DnaJ homolog subfamily B member 6 (DNAJB6)
The protein contains 326 amino acids for an estimated molecular weight of 36087 Da.
Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Isoform B but not isoform A inhibits huntingtin aggregation. Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70. Also reduces cellular toxicity and caspase-3 activity. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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Biological Process
Actin cytoskeleton organization
Chorio-allantoic fusion
Chorion development
Extracellular matrix organization
Intermediate filament organization
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of inclusion body assembly
Negative regulation of transcription, DNA-templated
Positive regulation of ATPase activity
Protein folding
Protein localization to nucleus
Regulation of cellular response to heat
Regulation of protein localization
Syncytiotrophoblast cell differentiation involved in labyrinthine layer development
Cellular Component
Cytoplasm
Cytosol
Membrane
Nucleoplasm
Nucleus
Perinuclear region of cytoplasm
Z disc
The reference OMIM entry for this protein is 603511
Muscular dystrophy, limb-girdle, type 1e; lgmd1e
Muscular dystrophy, limb-girdle, type 1d, formerly; lgmd1d, formerly
A number sign (#) is used with this entry because limb-girdle muscular dystrophy type 1E (LGMD1E) is caused by heterozygous mutation in the DNAJB6 gene (611332) on chromosome 7q36.2.
DESCRIPTION
LGMD1E is an autosomal dominant disorder characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region (Speer et al., 1999). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMD1A (159000).CLINICAL FEATURES
Schneiderman et al. (1969) reported a large 4-generation family with slowly progressive autosomal dominant limb-girdle muscular dystrophy. Symptom onset generally occurred during the third decade, with muscular weakness affecting both the upper and lower limbs, although most affected individuals recalled being slow and clumsy as children. Most retained ambulation, but 2 were bedridden in their seventies and eighties. None had facial involvement. Skeletal muscle biopsy showed dystrophic changes, including variation in fiber size, rounded fibers, vacuoles, and small basophilic fibers with vesicular nuclei. Electron microscopy showed focal degeneration and destruction of myofibrils, lamellar bodies, and dense granular lysosome-like structures. The Pelger-Huet anomaly (PHA; 169400) also segregated within this family, and linkage with muscular dystrophy was suggested. The recombination fraction was about 0.25, but the lod score was only 0.35. (The Pelger-Huet anomaly was later found to be caused by mutation in the lamin B receptor gene (LBR; 600024) on chromosome 1q42.) Using the diagnostic classification for LGMD outlined by Speer et al. (1992), Speer et al. (1995) described 2 families with autosomal dominant LGMD1. One of the families had previously been reported by Schneiderman et al. (1969) (family 1701). Individuals were considered affected when they had progressive proximal leg weakness with or without proximal arm weakness, absent ankle deep-tendon reflexes, and elevated creatine kinase values. The diagnostic evaluation of at least 1 affected member per family documented a myopathic process. Three of 15 members of family 1701 had moderately severe dysphagia. Clinically, they differed somewhat from other LGMD1 families linked to other chromosomes in their lack of other associated findings, i.e., dysarthria in LGMD1A, cardiac defects in LGMD1B (159001), and childhood onset in LGMD1C (607801). Linkage analysis excluded these families from the locus on chromosome 5q (LGMD1A). Sandell et al. (2010) reported a large 4-generation Finnish family with autosomal dominant LGMD. The age at onset ranged from 20 to 60 years, and all except 1 presented with difficulty climbing stairs; 1 patient presented with a slow running speed. All patients showed more severe involvement of the pelvic girdle than the shoulder girdle, resulting in a waddling gait, and 3 of 8 had no shoulder girdle signs at ages 69, 45, and 43 years. All were ambulatory except an 80-year-old patient. Some patients had mild calf hypertrophy. None had contractures, dysphagia, dysarthria, respiratory problems, or cardiac involvement. Most patients had increased serum creatine kinase and myopathic EMG. Muscle biopsies showed myopathic changes, such as fiber size variation, atrophic fibers, mild to moderate fibrosis, adipose tissue, rimmed vacuoles, and internal nuclei. Some biopsies showed cytoplasmic protei ... More on the omim web site
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 603511 was added.