HSP40: Protein Type

The DNAJ/HSP40 family represents a heterogeneous group of well-conserved proteins with molecular weights ranging from 10 kDa (DnaJC19) – 254 kDa (DnaJC13). Similarly, molecular masses of J-like proteins vary between 10 kDa (DnaJC24) and 520 kDa (DnaJC29/sacsin). Functional genes encoding DNAJ/HSP40 proteins map to human chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 19, 20, 21 and 22. It has been assumed that DNAJs/HSP40s are homodimeric proteins that reside in the cytosol of prokaryotes ⁹ and various subcellular compartments of eukaryotes as well as in the extracellular milieu (also see Localization). DNAJs/HSP40s can be expressed tissue-specifically or universally in all tissues in multicellular organisms. The tissue-specific expression can be achieved by alternative splicing of the corresponding DNAJ mRNA. In this regard, two transcript variants encoding DnaJA1/Hdj2 have been identified for the DNAJA1 gene as the result of alternative splicing leading to the expression of two DnaJA1/Hdj2 isoforms differing from each other by 95 amino acids ⁶⁹. While one of the alternatively spliced isoforms of DnaJA1/Hdj2 was found to locate to the nucleus, indicating that it acts as a nuclear co-chaperone, the other isoform was observed throughout the cell most likely due to the elimination of a putative nuclear localization signal sequence ⁶⁹. Moreover, isoform 1 of DnaJA1/Hdj2 was found as being highly expressed in brain and other tissues while the other alternatively spliced isoform was highly abundant in testis and sperm ⁷⁰. Intracellular residing DNAJ/HSP40 chaperones exist as soluble proteins or in a membrane-associated form, either as peripheral or as integral membrane proteins. In addition to their intracellular location, DNAJs/HSP40s have been found extracellularly in exosomes ⁷¹. In many cases, DNAJs/HSP40s are phosphoproteins (e.g. DnaJA1, DnaJB4, DnaJC1, DnaJC29) whose expressions and functions can be further modulated co- and post-translationally by acetylation (e.g. DnaJA1, DnaJB2, DnaJB12, DnaJC5, DnaJC8, DnaJC13), glycosylation (DnaJB11, DnaJC10, DnaJC16), palmitoylation (DnaJC5, DnaJC5B, DnaJC5G), methylation (DnaJA1 to -4), prenylation (DnaJA1, DnaJA2, DnaJA4), and formation of intramolecular disulfide bonds (DnaJB11, DnaJC3, DnaJC10), respectively.