Nuclear receptor coactivator 2

Last updated
NCOA2
PDB 1gwq EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NCOA2 , GRIP1, KAT13C, NCoA-2, SRC2, TIF2, bHLHe75, nuclear receptor coactivator 2
External IDs OMIM: 601993 MGI: 1276533 HomoloGene: 4768 GeneCards: NCOA2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001077695
NM_008678
NM_001302702

RefSeq (protein)

NP_001289631
NP_032704

Location (UCSC) Chr 8: 70.11 – 70.4 Mb Chr 1: 13.14 – 13.37 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).

Function

NCoA-2 is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA2 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA2 in turn acetylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA2 assists nuclear receptors in the upregulation of DNA expression. [5] [6]

GRIP1 is a transcriptional co-activator of the glucocorticoid receptor and interferon regulatory factor 1 (IRF1). [7]

Interactions

Nuclear receptor coactivator 2 has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

<span class="mw-page-title-main">EP300</span> Protein-coding gene in the species Homo sapiens

Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.

In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription. In humans several dozen to several hundred coregulators are known, depending on the level of confidence with which the characterisation of a protein as a coregulator can be made. One class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP dependent class modifies the conformation of chromatin.

<span class="mw-page-title-main">Aryl hydrocarbon receptor nuclear translocator</span> Protein-coding gene in the species Homo sapiens

The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL–ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.

<span class="mw-page-title-main">Nuclear receptor coactivator 1</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 1 (NCOA1), also called steroid receptor coactivator-1 (SRC-1), is a transcriptional coregulatory protein that contains several nuclear receptor–interacting domains and possesses intrinsic histone acetyltransferase activity. It is encoded by the gene NCOA1.

<span class="mw-page-title-main">Nuclear receptor coactivator 3</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene. NCOA3 is also frequently called 'amplified in breast 1' (AIB1), steroid receptor coactivator-3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1).

<span class="mw-page-title-main">Nuclear receptor co-repressor 1</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the NCOR1 gene.

<span class="mw-page-title-main">Retinoid X receptor alpha</span> Protein-coding gene in the species Homo sapiens

Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.

<span class="mw-page-title-main">TGFB1I1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta-1-induced transcript 1 protein is a protein that in humans is encoded by the TGFB1I1 gene. Often put together with and studied alongside TGFB1I1 is the mouse homologue HIC-5. As the name suggests, TGFB1I1 is an induced form of the larger family of TGFB1. Studies suggest TGFB1I1 plays a role in processes of cell growth, proliferation, migration, differentiation and senescence. TGFB1I1 is most localized at focal adhesion complexes of cells, although it may be found active in the cytosol, nucleus and cell membrane as well.

<span class="mw-page-title-main">FHL2</span> Protein-coding gene in the species Homo sapiens

Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the FHL2 gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.

<span class="mw-page-title-main">NRIP1</span> Protein-coding gene in the species Homo sapiens

Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.

<span class="mw-page-title-main">Serum response factor</span> Mammalian protein found in Homo sapiens

Serum response factor, also known as SRF, is a transcription factor protein.

<span class="mw-page-title-main">COUP-TFII</span> Protein found in humans

COUP-TFII, also known as NR2F2 is a protein that in humans is encoded by the NR2F2 gene. The COUP acronym stands for chicken ovalbumin upstream promoter.

<span class="mw-page-title-main">MED1</span> Protein-coding gene in the species Homo sapiens

Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the MED1 gene. MED1 functions as a nuclear receptor coactivator.

<span class="mw-page-title-main">NCOA6</span> Protein-coding gene in the species Homo sapiens

Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.

<span class="mw-page-title-main">MED14</span> Protein-coding gene in humans

Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene.

<span class="mw-page-title-main">TRIM24</span> Protein-coding gene in the species Homo sapiens

Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the TRIM24 gene.

<span class="mw-page-title-main">GRIP1 (gene)</span> Protein-coding gene in the species Homo sapiens

Glutamate receptor-interacting protein 1 is a protein that in humans is encoded by the GRIP1 gene.

<span class="mw-page-title-main">RNF14</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase RNF14 is an enzyme that in humans is encoded by the RNF14 gene.

Nuclear receptor coregulators are a class of transcription coregulators that have been shown to be involved in any aspect of signaling by any member of the nuclear receptor superfamily. A comprehensive database of coregulators for nuclear receptors and other transcription factors was previously maintained at the Nuclear Receptor Signaling Atlas website which has since been replaced by the Signaling Pathways Project website.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000140396 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000005886 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Voegel JJ, Heine MJ, Zechel C, Chambon P, Gronemeyer H (1996). "TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors". EMBO J. 15 (14): 3667–75. doi:10.1002/j.1460-2075.1996.tb00736.x. PMC   452006 . PMID   8670870.
  6. Hong H, Kohli K, Garabedian MJ, Stallcup MR (1997). "GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors". Mol Cell Biol. 17 (5): 2735–44. doi:10.1128/MCB.17.5.2735. PMC   232124 . PMID   9111344.
  7. Bhandare R, Damera G, Banerjee A, Flammer JR, Keslacy S, Rogatsky I, Panettieri RA, Amrani Y, Tliba O (January 2010). "Glucocorticoid receptor interacting protein-1 restores glucocorticoid responsiveness in steroid-resistant airway structural cells". Am. J. Respir. Cell Mol. Biol. 42 (1): 9–15. doi:10.1165/rcmb.2009-0239RC. PMC   2809222 . PMID   19805480.
  8. Song LN, Coghlan M, Gelmann EP (2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. 18 (1): 70–85. doi: 10.1210/me.2003-0189 . PMID   14593076.
  9. Ishitani K, Yoshida T, Kitagawa H, Ohta H, Nozawa S, Kato S (2003). "p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor". Biochem. Biophys. Res. Commun. 306 (3): 660–5. doi:10.1016/S0006-291X(03)01021-0. PMID   12810069.
  10. Wang Q, Udayakumar TS, Vasaitis TS, Brodie AM, Fondell JD (2004). "Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells". J. Biol. Chem. 279 (17): 17319–28. doi: 10.1074/jbc.M400970200 . PMID   14966121.
  11. 1 2 3 He B, Wilson EM (2003). "Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs". Mol. Cell. Biol. 23 (6): 2135–50. doi:10.1128/MCB.23.6.2135-2150.2003. PMC   149467 . PMID   12612084.
  12. Bai S, He B, Wilson EM (2005). "Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the interdomain interaction". Mol. Cell. Biol. 25 (4): 1238–57. doi:10.1128/MCB.25.4.1238-1257.2005. PMC   548016 . PMID   15684378.
  13. Beischlag TV, Wang S, Rose DW, Torchia J, Reisz-Porszasz S, Muhammad K, Nelson WE, Probst MR, Rosenfeld MG, Hankinson O (2002). "Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex". Mol. Cell. Biol. 22 (12): 4319–33. doi:10.1128/MCB.22.12.4319-4333.2002. PMC   133867 . PMID   12024042.
  14. Rodriguez M, Yu X, Chen J, Songyang Z (2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi: 10.1074/jbc.C300407200 . PMID   14578343.
  15. Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA (2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946–9. PMID   11085509.
  16. 1 2 3 4 Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (2001). "A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA". EMBO J. 20 (6): 1341–52. doi:10.1093/emboj/20.6.1341. PMC   145523 . PMID   11250900.
  17. 1 2 Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell. 113 (7): 905–17. doi: 10.1016/S0092-8674(03)00436-7 . PMID   12837248.
  18. Wärnmark A, Treuter E, Gustafsson JA, Hubbard RE, Brzozowski AM, Pike AC (2002). "Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha". J. Biol. Chem. 277 (24): 21862–8. doi: 10.1074/jbc.M200764200 . PMID   11937504.
  19. Fenne IS, Hoang T, Hauglid M, Sagen JV, Lien EA, Mellgren G (2008). "Recruitment of coactivator glucocorticoid receptor interacting protein 1 to an estrogen receptor transcription complex is regulated by the 3',5'-cyclic adenosine 5'-monophosphate-dependent protein kinase". Endocrinology. 149 (9): 4336–45. doi: 10.1210/en.2008-0037 . PMID   18499756.
  20. Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. 15 (4): 501–11. doi: 10.1210/mend.15.4.0624 . PMID   11266503.
  21. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE (2002). "Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition". Cell. 110 (1): 93–105. doi: 10.1016/S0092-8674(02)00817-6 . PMID   12151000.
  22. Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pagès C, Streuli M, Weinberg RJ, Sheng M (2002). "Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting". Neuron. 34 (1): 39–52. doi: 10.1016/S0896-6273(02)00640-2 . PMID   11931740.
  23. Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. 275 (43): 33201–4. doi: 10.1074/jbc.C000517200 . PMID   10944516.
  24. 1 2 Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN (2001). "Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription". J. Biol. Chem. 276 (44): 40614–20. doi: 10.1074/jbc.M106263200 . PMID   11514567.
  25. Lee WY, Noy N (2002). "Interactions of RXR with coactivators are differentially mediated by helix 11 of the receptor's ligand binding domain". Biochemistry. 41 (8): 2500–8. doi:10.1021/bi011764+. PMID   11851396.
  26. Herdick M, Steinmeyer A, Carlberg C (2000). "Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators". J. Biol. Chem. 275 (22): 16506–12. doi: 10.1074/jbc.M910000199 . PMID   10748178.

Further reading