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Gene Review

Ncoa6  -  nuclear receptor coactivator 6

Rattus norvegicus

Synonyms: ASC-2, Activating signal cointegrator 2, Aib3, Amplified in breast cancer protein 3, Cancer-amplified transcriptional coactivator ASC-2, ...
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Disease relevance of Ncoa6

  • At equal percentage of the NRC requirement, threonine- and lysine-deficient amino acid mixtures supported equal body weight, dry matter, lipid and ash gains [1].
  • Therefore, increasing or decreasing the calcium content above or below the NAS/NRC recommendation (supplemented to low fat diets) during the promotional phase of colon carcinogenesis altered the tumor incidence, but the effect was confined to the distal colon and to benign adenomatous polyps [2].
  • The results indicated that subsequent to femoral fracture, the nutritional requirement for copper, manganese, and zinc for minimal nitrogen loss were higher than the NRC requirements for the mature male rat [3].
  • In each case (valine, methionine, threonine and histidine), the dietary amino acid concentration required for maximal weight gain exceeded current NRC recommendations, which may be low because they fall in the more time-dependent portion of the response curve whereas maximum responses do not [4].

High impact information on Ncoa6

  • Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic beta-cells [5].
  • In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells [5].
  • Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/- mice [5].
  • Furthermore, relative to the wild type, ASC-2+/- mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/- islets [5].
  • These findings suggest that the lethality of Rap250(-/-) embryos is the result of obstructed placental blood circulation [6].

Biological context of Ncoa6


Anatomical context of Ncoa6

  • The results showed that RAP250 mRNA was primarily localized to granulosa cells of healthy follicles in immature, cycling, and pregnant rats and increased during PMSG-induced follicular development [7].
  • 5. Histological examination of placentas revealed a dramatically reduced spongiotrophoblast layer, a collapse of blood vessels in the region bordering the spongiotrophoblast, and labyrinthine layers in placentas from Rap250(-/-) embryos [6].
  • Moreover, the transcriptional activity of PPAR gamma is reduced in fibroblasts derived from Rap250(-/-) embryos, suggesting that RAP250 is an essential coactivator for this nuclear receptor in the placenta [6].
  • Disparities between binding data and functional bioassays of [Aib3] indicated that Phe3 was required for bioactivity in mouse vas deferens but not for interaction with delta opioid receptors in rat brain membranes [11].
  • Because CRBP(II) may play an important role in preventing the toxic effect of unbound retinol in the small intestine, consumption of excess vitamin A in amounts < 10 times the NRC recommended requirement may not cause a disturbance of the absorptive cell function.(ABSTRACT TRUNCATED AT 250 WORDS)[12]

Associations of Ncoa6 with chemical compounds

  • Male Sprague-Dawley rats were fed a commercial rat chow containing twice the amount of vitamin A recommended by the NRC for healthy rats [13].
  • Lysine- and threonine-deficient amino acid mixtures were incorporated into diets for young growing rats to provide 75 or 85% of the NRC requirement of the limiting amino acid in combination with zero or 50% of relative excess of the nonlimiting amino acids [1].
  • Diets containing 1, 10, 100, 175 or 250 times the NRC recommended level of pyridoxine HCl (7 mg/kg) were fed to rats (218 g, 12 per group) to evaluate the effects on tissue B-6 vitamer concentrations [14].
  • Supplemental retinyl acetate feeding at five times the NRC-suggested allowance resulted in a mild, but significantly increased postmortem wound tensile strength after 5 days compared to rats fed the suggested allowance [15].
  • The intake producing the half-maximal liver folacin concentration (1.3 mg folic acid/kg diet) compares well to the 1978 NRC recommendation for the rat [16].

Analytical, diagnostic and therapeutic context of Ncoa6

  • The RT-PCR results confirmed the presence of RAP250 mRNA in the rat ovary and strengthen the data from ISH [7].
  • In order to study its biological role, Rap250 null mice were generated by gene targeting [6].
  • The administration with Asc, Asc2P or Asc2G prevented some features of hepatic I/R injuries such as release of hepatic marker enzymes GOT and GPT into the blood vessel, cellular degenerative symptoms including vacuolation and cell fragmentation, and nuclear DNA strand cleavage as detected by TUNEL staining [17].
  • Coronary perfusion rate and left ventricular isovolemic developed pressure increased after NRC transfusion to 4.6 +/- 1.0 ml/min/g and 127 +/- 32 mmHg from basal values of 2.5 +/- 0.3 ml/min/g and 115 +/- 28 mmHg, respectively [10].


  1. The effect of amino acid excess on utilization by the rat of the limiting amino acid--lysine and threonine at equalized food intakes. Cieslak, D.G., Benevenga, N.J. J. Nutr. (1984) [Pubmed]
  2. Effect of dietary calcium on colon carcinogenesis induced by a single injection of 1,2-dimethylhydrazine in rats. Karkare, M.R., Clark, T.D., Glauert, H.P. J. Nutr. (1991) [Pubmed]
  3. Effect of dietary copper, manganese, and zinc on nitrogen equilibrium and mineral distribution subsequent to trauma in mature rats. Thompson, H.J., Griminger, P., Evans, J.L. J. Nutr. (1976) [Pubmed]
  4. Determination of nutritional requirements in rats: variation with time of weight gain responses to indispensable amino acids. Mercer, L.P., Yi, T., Dodds, S.J. J. Nutr. (1993) [Pubmed]
  5. Regulation of insulin secretion and beta-cell mass by activating signal cointegrator 2. Yeom, S.Y., Kim, G.H., Kim, C.H., Jung, H.D., Kim, S.Y., Park, J.Y., Pak, Y.K., Rhee, D.K., Kuang, S.Q., Xu, J., Han, D.J., Song, D.K., Lee, J.W., Lee, K.U., Kim, S.W. Mol. Cell. Biol. (2006) [Pubmed]
  6. Inactivation of the nuclear receptor coactivator RAP250 in mice results in placental vascular dysfunction. Antonson, P., Schuster, G.U., Wang, L., Rozell, B., Holter, E., Flodby, P., Treuter, E., Holmgren, L., Gustafsson, J.A. Mol. Cell. Biol. (2003) [Pubmed]
  7. Expression and localization of RAP250 mRNA in rat ovary: possible implications in follicular development and ovulation. Liu, D.L., Li, Q.L., Lin, H.Y., Liu, W.Z., Wang, H.M., Zhang, X., Zhu, C. Endocrine (2002) [Pubmed]
  8. Influence of dietary pyridoxine on selected immune capacities of rat dams and pups. Debes, S.A., Kirksey, A. J. Nutr. (1979) [Pubmed]
  9. Vascular response of current and potential dental etchants. Cehreli, Z.C., Onur, M.A., Taşman, F., Gümrükçuölu, A. Journal of endodontics. (2002) [Pubmed]
  10. Myocardial microvascular perfusion after transfusion of liposome-encapsulated hemoglobin evaluated in cross-circulated rat hearts using tracer digital radiography. Asano, T., Matsumoto, T., Tachibana, H., Takemoto, M., Kajiya, F. Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs. (2004) [Pubmed]
  11. Helix-inducing alpha-aminoisobutyric acid in opioid mimetic deltorphin C analogues. Bryant, S.D., Guerrini, R., Salvadori, S., Bianchi, C., Tomatis, R., Attila, M., Lazarus, L.H. J. Med. Chem. (1997) [Pubmed]
  12. Consumption of excess vitamin A, but not excess beta-carotene, causes accumulation of retinol that exceeds the binding capacity of cellular retinol-binding protein, type II in rat intestine. Suzuki, R., Goda, T., Takase, S. J. Nutr. (1995) [Pubmed]
  13. Impaired wound healing in streptozotocin diabetes. Prevention by supplemental vitamin A. Seifter, E., Rettura, G., Padawer, J., Stratford, F., Kambosos, D., Levenson, S.M. Ann. Surg. (1981) [Pubmed]
  14. Tissue B-6 vitamer concentrations in rats fed excess vitamin B-6. Schaeffer, M.C., Gretz, D., Mahuren, J.D., Coburn, S.P. J. Nutr. (1995) [Pubmed]
  15. Effect of dietary retinyl acetate, beta-carotene and retinoic acid on wound healing in rats. Gerber, L.E., Erdman, J.W. J. Nutr. (1982) [Pubmed]
  16. Integrated saturation model for tissue micronutrient concentrations applied to liver folacin. Keagy, P.M. J. Nutr. (1982) [Pubmed]
  17. Cytoprotection against ischemia-induced DNA cleavages and cell injuries in the rat liver by pro-vitamin C via hydrolytic conversion into ascorbate. Eguchi, M., Miyazaki, T., Masatsuji-Kato, E., Tsuzuki, T., Oribe, T., Miwa, N. Mol. Cell. Biochem. (2003) [Pubmed]
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