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Gene Review

Ncoa1  -  nuclear receptor coactivator 1

Mus musculus

Synonyms: KAT13A, NCoA-1, Nuclear receptor coactivator 1, Nuclear receptor coactivator protein 1, SRC-1, ...
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Disease relevance of Ncoa1


High impact information on Ncoa1

  • These results reveal that the relative level of TIF2/SRC-1 can modulate energy metabolism [3].
  • In white adipose tissue, lack of TIF2 decreases PPARgamma activity and reduces fat accumulation, whereas in brown adipose tissue it facilitates the interaction between SRC-1 and PGC-1alpha, which induces PGC-1alpha's thermogenic activity [3].
  • The results indicate that SRC-1 mediates steroid hormone responses in vivo and that loss of its coactivator function results in partial resistance to hormone [5].
  • Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1 [6].
  • Also found at the array by immunofluorescence were two different steroid receptor coactivators (SRC1 and CBP) with acetyltransferase activity, a chromatin remodeler (BRG1), and two transcription factors (NFI and AP-2) [7].

Chemical compound and disease context of Ncoa1

  • The SRC-1(-/-) mice showed high turnover osteopenia under physiological conditions and hardly responded to osteoanabolic actions of exogenous androgen and estrogen in males and females, respectively, after gonadectomies, indicating that SRC-1 is essential for the maintenance of bone mass by sex hormones [8].

Biological context of Ncoa1


Anatomical context of Ncoa1

  • Moreover, removal of SRC-1 in the PR(Cre/+) SRC-2(flox/flox) mouse uterus resulted in the absence of a decidual response, confirming that uterine SRC-2 and -1 cooperate in P-initiated transcriptional programs which lead to full decidualization [10].
  • The expression of both SRC-1 and PBP is prominent in the breast epithelium of nonpregnant, pregnant, and lactating mice, whereas PPARgamma expression appeared prominent during lactation [13].
  • In the colonic mucosa, PPARgamma expression occurs throughout the villi, whereas the expression of both SRC-1 and PBP is confined mostly to the crypts [13].
  • In the mammary gland, PR activity in the luminal epithelium of both wild-type and SRC-1(-/-) mice was induced by estrogen + progesterone treatment [14].
  • SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells [15].

Associations of Ncoa1 with chemical compounds

  • A reduction in blood glucose was observed in SRC-1-/- mice after chronic stress, consistent with a generalized state of glucocorticoid resistance [16].
  • However, after exposure to paradigms of acute and chronic stress, SRC-1-/- mice exhibited an elevation in serum corticosterone despite normal (nonsuppressed) ACTH, suggesting an increase in adrenal sensitivity as well as a concomitant defect in glucocorticoid-mediated feedback inhibition of the HPA axis [16].
  • Two serine residues in ER beta AF-1, of which one is contained within a motif present in other steroid receptors, are critical for physical interaction with SRC-1 and transcriptional activation [6].
  • Modulation by steroid receptor coactivator-1 of target-tissue responsiveness in resistance to thyroid hormone [2].
  • In contrast, lack of SRC-1 did not affect responsiveness in the liver in regulating serum cholesterol in either TR beta(PV/+) or TR beta(PV/PV) mice [2].

Physical interactions of Ncoa1

  • The minimal chimeric protein that is produced fuses MLL to the bromodomain, histone acetyltransferase (HAT) domain, EIA-binding domain and steroid-receptor coactivator binding domains of CBP [17].
  • We have shown that SRC-1 unexpectedly interacts with GR via its two nuclear receptor binding domains, thus providing a novel mechanism of GR signaling within the nervous system [18].
  • Ftz, on the other hand, influences Ftz-F1 activity by interacting with its AF-2 domain in a manner that mimics a nuclear receptor coactivator [19].
  • The vitellogenin promoter construct, however, was only weakly activated by the Brn-3/Src-1 complex in the ND7 cells and there was even less effect on this promoter in the BHK21 cells [20].
  • Our results suggest that the 50-kDa 12(S)-HETE binding protein is a receptor that may signal through interaction with a nuclear receptor coactivator protein [21].

Regulatory relationships of Ncoa1


Other interactions of Ncoa1

  • These results suggest that the physiological role of SRC-3 is different from that of SRC-1 and prove the diversity among coactivator family members [24].
  • Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice [9].
  • PPARgamma and PBP are expressed in the transitional epithelium of urinary bladder and in brown adipose tissue, but not SRC-1 [13].
  • PPARgamma and PBP expression overlapped in the brown fat and urogenital sinus at stage E15.5 of embryogenesis, whereas SRC-1 expression occurred mostly in neuroepithelium and cartilage between stages E9.5 and E13.5 of embryogenesis [13].
  • Thus, the present studies show that a coactivator such as SRC-1 could modulate the in vivo action of TR beta mutants in a tissue-dependent manner [2].

Analytical, diagnostic and therapeutic context of Ncoa1


  1. Regulation of expression of thyroid hormone receptor isoforms and coactivators in liver and heart by thyroid hormone. Sadow, P.M., Chassande, O., Koo, E.K., Gauthier, K., Samarut, J., Xu, J., O'Malley, B.W., Weiss, R.E. Mol. Cell. Endocrinol. (2003) [Pubmed]
  2. Modulation by steroid receptor coactivator-1 of target-tissue responsiveness in resistance to thyroid hormone. Kamiya, Y., Zhang, X.Y., Ying, H., Kato, Y., Willingham, M.C., Xu, J., O'Malley, B.W., Cheng, S.Y. Endocrinology (2003) [Pubmed]
  3. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Picard, F., Géhin, M., Annicotte, J., Rocchi, S., Champy, M.F., O'Malley, B.W., Chambon, P., Auwerx, J. Cell (2002) [Pubmed]
  4. Mouse steroid receptor coactivator-1 is not essential for peroxisome proliferator-activated receptor alpha-regulated gene expression. Qi, C., Zhu, Y., Pan, J., Yeldandi, A.V., Rao, M.S., Maeda, N., Subbarao, V., Pulikuri, S., Hashimoto, T., Reddy, J.K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Xu, J., Qiu, Y., DeMayo, F.J., Tsai, S.Y., Tsai, M.J., O'Malley, B.W. Science (1998) [Pubmed]
  6. Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1. Tremblay, A., Tremblay, G.B., Labrie, F., Giguère, V. Mol. Cell (1999) [Pubmed]
  7. Large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter. Müller, W.G., Walker, D., Hager, G.L., McNally, J.G. J. Cell Biol. (2001) [Pubmed]
  8. SRC-1 is necessary for skeletal responses to sex hormones in both males and females. Yamada, T., Kawano, H., Sekine, K., Matsumoto, T., Fukuda, T., Azuma, Y., Itaka, K., Chung, U.I., Chambon, P., Nakamura, K., Kato, S., Kawaguchi, H. J. Bone Miner. Res. (2004) [Pubmed]
  9. Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice. Ye, X., Han, S.J., Tsai, S.Y., DeMayo, F.J., Xu, J., Tsai, M.J., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Steroid receptor coactivator 2 is critical for progesterone-dependent uterine function and mammary morphogenesis in the mouse. Mukherjee, A., Soyal, S.M., Fernandez-Valdivia, R., Gehin, M., Chambon, P., Demayo, F.J., Lydon, J.P., O'Malley, B.W. Mol. Cell. Biol. (2006) [Pubmed]
  11. Role of the steroid receptor coactivator SRC-3 in cell growth. Zhou, G., Hashimoto, Y., Kwak, I., Tsai, S.Y., Tsai, M.J. Mol. Cell. Biol. (2003) [Pubmed]
  12. The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are regulated by CARM1-dependent methylation. Naeem, H., Cheng, D., Zhao, Q., Underhill, C., Tini, M., Bedford, M.T., Torchia, J. Mol. Cell. Biol. (2007) [Pubmed]
  13. Differential expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivators steroid receptor coactivator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse. Jain, S., Pulikuri, S., Zhu, Y., Qi, C., Kanwar, Y.S., Yeldandi, A.V., Rao, M.S., Reddy, J.K. Am. J. Pathol. (1998) [Pubmed]
  14. Steroid receptor coactivator (SRC)-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor. Han, S.J., DeMayo, F.J., Xu, J., Tsai, S.Y., Tsai, M.J., O'Malley, B.W. Mol. Endocrinol. (2006) [Pubmed]
  15. SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells. Nishihara, E., Yoshida-Komiya, H., Chan, C.S., Liao, L., Davis, R.L., O'Malley, B.W., Xu, J. J. Neurosci. (2003) [Pubmed]
  16. Steroid receptor coactivator-1-deficient mice exhibit altered hypothalamic-pituitary-adrenal axis function. Winnay, J.N., Xu, J., O'Malley, B.W., Hammer, G.D. Endocrinology (2006) [Pubmed]
  17. Chromatin-related properties of CBP fused to MLL generate a myelodysplastic-like syndrome that evolves into myeloid leukemia. Lavau, C., Du, C., Thirman, M., Zeleznik-Le, N. EMBO J. (2000) [Pubmed]
  18. Selective recruitment of p160 coactivators on glucocorticoid-regulated promoters in Schwann cells. Grenier, J., Trousson, A., Chauchereau, A., Amazit, L., Lamirand, A., Leclerc, P., Guiochon-Mantel, A., Schumacher, M., Massaad, C. Mol. Endocrinol. (2004) [Pubmed]
  19. The nuclear receptor Ftz-F1 and homeodomain protein Ftz interact through evolutionarily conserved protein domains. Yussa, M., Löhr, U., Su, K., Pick, L. Mech. Dev. (2001) [Pubmed]
  20. Functional interaction between Brn-3a and Src-1 co-activates Brn-3a-mediated transactivation. Dennis, J.H., Budhram-Mahadeo, V., Latchman, D.S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  21. A 12(S)-hydroxyeicosatetraenoic acid receptor interacts with steroid receptor coactivator-1. Kurahashi, Y., Herbertsson, H., Söderström, M., Rosenfeld, M.G., Hammarström, S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  22. cAMP-dependent protein kinase regulates ubiquitin-proteasome-mediated degradation and subcellular localization of the nuclear receptor coactivator GRIP1. Hoang, T., Fenne, I.S., Cook, C., Børud, B., Bakke, M., Lien, E.A., Mellgren, G. J. Biol. Chem. (2004) [Pubmed]
  23. Null mutation of peroxisome proliferator-activated receptor-interacting protein in mammary glands causes defective mammopoiesis. Qi, C., Kashireddy, P., Zhu, Y.T., Rao, S.M., Zhu, Y.J. J. Biol. Chem. (2004) [Pubmed]
  24. The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development. Xu, J., Liao, L., Ning, G., Yoshida-Komiya, H., Deng, C., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  25. The genomic analysis of the impact of steroid receptor coactivators ablation on hepatic metabolism. Jeong, J.W., Kwak, I., Lee, K.Y., White, L.D., Wang, X.P., Brunicardi, F.C., O'malley, B.W., Demayo, F.J. Mol. Endocrinol. (2006) [Pubmed]
  26. Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc9. Yokota, K., Shibata, H., Kurihara, I., Kobayashi, S., Suda, N., Murai-Takeda, A., Saito, I., Kitagawa, H., Kato, S., Saruta, T., Itoh, H. J. Biol. Chem. (2007) [Pubmed]
  27. Effects of loss of steroid receptor coactivator-1 on the skeletal response to estrogen in mice. Mödder, U.I., Sanyal, A., Kearns, A.E., Sibonga, J.D., Nishihara, E., Xu, J., O'Malley, B.W., Ritman, E.L., Riggs, B.L., Spelsberg, T.C., Khosla, S. Endocrinology (2004) [Pubmed]
  28. Expression of steroid receptor coactivator-1 mRNA in the developing mouse embryo: a possible role in olfactory epithelium development. Misiti, S., Koibuchi, N., Bei, M., Farsetti, A., Chin, W.W. Endocrinology (1999) [Pubmed]
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