Nuclear receptor coactivator 1

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.^[5][6] It is encoded by the gene NCOA1.^[7]

NCOA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1FM6, 1FM9, 1K74, 1K7L, 1KV6, 1K4W, 1N4H, 1NQ7, 1NRL, 1P8D, 1PZL, 1RDT, 1TFC, 1U3R, 1U3S, 1X76, 1XIU, 1XV9, 1XVP, 1YY4, 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, 4TUZ, 4TV1, 5AVI, 5AVL, 4Y29, 4RUJ, 4RUP, 5A86, 5E7V, 4UDB, 4UDA, 5AZT, 5HJS
Identifiers
Aliases	NCOA1, F-SRC-1, KAT13A, RIP160, SRC1, bHLHe42, bHLHe74, nuclear receptor coactivator 1
External IDs	OMIM: 602691; MGI: 1276523; HomoloGene: 7859; GeneCards: NCOA1; OMA:NCOA1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p23.3 Start 24,491,254 bp[1] End 24,770,702 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 A1.1 Start 4,247,362 bp[2] End 4,477,182 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus middle frontal gyrus paraflocculus of cerebellum Brodmann area 23 entorhinal cortex tibialis anterior muscle postcentral gyrus frontal pole endothelial cell Region I of hippocampus proper Top expressed in Rostral migratory stream retinal pigment epithelium lateral septal nucleus dentate gyrus of hippocampal formation granule cell lateral geniculate nucleus anterior amygdaloid area motor neuron ventromedial nucleus mammillary body subiculum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity DNA binding transcription coactivator activity protein dimerization activity protein N-terminus binding transcription factor binding chromatin binding histone acetyltransferase activity protein binding androgen receptor binding enzyme binding acyltransferase activity nuclear receptor coactivator activity aryl hydrocarbon receptor binding nuclear receptor binding estrogen receptor binding DNA-binding transcription factor activity, RNA polymerase II-specific progesterone receptor binding retinoic acid receptor binding protein-containing complex binding retinoid X receptor binding Cellular component nucleus nucleoplasm cytosol plasma membrane protein-containing complex cytoplasm neuron projection Biological process androgen receptor signaling pathway regulation of RNA biosynthetic process regulation of transcription, DNA-templated cellular response to Thyroglobulin triiodothyronine regulation of cellular response to drug transcription, DNA-templated positive regulation of transcription, DNA-templated labyrinthine layer morphogenesis positive regulation of neuron differentiation bile acid and bile salt transport positive regulation of apoptotic process histone H4 acetylation regulation of thyroid hormone mediated signaling pathway positive regulation of transcription by RNA polymerase II intracellular receptor signaling pathway positive regulation of transcription from RNA polymerase II promoter by galactose regulation of lipid metabolic process transcription by RNA polymerase II cellular response to hormone stimulus lactation male gonad development response to hormone cerebellum development hippocampus development hypothalamus development cerebral cortex development response to estradiol response to retinoic acid response to progesterone estrous cycle positive regulation of female receptivity male mating behavior Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8648 17977 Ensembl ENSG00000084676 ENSMUSG00000020647 UniProt Q15788 P70365 RefSeq (mRNA) NM_003743 NM_147223 NM_147233 NM_001362950 NM_001362952 NM_001362954 NM_001362955 NM_010881 RefSeq (protein) NP_003734 NP_671756 NP_671766 NP_001349879 NP_001349881 NP_001349883 NP_001349884 NP_035011 Location (UCSC) Chr 2: 24.49 – 24.77 Mb Chr 12: 4.25 – 4.48 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

NCOA1 is recruited to DNA promoter sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA1 assists nuclear receptors in the upregulation of DNA expression as a coactivator.^[5][6]

Interactions

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

• Androgen receptor,^[8][9][10]
• C-Fos,^[11][12]
• C-jun,^[11][12][13]
• CIITA,^[14]
• CREB-binding protein,^[15][16]
• Cyclin D1,^[17]

• Estrogen receptor alpha,^{[15][18][19][20]}
• Glucocorticoid receptor,^[21][22]
• NFKB1,^[11][23]
• PCAF,^[24]
• PPARGC1A,^[25]
• Peroxisome proliferator-activated receptor alpha,^[26][27]
• SNW1,^[28]
• STAT3,^[29]
• STAT6,^[30][31]
• TRIP4,^[32] and
• Thyroid hormone receptor beta.^[33][34]

References

1. GRCh38: Ensembl release 89: ENSG00000084676 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020647 – 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. 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): 1354–1357. Bibcode:1995Sci...270.1354O. doi:10.1126/science.270.5240.1354. PMID 7481822. S2CID 28749162.
6. 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". Journal of Biological Chemistry. 273 (20): 12101–12108. doi:10.1074/jbc.273.20.12101. PMID 9575154.
7. "NCOA1 Gene - Nuclear Receptor Coactivator 1". GeneCards: The Human Gene Database. 4 October 2023. Retrieved 22 November 2023.
8. 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". Molecular Endocrinology. 18 (10): 2388–2401. doi:10.1210/me.2003-0436. PMID 15256534.
9. 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". Journal of Biological Chemistry. 277 (41): 38087–38094. doi:10.1074/jbc.M203313200. PMID 12163482.
10. 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". Molecular and Cellular Biology. 19 (12): 8383–8392. doi:10.1128/mcb.19.12.8383. PMC 84931. PMID 10567563.
11. 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". Molecular Endocrinology. 14 (6): 915–925. doi:10.1210/mend.14.6.0471. PMID 10847592.
12. 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". Journal of Biological Chemistry. 273 (27): 16651–16654. doi:10.1074/jbc.273.27.16651. PMID 9642216.
13. 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". Journal of Biological Chemistry. 274 (48): 34283–34293. doi:10.1074/jbc.274.48.34283. PMID 10567404.
14. Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J (Dec 2003). "Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways". Molecular Endocrinology. 17 (12): 2509–2518. doi:10.1210/me.2002-0439. PMID 12933903.
15. 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". Molecular and Cellular Biology. 21 (1): 39–50. doi:10.1128/MCB.21.1.39-50.2001. PMC 86566. PMID 11113179.
16. 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". Molecular and Cellular Biology. 22 (10): 3549–3461. doi:10.1128/MCB.22.10.3549-3561.2002. PMC 133790. PMID 11971985.
17. 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 & Development. 12 (22): 3488–3498. doi:10.1101/gad.12.22.3488. PMC 317237. PMID 9832502.
18. 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". Molecular and Cellular Biology. 20 (20): 7541–7549. doi:10.1128/MCB.20.20.7541-7549.2000. PMC 86306. PMID 11003650.
19. 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 Journal. 17 (1): 232–243. doi:10.1093/emboj/17.1.232. PMC 1170374. PMID 9427757.
20. 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". Proceedings of the National Academy of Sciences, USA. 99 (5): 2642–2647. Bibcode:2002PNAS...99.2642K. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
21. 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". Molecular Endocrinology. 15 (4): 501–511. doi:10.1210/mend.15.4.0624. PMID 11266503.
22. 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". Journal of Biological Chemistry. 277 (29): 26098–260102. doi:10.1074/jbc.M204013200. PMID 12118039.
23. 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". Journal of Biological Chemistry. 273 (18): 10831–10834. doi:10.1074/jbc.273.18.10831. PMID 9556555.
24. 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): 194–198. Bibcode:1997Natur.389..194S. doi:10.1038/38304. PMID 9296499. S2CID 4404530.
25. 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): 1368–1371. doi:10.1126/science.286.5443.1368. PMID 10558993.
26. 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". Journal of Biological Chemistry. 272 (52): 33435–33443. doi:10.1074/jbc.272.52.33435. PMID 9407140.
27. Treuter E, Albrektsen T, Johansson L, Leers J, Gustafsson JA (Jun 1998). "A regulatory role for RIP140 in nuclear receptor activation". Molecular Endocrinology. 12 (6): 864–881. doi:10.1210/mend.12.6.0123. PMID 9626662.
28. 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". Journal of Biological Chemistry. 276 (44): 40614–40620. doi:10.1074/jbc.M106263200. PMID 11514567.
29. 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". Journal of Biological Chemistry. 277 (10): 8004–811. doi:10.1074/jbc.M111486200. PMID 11773079.
30. Litterst CM, Pfitzner E (Dec 2001). "Transcriptional activation by STAT6 requires the direct interaction with NCoA-1". Journal of Biological Chemistry. 276 (49): 45713–45721. doi:10.1074/jbc.M108132200. PMID 11574547.
31. Litterst CM, Pfitzner E (Sep 2002). "An LXXLL motif in the transactivation domain of STAT6 mediates recruitment of NCoA-1/SRC-1". Journal of Biological Chemistry. 277 (39): 36052–36060. doi:10.1074/jbc.M203556200. PMID 12138096.
32. 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". Molecular and Cellular Biology. 19 (9): 6323–6332. doi:10.1128/mcb.19.9.6323. PMC 84603. PMID 10454579.
33. 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): 4197–4204. doi:10.1210/endo.139.10.6218. PMID 9751500.
34. 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". Molecular Endocrinology. 11 (6): 755–767. doi:10.1210/mend.11.6.0003. PMID 9171239.

External links

• nuclear receptor coactivator 1 at the U.S. 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 Biochemistry and Biophysics. 32. Spring (1–3): 187–204. doi:10.1385/cbb:32:1-3:187. PMID 11330046. S2CID 31795393.