Genomes and Genes
Gene Symbol: Ncoa2
Description: nuclear receptor coactivator 2
Alias: D1Ertd433e, GRIP-1, Grip1, KAT13C, NCoA-2, SRC-2, TIF2, bHLHe75, nuclear receptor coactivator 2, glucocorticoid receptor interacting protein 1, steroid receptor coactivator 2, transcriptional intermediary factor 2
- Mukherjee A, Soyal S, Fernandez Valdivia R, Gehin M, Chambon P, DeMayo F, et al. Steroid receptor coactivator 2 is critical for progesterone-dependent uterine function and mammary morphogenesis in the mouse. Mol Cell Biol. 2006;26:6571-83 pubmed..We conclude that SRC-2 is appropriated by PR in a subset of transcriptional cascades obligate for normal uterine and mammary morphogenesis and function. ..
- Mark M, Yoshida Komiya H, Gehin M, Liao L, Tsai M, O Malley B, et al. Partially redundant functions of SRC-1 and TIF2 in postnatal survival and male reproduction. Proc Natl Acad Sci U S A. 2004;101:4453-8 pubmedBoth SRC-1 and TIF2 are members of the p160 steroid receptor coactivator family. Genetic analyses have shown that inactivation of TIF2, but not SRC-1, reduces postnatal survival, growth, and male reproductive function...
- Kim J, Li H, Stallcup M. CoCoA, a nuclear receptor coactivator which acts through an N-terminal activation domain of p160 coactivators. Mol Cell. 2003;12:1537-49 pubmed..Moreover, CoCoA cooperated synergistically with GRIP1, CARM1, and p300 to enhance ER-mediated transcription...
- Gehin M, Mark M, Dennefeld C, Dierich A, Gronemeyer H, Chambon P. The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP. Mol Cell Biol. 2002;22:5923-37 pubmed..Although the functions of hTIF2 and of its mouse homolog (GRIP1 or mTIF2) have been clearly established in vitro, their physiological role remains elusive...
- 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. ..
- Duteil D, Chambon C, Ali F, Malivindi R, Zoll J, Kato S, et al. The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal muscles. Cell Metab. 2010;12:496-508 pubmed publisherThe two p160 transcriptional coregulator family members SRC-1 and TIF2 have important metabolic functions in white and brown adipose tissues as well as in the liver...
- Picard F, Gehin M, Annicotte J, Rocchi S, Champy M, O Malley B, et al. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell. 2002;111:931-41 pubmedWe have explored the effects of two members of the p160 coregulator family on energy homeostasis. TIF2-/- mice are protected against obesity and display enhanced adaptive thermogenesis, whereas SRC-1-/- mice are prone to obesity due to ..
- Wang Z, Rose D, Hermanson O, Liu F, Herman T, Wu W, et al. Regulation of somatic growth by the p160 coactivator p/CIP. Proc Natl Acad Sci U S A. 2000;97:13549-54 pubmed..The actions of p/CIP are therefore required for full expression of a subset of genes critical for regulating physiological patterns of somatic growth in mammals. ..
- Weiss R, Gehin M, Xu J, Sadow P, O Malley B, Chambon P, et al. Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: evidence for haploinsufficiency. Endocrinology. 2002;143:1554-7 pubmed..This work demonstrates gene dosage effect in nuclear coactivators manifesting as haploinsufficiency and functional redundancy of SRC-1 and TIF-2. ..
- 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..DIP2 appears to be an alternatively spliced form of GRIP1, a protein known to bind AMPA glutamate receptors via PDZ domains. Thus, we named it GRIP1b...
- Fleet T, Stashi E, Zhu B, Rajapakshe K, Marcelo K, Kettner N, et al. Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology. J Biol Rhythms. 2016;31:443-60 pubmed publisher..Collectively, our studies demonstrate that SRC-2 provides an essential link between the behavioral activities influenced by light cues and the metabolic homeostasis maintained by the liver. ..
- 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. ..
- Gupte R, Muse G, Chinenov Y, Adelman K, Rogatsky I. Glucocorticoid receptor represses proinflammatory genes at distinct steps of the transcription cycle. Proc Natl Acad Sci U S A. 2013;110:14616-21 pubmed publisher..In conjunction with its corepressor GR-interacting protein-1 (GRIP1), GR tethers to the DNA-bound activator protein-1 and NF-?B and represses transcription of their target ..
- York B, Reineke E, Sagen J, Nikolai B, Zhou S, Louet J, et al. Ablation of steroid receptor coactivator-3 resembles the human CACT metabolic myopathy. Cell Metab. 2012;15:752-63 pubmed publisher..Moreover, these findings allow us to consider platform coactivators such as the SRCs as potential contributors to syndromes such as CACT deficiency, previously considered as monogenic. ..
- Hong H, Yang L, Stallcup M. Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3. J Biol Chem. 1999;274:22618-26 pubmed..3 (ERR3), was identified by yeast two-hybrid screening, using the transcriptional coactivator glucocorticoid receptor interacting protein 1 (GRIP1) as bait...
- 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. ..
- Schmidt M, Oitzl M, Steenbergen P, Lachize S, Wurst W, Muller M, et al. Ontogeny of steroid receptor coactivators in the hippocampus and their role in regulating postnatal HPA axis function. Brain Res. 2007;1174:1-6 pubmed
- Nishihara E, Yoshida Komiya H, Chan C, Liao L, Davis R, O Malley B, et al. SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells. J Neurosci. 2003;23:213-22 pubmed..Disruption of SRC-1 specifically delays the PC development and maturation in early stages and results in moderate motor dysfunction in adulthood. ..
- O Donnell K, Keng V, York B, Reineke E, Seo D, Fan D, et al. A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer. Proc Natl Acad Sci U S A. 2012;109:E1377-86 pubmed publisher..RNAi-mediated knockdown in a liver progenitor cell line further validate three of these genes, Ncoa2/Src-2, Zfx, and Dtnb, as tumor suppressors in liver cancer...
- Teyssier C, Chen D, Stallcup M. Requirement for multiple domains of the protein arginine methyltransferase CARM1 in its transcriptional coactivator function. J Biol Chem. 2002;277:46066-72 pubmed..The complex contains at least one of three p160 coactivators (SRC-1, GRIP1/TIF2, or pCIP/RAC3/ACTR/AIB1/TRAM1), a histone acetyltransferase such as CBP or p300, and the histone ..
- Rollins D, Kharlyngdoh J, Coppo M, Tharmalingam B, Mimouna S, Guo Z, et al. Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages. Nat Commun. 2017;8:1739 pubmed publisher..GR-interacting protein-1 (GRIP1) is a GR corepressor in macrophages, however, whether GRIP1 mediates GR-activated transcription, and what dictates ..
- Min G, Kemper J, Kemper B. Glucocorticoid receptor-interacting protein 1 mediates ligand-independent nuclear translocation and activation of constitutive androstane receptor in vivo. J Biol Chem. 2002;277:26356-63 pubmed..present studies, the interaction of CAR with the p160 coactivator glucocorticoid receptor-interacting protein 1 (GRIP1) was examined in vitro and in vivo...
- 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. ..
- Lee Y, Campbell H, Stallcup M. Developmentally essential protein flightless I is a nuclear receptor coactivator with actin binding activity. Mol Cell Biol. 2004;24:2103-17 pubmed..One important coactivator complex includes a p160 coactivator (e.g., GRIP1, SRC-1, or ACTR) that binds directly to activated NR, the histone acetyltransferase p300 or CBP, and the arginine-..
- Chen S, Loffler K, Chen D, Stallcup M, Muscat G. The coactivator-associated arginine methyltransferase is necessary for muscle differentiation: CARM1 coactivates myocyte enhancer factor-2. J Biol Chem. 2002;277:4324-33 pubmed..This work clearly demonstrates that the arginine methyltransferase CARM1 potentiates myogenesis and supports the positive role of arginine methylation in mammalian differentiation. ..
- Welch C, Xia Y, Hong H, Stallcup M, Lusis A. Localization of the mouse glucocorticoid receptor-interacting protein 1 gene (Grip1) to proximal chromosome 1 by linkage analysis. Mamm Genome. 1997;8:620-1 pubmed
- Yue W, Hassler M, Roe S, Thompson Vale V, Pearl L. Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase. EMBO J. 2007;26:4402-12 pubmed..Together with the absence of specificity subsites in the structure, this suggests an electrostatic sensing mechanism for communicating the modification status of vicinal residues as part of the syntax of the 'histone code.' ..
- Dettman E, Justice M. The zinc finger SET domain gene Prdm14 is overexpressed in lymphoblastic lymphomas with retroviral insertions at Evi32. PLoS ONE. 2008;3:e3823 pubmed publisher..Prdm14 is normally expressed early in embryonic development with the highest expression in undifferentiated embryonic stem (ES) cells. This study implicates Prdm14 as a proto-oncogene involved in lymphoblastic lymphoma formation. ..
- Li Y, Choi M, Cavey G, Daugherty J, Suino K, Kovach A, et al. Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1. Mol Cell. 2005;17:491-502 pubmed..These findings provide evidence that SF-1 is regulated by endogenous ligands and suggest an unexpected relationship between phospholipids and endocrine development and function. ..
- Gao L, Rabbitt E, Condon J, Renthal N, Johnston J, Mitsche M, et al. Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition. J Clin Invest. 2015;125:2808-24 pubmed publisher..These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2-dependent production of SP-A and PAF is crucial for this process. ..
- Huang J, Bi Y, Zhu G, He Y, Su Y, He B, et al. Retinoic acid signalling induces the differentiation of mouse fetal liver-derived hepatic progenitor cells. Liver Int. 2009;29:1569-81 pubmed publisher..RA was further shown to induce glycogen synthesis in HP14.5 cells, an important function of mature hepatocytes. Our results strongly suggest that RA signalling may play an important role in regulating hepatic differentiation. ..
- Jeong J, Lee K, Han S, Aronow B, Lydon J, O Malley B, et al. The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression. Endocrinology. 2007;148:4238-50 pubmedThe role of the p160 steroid receptor coactivator 2 (SRC-2) in the regulation of uterine function and progesterone (P4) signaling was investigated by determining the expression pattern of SRC-2 in the murine uterus during pregnancy and ..
- Stashi E, Wang L, Mani S, York B, O Malley B. Research resource: loss of the steroid receptor coactivators confers neurobehavioral consequences. Mol Endocrinol. 2013;27:1776-87 pubmed publisher..Collectively, these resource data suggest that loss of the SRCs results in behavioral phenotypes, underscoring the importance of understanding both the general and gender-based activity of SRCs in the brain. ..
- Fleet T, Zhang B, Lin F, Zhu B, Dasgupta S, Stashi E, et al. SRC-2 orchestrates polygenic inputs for fine-tuning glucose homeostasis. Proc Natl Acad Sci U S A. 2015;112:E6068-77 pubmed publisher..Herein, we demonstrate that Steroid Receptor Coactivator 2 (SRC-2) orchestrates a hierarchy of nutritionally responsive transcriptional complexes to precisely ..
- Gold D, Baek S, Schork N, Rose D, Larsen D, Sachs B, et al. RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways. Neuron. 2003;40:1119-31 pubmed
- Yoshida H, Miyachi M, Sakamoto K, Ouchi K, Yagyu S, Kikuchi K, et al. PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells. Oncogene. 2014;33:5601-8 pubmed publisher..rhabdomyosarcoma (RMS) and showed that it generates the fusion gene PAX3 (paired box 3)-NCOA2 (nuclear receptor coactivator 2)...
- Puustinen R, Sarvilinna N, Manninen T, Tuohimaa P, Ylikomi T. Localization of glucocorticoid receptor interacting protein 1 in murine tissues using two novel polyclonal antibodies. Eur J Endocrinol. 2001;145:323-33 pubmedb>Glucocorticoid receptor interacting protein 1 (GRIP1) is a coactivator that binds to the nuclear hormone receptors in a ligand-dependent manner and mediates transcriptional activation of the target genes...
- Oda Y, Uchida Y, Moradian S, Crumrine D, Elias P, Bikle D. Vitamin D receptor and coactivators SRC2 and 3 regulate epidermis-specific sphingolipid production and permeability barrier formation. J Invest Dermatol. 2009;129:1367-78 pubmed publisher..In contrast, DRIP silencing had no apparent effect on these processes indicating that the two classes of coactivators are differentially utilized. ..
- Kino T, Chrousos G. Tumor necrosis factor alpha receptor- and Fas-associated FLASH inhibit transcriptional activity of the glucocorticoid receptor by binding to and interfering with its interaction with p160 type nuclear receptor coactivators. J Biol Chem. 2003;278:3023-9 pubmed..we performed yeast two-hybrid screening using the NRB domain of the glucocorticoid receptor-interacting protein 1 (GRIP1) as bait...
- 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 ..
- 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..cDNA library that codes for a novel 812-aa long protein fragment, glucocorticoid receptor-interacting protein 1 (GRIP1), that can interact with the hormone binding domain (HBD) of the glucocorticoid receptor...
- Jimenez Lara A, Heine M, Gronemeyer H. PIAS3 (protein inhibitor of activated STAT-3) modulates the transcriptional activation mediated by the nuclear receptor coactivator TIF2. FEBS Lett. 2002;526:142-6 pubmedPIAS3, a member of the protein inhibitor of activated STAT family, was found to interact in vivo and in vitro with TIF2, a previously described coactivator for nuclear receptors...
- 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...
- Ou Z, Huang Q, Sun K, Wei S, Gong J, Tu B. [Liver X receptor alpha inhibits LPS-induced inflammation by down-regulating IFR3 and GRIP1 in mouse Kupffer cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29:848-51 pubmed..The expressions of LXRalpha, interferon regulatory factor 3 (IRF3) and glucocorticoid receptor interacting protein 1 (GRIP1) in the KCs were detected by Western blotting...
- Sanyal S, Matthews J, Bouton D, Kim H, Choi H, Treuter E, et al. Deoxyribonucleic acid response element-dependent regulation of transcription by orphan nuclear receptor estrogen receptor-related receptor gamma. Mol Endocrinol. 2004;18:312-25 pubmed
- 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. ..
- Ning G, Jurecic V, Baldini A, Xu J. Structure and chromosomal locations of mouse steroid receptor coactivator gene family. In Vitro Cell Dev Biol Anim. 1999;35:481-6 pubmed..This information is important for developing valuable animal models harboring multiple disruptions of the SRC gene family to study their biological functions. ..
- Dasgupta S, Putluri N, Long W, Zhang B, Wang J, Kaushik A, et al. Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis. J Clin Invest. 2015;125:1174-88 pubmed publisher..Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor ..
- Reily M, Pantoja C, Hu X, Chinenov Y, Rogatsky I. The GRIP1:IRF3 interaction as a target for glucocorticoid receptor-mediated immunosuppression. EMBO J. 2006;25:108-17 pubmed..activities of other DNA-bound regulators, activator protein 1 and nuclear factor kappaB, utilizing a p160 GRIP1 as a corepressor...
- Schuler M, Ali F, Metzger E, Chambon P, Metzger D. Temporally controlled targeted somatic mutagenesis in skeletal muscles of the mouse. Genesis. 2005;41:165-70 pubmed..HSA-Cre-ER(T2) mice should be of great value to analyze gene function in skeletal muscles, and to establish animal models of human skeletal muscle disorders. ..
- Chen D, Ma H, Hong H, Koh S, Huang S, Schurter B, et al. Regulation of transcription by a protein methyltransferase. Science. 1999;284:2174-7 pubmedThe p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors...
- Gregory C, Fei X, Ponguta L, He B, Bill H, French F, et al. Epidermal growth factor increases coactivation of the androgen receptor in recurrent prostate cancer. J Biol Chem. 2004;279:7119-30 pubmed..a post-transcriptional increase in the p160 coactivator transcriptional intermediary factor 2/glucocorticoid receptor interacting protein 1 (TIF2/GRIP1)...
- Bochkis I, Schug J, Rubins N, Chopra A, O Malley B, Kaestner K. Foxa2-dependent hepatic gene regulatory networks depend on physiological state. Physiol Genomics. 2009;38:186-95 pubmed publisher..We show that Foxa2 interacts with different transcription factors to achieve gene expression responses appropriate for each physiologic state. ..
- Xia J, Kemper B. Structural determinants of constitutive androstane receptor required for its glucocorticoid receptor interacting protein-1-mediated nuclear accumulation. J Biol Chem. 2005;280:7285-93 pubmed..We have shown that exogenous expression of the p160 coactivator glucocorticoid receptor interacting protein-1 (GRIP1) in hepatocytes in vivo can mediate PB-independent nuclear accumulation of murine CAR (mCAR)...
- Lazaro J, Bailey P, Lassar A. Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation. Genes Dev. 2002;16:1792-805 pubmed
- 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..Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light ..
- Lim H, Moon I, Han K. Transcriptional cofactors exhibit differential preference toward peroxisome proliferator-activated receptors alpha and delta in uterine cells. Endocrinology. 2004;145:2886-95 pubmed
- Grenier J, Trousson A, Chauchereau A, Amazit L, Lamirand A, Leclerc P, et al. Selective recruitment of p160 coactivators on glucocorticoid-regulated promoters in Schwann cells. Mol Endocrinol. 2004;18:2866-79 pubmed..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. ..
- Torchia J, Rose D, Inostroza J, Kamei Y, Westin S, Glass C, et al. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature. 1997;387:677-84 pubmed
- Wu H, Hamamori Y, Xu J, Chang S, Saluna T, Chang M, et al. Nuclear hormone receptor coregulator GRIP1 suppresses, whereas SRC1A and p/CIP coactivate, by domain-specific binding of MyoD. J Biol Chem. 2005;280:3129-37 pubmed..Both SRC1A and p/CIP function as coactivators for MyoD-mediated transcription whereas GRIP1 acts negatively as a (co)repressor...
- 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 pubmedThe p160 coactivators, steroid receptor coactivator 1, glucocorticoid receptor interacting protein 1 (GRIP1) and the activator of thyroid and retinoic acid receptor, have two activation domains, AD1 and AD2, which transmit the activation ..
- Lee Y, Koh S, Zhang X, Cheng X, Stallcup M. Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities. Mol Cell Biol. 2002;22:3621-32 pubmed..The p160 coactivators (e.g., SRC-1, GRIP1, and ACTR) bind directly to activated NR and can recruit a variety of secondary coactivators...