6u3s

Structural highlights

Disease

[DNJB6_HUMAN] Autosomal dominant limb-girdle muscular dystrophy type 1D. The disease is caused by mutations affecting the gene represented in this entry. There is evidence that LGMDD1 is caused by dysfunction of isoform B (PubMed:22366786).^[1]

Function

[DNJB6_HUMAN] 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.^{[2] [3] [4] [5] [6]}

References

1. ↑ Sarparanta J, Jonson PH, Golzio C, Sandell S, Luque H, Screen M, McDonald K, Stajich JM, Mahjneh I, Vihola A, Raheem O, Penttila S, Lehtinen S, Huovinen S, Palmio J, Tasca G, Ricci E, Hackman P, Hauser M, Katsanis N, Udd B. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat Genet. 2012 Feb 26;44(4):450-5, S1-2. doi: 10.1038/ng.1103. PMID:22366786 doi:http://dx.doi.org/10.1038/ng.1103
2. ↑ 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. J Biol Chem. 2000 Nov 3;275(44):34521-7. PMID:10954706 doi:http://dx.doi.org/10.1074/jbc.M003492200
3. ↑ 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. J Biol Chem. 2002 May 31;277(22):19831-8. Epub 2002 Mar 14. PMID:11896048 doi:http://dx.doi.org/10.1074/jbc.M109613200
4. ↑ Hageman J, Rujano MA, van Waarde MA, Kakkar V, Dirks RP, Govorukhina N, Oosterveld-Hut HM, Lubsen NH, Kampinga HH. A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol Cell. 2010 Feb 12;37(3):355-69. doi: 10.1016/j.molcel.2010.01.001. PMID:20159555 doi:http://dx.doi.org/10.1016/j.molcel.2010.01.001
5. ↑ Sarparanta J, Jonson PH, Golzio C, Sandell S, Luque H, Screen M, McDonald K, Stajich JM, Mahjneh I, Vihola A, Raheem O, Penttila S, Lehtinen S, Huovinen S, Palmio J, Tasca G, Ricci E, Hackman P, Hauser M, Katsanis N, Udd B. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat Genet. 2012 Feb 26;44(4):450-5, S1-2. doi: 10.1038/ng.1103. PMID:22366786 doi:http://dx.doi.org/10.1038/ng.1103
6. ↑ Tsai PC, Tsai YS, Soong BW, Huang YH, Wu HT, Chen YH, Lin KP, Liao YC, Lee YC. A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function. Clin Genet. 2017 Aug;92(2):150-157. doi: 10.1111/cge.13001. Epub 2017 Apr 12. PMID:28233300 doi:http://dx.doi.org/10.1111/cge.13001