DnaJ homolog subfamily B member 1 (DNAJB1)

The protein contains 340 amino acids for an estimated molecular weight of 38044 Da.

 

Interacts with HSP70 and can stimulate its ATPase activity. Stimulates the association between HSC70 and HIP. Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401). Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro) (PubMed:24318877). (updated: Dec. 20, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 67%
Model score: 50

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The reference OMIM entry for this protein is 604572

Dnaj/hsp40 homolog, subfamily b, member 1; dnajb1
Heat-shock 40-kd protein 1; hspf1
Hdj1 dnajb1/prkaca fusion gene, included

CLONING

The E. coli heat-shock protein DnaJ functions together with DnaK (HSPA1A; 140550) and GrpE (GRPEL1; 606173) as a molecular chaperone, involving them in assembly and disassembly of protein complexes, protein folding, renaturation of denatured proteins, prevention of protein aggregation, and protein export. By screening a human placenta cDNA library with anti-Hsp40 antibody, Ohtsuka (1993) isolated a cDNA encoding a 40-kD heat-shock protein designated HSPF1. The deduced 340-amino acid HSPF1 protein is 34% identical to E. coli DnaJ and 34% and 36% identical to HSJ1 (604139) and HSJ2 (602837), respectively. By Northern blot analysis, Hata and Ohtsuka (1998) showed that expression of a major 2.4-kb and a minor 1.4-kb HSPF1 transcript is drastically induced by heat shock.

GENE STRUCTURE

Hata et al. (1996) determined that the HSPF1 gene spans over 7 kb and contains 3 exons and 2 introns. The 5-prime region of the gene is highly GC rich, and there are multiple basal elements for transcription factors, including typical heat-shock elements (HSEs).

GENE FUNCTION

Hata and Ohtsuka (1998) found by gel mobility supershift assays that HSF1 (140580) but not HSF2 (140581) interacts with the 8 exonic HSEs of HSPF1. An intronic HSE in HSPF1 is inactive. Several dominant human neurodegenerative diseases involve the expansion of a polyglutamine within the disease proteins. This expansion confers toxicity on the proteins and is associated with nuclear inclusion formation. Data indicate that molecular chaperones can modulate polyglutamine pathogenesis. To elucidate the basis of polyglutamine toxicity and the mechanism by which chaperones suppress neurodegeneration, Chan et al. (2000) studied transgenic Drosophila disease models of Machado-Joseph disease (109150) and Huntington disease (143100). They demonstrated that Hsp70 (see 140559) and Hdj1, the Drosophila homolog to human HSP40 (see 604139), showed substrate specificity for polyglutamine proteins as well as synergy in suppression of neurotoxicity, and altered the solubility properties of the mutant polyglutamine protein. Using a Drosophila model for Huntington disease and other polyglutamine diseases to screen for genetic factors modifying the degeneration caused by expression of polyglutamine in the eye, Kazemi-Esfarjani and Benzer (2000) isolated several suppressor strains, 2 of which led to the discovery of suppressor genes. The predicted product of one is TPR2 (601964), which is homologous to the human tetratricopeptide repeat protein-2. That of the second is HDJ1. The suppression of polyglutamine toxicity was verified in transgenic flies.

MAPPING

By FISH, Hata et al. (1996) mapped the HSPF1 gene to chromosome 19p13.2.

CYTOGENETICS

Fibrolamellar hepatocellular carcinoma (see HCC, 114550) is a rare liver tumor affecting adolescents and young adults with no history of primary liver disease or cirrhosis. Honeyman et al. (2014) identified a chimeric transcript that is expressed in fibrolamellar HCC but not in adjacent normal liver and that arises as the result of an approximately 400-kb deletion on chromosome 19. The chimeric RNA is predicted to code for a protein containing the amino-terminal domain of DNAJB1, a homolog of the molecular chaperone DNAJ, fused in-frame with PRKACA (601639), the catalytic domain of protein kinase A. Immunoprecipitation and Western blot analyses confirmed that the chimeric protein is expressed in tumor tissue, a ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604572 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed