DnaJ homolog subfamily B member 2 (DNAJB2)

The protein contains 324 amino acids for an estimated molecular weight of 35580 Da.

 

Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:7957263, PubMed:22219199). In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins (PubMed:15936278, PubMed:21625540). Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes (PubMed:12754272, PubMed:20889486, PubMed:21719532, PubMed:22396390, PubMed:24023695). Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins (PubMed:15936278). (updated: Nov. 22, 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. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. 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: 100%
Model score: 100

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VariantDescription
dbSNP:rs34127289
DSMA5

The reference OMIM entry for this protein is 604139

Dnaj/hsp40 homolog, subfamily b, member 2; dnajb2
Heat-shock protein, dnaj-like 1; hsj1
Heat-shock 40-kd protein 3; hspf3

DESCRIPTION

The DNAJB2 gene encodes a molecular cochaperone member of the heat shock protein family. These proteins play important cellular roles in correct protein folding, in the response to protein misfolding, and in the degradation of misfolded proteins (summary by Blumen et al., 2012).

CLONING

The E. coli heat-shock protein DnaJ has been implicated in protein folding and protein complex dissociation. By screening a human frontal cortex cDNA expression library with antibody against paired helical filament proteins (see 157140), Cheetham et al. (1992) identified a novel gene, HSJ1, which shows sequence similarity to DnaJ. They isolated cDNAs corresponding to 2 alternatively spliced HSJ1 transcripts that differ by the presence or absence of a 1.1-kb insert. The cDNA lacking the insert encodes a deduced protein of 277 amino acids, whereas the cDNA containing the insert has an alternative C-terminal sequence that is 74 amino acids longer. The similarity between the HSJ1 and DnaJ proteins is restricted to the N-terminal region. In addition, the N-terminal and central regions of the HSJ1 proteins share sequence similarity with those regions of SIS1, a yeast homolog of DnaJ. Western blot analysis of human brain homogenates using antibodies against HSJ1 detected proteins with apparent molecular masses of approximately 42 and 36 kD. Northern blot analysis detected 3.0- and 2.0-kb HSJ1 transcripts in human brain; no HSJ1 expression was found in the other tissues examined. RNase protection analysis showed that HSJ1 is expressed almost exclusively in the brain, with the highest levels in the frontal cortex and hippocampus. In situ hybridization of human brain sections detected HSJ1 mRNA mainly in the neuronal layers. DNAJB2 isoform b is more abundant in brain than isoform a (Borrell-Pages et al., 2006).

GENE STRUCTURE

The DNAJB2 gene contains 10 exons and encodes 2 main transcripts, isoform a, encoded by exons 2-10, and isoform b, encoded by exons 2-9 (summary by Blumen et al., 2012).

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the HSJ1 gene to chromosome 2 (TMAP Cda0vf12).

GENE FUNCTION

Borrell-Pages et al. (2006) found that Hsj1 proteins protected rat striatal neurons from polyQ-huntingtin (613004)-induced cell death. Hsj1a reduced intranuclear inclusions by acting as a typical chaperone that unfolds misfolded proteins, whereas Hsj1b had a neuroprotective effect by inhibiting cell death without any major effects in polyQ-huntingtin aggregation. Hsj1b mediated its beneficial effects by promoting release of BDNF (113505) from the Golgi apparatus in neuronal cells. Postmortem brain tissue from patients with Huntington disease (HD; 143100) showed significantly decreased levels of HSJ1b compared to controls. Treatment with cystamine, a transglutaminase inhibitor, increased Hsj1b levels and increased levels of BDNF in mouse neuronal cells and in a mouse model of Huntington disease and showed a neuroprotective effect. Treatment of rodent and primate models of HD with cystamine and cysteamine resulted in a transient increase in peripheral blood levels of BDNF in these animals. Blumen et al. (2012) demonstrated that cotransfection of either DNAJB2 isoform reduced aggregation of mutant SOD1 (147450) in motor neuron-like cells. The antiaggregating effect was even more pronounced when both isoforms were transfected into these cells. These findings indicated that DNAJB2 has 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 604139 was added.

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