DNAJB1

Fig1. Model of chaperone-assisted protein folding by Hsp70-DnaJ/Hsp40 complex. (Takafumi Hasegawa, 2018)

What is DNAJB1 protein?

DNAJB1 (DnaJ heat shock protein family (Hsp40) member B1) gene is a protein coding gene which situated on the short arm of chromosome 19 at locus 19p13. This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. The DNAJB1 protein is consisted of 340 amino acids and its molecular mass is approximately 38.0 kDa.

What is the function of DNAJB1 protein?

DNAJB1 is involved in the correct folding of proteins, particularly in the endoplasmic reticulum, by interacting with members of the Hsp70 family. This function is essential for maintaining the stability and function of proteins within the cell. DNAJB1 plays a role in a variety of signaling pathways, including cell proliferation, differentiation, and apoptosis. DNAJB1 is involved in the regulation of the cell cycle, especially during the G1/S transition of the cell cycle. DNAJB1 also has antioxidant properties that help cells defend against oxidative stress.

DNAJB1 Related Signaling Pathway

DNAJB1 acts as a molecular chaperone that works with the heat shock protein HSP70 to help other proteins fold properly, preventing misfolding and aggregation, thereby ensuring the stability of protein mass within the cell. When cells are exposed to various stressful conditions (such as high temperature, hypoxia, chemical toxins, etc.), DNAJB1 expression is usually increased to help cells cope with stressful conditions and maintain protein homeostasis. DNAJB1 may also be involved in the regulation of apoptosis. Some studies have suggested that it may affect the activation state of apoptosis-related signaling pathways by interacting with other proteins.

DNAJB1 Related Diseases

DNAJB1 is highly expressed in neurons and has been implicated in the occurrence of a variety of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. DNAJB1 is expressed in the heart and vascular tissues, and is related to the pathogenesis of cardiovascular diseases such as myocardial hypertrophy and myocardial infarction. DNAJB1 plays a role in muscle cells, and its mutation may be related to the occurrence of muscle diseases such as muscular atrophy and myasthenia. DNAJB1 may also be associated with the occurrence and development of some other diseases, such as various tumors, diabetes, cataracts and so on.

Bioapplications of DNAJB1

DNAJB1's role in a variety of diseases makes it a potential target for drug development. By designing specific molecular compounds to regulate the activity of DNAJB1, it is possible to develop therapeutic drugs that target specific diseases. DNAJB1 also has potential applications in tissue engineering and regenerative medicine. Understanding the role of DNAJB1 in cell proliferation, differentiation and tissue repair may provide a theoretical basis for the development of new biomedical therapies.

Case Study 1: Jyoti Batra, 2016

A unique feature of influenza A virus (IAV) life cycle is replication of the viral genome in the host cell nucleus. The nuclear import of IAV genome is an indispensable step in establishing virus infection. IAV nucleoprotein (NP) is known to mediate the nuclear import of viral genome via its nuclear localization signals. This study demonstrates that cellular heat shock protein 40 (Hsp40/DnaJB1) facilitates the nuclear import of incoming IAV viral ribonucleoproteins (vRNPs) and is important for efficient IAV replication. Hsp40 was found to interact with NP component of IAV RNPs during early stages of infection. This interaction is mediated by the J domain of Hsp40 and N-terminal region of NP. Drug or RNAi mediated inhibition of Hsp40 resulted in reduced nuclear import of IAV RNPs, diminished viral polymerase function and attenuates overall viral replication. Hsp40 was also found to be required for efficient association between NP and importin alpha, which is crucial for IAV RNP nuclear translocation. These studies demonstrate an important role for cellular chaperone Hsp40/DnaJB1 in influenza A virus life cycle by assisting nuclear trafficking of viral ribonucleoproteins.

Fig1. RNase A treatment partially affects the interaction between NP and Hsp40.

Fig2. Western blot analysis further confirms the effect of Hsp40 knockdown on NP and PB2 localization.

Case Study 2: Xiaogang Cheng, 2008

Human immunodeficiency virus type 2 (HIV-2) Vpx is required for nuclear translocation of the viral preintegration complex (PIC) in quiescent cells. In order to decipher the mechanism of action of Vpx, a cDNA library was screened with the yeast two-hybrid assay, resulting in the identification of heat shock protein 40, Hsp40/DnaJB6, as a Vpx-interactive protein. Interaction with Vpx was confirmed by glutathione S-transferase (GST) pull-down and coimmunoprecipitation assays. Overexpression of Hsp40/DnaJB6 enhanced Vpx nuclear import, whereas overexpression of a nuclear localization mutant of Hsp40/DnaJB6 (H31Q) or down-regulation of Hsp40/DnaJB6 by small interfering RNA (siRNA) reduced the nuclear import of Vpx. Hsp40/DnaJB6 competed with the Pr55(Gag) precursor protein for the binding of Vpx and incorporation into virus-like particles. Overexpression of Hsp40/DnaJB6 promoted viral PIC nuclear import, whereas siRNA down-regulation of Hsp40/DnaJB6 inhibited PIC nuclear import. These results demonstrate a role for Hsp40/DnaJB6 in the regulation of HIV-2 PIC nuclear transport.

Fig3. Vpx was expressed in BSC40 cells with Hsp40/Mrj, various fragments of Hsp40/DnaJB6, or a control plasmid, as indicated.

Fig4. Western blot analysis of siRNA knockdown and recovery of Hsp40/DnaJB6 in U937 and HeLa cells.

DNAJB1 has several biochemical functions, for example, ATPase activator activity,ATPase binding,Hsp70 protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by DNAJB1 itself. We selected most functions DNAJB1 had, and list some proteins which have the same functions with DNAJB1. You can find most of the proteins on our site.

DNAJB1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with DNAJB1 here. Most of them are supplied by our site. Hope this information will be useful for your research of DNAJB1.

CDC37;TERF1;HSPA1A;OTUD4;IKBKE;ATG2A;Ttll12;Phlda1;MAP3K3;NRAS;CYP2C8;ZNF16;AKT1;PSEN2;PLEKHO1;ECSIT;MAST1