Nuclear receptor coactivator 1

Nuclear receptor coactivator 1
PDB rendering based on 1oj5.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1FM6​, 1FM9​, 1K4W​, 1K74​, 1K7L​, 1KV6​, 1N4H​, 1NQ7​, 1NRL​, 1P8D​, 1PZL​, 1RDT​, 1TFC​, 1U3R​, 1U3S​, 1X76​, 1X78​, 1X7B​, 1X7J​, 1XIU​, 1XV9​, 1XVP​, 1YY4​, 1YYE​, 1ZAF​, 2A3I​, 2C52​, 2FVJ​, 2GTK​, 2HBH​, 2HC4​, 2HCD​, 2HFP​, 2NPA​, 2NV7​, 2P54​, 2PRG​, 3BEJ​, 3BQD​, 3CTB​, 3CWD​, 3DCT​, 3DCU​, 3DR1​, 3ET1​, 3ET3​, 3FEI​, 3FEJ​, 3FUR​, 3FXV​, 3G8I​, 3G9E​, 3GYT​, 3GYU​, 3H0A​, 3HC5​, 3HC6​, 3HVL​, 3IPQ​, 3IPS​, 3IPU​, 3KMR​, 3LMP​, 3OKH​, 3OKI​, 3OLF​, 3OLL​, 3OLS​, 3OMK​, 3OMM​, 3OMO​, 3OMP​, 3OMQ​, 3OOF​, 3OOK​, 3P88​, 3P89​, 3QT0​, 3RUT​, 3RUU​, 3RVF​, 3S9S​, 3T03​, 3UU7​, 3UUA​, 3UUD​, 3V9Y​, 3VN2​, 4DK7​, 4DK8​, 4DM6​, 4DM8​, 4DQM​, 4F9M​, 4FGY​, 4G1D​, 4G1Y​, 4G1Z​, 4G20​, 4G21​, 4G2H​, 4HEE​, 4J5X​, 4JYG​, 4JYH​, 4JYI​, 4MG5​, 4MG6​, 4MG7​, 4MG8​, 4MG9​, 4MGA​, 4MGB​, 4MGC​, 4MGD​
Identifiers
Symbols	NCOA1 ; F-SRC-1; KAT13A; RIP160; SRC1; bHLHe42; bHLHe74
External IDs	OMIM: 602691 MGI: 1276523 HomoloGene: 7859 ChEMBL: 1615387 GeneCards: NCOA1 Gene
EC number	2.3.1.48
Gene ontology Molecular function • RNA polymerase II regulatory region DNA binding • RNA polymerase II transcription coactivator activity • chromatin binding • transcription coactivator activity • histone acetyltransferase activity • protein binding • ligand-dependent nuclear receptor binding • enzyme binding • estrogen receptor binding • ligand-dependent nuclear receptor transcription coactivator activity • protein complex binding • progesterone receptor binding • nuclear hormone receptor binding • retinoid X receptor binding • protein dimerization activity • protein N-terminus binding • androgen receptor binding Cellular component • nuclear chromatin • nucleus • nucleoplasm • cytoplasm • neuron projection Biological process • positive regulation of transcription from RNA polymerase II promoter by galactose • chromatin organization • transcription, DNA-templated • lactation • bile acid metabolic process • male gonad development • bile acid and bile salt transport • cerebellum development • hippocampus development • hypothalamus development • cerebral cortex development • androgen receptor signaling pathway • response to estradiol • response to retinoic acid • response to progesterone • cellular response to hormone stimulus • positive regulation of apoptotic process • histone H4 acetylation • cellular lipid metabolic process • small molecule metabolic process • estrous cycle • positive regulation of neuron differentiation • positive regulation of transcription, DNA-templated • positive regulation of female receptivity • positive regulation of transcription from RNA polymerase II promoter • male mating behavior • labyrinthine layer morphogenesis • regulation of cellular response to drug Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8648	17977
Ensembl	ENSG00000084676	ENSMUSG00000020647
UniProt	Q15788	P70365
RefSeq (mRNA)	NM_003743	NM_010881
RefSeq (protein)	NP_003734	NP_035011
Location (UCSC)	Chr 2: 24.49 – 24.77 Mb	Chr 12: 4.25 – 4.48 Mb
PubMed search

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 2.3.1.48). 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).

Interactions

Nuclear receptor coactivator 1 possesses a basic helix-loop-helix (bHLH) domain and has been shown to interact with:

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

References

1. Oñate 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. Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP (Oct 2004). "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells". Mol. Endocrinol. 18 (10): 2388–401. doi:10.1210/me.2003-0436. PMID 15256534.
4. Ueda T, Mawji NR, Bruchovsky N, Sadar MD (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. 277 (41): 38087–94. doi:10.1074/jbc.M203313200. PMID 12163482.
5. Bevan CL, Hoare S, Claessens F, Heery DM, Parker MG (Dec 1999). "The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1". Mol. Cell. Biol. 19 (12): 8383–92. doi:10.1128/mcb.19.12.8383. PMC 84931. PMID 10567563.
6. Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW (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. 14 (6): 915–25. doi:10.1210/mend.14.6.0471. PMID 10847592.
7. Lee SK, Kim HJ, Na SY, Kim TS, Choi HS, Im SY, Lee JW (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. 273 (27): 16651–4. doi:10.1074/jbc.273.27.16651. PMID 9642216.
8. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW (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. 274 (48): 34283–93. doi:10.1074/jbc.274.48.34283. PMID 10567404.
9. Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J (Dec 2003). "Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways". Mol. Endocrinol. 17 (12): 2509–18. doi:10.1210/me.2002-0439. PMID 12933903.
10. Sheppard HM, Harries JC, Hussain S, Bevan C, Heery DM (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. 21 (1): 39–50. doi:10.1128/MCB.21.1.39-50.2001. PMC 86566. PMID 11113179.
11. Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW (May 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase". Mol. Cell. Biol. 22 (10): 3549–61. doi:10.1128/MCB.22.10.3549-3561.2002. PMC 133790. PMID 11971985.
12. Zwijsen RM, Buckle RS, Hijmans EM, Loomans CJ, Bernards R (Nov 1998). "Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1". Genes Dev. 12 (22): 3488–98. doi:10.1101/gad.12.22.3488. PMC 317237. PMID 9832502.
13. 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. 20 (6): 1341–52. doi:10.1093/emboj/20.6.1341. PMC 145523. PMID 11250900.
14. 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. 20 (20): 7541–9. doi:10.1128/MCB.20.20.7541-7549.2000. PMC 86306. PMID 11003650.
15. Kalkhoven E, Valentine JE, Heery DM, Parker MG (Jan 1998). "Isoforms of steroid receptor co-activator 1 differ in their ability to potentiate transcription by the oestrogen receptor". EMBO J. 17 (1): 232–43. doi:10.1093/emboj/17.1.232. PMC 1170374. PMID 9427757.
16. Kang YK, Guermah M, Yuan CX, Roeder RG (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. 99 (5): 2642–7. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
17. Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (Apr 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.
18. Kucera T, Waltner-Law M, Scott DK, Prasad R, Granner DK (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. 277 (29): 26098–102. doi:10.1074/jbc.M204013200. PMID 12118039.
19. Na SY, Lee SK, Han SJ, Choi HS, Im SY, Lee JW (May 1998). "Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor kappaB-mediated transactivations". J. Biol. Chem. 273 (18): 10831–4. doi:10.1074/jbc.273.18.10831. PMID 9556555.
20. Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai MJ, O'Malley BW (Sep 1997). "Steroid receptor coactivator-1 is a histone acetyltransferase". Nature 389 (6647): 194–8. doi:10.1038/38304. PMID 9296499.
21. Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM (Nov 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science 286 (5443): 1368–71. doi:10.1126/science.286.5443.1368. PMID 10558993.
22. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (Dec 1997). "p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha". J. Biol. Chem. 272 (52): 33435–43. doi:10.1074/jbc.272.52.33435. PMID 9407140.
23. Treuter E, Albrektsen T, Johansson L, Leers J, Gustafsson JA (Jun 1998). "A regulatory role for RIP140 in nuclear receptor activation". Mol. Endocrinol. 12 (6): 864–81. doi:10.1210/mend.12.6.0123. PMID 9626662.
24. Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN (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. 276 (44): 40614–20. doi:10.1074/jbc.M106263200. PMID 11514567.
25. Giraud S, Bienvenu F, Avril S, Gascan H, Heery DM, Coqueret O (Mar 2002). "Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a". J. Biol. Chem. 277 (10): 8004–11. doi:10.1074/jbc.M111486200. PMID 11773079.
26. Litterst CM, Pfitzner E (Dec 2001). "Transcriptional activation by STAT6 requires the direct interaction with NCoA-1". J. Biol. Chem. 276 (49): 45713–21. doi:10.1074/jbc.M108132200. PMID 11574547.
27. Litterst CM, Pfitzner E (Sep 2002). "An LXXLL motif in the transactivation domain of STAT6 mediates recruitment of NCoA-1/SRC-1". J. Biol. Chem. 277 (39): 36052–60. doi:10.1074/jbc.M203556200. PMID 12138096.
28. Kim HJ, Yi JY, Sung HS, Moore DD, Jhun BH, Lee YC, Lee JW (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. 19 (9): 6323–32. doi:10.1128/mcb.19.9.6323. PMC 84603. PMID 10454579.
29. Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM (Oct 1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology 139 (10): 4197–204. doi:10.1210/endo.139.10.6218. PMID 9751500.
30. Jeyakumar M, Tanen MR, Bagchi MK (Jun 1997). "Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor". Mol. Endocrinol. 11 (6): 755–67. doi:10.1210/mend.11.6.0003. PMID 9171239.

External links

• nuclear receptor coactivator 1 at the US National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C89

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.