Falcon deep research report for DNAJB1
Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
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PANTHER phylogenetic-tree annotation propagates conserved class B DnaJ functions (HSP70 cochaperone, ATPase activator, protein folding chaperone, response to heat) to human DNAJB1.
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
A novel HSF1-mediated death pathway that is suppressed by heat shock proteins.
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HSF1 also induces a proapoptotic Tdag51 program; Hsps bind the Tdag51 PHL domain and suppress its death activity, contextualizing DNAJB1's broader role in HSF1-related stress responses (DNAJB1 is not individually named in this paper).
"Hsps bound directly to the N-terminal pleckstrin-homology like (PHL) domain of Tdag51, and suppressed death activity of the C-terminal proline/glutamine/histidine-rich domain."
Role of the cochaperone Tpr2 in Hsp90 chaperoning.
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DNAJB1, as a type II J protein, normally participates in Hsp90-dependent chaperoning of steroid receptors and Chk1; the TPR-domain cochaperone Tpr2 can functionally replace this J-protein requirement (i.e., Tpr2 substitutes for, rather than cooperates with, type II J proteins like DNAJB1).
"Surprisingly, Tpr2 replaced type I and II J proteins in the Hsp90-dependent chaperoning of the PR and the protein kinase, Chk1."
Large-scale proteomics and phosphoproteomics of urinary exosomes.
Chaperone-assisted selective autophagy is essential for muscle maintenance.
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Chaperone-assisted selective autophagy (CASA) employs the HSP70 ATPase cycle and is cited here as contextual evidence for DNAJB1's ATPase-activator role in the broader Hsc70 chaperone machinery; the paper itself primarily characterizes the BAG-3/HspB8/Hsc70 system and does not name DNAJB1.
"Stv and its mammalian ortholog BAG-3 coordinate the activity of Hsc70 and the small heat shock protein HspB8 during disposal that is initiated by the chaperone-associated ubiquitin ligase CHIP and the autophagic ubiquitin adaptor p62."
Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
Interactome mapping suggests new mechanistic details underlying Alzheimer's disease.
The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities.
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Functional comparison of human HSPA/HSP70 and DNAJ/HSP40 paralogs (including DNAJB1) for luciferase refolding versus polyQ aggregation suppression, defining substrate-specific differentiation within the HSP70/HSP40 machine.
"Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol. To test for possible functional differences and/or substrate specificity, we assessed the effect of overexpression of each of these HSPs on refolding of heat-denatured luciferase and on the suppression of aggregation of a non-foldable polyQ (polyglutamine)-expanded Huntingtin fragment."
Proteomic characterization of the human sperm nucleus.
Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation.
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METTL21A trimethylates a conserved lysine in HSPA family Hsp70 proteins (in vitro and in vivo) and alters HSPA8 chaperone affinity for α-synuclein; DNAJB1 is not directly tested in this paper but is captured here as context for post-translational regulation of the broader HSP70 machine that DNAJB1 partners with.
"In this study, we identified the methyltransferase METTL21A as the enzyme responsible for trimethylation of a conserved lysine residue found in several human Hsp70 (HSPA) proteins."
Binding of human nucleotide exchange factors to heat shock protein 70 (Hsp70) generates functionally distinct complexes in vitro.
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In vitro reconstitution combines Hsp70-NEF pairs (BAG1/2/3, Hsp105) with J-protein cochaperones including DnaJB1 to form 16 permutations whose ATPase and luciferase-refolding activities depend on the J-protein/NEF identity, supporting DNAJB1 as a productive HSP70 ATPase activator/cochaperone.
"Finally, we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. The activity of the combinations in ATPase and luciferase refolding assays were dependent on the identity and stoichiometry of both the J protein and NEF so that some combinations were potent chaperones, whereas others were inactive."
A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
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Quantitative AP-MS/LUMIER chaperone-cochaperone-client interactome in human cells; DNAJB1 is captured here as part of the proteostasis network rather than being individually dissected. Used as background interactome support, not for specific functional claims.
"We combined mass spectrometry and quantitative high-throughput LUMIER assays to systematically characterize the chaperone-cochaperone-client interaction network in human cells."
E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
Polyhydramnios, Transient Antenatal Bartter's Syndrome, and MAGED2 Mutations.
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Identification of MAGED2 mutations causing X-linked polyhydramnios/transient antenatal Bartter's syndrome; MAGE-D2 affects NKCC2/NCC expression possibly via adenylate cyclase/cAMP signaling and an unnamed cytoplasmic heat-shock protein. DNAJB1 is not directly named in the paper and the GO annotation citing this PMID is treated as incidental.
"We showed that MAGE-D2 affects the expression and function of the sodium chloride cotransporters NKCC2 and NCC (key components of salt reabsorption in the distal renal tubule), possibly through adenylate cyclase and cyclic AMP signaling and a cytoplasmic heat-shock protein."
An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
Architecture of the human interactome defines protein communities and disease networks.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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Y2H interactome map of ~500 neurodegenerative disease (ND) related proteins yielded ~30,000 candidate interactions; DNAJB1 is reported in the supplementary interaction list rather than the abstract, supporting only incidental detection within ND-associated networks rather than a specific functional role.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex 3.0 AP-MS interactome in 293T and HCT116 cells (118,162 interactions among 14,586 proteins); DNAJB1 is reported in the supplementary interaction list rather than the abstract, supporting only incidental detection within cell-specific chaperone modules rather than a specific functional role.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
A central chaperone-like role for 14-3-3 proteins in human cells.
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14-3-3 paralog interactomes were systematically mapped and shown to act as chaperone-like hubs preventing client coalescence/aggregation; DNAJB1 is reported in the supplementary interaction list rather than the abstract, supporting only incidental detection within 14-3-3-associated proteostasis networks.
Genomic cloning of a human heat shock protein 40 (Hsp40) gene (HSPF1) and its chromosomal localization to 19p13.2.
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DNAJB1 (HGMW symbol HSPF1) was isolated as a three-exon human Hsp40/DnaJ homolog with heat-shock elements in its 5' region and mapped by FISH to chromosome 19p13.2.
"We have isolated and characterized a genomic DNA clone encompassing the entire coding sequences of the human Hsp40 cDNA. The Hsp40 gene (HGMW-approved symbol HSPF1) is composed of three exons divided by two introns. The 5' region of the gene is highly GC rich, and there are multiple basal elements for transcription factors including typical heat shock elements. The Hsp40 gene has been assigned to chromosome 19 band p13.2 by in situ hybridization."
Molecular chaperones as HSF1-specific transcriptional repressors.
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Hsp70 and the cochaperone Hdj1 (DNAJB1) bind directly to the HSF1 transactivation domain to repress heat-shock gene transcription during attenuation, without affecting HSF1 DNA-binding or inducible phosphorylation; this is the foundational evidence for DNAJB1's role in HSF1 attenuation.
"Here, we show that the molecular chaperone Hsp70 and the cochaperone Hdj1 interact directly with the transactivation domain of HSF1 and repress heat shock gene transcription."
Regulation of HSF1-mediated heat shock response
HSF1 acetylation at Lys80
HSF1-mediated gene expression
Acetylated HSF1 dissociates from DNA
HSP40s activate intrinsic ATPase activity of HSP70s in the nucleoplasm
HSP40s activate intrinsic ATPase activity of HSP70s in the cytosol
p-T182 MAPKAPK5 binds DNAJB1
p-T182-MAPKAPK5 phoshphorylates DNAJB1
J-domain protein chaperone circuits in proteostasis and disease.
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Class B JDPs (including DNAJB1) have G/F-mediated autoinhibition of the J-domain; interaction between Hsp70's EEVD motif and DNAJB1 CTD-I relieves this autoinhibition for productive Hsp70 engagement.
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JDP scaffolding and hetero-oligomerization, including DNAJB1 participation, creates potent Hsp70-based disaggregases; DNAJB1 remains associated with aggregates to recruit multiple Hsp70 molecules.
Regulation of p53 and cancer signaling by heat shock protein 40/J-domain protein family members.