Gene Symbol: Ncoa2
Description: nuclear receptor coactivator 2
Alias: Tif2, nuclear receptor coactivator 2, NCoA-2, transcriptional intermediary factor 2
Species: rat
Products:     Ncoa2

Top Publications

  1. Chmelar R, Buchanan G, Need E, Tilley W, Greenberg N. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer. 2007;120:719-33 pubmed
  2. Yang J, Fuller P. Interactions of the mineralocorticoid receptor--within and without. Mol Cell Endocrinol. 2012;350:196-205 pubmed publisher
    ..This review will discuss the current understanding of interactions involving the MR and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic targets. ..
  3. Konno T, Graham A, Rempel L, Ho Chen J, Alam S, Bu P, et al. Subfertility linked to combined luteal insufficiency and uterine progesterone resistance. Endocrinology. 2010;151:4537-50 pubmed publisher
    ..levels for the P4 receptor (Pgr), a P4 receptor chaperone (Fkbp4), and P4 receptor coactivators (Ncoa1 and Ncoa2)...
  4. Winnay J, Hammer G. Adrenocorticotropic hormone-mediated signaling cascades coordinate a cyclic pattern of steroidogenic factor 1-dependent transcriptional activation. Mol Endocrinol. 2006;20:147-66 pubmed
    ..In addition, the current study demonstrates that specific enzymatic activities are capable of regulating distinct facets of a highly ordered transcriptional response...
  5. Apostolakis E, Ramamurphy M, Zhou D, Onate S, O Malley B. Acute disruption of select steroid receptor coactivators prevents reproductive behavior in rats and unmasks genetic adaptation in knockout mice. Mol Endocrinol. 2002;16:1511-23 pubmed
    ..In the genetic, but not acute, absence of SRC-1, up-regulation of SRC-2 serves as a critical adaptive mechanism during female development. ..
  6. Atkins G, Hu X, Guenther M, Rachez C, Freedman L, Lazar M. Coactivators for the orphan nuclear receptor RORalpha. Mol Endocrinol. 1999;13:1550-7 pubmed
    ..GRIP-1 functioned as a coactivator for the RORalpha both in yeast and in mammalian cells. Thus, GRIP-1 is the first proven coactivator for RORalpha. ..
  7. Cho S, Kagan B, Blackford J, Szapary D, Simons S. Glucocorticoid receptor ligand binding domain is sufficient for the modulation of glucocorticoid induction properties by homologous receptors, coactivator transcription intermediary factor 2, and Ubc9. Mol Endocrinol. 2005;19:290-311 pubmed
    ..They also reveal mechanistic differences both among individual modulators and between the ability of the same factors to regulate the total amount of gene expression. ..
  8. Heemers H, Schmidt L, Kidd E, Raclaw K, Regan K, Tindall D. Differential regulation of steroid nuclear receptor coregulator expression between normal and neoplastic prostate epithelial cells. Prostate. 2010;70:959-70 pubmed publisher
    ..These findings emphasize the important potential of targeting the mechanisms regulating coregulator expression for therapeutic intervention in PCa. ..
  9. Jonason A, Baker S, Sweasy J. Interaction of DNA polymerase beta with GRIP1 during meiosis. Chromosoma. 2001;110:402-10 pubmed
    ..Our findings are consistent with the possibility that GRIP1 acts as a scaffold to promote interaction between proteins that function during meiosis. ..

More Information


  1. Hong H, Kohli K, Trivedi A, Johnson D, Stallcup M. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc Natl Acad Sci U S A. 1996;93:4948-52 pubmed
    ..Thus, in yeast, GRIP1 can serve as a coactivator, potentiating the transactivation functions in steroid receptor HBDs, possibly by acting as a bridge between HBDs of the receptors and the basal transcription machinery. ..
  2. Kruse S, Suino Powell K, Zhou X, Kretschman J, Reynolds R, Vonrhein C, et al. Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor. PLoS Biol. 2008;6:e227 pubmed publisher
  3. Wang L, Tankersley L, Tang M, Potter J, Mezey E. Regulation of alpha 2(I) collagen expression in stellate cells by retinoic acid and retinoid X receptors through interactions with their cofactors. Arch Biochem Biophys. 2004;428:92-8 pubmed
  4. Deguchi K, Ayton P, Carapeti M, Kutok J, Snyder C, Williams I, et al. MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. Cancer Cell. 2003;3:259-71 pubmed
    The MOZ-TIF2 fusion is associated with acute myeloid leukemia (AML) with inv(8)(p11q13). MOZ is a MYST family histone acetyltransferase (HAT), whereas TIF2 is a nuclear receptor coactivator that associates with CREB binding protein (CBP)...
  5. Lin C, Hare B, Wagner G, Harrison S, Maniatis T, Fraenkel E. A small domain of CBP/p300 binds diverse proteins: solution structure and functional studies. Mol Cell. 2001;8:581-90 pubmed
    ..We demonstrate the significance both in vitro and in vivo of interactions between IBiD and a number of diverse partners. Thus, IBiD is an important contributor to signal integration by CBP and p300. ..
  6. Stashi E, Lanz R, Mao J, Michailidis G, Zhu B, Kettner N, et al. SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm. Cell Rep. 2014;6:633-45 pubmed publisher
    ..Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circadian clock. ..
  7. Martinez de Arrieta C, Koibuchi N, Chin W. Coactivator and corepressor gene expression in rat cerebellum during postnatal development and the effect of altered thyroid status. Endocrinology. 2000;141:1693-8 pubmed
    ..To examine this hypothesis, we cloned rat complementary DNA fragments corresponding to coactivators (SRC1, TIF2 and TRAM1) and corepressors (N-CoR and SMRT), and studied the ontogenic changes in their corresponding messenger ..
  8. Yore M, Im D, Webb L, Zhao Y, Chadwick J, Molenda Figueira H, et al. Steroid receptor coactivator-2 expression in brain and physical associations with steroid receptors. Neuroscience. 2010;169:1017-28 pubmed publisher
    ..Finally, SRC-2 from brain interacts with ER and PR in a subtype-specific manner, which may contribute to the functional differences of these steroid receptor subtypes in brain. ..
  9. Barbieri C, Bangma C, Bjartell A, Catto J, Culig Z, Gronberg H, et al. The mutational landscape of prostate cancer. Eur Urol. 2013;64:567-76 pubmed publisher
  10. Xie H, Sadim M, Sun Z. RORgammat recruits steroid receptor coactivators to ensure thymocyte survival. J Immunol. 2005;175:3800-9 pubmed
    ..Our results thus clearly demonstrate that RORgammat recruits SRCs to impose a gene expression pattern required to expand the life span of thymocytes in vivo, which increases the opportunities for assembling a functional TCR. ..
  11. Trousson A, Grenier J, Fonte C, Massaad Massade L, Schumacher M, Massaad C. Recruitment of the p160 coactivators by the glucocorticoid receptor: dependence on the promoter context and cell type but not hypoxic conditions. J Steroid Biochem Mol Biol. 2007;104:305-11 pubmed
    ..Altogether, these results reveal that the p160s are not interchangeable and that their recruitment by the GR is a multiparametric event. ..
  12. Nicolaides N, Galata Z, Kino T, Chrousos G, Charmandari E. The human glucocorticoid receptor: molecular basis of biologic function. Steroids. 2010;75:1-12 pubmed publisher
    ..This review summarizes the basic aspects of the structure and actions of the human (h) GR, and the molecular basis of its biologic functions. ..
  13. Chopra A, Louet J, Saha P, An J, DeMayo F, Xu J, et al. Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science. 2008;322:1395-9 pubmed publisher
    ..In addition, SRC-2 ablation, in both a whole-body and liver-specific manner, resulted in a Von Gierke's disease phenotype in mice. Our results position SRC-2 as a critical regulator of mammalian glucose production. ..
  14. Leers J, Treuter E, Gustafsson J. Mechanistic principles in NR box-dependent interaction between nuclear hormone receptors and the coactivator TIF2. Mol Cell Biol. 1998;18:6001-13 pubmed the screening for and cloning of a peroxisome proliferator receptor-interacting protein, the rat homolog of TIF2. By sequence comparison with the related coactivator SRC-1, we identified three short conserved motifs (NR boxes) ..
  15. Li R, Serwanski D, Miralles C, Li X, Charych E, Riquelme R, et al. GRIP1 in GABAergic synapses. J Comp Neurol. 2005;488:11-27 pubmed
    ..The results suggest that GRIP1 splice forms might play important roles in brain GABAergic synapses. ..
  16. Wansa K, Harris J, Yan G, Ordentlich P, Muscat G. The AF-1 domain of the orphan nuclear receptor NOR-1 mediates trans-activation, coactivator recruitment, and activation by the purine anti-metabolite 6-mercaptopurine. J Biol Chem. 2003;278:24776-90 pubmed
    ..We hypothesize that the NR4A subgroup mediates the genotoxic stress response and suggest that this subgroup may function as sensors that respond to genotoxicity. ..
  17. Hong C, Hsueh Y. CASK associates with glutamate receptor interacting protein and signaling molecules. Biochem Biophys Res Commun. 2006;351:771-6 pubmed
    ..In conclusion, our study suggests that the CASK protein complex not only functions as a scaffold but also recruits signaling molecules and may contribute to signal transduction. ..
  18. Rochette Egly C, Germain P. Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs). Nucl Recept Signal. 2009;7:e005 pubmed publisher
    ..Here we will review these mechanisms, focusing on how kinase signaling and the proteasome pathway cooperate to influence the dynamics of RAR transcriptional activity. ..
  19. Watt K, Jess T, Kelly S, Price N, McEwan I. Induced alpha-helix structure in the aryl hydrocarbon receptor transactivation domain modulates protein-protein interactions. Biochemistry. 2005;44:734-43 pubmed
    ..transcription machinery [TATA-binding protein (TBP), TAF4, and TAF6] as well as the coactivator proteins SRC-1a and TIF2. The binding site for TBP mapped to the acidic subdomain, while SRC-1a bound preferentially to the Q-rich sequence...
  20. Khan S, Awasthi S, Guo C, Goswami D, Ling J, Griffin P, et al. Binding of the N-terminal region of coactivator TIF2 to the intrinsically disordered AF1 domain of the glucocorticoid receptor is accompanied by conformational reorganizations. J Biol Chem. 2012;287:44546-60 pubmed publisher
    ..Earlier, we reported an N-terminal fragment of the p160 coactivator TIF2, called TIF2.0, that binds the GR N-terminal domain and alters GR transcriptional activity...
  21. Igarashi Migitaka J, Takeshita A, Koibuchi N, Yamada S, Ohtani Kaneko R, Hirata K. Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis. Eur J Endocrinol. 2005;153:595-604 pubmed
    ..Such coactivators include three members of the 160 kDa proteins (p160s): SRC-1, TIF2/GRIP1, and p/CIP/RAC3/ACTR/AIB1/TRAM-1...
  22. Huang S, Huang C, Wang W, Kang J, Hsu W. The enhancement of nuclear receptor transcriptional activation by a mouse actin-binding protein, alpha actinin 2. J Mol Endocrinol. 2004;32:481-96 pubmed
    ..These findings suggested that mACTN2 might play an important role in GRIP1-induced NR coactivator functions. ..
  23. Yu G, Zerucha T, Ekker M, Rubenstein J. Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins. Brain Res Dev Brain Res. 2001;130:217-30 pubmed
    ..Furthermore, these results suggest a link between glutamate receptors, PDZ proteins and the DLX transcription factors, all of which are co-expressed in the developing basal ganglia. ..
  24. Chung H, Xia J, Scannevin R, Zhang X, Huganir R. Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci. 2000;20:7258-67 pubmed
    ..These results suggest that GluR2 phosphorylation of serine-880 may be important in the regulation of the AMPA receptor internalization during synaptic plasticity. ..
  25. Vella K, Ramadoss P, Costa e Sousa R, Astapova I, Ye F, Holtz K, et al. Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors. Mol Cell Biol. 2014;34:1564-75 pubmed publisher
    ..Thus, T(3) targets require a critical balance between NCoR1 and SRC-1. Furthermore, replacement of NCoR1 with NCoR?ID corrects RTH in Src-1(-/-) mice through increased SRC-2 recruitment to T(3) target genes. ..
  26. Flajollet S, Lefebvre B, Cudejko C, Staels B, Lefebvre P. The core component of the mammalian SWI/SNF complex SMARCD3/BAF60c is a coactivator for the nuclear retinoic acid receptor. Mol Cell Endocrinol. 2007;270:23-32 pubmed
    ..This coactivating property is dependent on SRC1 expression, showing that HATs and SWI/SNF cooperate in this retinoid-controlled transcriptional process. ..
  27. Hall J, McDonnell D. Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting. Mol Interv. 2005;5:343-57 pubmed
    ..This review also describes current efforts aimed at developing pharmaceutical agents that target ER-cofactor interactions as therapeutics for estrogen-associated pathologies. ..
  28. Kim J, Stallcup M. Role of the coiled-coil coactivator (CoCoA) in aryl hydrocarbon receptor-mediated transcription. J Biol Chem. 2004;279:49842-8 pubmed
    ..Our data support a physiological role for CoCoA as a transcriptional coactivator in AHR/ARNT-mediated transcription. ..
  29. Jenkins B, Pullen C, Darimont B. Novel glucocorticoid receptor coactivator effector mechanisms. Trends Endocrinol Metab. 2001;12:122-6 pubmed
    ..The emerging picture shows coactivators as flexible, but precise, coordinators of complex and dynamic networks, in which transcriptional regulation by GR and other NRs is linked to other signaling pathways. ..