{PDOC00553} {PS00636; DNAJ_1} {PS50076; DNAJ_2} {PS51188; ZF_CR} {BEGIN} *************************************************** * J-protein family domains signature and profiles * *************************************************** The hsp70 chaperone machine (see ) performs many diverse roles in the cell, including folding of nascent proteins, translocation of polypeptides across organelle membranes, coordinating responses to stress, and targeting selected proteins for degradation. DnaJ is a member of the hsp40 family of molecular chaperones, which is also called the J-protein family, the members of which regulate the activity of hsp70s. DnaJ (hsp40) binds to dnaK (hsp70) and stimulates its ATPase activity, generating the ADP-bound state of dnaK, which interacts stably with the polypeptide substrate [1,2]. DnaJ consists of an N-terminal conserved domain (called 'J' domain) of about 70 amino acid residues, a glycine and phenylalanine-rich domain ('G/F' domain), a central cysteine rich domain (CR-type zinc finger) containing four repeats of a CXXCXGXG motif which can coordinate two zinc atom and a C-terminal domain (CTD) [2]. Such a structure is shown in the following schematic representation: +------------+-+-----------+-----+-----------+-------------+ | J-domain | | Gly/Phe-R | | CXXCXGXG | CTD | +------------+-+-----------+-----+-----------+-------------+ The structures of the 'J' domain (see ) and the 'CR' domain (see ) have been solved [3,4]. The J domain consists of four helices, the second of which has a charged surface that includes basic residues that are essential for interaction with the ATPase domain of hsp70 [5]. The CR-type zinc finger has an overall V-shaped extended beta-hairpin topology and two symmetrical zinc binding sites, designated as Zn1 and Zn2: Zn1 is formed by the two cysteine motifs that are furthest apart in the primary sequence, while Zn2 is formed by the two central, adjacent cysteine motifs [4]. It has been shown that Zn1 is important for the autonomous, dnaK-independent chaperone activity, while Zn2 is a necessary interaction site with dnaK, which seems to be crucial for in vivo function in the dnaJ/dnaK system [6]. J-protein family are classified in three classes [2]: The type 1 contains proteins with a J-domain, a G/F domain, a CR zinc finger and a CTD domain (true homologues of dnaJ): - Yeast protein MAS5/YDJ1 that is involved in protein folding and mitochondrial protein import. - Yeast protein MDJ1 that is involved in protein folding and mitochondrial protein import. - Yeast protein SCJ1 that is involved in protein folding in the lumen of the endoplasmic reticulum. - Yeast protein APJ1/YNL077w, that might modulate folding reaction. - Cucumber dnaJ homolog anchored at the glyoxysomal membrane. - Yeast protein XDJ1. - Human protein HDJ2. The type 2 contains proteins with a J-domain, a G/F domain and a CTD domain: - Rhizobium fredii nolC, a protein involved in cultivar-specific nodulation of soybean. - Escherichia coli cbpA, a protein that binds curved DNA. - Yeast protein SIS1, required for nuclear migration during mitosis. - Yeast protein CAJ1. - Yeast hypothetical protein YFR041c. - Yeast hypothetical protein YIR004w. - Yeast hypothetical protein YJL162c. - Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA). RESA, whose function is not known, is associated with the membrane skeleton of newly invaded erythrocytes. - Human HDJ1. - Human HSJ1, a neuronal protein. - Drosophila cysteine-string protein (csp). The type 3 subgroup contains proteins that have only the J-domain: - Yeast protein SEC63/NPL1. It is important for protein assembly into the endoplasmic reticulum and the nucleus. - Eukaryotic Tim14 protein. An essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. In the complex, it is required to stimulate activity of mtHSP70 (SSC1). - Yeast Jac1 protein and HscB eukaryotic homologues. They may act as co-chaperones in iron-sulfur cluster assembly in mitochondria. - Yeast Zuo1 protein. Zuo1 and Ssz1 (hsp70) are targeted to ribosomes, where they form the functionally active RAC complex. - Yeast Jjj1 to 3, Erj5 and Jid1 proteins of unknown function. We developed a signature pattern for the 'J' domain, based on conserved positions in the C-terminal half of this domain. We also developed two profiles, one which covers the entire 'J' domain and the other that spans the whole CR-type zinc finger. -Consensus pattern: [FY]-{GL}-x-[LIVMA]-{IP}-x(2)-[FYWHNT]-[DENQSA]-x-L-x- [DN]-x(3)-[KR]-x(2)-[FYI] -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the first profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the second profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Expert(s) to contact by email: Kelley W.; kelley@medecine.unige.ch -Last update: April 2006 / Text revised; profiles added; pattern deleted. [ 1] Frydman J. "Folding of newly translated proteins in vivo: the role of molecular chaperones." Annu. Rev. Biochem. 70:603-647(2001). Pubmed=11395418 [ 2] Walsh P., Bursac D., Law Y.C., Cyr D., Lithgow T.; "The J-protein family: modulating protein assembly, disassembly and translocation." EMBO Rep. 5:567-571(2004). [ 3] Pellecchia M., Szyperski T., Wall D., Georgopoulos C., Wuthrich K. "NMR structure of the J-domain and the Gly/Phe-rich region of the Escherichia coli DnaJ chaperone." J. Mol. Biol. 260:236-250(1996). PubMed=8764403; DOI=10.1006/jmbi.1996.0395 [ 4] Martinez-Yamout M., Legge G.B., Zhang O., Wright P.E., Dyson H.J. "Solution structure of the cysteine-rich domain of the Escherichia coli chaperone protein DnaJ." J. Mol. Biol. 300:805-818(2000). PubMed=10891270 [ 5] Genevaux P., Schwager F., Georgopoulos C., Kelley W.L. "Scanning mutagenesis identifies amino acid residues essential for the in vivo activity of the Escherichia coli DnaJ (Hsp40) J-domain." Genetics 162:1045-1053(2002). PubMed=12454054 [ 6] Linke K., Wolfram T., Bussemer J., Jakob U. "The roles of the two zinc binding sites in DnaJ." J. Biol. Chem. 278:44457-44466(2003). PubMed=12941935 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}