Nuclear receptor coactivator 1

Nuclear receptor coactivator 1
Nuclear receptor coactivator 1

PDB rendering based on 1oj5.
Symbols NCOA1; F-SRC-1; KAT13A; MGC129719; MGC129720; RIP160; SRC1; bHLHe42; bHLHe74
External IDs OMIM602691 MGI1276523 HomoloGene7859 GeneCards: NCOA1 Gene
EC number
RNA expression pattern
PBB GE NCOA1 209106 at tn.png
PBB GE NCOA1 209105 at tn.png
PBB GE NCOA1 209107 x at tn.png
More reference expression data
Species Human Mouse
Entrez 8648 17977
Ensembl ENSG00000084676 ENSMUSG00000020647
UniProt Q15788 Q3U3A3
RefSeq (mRNA) NM_003743.4 NM_010881.2
RefSeq (protein) NP_003734.3 NP_035011.1
Location (UCSC) Chr 2:
24.71 – 24.99 Mb
Chr 12:
4.25 – 4.48 Mb
PubMed search [1] [2]

The nuclear receptor coactivator 1 (NCOA1) is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity (EC NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates histones, which makes downsteam DNA more accessible to transcription. Hence, NCOA1 assists nuclear receptors in the upregulation of DNA expression.[1][2]

NCOA1 is also frequently called steroid receptor coactivator-1 (SRC-1).



Nuclear receptor coactivator 1 has been shown to interact with Thyroid hormone receptor beta,[3][4] CIITA,[5] DDX17,[6] SNW1,[7] Androgen receptor,[8][9][10] STAT3,[11] CREB-binding protein,[12][13] Glucocorticoid receptor,[14][15] Peroxisome proliferator-activated receptor alpha,[16][17] TRIP4,[18] C-Fos,[19][20] STAT6,[21][22] PCAF,[23] PPARGC1A,[24] NFKB1,[19][25] Cyclin D1,[26] Estrogen receptor alpha,[6][12][27][28][29] DDX5[6] and C-jun.[19][20][30]


  1. ^ Onate SA, Tsai SY, Tsai MJ, O'Malley BW (1995). "Sequence and characterization of a coactivator for the steroid hormone receptor superfamily". Science 270 (5240): 1354–7. doi:10.1126/science.270.5240.1354. PMID 7481822. 
  2. ^ Onate SA, Boonyaratanakornkit V, Spencer TE, Tsai SY, Tsai MJ, Edwards DP, O'Malley BW (1998). "The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AF1) and AF2 domains of steroid receptors". J Biol Chem 273 (20): 12101–8. doi:10.1074/jbc.273.20.12101. PMID 9575154. 
  3. ^ Liu, Y; Takeshita A, Misiti S, Chin W W, Yen P M (Oct. 1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology (UNITED STATES) 139 (10): 4197–204. doi:10.1210/en.139.10.4197. ISSN 0013-7227. PMID 9751500. 
  4. ^ Jeyakumar, M; Tanen M R, Bagchi M K (Jun. 1997). "Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor". Mol. Endocrinol. (UNITED STATES) 11 (6): 755–67. doi:10.1210/me.11.6.755. ISSN 0888-8809. PMID 9171239. 
  5. ^ Tzortzakaki, Eleni; Spilianakis Charalambos, Zika Eleni, Kretsovali Androniki, Papamatheakis Joseph (Dec. 2003). "Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways". Mol. Endocrinol. (United States) 17 (12): 2509–18. doi:10.1210/me.2002-0439. ISSN 0888-8809. PMID 12933903. 
  6. ^ a b c Watanabe, M; Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (Mar. 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. (England) 20 (6): 1341–52. doi:10.1093/emboj/20.6.1341. ISSN 0261-4189. PMC 145523. PMID 11250900. 
  7. ^ Zhang, C; Baudino T A, Dowd D R, Tokumaru H, Wang W, MacDonald P N (Nov. 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. (United States) 276 (44): 40614–20. doi:10.1074/jbc.M106263200. ISSN 0021-9258. PMID 11514567. 
  8. ^ Masiello, David; Chen Shao-Yong, Xu Youyuan, Verhoeven Manon C, Choi Eunis, Hollenberg Anthony N, Balk Steven P (Oct. 2004). "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells". Mol. Endocrinol. (United States) 18 (10): 2388–401. doi:10.1210/me.2003-0436. ISSN 0888-8809. PMID 15256534. 
  9. ^ Ueda, Takeshi; Mawji Nasrin R, Bruchovsky Nicholas, Sadar Marianne D (Oct. 2002). "Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells". J. Biol. Chem. (United States) 277 (41): 38087–94. doi:10.1074/jbc.M203313200. ISSN 0021-9258. PMID 12163482. 
  10. ^ Bevan, C L; Hoare S, Claessens F, Heery D M, Parker M G (Dec. 1999). "The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1". Mol. Cell. Biol. (UNITED STATES) 19 (12): 8383–92. ISSN 0270-7306. PMC 84931. PMID 10567563. 
  11. ^ Giraud, Sandrine; Bienvenu Frédéric, Avril Sylvie, Gascan Hugues, Heery David M, Coqueret Olivier (Mar. 2002). "Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a". J. Biol. Chem. (United States) 277 (10): 8004–11. doi:10.1074/jbc.M111486200. ISSN 0021-9258. PMID 11773079. 
  12. ^ a b Sheppard, H M; Harries J C, Hussain S, Bevan C, Heery D M (Jan. 2001). "Analysis of the steroid receptor coactivator 1 (SRC1)-CREB binding protein interaction interface and its importance for the function of SRC1". Mol. Cell. Biol. (UNITED STATES) 21 (1): 39–50. doi:10.1128/MCB.21.1.39-50.2001. ISSN 0270-7306. PMC 86566. PMID 11113179. 
  13. ^ Wu, Ray-Chang; Qin Jun, Hashimoto Yoshihiro, Wong Jiemin, Xu Jianming, Tsai Sophia Y, Tsai Ming-Jer, O'Malley Bert W (May. 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase". Mol. Cell. Biol. (United States) 22 (10): 3549–61. doi:10.1128/MCB.22.10.3549-3561.2002. ISSN 0270-7306. PMC 133790. PMID 11971985. 
  14. ^ Zilliacus, J; Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson J A (Apr. 2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. (United States) 15 (4): 501–11. doi:10.1210/me.15.4.501. ISSN 0888-8809. PMID 11266503. 
  15. ^ Kucera, Tomas; Waltner-Law Mary, Scott Donald K, Prasad Ratna, Granner Daryl K (Jul. 2002). "A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1". J. Biol. Chem. (United States) 277 (29): 26098–102. doi:10.1074/jbc.M204013200. ISSN 0021-9258. PMID 12118039. 
  16. ^ Dowell, P; Ishmael J E, Avram D, Peterson V J, Nevrivy D J, Leid M (Dec. 1997). "p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha". J. Biol. Chem. (UNITED STATES) 272 (52): 33435–43. doi:10.1074/jbc.272.52.33435. ISSN 0021-9258. PMID 9407140. 
  17. ^ Treuter, E; Albrektsen T, Johansson L, Leers J, Gustafsson J A (Jun. 1998). "A regulatory role for RIP140 in nuclear receptor activation". Mol. Endocrinol. (UNITED STATES) 12 (6): 864–81. doi:10.1210/me.12.6.864. ISSN 0888-8809. PMID 9626662. 
  18. ^ Kim, H J; Yi J Y, Sung H S, Moore D D, Jhun B H, Lee Y C, Lee J W (Sep. 1999). "Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation". Mol. Cell. Biol. (UNITED STATES) 19 (9): 6323–32. ISSN 0270-7306. PMC 84603. PMID 10454579. 
  19. ^ a b c Lee, S K; Na S Y, Jung S Y, Choi J E, Jhun B H, Cheong J, Meltzer P S, Lee Y C, Lee J W (Jun. 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Mol. Endocrinol. (UNITED STATES) 14 (6): 915–25. doi:10.1210/me.14.6.915. ISSN 0888-8809. PMID 10847592. 
  20. ^ a b Lee, S K; Kim H J, Na S Y, Kim T S, Choi H S, Im S Y, Lee J W (Jul. 1998). "Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with the c-Jun and c-Fos subunits". J. Biol. Chem. (UNITED STATES) 273 (27): 16651–4. doi:10.1074/jbc.273.27.16651. ISSN 0021-9258. PMID 9642216. 
  21. ^ Litterst, C M; Pfitzner E (Dec. 2001). "Transcriptional activation by STAT6 requires the direct interaction with NCoA-1". J. Biol. Chem. (United States) 276 (49): 45713–21. doi:10.1074/jbc.M108132200. ISSN 0021-9258. PMID 11574547. 
  22. ^ Litterst, Claudia M; Pfitzner Edith (Sep. 2002). "An LXXLL motif in the transactivation domain of STAT6 mediates recruitment of NCoA-1/SRC-1". J. Biol. Chem. (United States) 277 (39): 36052–60. doi:10.1074/jbc.M203556200. ISSN 0021-9258. PMID 12138096. 
  23. ^ Spencer, T E; Jenster G, Burcin M M, Allis C D, Zhou J, Mizzen C A, McKenna N J, Onate S A, Tsai S Y, Tsai M J, O'Malley B W (Sep. 1997). "Steroid receptor coactivator-1 is a histone acetyltransferase". Nature (ENGLAND) 389 (6647): 194–8. doi:10.1038/38304. ISSN 0028-0836. PMID 9296499. 
  24. ^ Puigserver, P; Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman B M (Nov. 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science (UNITED STATES) 286 (5443): 1368–71. doi:10.1126/science.286.5443.1368. ISSN 0036-8075. PMID 10558993. 
  25. ^ Na, S Y; Lee S K, Han S J, Choi H S, Im S Y, Lee J W (May. 1998). "Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor kappaB-mediated transactivations". J. Biol. Chem. (UNITED STATES) 273 (18): 10831–4. doi:10.1074/jbc.273.18.10831. ISSN 0021-9258. PMID 9556555. 
  26. ^ Zwijsen, R M; Buckle R S, Hijmans E M, Loomans C J, Bernards R (Nov. 1998). "Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1". Genes Dev. (UNITED STATES) 12 (22): 3488–98. doi:10.1101/gad.12.22.3488. ISSN 0890-9369. PMC 317237. PMID 9832502. 
  27. ^ DiRenzo, J; Shang Y, Phelan M, Sif S, Myers M, Kingston R, Brown M (Oct. 2000). "BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation". Mol. Cell. Biol. (UNITED STATES) 20 (20): 7541–9. doi:10.1128/MCB.20.20.7541-7549.2000. ISSN 0270-7306. PMC 86306. PMID 11003650. 
  28. ^ Kalkhoven, E; Valentine J E, Heery D M, Parker M G (Jan. 1998). "Isoforms of steroid receptor co-activator 1 differ in their ability to potentiate transcription by the oestrogen receptor". EMBO J. (ENGLAND) 17 (1): 232–43. doi:10.1093/emboj/17.1.232. ISSN 0261-4189. PMC 1170374. PMID 9427757. 
  29. ^ Kang, Yun Kyoung; Guermah Mohamed, Yuan Chao-Xing, Roeder Robert G (Mar. 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (5): 2642–7. doi:10.1073/pnas.261715899. ISSN 0027-8424. PMC 122401. PMID 11867769. 
  30. ^ Lee, S K; Anzick S L, Choi J E, Bubendorf L, Guan X Y, Jung Y K, Kallioniemi O P, Kononen J, Trent J M, Azorsa D, Jhun B H, Cheong J H, Lee Y C, Meltzer P S, Lee J W (Nov. 1999). "A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo". J. Biol. Chem. (UNITED STATES) 274 (48): 34283–93. doi:10.1074/jbc.274.48.34283. ISSN 0021-9258. PMID 10567404. 

External links

Further reading

  • Qi C, Zhu Y, Reddy JK (2001). "Peroxisome proliferator-activated receptors, coactivators, and downstream targets.". Cell Biochem. Biophys.. 32 Spring: 187–204. PMID 11330046. 

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