HSP40: Species Variation
ICC staining of Hsp47 in heat shocked HeLa cells using Anti-Hsp47 (clone: 1C4-1A6) and a FITC secondary (green: cytoplasm; blue: DAPI nuclear stain)
Genes for Hsp40/DnaJ homologs are only found in a subset of Archaea including Halobacterium spec., Methanosarcina spec., and Methanobacterium spec. 100. Archeal DNAJs/HSP40s are expressed by at least four dnaJ genes (for a review see Macario et al., 1999 100). Archaeal DNAJs/HSP40s show a high similarity to each other and to their bacterial homologs with the most similar pair represented by the two DNAJ/HSP40 proteins found in Methanosarcina (Table 2). In Halobacterium cutirubrum, the G/F-rich domain in DnaJ is longer with a larger number of Gly residues compared to those of the other DNAJs/HSP40s from methanogens 100. In addition, H. cutirubrum DnaJ shows a different arrangement of the four repeats of the conserved CXXCXGXG motif compared to the molecules in the methanogens. It is worth mentioning that motif 1 is located closer to the C-terminus in H. cutirubrum DnaJ than in the others. As a consequence, the CXXCXGXG motif 4 in H. cutirubrum DnaJ is located much closer to the C-terminus than motif 4 in those from the methanogens 100. Whether this phenomenon represents a unique feature of H. cutirubrum DnaJ in order to adapt to life under high-salinity conditions and/or to cope with salinity changes is still unclear.
The plant genomes of Arabidopsis thaliana and rice (Oryza sativa) encode approximately 90 and 104 DNAJ/HSP40 proteins, respectively 101, 102. ERDJ genes encoding the ER-resident HSP40/DNAJ (also termed ERdj) proteins are present in different copy numbers in Arabidopsis and rice. While Arabidopsis has two copies of ERDJ2A (ATERDJ2A and ATERDJ2B) 103, rice bears one copy, OSERDJ2 104. Rice has two P58IPK gene copies (OSP58A and OSP58B) 104, whereas Arabidopsis has only one copy 103. Expression of AtERdj2B is induced by ER stress, while AtERdj2A is constitutively expressed 103. ER stress also differentially impacts rice Osp58AIPK and Osp58BIPK expression. Whereas Osp58AIPK represents the constitutively expressed isoform, Osp58BIPK is induced by ER stress implying diverse functions of duplicated genes encoding ER-resident DNAJs/HSP40s in different plants 104.
The haploid genome of the green alga Chlamydomonas reinhardtii encodes 63 DNAJ/HSP40 proteins, with more than half of these localized to the cytosol, suggesting an interaction of various DNAJ/HSP40 proteins with single cytosolic HSP70s 105, 106. However, only three DNAJs/HSP40s are type 1 proteins with ZF domains containing CXXCXGXG motifs. These proteins are targeted separately to the mitochondrial (Mdj1), plastidic (Cdj1), and cytosolic (Dnj1) compartments 107. The DNJ1 gene contains an open reading frame interrupted by six introns encoding a protein of 450 amino acids 108. The protein harbors the J-domain, the G/F-rich region as well as the C-rich ZF domain what classifies it as type 1 DNAJ/HSP40 protein. Phylogenetic studies revealed the most highly conserved homologs as cytosolic DNAJ/HSP40 proteins from plants 107. Alignment of the Chlamydomonas protein with the plant proteins led to the identification of an N-terminal extension of 19 amino acids enriched in methionine, glycine, phenylalanine, and proline. Similar to the other DNAJ/HSP40 proteins from plants, Chlamydomonas Dnj1 contains a CAQQ motif at the C-terminus 109, 110, indicating a putative post-translational modification by prenylation as has been reported in numerous plant DNAJs/HSP40s 111 and for Ydj1 from S. cerevisiae 112. As demonstrated by Silflow and colleagues, Dnj1 from Chlamydomonas obviously plays a critical role in regulating the stability of cytoplasmic microtubules in conjunction with Hsp70A (HspA1A) 108.Table 2) 6. DnaJ is composed of 376 amino acid residues and functions as a chaperone with thioldisulfide oxidoreductase activity (Figure 1). As the defining feature, DnaJ possesses an N-terminal J-domain bearing the highly conserved tripeptide HPD critical for the interaction with Hsp70. Adjacent to the J-domain, DnaJ bears the G/F-rich region followed by a central Cys-rich region consisting of four repeats of the ZF motif CXXCXGXG, and a C-terminal region involved in binding of client proteins 48, 65, 66. Moreover, the extreme C-terminus possesses a dimerization domain which functions in enhancing affinity for client proteins 67. A small angle X-ray scattering study revealed that DnaJ is a distorted omega-shaped homodimeric molecule with the C-terminus of each subunit forming the central part of the omega 113. Dimerization occurs through the C-terminal residues (331-376) resulting in the formation of a large cleft constituted between the two DnaJ monomers 113. As stated by the authors, the interaction between the two subunits may occur in different ways: firstly, the 331–376 amino acid stretch from each of the subunits may interact with each other; and secondly, this stretch on each submit may interact with another part of the other subunit, as can be found in yeast Sis1 114 and Ydj 65, respectively. From these findings it can be concluded that the simultaneous binding of a non-native polypeptide to each monomer might ensure maintaining the transfer-competent form of the molecule 6.
In addition to DnaJ, E. coli contains five other DnaJ homologs, including CbpA (curved DNA-binding protein A), which was first identified as a DNA-binding protein 115. CbpA binds DNA efficiently, with a preference for curved DNA, and has been localized to the nucleoids of stationary-phase cells 115, 116. DNA binding to CbpA has been found to depend on the presence of the G/F-rich as well as the C-terminal domain (CTD) crucially involved in binding of polypeptides 117. In recent years a wealth of evidence has been collected to demonstrate that CbpA functions as a co-chaperone of DnaK. In this regard, CbpA upregulation has been found to suppress several phenotypes associated with dnaJ deletions, including temperature sensitivity and λ replication defects 115. Any CbpA co-chaperone function is also blocked by DNA binding indicating a possible covering of the substrate binding site and impeding of the DnaK/DnaJ interaction 117, 118. CbpA differs from DnaJ in that it is a type 2 DNAJ/HSP40 protein, lacking the ZF domain characteristic of E. coli DnaJ and other type 1 DNAJ/HSP40 proteins. Like DnaJ, CbpA forms homodimers in solution with dimerization occurring at the extreme C-terminus 117, 118. In E. coli, the cbpA gene forms an operon together with the downstream gene cbpM encoding a CbpA modulator. Based on the fact that the corresponding proteins accumulate in the stationary phase, one can hypothesize that they are under control of the same σs-dependent promoter 118. This intriguing operon structure is conserved in numerous bacteria including Coxiella burnetii, Pseudomonas fluorescens, Salmonella enterica serovar Typhimurium, Shigella flexneri as well as in enterophila and putida.
DljA is a 30 kDa membrane-anchored type 3 DNAJ/HSP40 protein localized to the inner membrane of E. coli and characterized by the presence of the C-terminal J-domain and an N-terminal transmembrane domain (TMD) with dimerizing capacity 119,120,121,122. It is interesting to note that the conserved Gly residues within the TMD are obviously not involved in dimerization of DljA 119.The DjlA J-domain shows 31% identity and 44% similarity to the J-domain of DnaJ, including the highly conserved HPD tripeptide 120, 123. It is noteworthy that the J-domain of DjlA lacks the QKRAA motif which has been described as a possible interaction site with DnaK 123, 124. Although DjlA possesses a functional J-domain, it cannot be considered as being a functional ortholog of DnaJ and CbpA. As demonstrated previously, DjlA is unable to adequately complement DnaJ function in a strain lacking both dnaJ and cbpA, even when expressed to the same levels of DnaJ 120, 121. Overexpression of the DjlA cytoplasmic fragment could not support bacterial growth of the dnaJ/cbpA-deficient strain at temperatures below 20 °C and above 39 °C, respectively 120, 121. Additionally, DjlA has been found in these studies as being unable to replace either DnaJ or CbpA in promoting bacteriophage λ growth. DjlA is classified as a bona fide co-chaperone of DnaK, although it does not apparently possess intrinsic chaperone activity alone as can be found in DnaJ 125. Of note, the djlA gene is not essential and a single djlA mutant does not have a distinguishable phenotypic effect 123. As demonstrated previously, djlA and dnaJ obviously interact synergistically in supporting growth of E. coli 123. A growing body of evidence now indicates the expression of genes with sequence similarities to E. coli djlA in a broad spectrum of Gram-negative bacteria such as Legionella spec., S. flexneri, Shewanella putrefacians, S. typhimurium, Vibrio cholerae, C. burnetii, Haemophilus influenzae as well as Yersinia pestis and Y. entercolitica 6. Expression of DjlA has been reported recently as being a prerequisite for intracellular growth and organelle trafficking as well as resistance to environmental stress in L. dumoffii, one of the common causes of Legionnaires’ disease 126.
E. coli further expresses the djlB and djlC genes encoding two type 3 DNAJs/HSP40s 127. These proteins exhibit an amino acid sequence similarity of ≈70% and bear an N-terminal J-domain as well as a putative C-terminal TMD. Due to the high homlogy of DjlB and DjlC, these DNAJs/HSP40s can be considered as being bona fide co-chaperones of HscC/Hsc62 in E. coli. A characteristic structural feature of J-domains is the presence of the highly conserved tripeptide HPD critical for the interaction with Hsp70. It is noteworthy that DjlB and DjlC possess an HPE motif in place of the canonical HPD motif in their particular J-domains 6. In this regard, HscC/Hsc62 represents a rare example of an Hsp70 chaperone interacting with a J domain-bearing co-chaperone lacking the conserved HPD tripeptide. Functionally, DjlC has been reported to stimulate the ATPase activity of HscC/Hsc62 while CbpA, DnaJ, and HscB/Hsc20 do not 128.
HscB, also known as Hsc20, is a 20 kDa monomeric type 3 DNAJ/HSP40 protein that regulates the ATPase activity and peptide-binding specificity of HscA/Hsc66 in E.coli 56. HscB bears an N-terminal J-domain resembling the J-domain of human DnaJB1/Hdj1 and showing 20% identity to the J-domain of DnaJ 6, 56. Unlike the CTD found in type 1 DNAJs/HSP40s, the C-terminal region of HscB/Hsc20, implicated in binding and targeting proteins to DnaJB1/Hsc66, consists of a three-helix bundle in which two helices comprise an anti-parallel coiled-coil 56. Moreover, HscB/Hsc20, unlike DnaJ, does not possess intrinsic chaperone activity and appears to function solely as a regulatory co-chaperone protein for DnaJB1/Hsc66 129. HscB/Hsc20 also plays a critical role in the assembly of [Fe-S] proteins. The group of Larry E. Vickery found out that HscB/Hsc20 interacts with the ATP-bound state of the [Fe-S] cluster scaffold protein IscU, an essential component of the [Fe-S] cluster biogenesis pathway, thereby synergistically stimulating the IscU-binding capacity of HscA 130. As demonstrated by Chandramouli and Johnson, the Isc/HscA/HscB co-chaperone system facilitates efficient [2Fe-2S] cluster transfer from the IscU scaffold protein to acceptor proteins in an ATP-dependent manner 131.
Twenty-two DnaJ homologs with well-conserved J-domains can be found in the yeast S. cerevisiae (Table 2) 10. Five DnaJ homologs have been classified as type 1 (Ydj1, XDj1, Apj1, Mdj1, Scj1), four as type 2 (Caj1, Djp1, Hlj1, Sis1), and the remaining 13 as type 3 DNAJs/HSP40s 10, 68. All yeast type 1 family members are true functional homologs of the E. coli DnaJ 10. Amongst them, Xdj1 and Ydj1 are closely related fulfilling analogous functions in the cytosol. Ydj1 is a molecular chaperone crucially involved in import of proteins into mitochondria, secretion of mating pheromones, and regulation of cytoplasmic HSP70s 10, 132. Ydj1 which acts as a homodimer 67 has been found to stimulate the ATPase activity of the cytosolic HSP70s in yeast, Ssa1 and Ssa2 and the re-folding of denatured polypeptides 133, 134. In contrast to the type 2 DNAJ/HSP40 Sis1, Ydj1 itself can act as a chaperone in vitro, blocking protein aggregation by forming stable complexes with folding intermediates 133, 135. More recent investigations suggested that Ydj1 is able to act autonomously in inhibiting prion-like aggregation of the yeast protein Ure2 by direct interacting with the native state of Ure2, prior to the onset of oligomerization 136. These findings highlight the potential of native state stabilization as a therapeutic strategy in controlling the process of protein misfolding and aggregation.
Apj1 is a further cytosolic DNAJ/HSP40 molecule whose exact function is still unclear. Apart from its proposed chaperoning function, Apj1 has been shown as being required for growth of a natural Saccharomyces sensu stricto hybrid yeast in xylose thereby underlining its role in xylose metabolism 137. Like Ydj1 overexpression, upregulation of Apj1 has been found to abolish growth retardation of cells expressing the yeast prion [PSI] 138. This was a first observation of a phenotypic effect for Apj1 supporting a putative chaperone function of this type 1 DNAJ/HSP40 protein in conjunction with Ssa1/2.
Mdj1 is located to mitochondria and supports folding of proteins imported into the mitochondrial matrix by enhancing the ATPase activity of the HSP70/HSPA family member Ssc1 139. Scj1 represents the ER-resident member of the type 1 DNAJ/HSP40 family supporting protein folding in the lumen of the ER mediated by the yeast HSP70/HSPA family member Grp78 (BiP, Kar2) 140. It is of note that the conserved Cys residues in the ZF domain of Scj1 are obviously arranged by disulphide bridges rather than the co-ordination of metal ions in the oxidizing ER environment 10.
Due to the presence of the G/F-rich repeats, four DNAJs/HSP40s in S. cerevisiae have been classified as type 2 DNAJ/HSP40, namely Caj1, Djp1, Hlj1, and Sis1. Two of them (Sis1, Djp1) are found in the cytosol, while Hlj1 represents the ER-specific and Caj1 the nuclear isoform. Sis1 has been identified as being an essential type 2 DNAJ/HSP40 family member in S. cerevisiae which forms a homodimer through a short C-terminal amino acid stretch 114. As demonstrated in the same study, Sis1 monomers are elongated and consist of two domains with similar folds. The Sis1 dimer has a U-shaped architecture with a large cleft formed between the two elongated monomers. Deletion of the C-terminal dimerization motif leads to severe chaperoning defects underlining the critical role of dimer formation in Sis1 chaperone function 114. By comparing the structures of dimeric Sis1 with that of dimeric type 1 DNAJ/HSP40 Ydj1 it became apparent that both DNAJs/HSP40s bear a large cleft between the two monomers critical for the interaction with Hsp70 64. However, the C-terminal dimerization motif in Sis1 is much shorter than that of Ydj1 suggesting less extensive interactions between single Sis1 monomers compared to Ydj1 67. Although Sis1 lacks the ZF domain, its CTD binds polypeptides to the same degree as the joined ZF/CTD of Ydj1 141. Fan and collaborators present experimental evidence that conserved protein modules located within the middle of Ydj1 and Sis1 control specific functions of type I and type II DNAJs/HSP40s. As demonstrated in this study, exchangable chaperone modules of Ydj1 and Sis1 were found to control the protein folding activity, substrate binding specificity and in vivo function of these different DNAJs/HSP40s 141. In addition, Ydj1 and Sis1 were both able to bind phage displayed peptides enriched in aromatic and hydrophobic amino acids, but with differential selectivity. Based on these findings it can be speculated that discrepancies in the capability of type I and type II DNAJs/HSP40s to identify certain structural features in non-native polypeptides might contribute to their ability to determine certain Hsp70 functions.
Type 3 DNAJ/HSP40 family members comprise the largest subgroup of DNAJs/HSP40s in yeast. Amongst them, Swa2 is an auxilin-like protein associated with clathrin-coated vesicles in the cytosol involved in vesicular transport. Swa2 functions as a clathrin-binding protein interacting with Ssa1/2 through its J-domain thereby stimulating the uncoating of clathrin-coated vesicles 87. Additionally, Swa2 has been identified to localize to ER membranes where it plays a pivotal role in cortical ER inheritance 142. Sec63 is an integral membrane protein spanning the ER membrane three times and showing 43% identity with DnaJ over a span of 70 amino acids 143, 144. The lumenal part of Sec63 has been demonstrated to interact with the HSP70/HSPA family member HspA5 (Grp78, BiP, Kar2) through its J-domain at the translocation apparatus or translocon at the lumenal face of the ER thus playing an essential role in protein translocation into the ER 144, 145.
Pam18/Tim14 is an integral protein of the mitochondrial inner membrane with a typical J-domain exposed to the matrix space 146. Pam18/Tim14 is a constituent of the mitochondrial import machinery of the mitochondrial protein translocase. It stimulates the ATPase activity of the major Hsp70 of the mitochondrial matrix in yeast, Ssc1 thereby facilitation protein import into mitochondria 147. This finding is supported by the observation that in vivo depletion of Pam18/Tim14 blocked protein translocation to mitochondria 147.
Zuo1 (Zuotin) is a ribosome-associated Type 3 DNAJ/HSP40 which is crucially involved in ribosome biogenesis. Together with Ssz1 and Ssb1/2, it functions as a chaperone for ribosome-bound nascent polypeptide chains 148. Zuotin and Ssz1 form a heterodimeric ribosome-associated complex (RAC) that is bound to the ribosome via zuotin. In vitro, RAC stimulates the translocation of a ribosome-bound mitochondrial precursor protein into mitochondria, providing evidence for its chaperone function on nascent polypeptide chains 149.
Cwc23 has been described to locate to the cytosol as well as the nucleoplasm 150. It plays a major role in pre-mRNA splicing and the assembly and disassembly of the spliceosome 151. Cwc23 may also be involved in ER-associated protein degradation (ERAD) 152 and may be required for growth at low and high temperatures 153. Jem1 is anchored in the ER membrane with its J-domain facing the ER lumen 154. It facilitates the nuclear membrane fusion during mating 154, 155 and plays a role in nuclear fusion through regulating the functions of the essential nuclear envelope protein Nep98p enriched in the spindle-pole body 156, the sole microtubule-organizing center of budding yeast and a functional homolog of the centrosome in mammalian cells 157.
The functions of the remaining type 3 DNAJs/HSP40s from yeast are unclear up to date. The group of Lars M. Steinmetz experimentally validated the localization of Jid1 in mitochondria 158, while Erj5 has been identified to associate with the ER 150, 159. Jjj1-3 can be found in the cytosol and nucleus 150. Jjj3 has recently been shown to exhibit an iron-binding property comparable to that of its human ortholog, DnaJC24/Dph4, highlighting the conservation of iron sequestration across species 160.
The genome of S. cerevisiae also encodes three J-like proteins, termed Jlp1/2 and Pam16/Tim16 (for a review see Walsh et al., 2004 10). Only little information is available on these molecules. For instance, Jlp1 bears a Tyr residue in place of the His in the consensus HPD motif and its subcellular location is still unclear. Meanwhile it became apparent that Jlp1 acts as an alpha-ketoglutarate-dependent dioxygenase active on sulfonates thus mediating organosulfur degradation 161. Jlp2 is a cytosolic DNAJ/HSP40 with unknown function whose J-domain shares high significance with the J-domain of the ER-resident Sec63, but harbors an Ala residue in place of the Pro residue in the HPD motif 10, 150. In contrast, Pam16/Tim16 is a peripheral membrane protein of the mitochondrial inner membrane and part of the mitochondrial Tim23 preprotein translocase 162, 163. According to Frazier et al., Pam16/Tim16 interacts with Pam18/Tim14 and is required for the association of Pam18/Tim14 with the presequence translocase and for formation of an Ssc1/Tim44 complex 163. The J-like domain in Pam16 possesses a similar length and predicted secondary structure as the corresponding Pam18/Tim14 domain, but the characteristic sequence motif HPD that is strictly conserved in all known DNAJs/HSP40s is missing in Pam16/Tim16 164. Instead, Pam16/Tim16 bears the DKE tripeptide which does not confer ability to stimulate the ATPase activity of the mtHsp70, Ssc1 164. Evidence has accumulated demonstrating that Pam16/Tim16 associates with Mdj2 and is recruited to the Tim23 translocase where it stimulates the ATPase activity of Ssc1 to the same extend as Pam18/Tim14 165.
Table 2: HSP40s/DNAJs of various pro- and eukaryotic organisms
|Gene||Protein||Aliases||UniProt ID||Gene ID|
|Type 1 (subfamily A)|
|dnaJ||DnaJ||Chaperone protein DnaJ, Hsp40, NP_634528.1||P0CW07||1480846|
|Type 1 (subfamily A)|
|dnaJ||DnaJ||Chaperone protein DnaJ, Hsp40, NP_616413.1||Q8TQR1||1473367|
|Type 1 (subfamily A)|
|dnaJ||DnaJ||Hsp40, HspJ, HSP40, GroP||P08622||944753|
|Type 2 (subfamily B)|
|cbpA||CbpA||Curved DNA-binding protein, YP_489273.1||P36659||12932265|
|Type 3 (subfamily C)|
|djlB||DjlB||J domain-containing protein DjlB, YP_488937.1||P77381||12930913|
|djlC||DjlC||J domain-containing protein DjlC, Hsc56 co-chaperone of HscC, YP_488940.1||P77359||12932384|
|hscB||HscB||Hsc20, DnaJ-like molecular chaperone-specific for IscU||P0A6L9||12934043|
|Type 1 (subfamily A)|
|YDJ1||Ydj1||Mas5, Mab3, type I Hsp40 co-chaperone YDJ1||P25491||855661|
|XDJ1||Xdj1||DnaJ homolog protein XDJ1, NP_013191.1||P39102||850779|
|APJ1||Apj1||J domain-containing protein APJ1, Ynl077w, NP_014322.1||P53940||855647|
|MDJ1||Mdj1||DnaJ homolog 1, mitochondrial; NP_116638.1||P35191||850530|
|SCJ1||Scj1||DnaJ-related protein SCJ1, NP_013941.2||P25303||855254|
|Type 2 (subfamily B)|
|SIS1||Sis1||SIS1, Sis-1, NP_014391.1||P25294||855725|
|DJP1||Djp1||DnaJ-like protein 1, peroxisome assembly protein 22 (Pas22), Ics1, NP_012269.1||P40564||854820|
|Type 3 (subfamily C)|
|CWC23||Cwc23||Pre-mRNA-splicing factor CWC23, NP_011387.2, complexed with CEF1 protein 23||P52868||852749|
|ERJ5||Erj5||ER-localized J domain-containing protein 5, NP_116699.3||P43613||850602|
|SWA2||Swa2||Auxilin-like clathrin uncoating factor SWA2, bud site selection protein 24, synthetic lethal with ARF1 protein 2, NP_010606.1||Q06677||851918|
|SEC63||Sec63||Protein translocation protein SEC63, Sec62/63 complex 73 kDa subunit, Ptl1, Npl1, NP_014897.1||P14906||854428|
|PAM18||Pam18||Mitochondrial import inner membrane translocase subunit Tim14, NP_013108.1||Q07914||850694|
|MDJ2||Mdj2||Mitochondrial DnaJ homolog 2, NP_014071.1||P42834||855388|
|JAC1||Jac1||J-type co-chaperone JAC1, mitochondrial; J-type accessory chaperone 1, NP_011497.1||P53193||852866|
|JEM1||Jem1||DnaJ-like protein of the ER membrane 1, Kar-8, NP_012462.3||P40358||853372|
|JID1||Jid1||J domain-containing protein 1, NP_015386.1||Q12350||856174|
|JJJ1||Jjj1||J protein JJJ1, NP_014172.1||P53863||855495|
|JJJ2||Jjj2||J proptein JJJ2, NP_012373.2||P46997||853277|
|JJJ3||Jjj3||Diphthamide biosynthesis protein 4, Dph4, NP_012631.3||P47138||853560|
|ZUO1||Zuo1||Zuotin, DnaJ-related protein ZUO1, heat shock protein 40 homolog ZUO1, ribosome-associated complex subunit ZUO1, NP_011801.1||P32527||853202|
|JLP1||Jlp1||DnaJ-like protein, Jlp1p, NP_013043.1, alpha-ketoglutarate-dependent sulfonate dioxygenase||A7A0K3Q12358||850669|
|JLP2||Jlp2||DnaJ-like protein 2, Jlp2p, NP_013851.1||P40206||855162|
|PAM16||Pam16||Mitochondrial import inner membrane translocase subunit Tim16, presequence translocated-associated motor subunit PAM16, Pam16p, NP_012431.1||P42949||853340|
|Type 1 (subfamily A)|
|DNAJA1||DnaJA1||HSDJ, DJ2, human DnaJ protein 2 (hDj-2), Hsj2, HSPF4, Hdj2, DjA1||P31689||3301|
|DNAJA2||DnaJA2||Dnj3, Dn3, HIRA-interacting protein 4, renal carcinoma antigen NY-REN-14, HIRIP4, DjA2||O60884||10294|
|DNAJA3||DnaJA3||Tid-1, hTID-1, hepatocellular carcinoma-associated antigen 57 (HCA57),||Q96EY1||9093|
|DNAJA4||DnaJA4||Dj4, Hsj-4, MST104, MSTP104, PRO1472||Q8WW22||55466|
|Type 2 (subfamily B)|
|DNAJB1||DnaJB1||Hsp40, Hdj1, hDj-1, HSPF1, Sis1, RSPH16B||P25685||3337|
|DNAJB2||DnaJB2||HSJ1, HSPF3, Hsj1, Dnajb10, mDj8, DSMA5||P25686||3300|
|DNAJB3||DnaJB3||Hcg-3, Hsj-3, Msj1, MSJ-1||Q8WWF6||414061|
|DNAJB4||DnaJB4||human liver DnaJ-like protein, HLJ-1, Hlj1, DjB4, Dnajw||Q9UDY4||11080|
|DNAJB5||DnaJB5||Hsc40, Hsp40-2, Hsp40-3||O75953||25822|
|DNAJB6||DnaJB6||DJ4, DnaJ, HHDJ1, HSJ-2, Hsj2, LGMD1D, LGMD1E, Mrj, MSJ-1||O75190||10049|
|DNAJB7||DnaJB7||Dj5, HSC3, mDj5||Q7Z6W7||150353|
|DNAJB9||DnaJB9||ER-resident protein ERdj4; Mdg1, mDj7||Q9UBS3||4189|
|DNAJB11||DnaJB11||ER-resident protein ERdj3, hDj9, PWP1-interacting protein 4, APOBEC1-binding protein 2 (ABBP-2), HEDJ||Q9UBS4||51726|
|DNAJB13||DnaJB13||testis spermatogenesis apoptosis-related gene 6/3 protein (Tsarg-6/-3),||P59910||374407|
|DNAJB14||DnaJB14||ER-resident EGNR9427, PRO34683, FLJ14281||Q8TBM8||79982|
|Type 3 (subfamily C)|
|DNAJC1||DnaJC1||ER-resident protein ERdj1, MTJ1, Htj1, Dnajl1||Q96KC8||64215|
|DNAJC2||DnaJC2||M-phase phosphatase protein 11 (MPHOSPH11), M-phase phosphoprotein 11 (MPP11), zuotin-related factor 1 (Zrf1)||Q99543||27000|
|DNAJC3||DnaJC3||ER-resident protein ERdj6, p58, Prkri, protein kinase inhibitor p58 (p58IPK)||Q13217||5611|
|DNAJC4||DnaJC4||F2, multiple endocrine neoplasia type 1 candidate protein number 18||Q9NNZ3||3338|
|DNAJC5||DnaJC5||cysteine string protein (Csp) alpha||Q9H3Z4||80331|
|DNAJC6||DnaJC6||Auxilin, mKIAA0473, DjC6, Park19||O75061||9829|
|DNAJC7||DnaJC7||Dj11, mDj11, DjC7, tetratricopeptide repeat protein 2 (TPR2, mTpr-2)||Q99615||7266|
|DNAJC8||DnaJC8||splicing protein spf31, Hspc315, Hspc331||O75937||22826|
|DNAJC9||DnaJC9||DnaJ protein SB73, HdjC9||Q8WXX5||23234|
|DNAJC10||DnaJC10||ER-resident protein ERdj5, macrothioredoxin (MTHr), JPD1||Q8IXB1||54431|
|DNAJC11||DnaJC11||dJ126A5.1, FLJ10737, RP1-126A5.3||Q9NVH1||55735|
|DNAJC12||DnaJC12||J-domain containing protein 1 (Jdp-1, mJDP1)||Q9UKB3||56521|
|DNAJC13||DnaJC13||DNA J-domain containing protein Rme-8 (RME-8), mKIAA0678, Gm1124||O75165||23317|
|DNAJC14||DnaJC14||Hdj3, hDj-3, LYST-interactimng protein 6 (LIP6), dopamine receptor-interacting protein of 78 kDa (DRIP78, Drip-78)||Q6Y2X3||85406|
|DNAJC15||DnaJC15||Dnajd1, cell growth-inhibiting gene 22 protein, methylation-controlled J protein(MCJ, Mcj)||Q9Y5T4||29103|
|DNAJC17||DnaJC17||DnaJ homolog subfamily C member 17; C87112||Q9NVM6||55192|
|DNAJC18||DnaJC18||DnaJ homolog subfamily C member 18, AU041129||Q9H819||202052|
|DNAJC19||DnaJC19||mitochondrial import inner membrane translocase subunit 14 (TIM14, TIMM14)||Q96DA6||131118|
|DNAJC20||DnaJC20||Jac1; Hsc20, HscB||Q8IWL3||150274|
|DNAJC21||DnaJC21||Dnaja5, GS3, Jjj1||Q5F1R6||134218|
|DNAJC22||DnaJC22||Wus, wurst homolog (Wurst), AI506245||Q8N4W6||79962|
|DNAJC23||DnaJC23||ER-resident protein ERdj2, Sec63L, Dnajc23||Q9UGP8||11231|
|DNAJC24||DnaJC24||CSL-type zinc finger-containing protein 3 (ZCSL3), JJJ3, diphthamide biosynthesis protein 4 (DPH4, Dph-4), 1700030A21Rik||Q6P3W2||120526|
|DNAJC25||DnaJC25||DnaJ homolog subfamily C member 25, bA16L21.2.1, 2010109C08Rik, 2010203O07Rik,||Q9H1X3||548645|
|DNAJC26||DnaJC26||Cyclin-G-associated kinase (GAK), auxilin-2||O14976||2580|
|DNAJC27||DnaJC27||RBJ, RabJs, Ras-associated protein 1 (Rap‑1), Rab and DnaJ-domain containing protein||Q9NZQ0||51277|
|DNAJC28||DnaJC28||C21orf55; C21orf78, Orf28, oculomedin||Q9NX36||54943|
|DNAJC29||DnaJC29||Sacsin (spastic ataxia of Charlevoix-Saguenay), SPAX6, protein phosphatase 1, regulatory subunit 138, KIAA0730||Q9NZJ4||26278|
|DNAJC30||DnaJC30||Williams-Beuren syndrome chromosomal region 18 protein (WBSCR18)||Q96LL9||84277|