DNAJB6 explained

DnaJ homolog subfamily B member 6 is a protein that in humans is encoded by the DNAJB6 gene.

^{[1] [2] [3]}

Function

This gene encodes a member of the DNAJ protein family. 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. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described.

Interactions

DNAJB6 has been shown to interact with keratin 18.^[4] It has been also shown that the aggregation of Aβ42 (a process involved in e.g. Alzheimer's disease) is retarded by DNAJB6 in a concentration-dependent manner, extending to very low sub-stoichiometric molar ratios of chaperone to peptide.^[5] Dominant mutations in DNAJB6 have also been found to cause a late-onset muscle disease termed limb-girdle muscular dystrophy type D1 (LGMDD1), which is characterized by protein aggregation and vacuolar myopathology.^[6]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Izawa I, Nishizawa M, Ohtakara K, Ohtsuka K, Inada H, Inagaki M . Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament regulatory protein . The Journal of Biological Chemistry . 275 . 44 . 34521–7 . November 2000 . 10954706 . 10.1074/jbc.M003492200 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Ohtsuka K, Hata M . Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature . Cell Stress & Chaperones . 5 . 2 . 98–112 . April 2000 . 10.1379/1466-1268(2000)005<0098:mhdhco>2.0.co;2 . 1 November 2024 . 11147971 . 312896 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . March 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Chuang JZ, Zhou H, Zhu M, Li SH, Li XJ, Sung CH . Characterization of a brain-enriched chaperone, MRJ, that inhibits Huntingtin aggregation and toxicity independently . The Journal of Biological Chemistry . 277 . 22 . 19831–8 . May 2002 . 11896048 . 10.1074/jbc.M109613200 . free .
• Farinha CM, Nogueira P, Mendes F, Penque D, Amaral MD . The human DnaJ homologue (Hdj)-1/heat-shock protein (Hsp) 40 co-chaperone is required for the in vivo stabilization of the cystic fibrosis transmembrane conductance regulator by Hsp70 . The Biochemical Journal . 366 . Pt 3 . 797–806 . September 2002 . 12069690 . 1222832 . 10.1042/BJ20011717 .
• Hanai R, Mashima K . Characterization of two isoforms of a human DnaJ homologue, HSJ2 . Molecular Biology Reports . 30 . 3 . 149–53 . September 2003 . 12974469 . 10.1023/A:1024916223616 . 24105834 .
• Liu Y, Zhu MC, Wang YJ, Zhan Z, Liu CG . [Cloning of a DnaJ homolog chaperon PBP and its subcellular localization] . Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology . 19 . 6 . 531–4 . November 2003 . 15182641 .
• Berruti G, Martegani E . The deubiquitinating enzyme mUBPy interacts with the sperm-specific molecular chaperone MSJ-1: the relation with the proteasome, acrosome, and centrosome in mouse male germ cells . Biology of Reproduction . 72 . 1 . 14–21 . January 2005 . 15342353 . 10.1095/biolreprod.104.030866 . free .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . October 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Dai YS, Xu J, Molkentin JD . The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment . Molecular and Cellular Biology . 25 . 22 . 9936–48 . November 2005 . 16260608 . 1280278 . 10.1128/MCB.25.22.9936-9948.2005 .
• Linse S, Thalberg K, Knowles TP . The unhappy chaperone . QRB Discovery . Cambridge University Press . 2021 . 2 . e7 . 10.1017/qrd.2021.5 . 37529680 . 10392682 .

Notes and References

1. Seki N, Hattori A, Hayashi A, Kozuma S, Miyajima N, Saito T . Cloning, tissue expression, and chromosomal assignment of human MRJ gene for a member of the DNAJ protein family . Journal of Human Genetics . 44 . 3 . 185–9 . June 1999 . 10319584 . 10.1007/s100380050139 . free .
2. Pei L . Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells . The Journal of Biological Chemistry . 274 . 5 . 3151–8 . January 1999 . 9915854 . 10.1074/jbc.274.5.3151 . free .
3. Web site: Entrez Gene: DNAJB6 DnaJ (Hsp40) homolog, subfamily B, member 6.
4. Izawa I, Nishizawa M, Ohtakara K, Ohtsuka K, Inada H, Inagaki M . Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament regulatory protein . The Journal of Biological Chemistry . 275 . 44 . 34521–7 . November 2000 . 10954706 . 10.1074/jbc.M003492200 . free .
5. Månsson C, Arosio P, Hussein R, Kampinga HH, Hashem RM, Boelens WC, Dobson CM, Knowles TP, Linse S, Emanuelsson C . Interaction of the molecular chaperone DNAJB6 with growing amyloid-beta 42 (Aβ42) aggregates leads to sub-stoichiometric inhibition of amyloid formation . The Journal of Biological Chemistry . 289 . 45 . 31066–76 . November 2014 . 25217638 . 4223311 . 10.1074/jbc.M114.595124 . free .
6. Bengoechea R, Findlay AR, Bhadra AK, Shao H, Stein KC, Pittman SK, Daw JA, Gestwicki JE, True HL, Weihl CC . Inhibition of DNAJ-HSP70 interaction improves strength in muscular dystrophy . The Journal of Clinical Investigation . 130 . 8 . 4470–4485 . August 2020 . 32427588 . 7410071 . 10.1172/JCI136167 .