Details for: DNAJB5

Gene ID: 25822

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: DNAJB5

Ensembl ID: ENSG00000137094

Description: DnaJ heat shock protein family (Hsp40) member B5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • progenitor cell CL0011026
    CSI 5.9
    rCSI 12.56%
    PRS 98.64
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 3.06
    rCSI 3.93%
    PRS 99.13
  • enteric smooth muscle cell CL0002504
    CSI 2.57
    rCSI 3.67%
    PRS 99.7
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.32
    rCSI 4.1%
    PRS 98.19
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.29
    rCSI 3.74%
    PRS 99.45
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.06
    rCSI 3.32%
    PRS 98.17

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [DNAJB5](/details-gene/25822) is a protein-coding gene that encodes DnaJ heat shock protein family (Hsp40) member B5, a molecular chaperone cofactor. Functionally, it is involved in protein quality control, specifically in processes such as chaperone cofactor-dependent protein refolding and responding to unfolded proteins. **Overall**, its expression profile indicates a significant role in cells undergoing differentiation or maintaining complex proteomes, with the highest significance observed in [progenitor cell](/details-cell/CL0011026)s and developing neurons like the [neuroblast (sensu Vertebrata)](/details-cell/CL0000031). This suggests that [DNAJB5](/details-gene/25822) is critical for managing protein folding fidelity during cellular development and in specialized cell types. ## Cellular Roles and Expression Landscape The expression pattern of [DNAJB5](/details-gene/25822) points towards a specialized role in cellular development and maintenance rather than a ubiquitous housekeeping function. * **Development and Differentiation:** The gene shows the highest significance in [progenitor cell](/details-cell/CL0011026)s (CSI: 5.90) and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s (CSI: 3.06). This strong association suggests that [DNAJB5](/details-gene/25822) is a key component of the cellular machinery required to manage the high translational load and protein folding demands during cell division and lineage commitment, particularly within the nervous system. Its notable expression in specific interneuron populations, such as [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064), further supports a role in neuronal specification and maturation. * **Specialized Tissue Maintenance:** Beyond development, [DNAJB5](/details-gene/25822) is also significantly expressed in contractile cell types, including [enteric smooth muscle cell](/details-cell/CL0002504) (CSI: 2.57) and [microcirculation associated smooth muscle cell](/details-cell/CL0008035) (CSI: 1.29). This may indicate an ongoing requirement for chaperone activity to maintain the integrity and function of the complex protein assemblies that constitute the contractile apparatus in these cells. Early research has noted that the expression profile of this gene, also known as Hsc40, is similar to that of hsc70, a major heat shock cognate protein, which is consistent with its role as a co-chaperone in cellular proteostasis [Link](https://doi.org/10.1016/s0378-1119(99)00333-9). ## Pathways and Molecular Function The functional annotations for [DNAJB5](/details-gene/25822) are highly consistent with its role as a molecular chaperone and align with its observed expression pattern. * **Molecular Function:** The gene is primarily associated with [protein binding](/details-go/GO:0005515), specifically [unfolded protein binding](/details-go/GO:0051082) and [protein-folding chaperone binding](/details-go/GO:0051087). This defines its core activity as a co-chaperone that identifies and binds to non-native protein structures, targeting them for refolding or degradation. * **Biological Process:** [DNAJB5](/details-gene/25822) participates in the [response to unfolded protein](/details-go/GO:0006986) and [chaperone cofactor-dependent protein refolding](/details-go/GO:0051085). These processes are crucial in cells with high rates of protein synthesis, such as dividing [progenitor cell](/details-cell/CL0011026)s, or in cells susceptible to proteotoxic stress. * **Cellular Component:** Its localization to the [cytosol](/details-go/GO:0005829) places it in the primary compartment for protein synthesis and folding, where it can readily engage with newly synthesized or stress-denatured proteins. ## Research Directions The specific expression of [DNAJB5](/details-gene/25822) in progenitor and neural cell types, combined with its fundamental role in protein folding, opens several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s and specific cortical neurons, [DNAJB5](/details-gene/25822) is essential for neuronal differentiation and maturation. Its depletion may lead to an accumulation of misfolded proteins, triggering the unfolded protein response (UPR) and impairing the ability of neuroblasts to properly exit the cell cycle and form functional synapses. 2. [DNAJB5](/details-gene/25822) may play a neuroprotective role in diseases characterized by protein aggregation, such as Alzheimer's or Parkinson's disease. Its activity could be crucial for preventing the formation of toxic protein oligomers, and downregulation of [DNAJB5](/details-gene/25822) with age or environmental stress could be a contributing factor to disease onset or progression. **Experimental Approach:** To test the first hypothesis regarding the role of [DNAJB5](/details-gene/25822) in neuronal differentiation, a compelling experiment would involve using a human induced pluripotent stem cell (iPSC) model of cortical development. * **Methodology:** Generate a stable [DNAJB5](/details-gene/25822) knockdown iPSC line using CRISPR interference (CRISPRi). Differentiate both the knockdown and control iPSC lines into cortical organoids. * **Analysis:** At various time points during differentiation, perform single-cell RNA sequencing (scRNA-seq) to map developmental trajectories and identify cell populations. This would reveal if the loss of [DNAJB5](/details-gene/25822) causes a stall in the progenitor state or skews differentiation towards non-neuronal lineages. Concurrently, proteomic analysis combined with immunofluorescence for markers of UPR activation (e.g., BiP, CHOP) and protein aggregation could directly assess the impact on proteostasis. **Therapeutic Potential:** As a cytosolic chaperone involved in maintaining protein health, [DNAJB5](/details-gene/25822) is more likely a target for activation or enhancement rather than inhibition. Its upregulation could be beneficial in neurodegenerative contexts characterized by protein misfolding. The development of small-molecule chaperones or compounds that specifically enhance the activity or expression of Hsp40 family members like [DNAJB5](/details-gene/25822) could represent a viable therapeutic strategy. However, because it is an intracellular protein without known enzymatic activity, direct targeting is challenging. A more feasible approach may involve targeting upstream transcriptional regulators to boost its expression in at-risk neuronal populations.

Genular Protein ID: 1834054931

Symbol: DNJB5_HUMAN

Name: DnaJ homolog subfamily B member 5

UniProtKB Accession Codes:

O75953 B3KN14 B4DSA6 J3KQM9 J3KR08 Q5T656 Q8TDR7 Q96EM4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 5 ExpressionAtlas 1 GO 5 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 6 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10570961

Title: Hsc40, a new member of the hsp40 family, exhibits similar expression profile to that of hsc70 in mammalian cells.

PubMed ID: 10570961

DOI: 10.1016/s0378-1119(99)00333-9

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 348
  • Mass: 39133
  • Checksum: DC9FE45DE4FD8CFC
  • Sequence:
    • MGKDYYKILG IPSGANEDEI KKAYRKMALK YHPDKNKEPN AEEKFKEIAE AYDVLSDPKK 
RGLYDQYGEE GLKTGGGTSG GSSGSFHYTF HGDPHATFAS FFGGSNPFDI FFASSRSTRP 
FSGFDPDDMD VDEDEDPFGA FGRFGFNGLS RGPRRAPEPL YPRRKVQDPP VVHELRVSLE 
EIYHGSTKRM KITRRRLNPD GRTVRTEDKI LHIVIKRGWK EGTKITFPKE GDATPDNIPA 
DIVFVLKDKP HAHFRRDGTN VLYSALISLK EALCGCTVNI PTIDGRVIPL PCNDVIKPGT 
VKRLRGEGLP FPKVPTQRGD LIVEFKVRFP DRLTPQTRQI LKQHLPCS