Alternative titles; symbols
HGNC Approved Gene Symbol: GMEB1
Cytogenetic location: 1p35.3 Genomic coordinates (GRCh38) : 1:28,668,229-28,719,353 (from NCBI)
Using heat-shock protein-27 (HSP27; 602195) as bait in a yeast 2-hybrid assay, Theriault et al. (1999) cloned a human cDNA encoding a deduced 573-amino acid protein that they called glucocorticoid modulatory element-binding protein-1 (GMEB1). The GMEB1 protein has a KDWK domain, contains sequences that are 95% identical to 3 tryptic peptides of rat GMEB1, and shares 38% identity with rat GMEB2. A rabbit antibody raised against a recombinant GMEB1 fusion protein detected an 85-kD polypeptide in several human and mouse cell lines, in rat liver, and in different mouse tissues. The authors suggested that the difference between the apparent molecular mass of this polypeptide and the calculated molecular mass of 62.5-kD derived from the protein sequence might reflect the high content of acidic residues in GMEB1. By immunofluorescence of HeLa cells expressing recombinant GMEB1, the authors localized the protein to the nucleus. Coimmunoprecipitation experiments confirmed the in vivo interaction of HSP27 with GMEB1. GMEB1 translated in reticulocyte lysates bound to 21-bp GME oligonucleotides in a gel-shift assay. The resulting complex was similar in size to the complex obtained using rat liver nucleotide extracts. Both complexes were supershifted with an antibody specific to human GMEB1. The authors concluded that GMEB1 is a trans-acting DNA-binding protein that may mediate the demonstrated functions of GME as a positive modulator of the glucocorticoid response.
Christensen et al. (1999) copurified GMEB1 in a complex with GMEB2 (607451) from HeLa cell nuclear extracts. Using degenerate primers designed from the amino acid sequence followed by 5-prime and 3-prime RACE, they cloned the full-length cDNAs. The deduced GMEB1 protein, which they called p96, contains 563 amino acids and has a calculated molecular mass of 60.4 kD. By SDS/PAGE analysis, the apparent molecular mass was 96 kD. GMEB1 contains an N-terminal KDWK domain, and a highly acidic C terminus that likely forms a coiled-coil structure. Recombinant and endogenous GMEB1 share identical mobilities when analyzed by SDS/PAGE analysis, indicating a lack of posttranslational modification. Within the N-terminal KDWK domain, GMEB1 shares about 80% identity with GMEB2; overall, they share about 40% identity.
Christensen et al. (1999) noted that the complex of GMEB1 and GMEB2, which they designated parvovirus initiation factor (PIF) subunits p96 and p79, respectively, was originally recognized as a site-specific DNA-binding complex essential for parvovirus DNA replication. Christensen et al. (1999) found that GMEB2 and GMEB1 self-associate when expressed alone, and that they form heterodimers when expressed together. Cross-linking experiments indicated that no higher-order multimers were formed. Each protein was active in promoter activation assays, and the complex bound regulatory elements within the promoter regions of tyrosine animotransferase (613018) and the transferrin receptor gene (190010). Within its recognition site, PIF coordinately bound 2 copies of the tetranucleotide PuCGPy, and these could be spaced from 1 to 15 nucleotides apart.
The International Radiation Hybrid Mapping Consortium mapped the GMEB1 gene to chromosome 1 (stSG1681R).
Christensen, J., Cotmore, S. F., Tattersall, P. Two new members of the emerging KDWK family of combinatorial transcription modulators bind as a heterodimer to flexibly spaced PuCGPy half sites. Molec. Cell. Biol. 19: 7741-7750, 1999. [PubMed: 10523663] [Full Text: https://doi.org/10.1128/MCB.19.11.7741]
Theriault, J. R., Charette, S. J., Lambert, H., Landry, J. Cloning and characterization of hGMEB1, a novel glucocorticoid modulatory element binding protein. FEBS Lett. 452: 170-176, 1999. [PubMed: 10386584] [Full Text: https://doi.org/10.1016/s0014-5793(99)00634-1]