Nuclear receptor coactivator 2

NCOA2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1GWQ, 1GWR, 1M2Z, 1MV9, 1MVC, 1MZN, 1P93, 1T63, 1T65, 1UHL, 1YOK, 1ZDT, 1ZDU, 1ZKY, 2AO6, 2B1V, 2B1Z, 2B23, 2FAI, 2G44, 2G5O, 2P15, 2P1T, 2P1U, 2P1V, 2Q7J, 2Q7L, 2ZXZ, 2ZY0, 3A9E, 3DZU, 3DZY, 3E00, 3E7C, 3E94, 3FUG, 3GN8, 3K23, 3KWY, 3KYT, 3L0E, 3L0L, 3O1D, 3O1E, 3OAP, 3OZJ, 3PCU, 3PLZ, 3Q95, 3Q97, 3R5M, 3UP0, 3UP3, 4DOS, 4E2J, 4FHH, 4FHI, 4IA1, 4IA2, 4IA3, 4IA7, 4IQR, 4IU7, 4IUI, 4IV2, 4IV4, 4IVW, 4IVY, 4IW6, 4IW8, 4IWC, 4IWF, 2LDC, 2YJD, 3CLD, 3ERD, 3K22, 4CSJ, 4K4J, 4K6I, 4M8E, 4M8H, 4NIE, 4NQA, 4OC7, 4P6W, 4P6X, 4POH, 4POJ, 4PP3, 4PP5, 4PP6, 4PPP, 4PPS, 4PXM, 4Q0A, 4WG0, 4QE6, 4QE8, 4RFW, 4RMC, 4RMD, 4RME, 4ZN9, 4ZO1, 4RUO, 5APJ, 4UDD, 4PLD, 4PLE, 4UDC, 5APH, 5DMC, 5DKB, 5DMF, 4ZNV, 5DVS, 5DL4, 5E0W, 5E19, 4ZUC, 5DI7, 5I4V, 5E0X, 5E1C, 4ZWK, 5DYD, 5DIG, 5DKG, 5DTV, 5EC9, 5DX3, 5DRM, 5BP6, 5DYB, 5DLR, 5E14, 5DXK, 5DUH, 5DVV, 5DU5, 5DXP, 5DP0, 4ZNS, 5DZ3, 5DXR, 5DXQ, 5DZI, 4ZNT, 4ZNW, 5DID, 5DXM, 5EHJ, 5BQ4, 5DY8, 4ZSH, 5DXB, 5DUG, 5DK9, 5EIT, 5BPR, 5DWJ, 5DWI, 5HYR, 5DKS, 4ZUB, 5EI1, 5DZ0, 4ZNU, 4ZNH, 5E15, 4ZN7, 5DZ1, 5DUE, 4ZWH, 5EGV, 5BNU, 5DIE, 5DKE, 5DWG, 5DZH, 5DRJ, 5DWE
Identifiers
Aliases	NCOA2, GRIP1, KAT13C, NCoA-2, SRC2, TIF2, bHLHe75, nuclear receptor coactivator 2
External IDs	OMIM: 601993; MGI: 1276533; HomoloGene: 4768; GeneCards: NCOA2; OMA:NCOA2 - orthologs
Gene location (Human)
Chr.	Chromosome 8 (human)
End	70,403,808 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	13,374,083 bp
RNA expression pattern
	Top expressed in
	corpus epididymis; ; endothelial cell; ; secondary oocyte; ; seminal vesicula; ; jejunal mucosa; ; amniotic fluid; ; tibia; ; Epithelium of choroid plexus; ; buccal mucosa cell; ; oral cavity;
	Top expressed in
	substantia nigra; ; lacrimal gland; ; ciliary body; ; left lung lobe; ; retinal pigment epithelium; ; lateral geniculate nucleus; ; habenula; ; median eminence; ; lobe of cerebellum; ; cerebellar vermis;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein dimerization activity; transcription coactivator activity; transcription factor binding; chromatin binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; protein binding; nuclear receptor coactivator activity; RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding; signaling receptor binding; nuclear receptor binding; aryl hydrocarbon receptor binding; protein domain specific binding; DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	cytoplasm; nucleoplasm; nucleus; nuclear body; protein-containing complex;
Biological process	regulation of transcription, DNA-templated; cellular response to Thyroglobulin triiodothyronine; rhythmic process; negative regulation of transcription by RNA polymerase II; circadian regulation of gene expression; transcription, DNA-templated; cellular response to hormone stimulus; regulation of glucose metabolic process; circadian rhythm; bile acid and bile salt transport; negative regulation of transcription, DNA-templated; positive regulation of transcription by RNA polymerase II; locomotor rhythm; intracellular receptor signaling pathway; regulation of lipid metabolic process; regulation of gene expression; response to progesterone;
	Sources:Amigo / QuickGO
Orthologs
	10499
	17978
	ENSG00000140396
	ENSMUSG00000005886
	Q15596
	Q61026
NM_006540; NM_001321703; NM_001321707; NM_001321711; NM_001321712;
	NM_001321713
	NM_001077695; NM_008678; NM_001302702
NP_001308632; NP_001308636; NP_001308640; NP_001308641; NP_001308642;
	NP_006531
	NP_001289631; NP_032704
	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:

AR,^[8]^[9]^[10]^[11]^[12]
ARNT,^[13]
BRCA1,^[14]^[15]
ESR1,^[11]^[16]^[17]
NR3C1,^[18]^[19]
PPFIA4,^[20]
RXRA,^[21]^[22]
VDR.^[11]^[21]^[23]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000140396 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000005886 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b ^c 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.

External links

nuclear receptor coactivator 2 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
NURSA C90
Overview of all the structural information available in the PDB for UniProt: Q15596 (Human Nuclear receptor coactivator 2) at the PDBe-KB.
Overview of all the structural information available in the PDB for UniProt: Q61026 (Mouse Nuclear receptor coactivator 2) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000140396 – Ensembl, May 2017

[refGRCm38Ensembl-2] 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.

[Voegel_1996-5] 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.

[Hong_1997-6] 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.

[pmid19805480-7] 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.

[pmid14593076-8] 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.

[pmid12810069-9] 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.

[pmid14966121-10] 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.

[pmid12612084-11] 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.

[pmid15684378-12] 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.

[pmid12024042-13] 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.

[pmid14578343-14] 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.

[pmid11085509-15] 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.

[pmid11937504-16] 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.

[pmid18499756-17] 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.

[pmid11266503-18] 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.

[pmid12151000-19] 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.

[pmid11931740-20] 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.

[pmid11514567-21] 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.

[pmid11851396-22] 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.

[pmid10748178-23] 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.

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v t e Transcription coregulators
Coactivators	ARA (54, 55, 70) BCAS3 CARM1 p300-CBP (EP300, CREBBP) CRTC (1, 2, 3) DRIP/TRAP (MED1 Drip205/Trap220) MN1 PCAF PNRC (1, 2) PPARGC (1A, 1B) TGFB1I1 NCOA1 (SRC-1) NCOA2 (GRIP1/SRC-2/TIF2) NCOA3 (AIB/SRC-3/TRAM-1) NCOA4 (ARA70) NCOA5 (CIA) NCOA6 (RAP250) NCOA7 (ERAP140)
Corepressors	CTBP (1, 2) Hairless homolog LCOR NRIP1 (RIP140) PELP-1 RCOR1 Rb SIN3A SIN3B Tripartite motif family TRIM (24, 28, 33) NCOR1 NCOR2 (SMRT)
ATP-dependent remodeling factors	Chromatin Structure Remodeling (RSC) Complex SWI/SNF

Function

Interactions

References

Further reading

External links