immunofluorescence microscopy for HDJ-2 localization, siRNA knockdown and overexpression with clonogenic survival assays Cancer research Medium 16818651
2016 DNAJA1 stabilizes misfolded/conformational mutant p53 by direct interaction, preventing CHIP ubiquitin ligase-mediated ubiquitylation and proteasomal degradation. Knockdown of DNAJA1 induces CHIP-mediated nuclear export, ubiquitylation, and degradation of mutant p53. Mevalonate-5-phosphate (reduced by statins) is required for this DNAJA1-mutp53 protective interaction. siRNA knockdown, co-immunoprecipitation, high-throughput statin screening, overexpression rescue experiments in cancer cell lines Nature cell biology High 27775703
2019 Farnesylation of DNAJA1 at its C-terminal CAAX motif is required for its ability to bind and stabilize mutant p53. A C394S CAAX-box mutation abolishes DNAJA1 farnesylation and eliminates its capacity to maintain mutant p53 stabilization. Farnesyl pyrophosphate supplementation rescues atorvastatin-induced mutant p53 degradation. Site-directed mutagenesis of DNAJA1 CAAX box, co-immunoprecipitation with anti-DNAJA1/p53 antibodies, farnesyltransferase inhibitor (tipifarnib) treatment, FTase gene knockdown, genetically engineered mouse model Molecular carcinogenesis High 31397499
2014 DNAJA1 is a substrate of HDAC6 deacetylase; HDAC6 interacts with DNAJA1 and negatively regulates its acetylation levels. HDAC6-mediated deacetylation modulates the interaction between Hsc70 and DNAJA1. Quantitative proteomics of lysine acetylation in HDAC6 knockout mouse liver, co-immunoprecipitation validation, functional interaction assays in cultured cells Protein & cell Medium 25311840
2014 DnaJA1 associates with the PB2 and PA subunits of influenza A virus RNA polymerase and enhances viral RNA synthesis in vivo and in vitro. Upon influenza infection, DnaJA1 translocates from cytoplasm to nucleus along with PB1-PA nuclear import. The enhancement of viral RNA synthesis is dependent on DnaJA1's C-terminal substrate-binding domain, not the J-domain (Hsp70-interaction domain). Co-immunoprecipitation, in vitro RNA synthesis assay, immunofluorescence for nuclear translocation, domain deletion/mutation analysis Journal of virology High 25253355
2012 DnaJA1 overexpression promotes tau clearance via ubiquitin-dependent mechanisms, while DnaJA1 knockdown facilitates tau accumulation. DnaJA1-mediated tau reduction requires lysines known to be poly-ubiquitinated in Alzheimer's brain. Hsp70 co-induction attenuates DnaJA1-driven tau clearance. In vivo, DnaJA1 and tau levels are inversely correlated. Overexpression and siRNA knockdown in cell lines, in vivo correlation studies, ubiquitination site mutant analysis Journal of molecular biology Medium 22343013
2011 DnaJa1 (but not the paralog DnaJa2) specifically stabilizes activation-induced deaminase (AID), maintaining its protein levels and biological activity. DnaJa1 depletion reduces AID levels, stability, and isotype switching in B cells. DnaJa1-deficient mice show compromised immunization responses and reduced AID protein and isotype switching by ~50%. DnaJa1 farnesylation is required for AID stabilization. Overexpression and siRNA knockdown in cell lines, DnaJa1 knockout mice, farnesyltransferase inhibitor treatment, isotype-switching assays, in vitro interaction studies The EMBO journal High 22085931
2014 NMR solution structure of the J-domain of DNAJA1 was solved, identifying a potential DnaK (Hsp70) binding site that overlaps with a predicted inhibitory binding site, suggesting DNAJA1 activity is regulated at this interface. DNAJA1 overexpression suppresses c-Jun hyperphosphorylation and the JNK pathway in pancreatic cancer cells. NMR structure determination, ligand affinity screen, bioinformatics analysis, overexpression in cell lines with JNK pathway readouts Biochemistry Medium 24512202
2003 Two isoforms of HSJ2 (DNAJA1) arise from alternative splicing: HSJ2a (326 aa) localizes to the nucleus when fused to GFP in HeLa cells, while HSJ2b (241 aa, lacking a putative NLS) distributes throughout the cell. GFP-fusion protein expression in HeLa cells, fluorescence microscopy Molecular biology reports Medium 12974469
2016 DNAJA1 is identified as a novel interacting partner and substrate of transglutaminase 2 (TG2). The catalytic core domain of TG2 is essential for interaction. DNAJA1 interacts with the open (active) conformation of TG2 and regulates its transamidation activity in vitro and in situ. DNAJA1 itself serves as a glutamine-donor substrate of TG2. GST pull-down assay, mass spectrometry, ELISA, surface plasmon resonance, domain variant interaction studies, in vitro and in situ transamidation activity assays The Biochemical journal High 27551108
2019 DNAJA1 physically interacts with PIWI protein SMEDWI-2 in planarian S. mediterranea (validated by yeast two-hybrid and co-IP). DNAJA1 is required for stability of SMEDWI-1 and SMEDWI-2 proteins. Human DNAJA1 similarly binds PIWIL1 and is required for PIWIL1 stability in human gastric cancer cells, demonstrating evolutionary conservation of this chaperone-client relationship. Yeast two-hybrid screen, co-immunoprecipitation, RNAi knockdown, protein stability assays in planarian and human cells The Journal of biological chemistry Medium 31076507
2019 DNAJA1 is activated transcriptionally by E2F1 and stabilizes CDC45 protein, thereby promoting cell cycle progression in colorectal cancer cells. KNK437 treatment sharply reduces DNAJA1 levels and reverses CDC45 stabilization. siRNA knockdown, overexpression, in vitro and in vivo tumor growth assays, ChIP/reporter assays for E2F1-DNAJA1 transcriptional regulation, western blot for CDC45 protein levels Oncogene Medium 31477839
2020 In silico homology modeling and site-directed mutagenesis identified a druggable interacting pocket in the DNAJA1 glycine/phenylalanine-rich region critical for interaction with mutant p53 R175H. Mutations in this pocket disrupted DNAJA1-mutp53 interaction and reduced mutp53 stability. 3D homology modeling, site-directed mutagenesis, co-immunoprecipitation, virtual drug screening, in vitro and in vivo cancer growth assays The Journal of biological chemistry Medium 33208462
2021 DNAJA1 selectively binds to unfolded (conformational) mutant p53 but not DNA-contact mutant p53, wild-type p53, or p53-null. DNAJA1 knockdown decreases mutp53 levels, reduces filopodia/lamellipodia formation, and decreases active CDC42/RAC1 in HNSCC cells in a mutp53-dependent manner. DNAJA1 knockdown inhibits primary tumor growth and metastasis to lymph nodes and lungs. siRNA knockdown, co-immunoprecipitation, in vitro migration assays, Rho GTPase activity assays, in vivo xenograft metastasis models Oncogene High 34183772
2021 Cereblon (CRBN), a substrate-recruiting subunit of cullin4-RING-E3-ligase, targets DNAJA1 (DJ2) and Hsp70 for ubiquitin-mediated degradation. CRBN knockout enhances DJ2 chaperone activity, reducing tau phosphorylation and aggregation, improving tau-microtubule association, and reducing accumulation of pathologic tau. DJ2 overexpression prevents tau aggregation induced by okadaic acid and heparin. Co-immunoprecipitation, CRBN knockout mouse model, tau aggregation assays, kinase activity assays (GSK3, ERK, p38), in vivo tau pathology assessment The Journal of neuroscience Medium 33972400
2023 Zinc binding is required for DNAJA1 structural stability and chaperone function (protection of client proteins from aggregation). Zinc removal destabilizes DNAJA1 and impairs its chaperone activity; reintroduction of zinc restores native properties. Copper can partially substitute for zinc in restoring DNAJA1 function. In vitro chaperone activity assay (aggregation suppression), metal chelation and reconstitution, yeast complementation assay (ydj1-deletion strain), biophysical stability measurements Biochimie Medium 37244380
2020 DNAJA1 knockout results in a 4-fold decrease in polyglutamine74-huntingtin (polyQ74htt) aggregation in HEK293 cells, opposite to the 5-fold increase seen with DNAJB6 knockout, demonstrating that DNAJA1 and DNAJB6 modulate polyQ aggregation in opposing manners. CRISPR/Cas9 knockout in HEK293 cells, fluorescence microscopy, filter trap assay, cell viability assays Scientific reports Medium 32424160
2024 DNAJA1 knockout significantly reduces protein polyubiquitination in mouse testis and results in complete male infertility with spermatogenesis defects. DNAJA1 is co-localized with residual bodies in elongating spermatids, and its expression peaks during postnatal spermatogenesis. DNAJA1 knockout mice, Western blotting, immunofluorescence, fertility assays Reproductive toxicology Medium 39208916
2025 PSMD9 directly interacts with DNAJA1 via an EXKK motif. This interaction was confirmed by in vitro binding assays with purified proteins, and mutations in DNAJA1 disrupting the EXKK motif abolished binding. PSMD9 depletion led to elevated mitochondrial membrane potential, linking the PSMD9-DNAJA1 interaction to mitochondrial regulation. Proteasomal inhibition enhanced the PSMD9-DNAJA1 interaction and correlated with increased DNAJA1 stability. Mass spectrometry, in vitro binding assays with purified proteins, site-directed mutagenesis of DNAJA1, co-immunoprecipitation from MCF7 cells, mitochondrial membrane potential measurement Biochemical and biophysical research communications Medium 40412052
2026 YOD1 deubiquitinase stabilizes DNAJA1 through deubiquitination, identified by molecular docking, co-immunoprecipitation, and protein stability assays. Stabilized DNAJA1 binds HSP70 to activate the mitochondrial unfolded protein response (UPRmt), reducing neuronal apoptosis and mitochondrial damage after subarachnoid hemorrhage. Molecular docking, co-immunoprecipitation, protein stability assays, YOD1 overexpression in vivo and in vitro models of SAH, mitochondrial function assays Free radical biology & medicine Medium 42103167
2022 The first 107 amino acid NMR structure of DNAJA1 (J-domain and linker region) was solved, identifying protein and ligand binding sites. Pull-down assays identified 8 novel protein binding partners. NMR and isothermal titration calorimetry confirmed 5 drug-like compounds binding to two distinct sites on DNAJA1. NMR structure determination, virtual drug screening, NMR binding assays, isothermal titration calorimetry, pull-down assay with mass spectrometry Biomolecules Medium 36291603
2022 A compound A11 (analog of virtual-screen hit 7-3) reduces DNAJA1 and conformational mutant p53 levels by binding to the J-domain of DNAJA1 at residues Y7, K44, and Q47. Alanine mutations at these positions prevent A11 binding and render cells insensitive to A11-mediated DNAJA1 and mutp53 depletion and inhibition of cell migration. In silico docking of ~10 million compounds, site-directed mutagenesis, cell-based assays for DNAJA1 and mutp53 levels, migration assays, filopodia formation assays Cell death discovery Medium 36316326
2000 HDJ-2/HSDJ overexpression increased polyglutamine huntingtin exon 1 inclusion formation in COS-7 cells (a pro-aggregation effect), while having no significant effect on inclusion formation in PC12 and SH-SY5Y cells, demonstrating a cell-type-dependent and potentially aggregation-promoting role for DNAJA1 with mutant huntingtin. Transient transfection in COS-7, PC12, and SH-SY5Y cells, fluorescence microscopy for inclusion counting Proceedings of the National Academy of Sciences of the United States of America Low 10717003
2022 In yeast and Drosophila models of Alzheimer's disease, the DNAJA1 ortholog Ydj1 physically interacts with amyloid-beta (Abeta) peptides, facilitates Abeta aggregation into small oligomers, and promotes their translocation to mitochondria. Deletion or downregulation of this chaperone protected from Abeta-mediated toxicity. Genetic screen in yeast, molecular interaction assays, Drosophila AD model with knockdown, mitochondrial fractionation Cell stress Medium 36448030
2024 DNAJA1 knockout alleviates heat-stroke-induced endothelial barrier disruption by suppressing the MLCK-MLC signaling pathway and protecting cell junction protein expression (ZO-1, claudin-5, JAM-A, occludin). Proteomic analysis identified 102 proteins activated by heat stroke and inhibited by DNAJA1 knockout, enriched in calcium signaling and vascular-barrier regulation pathways. DNAJA1 knockout cells (lentivirus-mediated) and mice, transepithelial electrical resistance, FITC-Dextran permeability, flow cytometry, western blotting, quantitative proteomics, in vivo heat stroke mouse model Molecular medicine reports Medium 38551163

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Human molecular genetics 377 10196362
2000 Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease. Proceedings of the National Academy of Sciences of the United States of America 279 10717003
1999 The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis. The EMBO journal 275 10075921
2016 DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway. Nature cell biology 209 27775703
2014 Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity. Protein & cell 62 25311840
2019 KNK437 restricts the growth and metastasis of colorectal cancer via targeting DNAJA1/CDC45 axis. Oncogene 56 31477839
2006 HDJ-2 as a target for radiosensitization of glioblastoma multiforme cells by the farnesyltransferase inhibitor R115777 and the role of the p53/p21 pathway. Cancer research 56 16818651
2014 DnaJA1/Hsp40 is co-opted by influenza A virus to enhance its viral RNA polymerase activity. Journal of virology 52 25253355
2014 Structure and function of human DnaJ homologue subfamily a member 1 (DNAJA1) and its relationship to pancreatic cancer. Biochemistry 51 24512202
2012 DnaJA1 antagonizes constitutive Hsp70-mediated stabilization of tau. Journal of molecular biology 51 22343013
1997 A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation, and transrepression defects of a glucocorticoid receptor zinc finger mutant. Molecular biology of the cell 45 9168467
2020 Co-chaperones DNAJA1 and DNAJB6 are critical for regulation of polyglutamine aggregation. Scientific reports 44 32424160
2010 Genetic variability and linkage disequilibrium patterns in the bovine DNAJA1 gene. Molecular biotechnology 38 20012712
2019 Inhibition of mutant Kras and p53-driven pancreatic carcinogenesis by atorvastatin: Mainly via targeting of the farnesylated DNAJA1 in chaperoning mutant p53. Molecular carcinogenesis 37 31397499
2021 DNAJA1 promotes cancer metastasis through interaction with mutant p53. Oncogene 33 34183772
2011 Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1. The EMBO journal 33 22085931
2003 Characterization of two isoforms of a human DnaJ homologue, HSJ2. Molecular biology reports 32 12974469
1998 Characterization of HDJ-2, a human 40 kD heat shock protein. The international journal of biochemistry & cell biology 31 9839446
2020 Chemogenomic screening identifies the Hsp70 co-chaperone DNAJA1 as a hub for anticancer drug resistance. Scientific reports 28 32796891
2020 Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1. The Journal of biological chemistry 24 33208462
2002 In situ expression of heat shock proteins, Hsc73, Hsj2 and Hsp86 in the developing tooth germ of mouse lower first molar. The Histochemical journal 20 12495215
2018 Association of CAST2, HSP90AA1, DNAJA1 and HSPB1 genes with meat tenderness in Nellore cattle. Meat science 19 29331838
2016 Knock-down of Hdj2/DNAJA1 co-chaperone results in an unexpected burst of tumorigenicity of C6 glioblastoma cells. Oncotarget 19 26959111
2022 DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p. Journal of oncology 17 35586205
1996 Increased expression of the HDJ-2 heat shock protein in biopsies of human rejected kidney. Transplantation 17 8623167
2018 Environmental Stress Responses of DnaJA1, DnaJB12 and DnaJC8 in Apis cerana cerana. Frontiers in genetics 16 30349556
1998 Increased expression of HDJ-2 (heat shock protein 40) and heat shock protein 70 in biopsy specimens of transplanted human lungs. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 16 9563600
2019 Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea. The Journal of biological chemistry 15 31076507
2001 Increased expression of HDJ-2 (hsp40) in carotid artery atherosclerosis: a novel heat shock protein associated with luminal stenosis and plaque ulceration. Journal of vascular surgery 15 11331850
2003 Overexpression of HDJ-2 protects astrocytes from ischemia-like injury and reduces redistribution of ubiquitin staining in vitro. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 14 14526221
2004 Expression of a novel DnaJA1 alternative splicing in human testis and sperm. International journal of andrology 13 15595953
2021 DNAJA1 Dysregulates Metabolism Promoting an Antiapoptotic Phenotype in Pancreatic Ductal Adenocarcinoma. Journal of proteome research 11 34264680
2022 DNAJA1- and conformational mutant p53-dependent inhibition of cancer cell migration by a novel compound identified through a virtual screen. Cell death discovery 10 36316326
2021 Cereblon Regulates the Proteotoxicity of Tau by Tuning the Chaperone Activity of DNAJA1. The Journal of neuroscience : the official journal of the Society for Neuroscience 10 33972400
2016 Identification of DNAJA1 as a novel interacting partner and a substrate of human transglutaminase 2. The Biochemical journal 10 27551108
2021 High expression of DNAJA1 (HDJ2) predicts unfavorable survival outcomes in breast cancer. Biomarkers in medicine 9 34236236
2011 Expression of DNAJA1 in bovine muscles according to developmental age and management factors. Animal : an international journal of animal bioscience 9 22440026
2023 Novel insights into the post-translational modifications of Ydj1/DNAJA1 co-chaperones. Cell stress & chaperones 8 38309209
2024 DNAJA1‑knockout alleviates heat stroke‑induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK‑MLC signaling pathway. Molecular medicine reports 7 38551163
2024 Itaconate Ameliorates Experimental Autoimmune Uveitis by Modulating Teff/Treg Cell Imbalance Via the DNAJA1/CDC45 Axis. Investigative ophthalmology & visual science 5 39661355
2023 DNAJA1 promotes proliferation and metastasis of breast cancer by activating mutant P53/NF-κB pathway. Pathology, research and practice 5 37977037
2022 BAG1, MGMT, FOXO1, and DNAJA1 as potential drug targets for radiosensitizing cancer cell lines. International journal of radiation biology 5 35511481
2022 A pathological role of the Hsp40 protein Ydj1/DnaJA1 in models of Alzheimer's disease. Cell stress 5 36448030
2024 DNAJA1 positively regulates amino acid-stimulated milk protein and fat synthesis in bovine mammary epithelial cells. Cell biochemistry and function 2 38269516
2024 DNAJA1 regulates protein ubiquitination and is essential for spermatogenesis in the testes of mice and rats. Reproductive toxicology (Elmsford, N.Y.) 2 39208916
2023 The stability and function of human cochaperone Hsp40/DNAJA1 are affected by zinc removal and partially restored by copper. Biochimie 2 37244380
2022 Druggable sites/pockets of the p53-DNAJA1 protein-protein interaction: In silico modeling and in vitro/in vivo validation. Methods in enzymology 2 36220282
2022 Leveraging the Structure of DNAJA1 to Discover Novel Potential Pancreatic Cancer Therapies. Biomolecules 2 36291603
2019 Truncating biallelic variant in DNAJA1, encoding the co-chaperone Hsp40, is associated with intellectual disability and seizures. Neurogenetics 2 30972502
2018 Genetic variation in N- and C-terminal regions of bovine DNAJA1 heat shock protein gene in African, Asian and American cattle. Journal of genomics 2 29290829
2025 Novel interaction with PSMD9 regulates DNAJA1 turnover and mitochondrial polarity. Biochemical and biophysical research communications 1 40412052
2026 YOD1 Regulates Neuronal Mitochondrial Unfolded Protein Response Activation by Deubiquitinating DNAJA1 After Subarachnoid Hemorrhage. Free radical biology & medicine 0 42103167
2025 Exploring the obesity-lung inflammation connection: DNAJA1 in focus. Gene 0 40505999
2025 The Effect and Mechanism of DNAJA1-Mediated Met/Leu Promoting the Proliferation of Bovine Mammary Epithelial Cells. Journal of cellular physiology 0 41222153

Missed literature

Know a paper Affinage missed for DNAJA1? Flag it for the maintainers and the community.

No submissions yet.