Alternative titles; symbols
HGNC Approved Gene Symbol: MLXIP
Cytogenetic location: 12q24.31 Genomic coordinates (GRCh38) : 12:122,078,756-122,147,344 (from NCBI)
MONDOA forms heterodimers with MLX (602976) that can bind to and activate transcription from CACGTG E boxes (Billin et al., 2000).
By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1998) cloned MONDOA, which they designated KIAA0867. The MONDOA transcript contains an Alu sequence within the 3-prime untranslated region. RT-PCR ELISA detected low to moderate expression in most tissues examined, with highest expression in brain, liver, skeletal muscle, and ovary, and little to no expression in spleen.
Using human MLX as bait in a yeast 2-hybrid screen, Billin et al. (2000) cloned mouse Mondoa from a whole embryo cDNA library. They cloned human MONDOA by screening an erythroleukemia cell line cDNA library using mouse Mondoa as probe. The deduced 919-amino acid protein contains a central serine-threonine-proline (STP)-rich domain, a basic helix-loop-helix domain, a zipper region, and a C-terminal MLX homology domain. The N terminus of MONDOA is conserved among MONDO proteins of other species. Northern blot analysis detected a major transcript of about 9.0 kb and a minor transcript of about 5.5 kb in most human tissues tested, with highest expression in skeletal muscle. In situ hybridization of mouse embryos detected broad Mondoa expression, with slightly elevated levels in the developing central nervous system.
Billin et al. (2000) characterized mouse Mondoa. Mondoa and Mlx associated in vivo, and the dimer localized primarily to the cytoplasm of mouse embryonic carcinoma cells. Treatment of cells with a nuclear export inhibitor resulted in nuclear accumulation of Mondoa and Mlx, demonstrating that the heterodimer shuttles between the cytoplasmic and nuclear compartments. The Mondoa-Mlx complex bound to the CACGTG E box in vitro and, when artificially targeted to the nucleus of mouse fibroblasts, drove reporter gene expression from the E box. Coexpression of MLX with truncation mutants of human MONDOA identified a transcription activation domain within the central STP-rich region of MONDOA. By mutation analysis, Billin et al. (2000) identified a cytoplasmic localization signal within the N terminus of human MONDOA that contributed to the cytoplasmic localization of the MONDOA-MLX complex.
Eilers et al. (2002) determined that 2 regions within the MONDOA N terminus contribute to the cytoplasmic localization of the MONDOA-MLX complex by functioning as a CRM1 (602559)-dependent nuclear export signal and as a binding site for 14-3-3 (see 601289) proteins, respectively. The conserved C terminus of MONDOA and MLX contains a cytoplasmic localization signal that directs cytoplasmic localization of the monomers and a protein-protein interaction domain that mediates interaction between MONDOA and MLX. Heterodimerization of MONDOA and MLX, via either the leucine zipper or the C-terminal domain, inactivates the C-terminal cytoplasmic localization signal. Inactivation of this domain is necessary but not sufficient for nuclear accumulation of the heterodimer.
By radiation hybrid analysis, Nagase et al. (1998) mapped the MLXIP gene to chromosome 12. Billin et al. (2000) mapped the MLXIP gene to chromosome 12q21.31 by in situ hybridization.
Billin, A. N., Eilers, A. L., Coulter, K. L., Logan, J. S., Ayer, D. E. MondoA, a novel basic helix-loop-helix-leucine zipper transcriptional activator that constitutes a positive branch of a Max-like network. Molec. Cell. Biol. 20: 8845-8854, 2000. [PubMed: 11073985] [Full Text: https://doi.org/10.1128/MCB.20.23.8845-8854.2000]
Eilers, A. L., Sundwall, E., Lin, M., Sullivan, A. A., Ayer, D. E. A novel heterodimerization domain, CRM1, and 14-3-3 control subcellular localization of the MondoA-Mlx heterocomplex. Molec. Cell. Biol. 22: 8514-8526, 2002. [PubMed: 12446771] [Full Text: https://doi.org/10.1128/MCB.22.24.8514-8526.2002]
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 5: 355-364, 1998. [PubMed: 10048485] [Full Text: https://doi.org/10.1093/dnares/5.6.355]