Alternative titles; symbols
HGNC Approved Gene Symbol: DNAJC2
Cytogenetic location: 7q22.1 Genomic coordinates (GRCh38): 7:103,312,289-103,344,767 (from NCBI)
Progression of cells from interphase to mitosis involves alterations in cell structures and activities. The transition from G2 to M phase is induced by M phase-promoting factor, or MPF (see CCNB1; 123836). In M phase, many proteins are phosphorylated directly by MPF or indirectly by kinases activated by MPF. These M-phase phosphoproteins (MPPs, or MPHOSPHs) permit disassembly of interphase structures and generation of M-phase enzymatic activities and structures. By treating bacterial expression libraries with M-phase cytosol containing the relevant kinases in the presence of a phosphatase inhibitor, followed by immunoscreening with MPM2 antibody, Matsumoto-Taniura et al. (1996) isolated cDNAs for a number of MPHOSPHs, including MPHOSPH11, or ZRF1 (zuotin-related factor-1), which they called MPP11. Zuotin is a nucleic acid-binding protein and ribosomal chaperone identified in yeast (Yan et al., 1998). By immunoblot analysis, Matsumoto-Taniura et al. (1996) showed that when phosphorylated, ZRF1 is expressed as a 130-kD protein in M-phase cells. Immunofluorescence microscopy localized ZRF1 in punctate foci throughout the cell, including the nucleus, in both interphase and mitotic cells.
Otto et al. (2005) cloned human MPP11. The deduced 568-amino acid protein contains an N-terminal domain, followed by a J domain, a central charged region, and 2 C-terminal MYB (189990)-like domains.
Hundley et al. (2005) reported that ribosome-associated molecular chaperones have been maintained throughout eukaryotic evolution, as illustrated by MPP11, the human ortholog of the yeast ribosome-associated J protein Zuo. When expressed in yeast, MPP11 partially substituted for Zuo by partnering with the multipurpose Hsp70 Ssa, the homolog of mammalian Hsc70 (600816). Hundley et al. (2005) proposed that in metazoans, ribosome-associated MPP11 recruits the multifunctional soluble Hsc70 to nascent polypeptide chains as they exit the ribosome.
Otto et al. (2005) found that MPP11 and HSP70L1 (HSPA14; 610369) formed a complex in HeLa cells, rat liver, and rabbit reticulate lysate. The 2 proteins coeluted on cation and anion exchange columns, and sucrose density gradients showed that they comigrated with polysomes and ribosomes. The 200-kD dimeric ribosome-associated complex (RAC) formed by MPP11 and HSP70L1 was sensitive to salt treatment and could rescue growth defects in yeast strains lacking functional RAC.
Richly et al. (2010) showed in human cell lines that ZRF1 is specifically recruited to histone H2A (see 613499) when it is ubiquitinated at lys119 by means of a novel ubiquitin-interacting domain that is located in the evolutionarily conserved zuotin domain. At the onset of differentiation, ZRF1 specifically displaces polycomb-repressive complex-1 (PRC1; see 603079) from chromatin and facilitates transcriptional activation. A genomewide mapping of ZRF1, RING1B (608985), and H2A-ubiquitin targets revealed its involvement in the regulation of a large set of polycomb target genes, emphasizing the key role ZRF1 has in cell fate decisions. Richly et al. (2010) provided a model of the molecular mechanism of switching polycomb-repressed genes to an active state.
The International Radiation Hybrid Mapping Consortium mapped the ZRF1 gene to chromosome 7 (WI-14926).
Hundley, H. A., Walter, W., Bairstow, S., Craig, E. A. Human Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous. Science 308: 1032-1034, 2005. [PubMed: 15802566] [Full Text: https://doi.org/10.1126/science.1109247]
Matsumoto-Taniura, N., Pirollet, F., Monroe, R., Gerace, L., Westendorf, J. M. Identification of novel M phase phosphoproteins by expression cloning. Molec. Biol. Cell 7: 1455-1469, 1996. [PubMed: 8885239] [Full Text: https://doi.org/10.1091/mbc.7.9.1455]
Otto, H., Conz, C., Maier, P., Wolfle, T., Suzuki, C. K., Jeno, P., Rucknagel, P., Stahl, J., Rospert, S. The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex. Proc. Nat. Acad. Sci. 102: 10064-10069, 2005. [PubMed: 16002468] [Full Text: https://doi.org/10.1073/pnas.0504400102]
Richly, H., Rocha-Viegas, L., Ribeiro, J. D., Demajo, S., Gundem, G., Lopez-Bigas, N., Nakagawa, T., Rospert, S., Ito, T., Di Croce, L. Transcriptional activation of polycomb-repressed genes by ZRF1. Nature 468: 1124-1128, 2010. [PubMed: 21179169] [Full Text: https://doi.org/10.1038/nature09574]
Yan, W., Schilke, B., Pfund, C., Walter, W., Kim, S., Craig, E. A. Zuotin, a ribosome-associated DnaJ molecular chaperone. EMBO J. 17: 4809-4817, 1998. [PubMed: 9707440] [Full Text: https://doi.org/10.1093/emboj/17.16.4809]