8.A.192.  The DnaJ Homolog (DnaJ) Family

  The DnaJ family members are found in several TC families: 1.P.1, 3.A.16, 3.A.30 and 3.A.5.  These proteins are chaparone proteins that often function with DnaK (Barriot et al. 2020). Mutations in DNAJC5/CSPalpha are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent storage materials (AFSMs) termed lipofuscin. Functionally, DnaJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (Lee et al. 2022).


 

References:

Barriot, R., J. Latour, M.P. Castanié-Cornet, G. Fichant, and P. Genevaux. (2020). J-Domain Proteins in Bacteria and Their Viruses. J. Mol. Biol. 432: 3771-3789.

Boal, F., M. Laguerre, A. Milochau, J. Lang, and P.A. Scotti. (2011). A charged prominence in the linker domain of the cysteine-string protein Cspα mediates its regulated interaction with the calcium sensor synaptotagmin 9 during exocytosis. FASEB J. 25: 132-143.

Drwesh, L., B. Heim, M. Graf, L. Kehr, L. Hansen-Palmus, M. Franz-Wachtel, B. Macek, H. Kalbacher, J. Buchner, and D. Rapaport. (2022). A network of cytosolic (co)chaperones promotes the biogenesis of mitochondrial signal-anchored outer membrane proteins. Elife 11:.

Fujibayashi, A., T. Taguchi, R. Misaki, M. Ohtani, N. Dohmae, K. Takio, M. Yamada, J. Gu, M. Yamakami, M. Fukuda, S. Waguri, Y. Uchiyama, T. Yoshimori, and K. Sekiguchi. (2008). Human RME-8 is involved in membrane trafficking through early endosomes. Cell Struct Funct 33: 35-50.

Girard, M. and P.S. McPherson. (2008). RME-8 regulates trafficking of the epidermal growth factor receptor. FEBS Lett. 582: 961-966.

Hon, T., H.C. Lee, A. Hach, J.L. Johnson, E.A. Craig, H. Erdjument-Bromage, P. Tempst, and L. Zhang. (2001). The Hsp70-Ydj1 molecular chaperone represses the activity of the heme activator protein Hap1 in the absence of heme. Mol. Cell Biol. 21: 7923-7932.

Lee, J., Y. Xu, L. Saidi, M. Xu, K. Zinsmaier, and Y. Ye. (2022). Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation. Autophagy 1-20. [Epub: Ahead of Print]

Norris, A., C.T. McManus, S. Wang, R. Ying, and B.D. Grant. (2022). Mutagenesis and structural modeling implicate RME-8 IWN domains as conformational control points. PLoS Genet 18: e1010296.

Sharma, M., J. Burré, P. Bronk, Y. Zhang, W. Xu, and T.C. Südhof. (2012). CSPα knockout causes neurodegeneration by impairing SNAP-25 function. EMBO. J. 31: 829-841.

Examples:

TC#NameOrganismal TypeExample
8.A.192.1.1

DnaJC5 chaparone protein of 198 aas and 1 or 2 adjacent TMSs, including residues 95 - 120.  Mutations in DNAJC5/CSPalpha are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent storage materials (AFSMs) termed lipofuscin. Functionally, DNAJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (Lee et al. 2022).

DnaJC5 of Mus musculus (Mouse)

 
8.A.192.1.2

DnaJ homolog subfamily C member 5, DnaJ-C5 of 377 aas and 1 - 3 possible TMSs. It acts as a co-chaperone for the SNARE protein SNAP-25 (Sharma et al. 2012) and is involved in the calcium-mediated control of a late stage of exocytosis (Boal et al. 2011). It also acts as a general chaperone in regulated exocytosis. It may play an important role in presynaptic function and may be involved in calcium-dependent neurotransmitter release at nerve endings.

 

DnaJ-C5 of Mus musculus (Mouse)

 
8.A.192.1.3

DnaJ homolog subfamily B member 8, DnaJ-B8 of 233 aas and 0 TMSs.

DnaJ of Myotis davidii

 
8.A.192.1.4

Molecular chaperone DnaJ of 374 aas and 0 TMSs.

DnaJ of Candidatus Marinimicrobia bacterium (marine metagenome)

 
8.A.192.1.5

J domain-containing protein, DnaJ, of 335 aas and 0 TMSs.

DnaJ of Kovacikia minuta

 
8.A.192.1.6

Ydj1 or MASS, a cytoplasmic co-chaparone Hsp40 family protein of 409 aas. It is probably involved in mitochondrial protein import and in heme regulation of HAP1, as a component of the high-molecular-weight (HMC) complex (Hon et al. 2001). It also plays a role in the insertion of outer membrane mitochondrial signal-anchored (SA) proteins (Drwesh et al. 2022).

Ydj1 of Saccharomyces cerevisiae

 
Examples:

TC#NameOrganismal TypeExample
8.A.192.2.1

DnaJ homolog subfamily C, member 13, DnaJC13 or RME8 or RME-8, of 2243 aas and 0 - 7 possible TMSs. It is involved in membrane trafficking through early endosomes, such as the early endosome to recycling endosome transport implicated in the recycling of transferrin and the early endosome to late endosome transport implicated in degradation of EGF and EGFR (Fujibayashi et al. 2008, Girard and McPherson 2008). SNX-1 and the IWN domains control the conformation of RME-8 and hence the productive exposure of the DNAJ domain (Norris et al. 2022).

DnaJC13 of Mus musculus

 
8.A.192.2.2

RME-8 of 2279 aas and 0 - 7 possible TMSs based on a hydropathy plot. It is a DnaJ homolog subfamily C member 13 isoform 2

RME-8 of Caenorhabditis elegans 

 
8.A.192.2.3

RME-8 or receptor mediated endocytosis 8, isoform B of 2407 aas.

RME-8 of Drosophila melanogaster

 
8.A.192.2.4

GRV2 (GFS2; KAM2) of 2554 aas.

GRV2 of Arabidopsis thaliana