Alternative titles; symbols
HGNC Approved Gene Symbol: MAS1
Cytogenetic location: 6q25.3 Genomic coordinates (GRCh38): 6:159,888,787-159,917,447 (from NCBI)
The MAS1 oncogene was isolated from DNA of a human epidermoid carcinoma cell line using the cotransfection and tumorigenicity assay (Young et al., 1984). Based on its deduced amino acid sequence, the MAS1 gene product contains 7 potential transmembrane domains. The MAS1 protein is, therefore, probably an integral membrane protein. Young et al. (1984) suggested that the MAS1-encoded protein may be a receptor that, when activated, modulates a critical component in a growth-regulating pathway to bring about its oncogenic effects.
The structure of the MAS oncogene indicates that it belongs to the class of receptors that are coupled to GTP-binding proteins and share a conserved structural motif, which is described as a '7-transmembrane segment' following the prediction that these hydrophobic segments form membrane-spanning alpha-helices. Examples include the adrenergic receptors (e.g., 104210, 104250, 109690). Jackson et al. (1988) found that the MAS oncogene shows the greatest sequence similarity to the substance-K receptor (162321). On this basis, they predicted that it would encode a peptide receptor with mitogenic activity which would act through the inositol lipid signaling pathways. Expression in Xenopus oocytes and a transfected mammalian cell line demonstrated that the MAS gene product is a functional angiotensin receptor.
Lyle et al. (2000) determined the genomic sequence of mouse Mas1 and determined that the gene contains 4 exons.
By in situ hybridization, Rabin et al. (1987) mapped the MAS1 gene to 6q24-q27. The ROS (165020) and MYB (189990) oncogenes are also located on 6q. It is of note that the estrogen receptor gene (133430) maps to the same region as MAS1. Al-Ubaidi et al. (1992) confirmed the assignment of the human MAS1 gene to chromosome 6 by Southern blot analysis of somatic cell hybrids. Riesewijk et al. (1996) mapped the human MAS gene to 6q25.3-q26 by fluorescence in situ hybridization (FISH) in a region very close to the IGF2R gene (147280), which had been mapped to 6q26. Moreover, FISH signals obtained with YACs carrying the IGF2R gene and the MAS gene were partially overlapping on metaphase chromosomes and in 91 of 100 interphase nuclei. Since for cosmid probes the resolution of interphase FISH is approximately 50 kb, these findings suggested to the authors that in humans the physical distance between MAS and IGF2R is at most several hundred kb (it is less than 300 kb in the mouse).
By 2 interspecific backcrosses, Cebra-Thomas et al. (1992) mapped the mouse homolog to the proximal portion of chromosome 17. They further demonstrated that Mas maps to a 1-Mb region which also contains Igf2r (147280). Al-Ubaidi et al. (1992) also assigned the Mas1 gene to mouse chromosome 17.
Villar and Pedersen (1994), who characterized the MAS gene product as a mitogenic G protein-coupled cell surface receptor, investigated the allele-specific expression pattern of the mouse Mas gene on the basis of its proximity to the known imprinted gene for insulin growth factor type II receptor. Their results demonstrated parental imprinting of Mas and suggested that the maternally inherited allele is transcriptionally repressed in a developmental and tissue-specific manner. Riesewijk et al. (1996) demonstrated that the MAS gene, like the IGF2R gene, is not imprinted in the human. Lyle et al. (2000) found that the last exon of Mas1 overlaps an antisense Igf2r RNA (604893) that represents a paternally expressed imprinted gene. The overlap of this last exon explains the previous erroneous finding of Villar and Pedersen (1994) that Mas1 was a paternally expressed imprinted gene.
Walther et al. (1998) generated mice deficient in Mas by targeted disruption. Mas -/- mice had increased durability of long-term potentiation in the dentate gyrus, without affecting hippocampal morphology, basal synaptic transmission, and presynaptic function. In addition, Mas -/- mice showed alterations in the onset of depotentiation. The permissive influence of Mas ablation on hippocampal synaptic plasticity is paralleled by behavioral changes. While spatial learning in the Morris water maze was not significantly influenced, Mas-deficient mice displayed an increased anxiety, as assessed in the elevated-plus maze. Walther et al. (1998) concluded that Mas is an important modulating factor in the electrophysiology of the hippocampus and is involved in behavioral pathways in the adult brain.
The renin-angiotensin system plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. The cardiovascular and baroreflex actions of angiotensin 1-7 counteract those of angiotensin II (see 106150). Santos et al. (2003) demonstrated that genetic deletion of the G protein-coupled receptor encoded by the Mas protooncogene abolished the binding of angiotensin 1-7 to mouse kidneys. Accordingly, Mas-deficient mice completely lacked the entire antidiuretic action of angiotensin 1-7 after an acute water load. Angiotensin 1-7 binds to Mas-transfected cells and elicits arachidonic acid release. Furthermore, Mas-deficient aortas lost their angiotensin 1-7-induced relaxation response. Collectively, these findings identified Mas as a functional receptor for angiotensin 1-7 and provided a clear molecular basis for the physiologic actions of this biologically active peptide.
Al-Ubaidi, M. R., Brock, D., Siciliano, M. J. Assignment of the homolog of the MAS1 oncogene to mouse chromosome 17. Genomics 13: 487 only, 1992. [PubMed: 1612611] [Full Text: https://doi.org/10.1016/0888-7543(92)90281-v]
Cebra-Thomas, J. A., Tsai, J.-Y., Pilder, S. H., Copeland, N. G., Jenkins, N. A., Silver, L. M. Localization of the Mas proto-oncogene to a densely marked region of mouse chromosome 17 associated with genomic imprinting. Genomics 13: 444-446, 1992. Note: Erratum: Genomics 14: 208 only, 1992. [PubMed: 1612602] [Full Text: https://doi.org/10.1016/0888-7543(92)90267-v]
Jackson, T. R., Blair, L. A. C., Marshall, J., Goedert, M., Hanley, M. R. The mas oncogene encodes an angiotensin receptor. Nature 335: 437-440, 1988. [PubMed: 3419518] [Full Text: https://doi.org/10.1038/335437a0]
Lyle, R., Watanabe, D., te Vruchte, D., Lerchner, W., Smrzka, O. W., Wutz, A., Schageman, J., Hahner, L., Davies, C., Barlow, D. P. The imprinted antisense RNA at the Igf2r locus overlaps but does not imprint Mas1. Nature Genet. 25: 19-21, 2000. [PubMed: 10802648] [Full Text: https://doi.org/10.1038/75546]
Rabin, M., Birnbaum, D., Young, D., Birchmeier, C., Wigler, M., Ruddle, F. H. Human ROS1 and MAS1 oncogenes located in regions of chromosome 6 associated with tumor-specific rearrangements. Oncogene Res. 1: 169-178, 1987. [PubMed: 3329713]
Riesewijk, A. M., Schepens, M. T., Mariman, E. M., Ropers, H.-H., Kalscheuer, V. M. The MAS proto-oncogene is not imprinted in humans. Genomics 35: 380-382, 1996. [PubMed: 8661154] [Full Text: https://doi.org/10.1006/geno.1996.0372]
Santos, R. A. S., Simoes e Silva, A. C., Maric, C., Silva, D. M. R., Machado, R. P., de Buhr, I., Heringer-Walther, S., Pinheiro, S. V. B., Lopes, M. T., Bader, M., Mendes, E. P., Lemos, V. S., Campagnole-Santos, M. J., Schultheiss, H.-P., Speth, R., Walther, T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc. Nat. Acad. Sci. 100: 8258-8263, 2003. [PubMed: 12829792] [Full Text: https://doi.org/10.1073/pnas.1432869100]
Villar, A. J., Pedersen, R. A. Parental imprinting of the Mas protooncogene in mouse. Nature Genet. 8: 373-379, 1994. [PubMed: 7894489] [Full Text: https://doi.org/10.1038/ng1294-373]
Walther, T., Balschun, D., Voigt, J.-P., Fink, H., Zuschratter, W., Birchmeier, C., Ganten, D., Bader, M. Sustained long term potentiation and anxiety in mice lacking the Mas protooncogene. J. Biol. Chem. 273: 11867-11873, 1998. [PubMed: 9565612] [Full Text: https://doi.org/10.1074/jbc.273.19.11867]
Young, D., Waitches, G., Birchmeier, C., Fasano, O., Wigler, M. Isolation and characterization of a new cellular oncogene encoding a protein with multiple transmembrane domains. Cell 45: 711-719, 1984.