Alternative titles; symbols
HGNC Approved Gene Symbol: EDC4
Cytogenetic location: 16q22.1 Genomic coordinates (GRCh38) : 16:67,873,052-67,884,499 (from NCBI)
Antibodies directed against nuclear and cytoplasmic components are a characteristic feature of autoimmune disease. By screening a hepatocellular carcinoma cDNA expression library with serum from a patient (GE) with Sjogren syndrome (270150), followed by probing an endothelial cell cDNA library, Bloch et al. (1994) identified a cDNA encoding GE1. The deduced 1,215-amino acid protein contains a central serine-rich region and a putative nuclear localization sequence (NLS) near its C terminus; however, it lacks zinc finger, leucine zipper, and RNA-binding motifs, which are found in other autoantigens. Immunoblot analysis indicated that GE1 is expressed as a 160-kD protein. Epitope mapping analysis suggested that the functional NLS-containing hydrophilic region of GE1 is the site recognized by patient serum. Immunofluorescence microscopy using rat antisera to the recombinant protein demonstrated speckled, mostly nuclear expression.
Using human RCD serum, which recognizes strictly cytoplasmic components, to screen an expression cDNA library, Garcia-Lozano et al. (1997) obtained a cDNA encoding RCD8. Sequence analysis predicted that the 968-amino acid RCD8 protein is nearly identical to the GE1 protein identified by Bloch et al. (1994). However, due to a nucleotide insertion at position 2341, RCD8 is 186 amino acids longer at the C-terminal end than GE1, whereas GE1 is 433 amino acids longer at the N-terminal end. Immunoblot analysis showed expression of a 160-kD protein. Immunofluorescence microscopy demonstrated cytoplasmic expression. Garcia-Lozano et al. (1997) mapped the immunoreactive region to an area between amino acids 435 and 500, identical to the area identified by Bloch et al. (1994).
Using mass spectroscopy, Fenger-Gron et al. (2005) found that EDC3 (609842), RCK (DDX6; 600326), and EDC4, which they called HEDLS, coimmunopurified with the mRNA-decapping enzymes DCP1A and DCP2 (609844) from HEK293 cell lysates. RCD8 promoted the association of DCP1A and DCP2, and overexpressed DCP1A and DCP2 did not associate in its absence. RCD8 associated with DCP2 and stimulated its decapping activity in vitro. Overexpression of RCD8 caused accumulation of deadenylated mRNA and formation of multiple enlarged cytoplasmic processing body-like structures containing EDC4, DCP1 and XRN1 (607994).
The International Radiation Hybrid Mapping Consortium mapped the EDC4 gene to chromosome 16 (stSG43158).
Bloch, D. B., Rabkina, D., Quertermous, T., Bloch, K. D. The immunoreactive region in a novel autoantigen contains a nuclear localization sequence. Clin. Immun. Immunopath. 72: 380-389, 1994. [PubMed: 7520377] [Full Text: https://doi.org/10.1006/clin.1994.1156]
Fenger-Gron, M., Fillman, C., Norrild, B., Lykke-Andersen, J. Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping. Molec. Cell 20: 905-915, 2005. [PubMed: 16364915] [Full Text: https://doi.org/10.1016/j.molcel.2005.10.031]
Garcia-Lozano, J. R., Gonzalez-Escribano, M. F., Wichmann, I., Nunez-Roldan, A. Cytoplasmic detection of a novel protein containing a nuclear localization sequence by human autoantibodies. Clin. Exp. Immun. 107: 501-506, 1997. [PubMed: 9067524] [Full Text: https://doi.org/10.1046/j.1365-2249.1997.d01-955.x]