COUP-TFII

Nuclear receptor subfamily 2, group F, member 2

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
3CJW

Identifiers

Symbols

NR2F2 ; ARP1; CHTD4; COUPTFB; COUPTFII; NF-E3; NR2F1; SVP40; TFCOUP2

External IDs

OMIM: 107773 MGI: 1352452 HomoloGene: 7628 IUPHAR: 618 GeneCards: NR2F2 Gene

Gene ontology
Molecular function	• retinoic acid binding • transcription factor activity, sequence-specific DNA binding • steroid hormone receptor activity • transcription corepressor activity • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding • protein binding • zinc ion binding • protein homodimerization activity • sequence-specific DNA binding
Cellular component	• nucleus
Biological process	• negative regulation of transcription from RNA polymerase II promoter • neuron migration • maternal placenta development • negative regulation of endothelial cell proliferation • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • lipid metabolic process • signal transduction • skeletal muscle tissue development • fertilization • anterior/posterior pattern specification • radial pattern formation • negative regulation of endothelial cell migration • intracellular receptor signaling pathway • forebrain development • response to estradiol • steroid hormone mediated signaling pathway • negative regulation of cyclin-dependent protein serine/threonine kinase activity • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • blood vessel morphogenesis • limb development • placenta blood vessel development • trophoblast giant cell differentiation • regulation of transcription involved in lymphatic endothelial cell fate commitment
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 15:
96.33 – 96.34 Mb

Chr 7:
70.35 – 70.37 Mb

PubMed search

COUP-TFII (COUP transcription factor 2), also known as NR2F2 (nuclear receptor subfamily 2, group F, member 2) is a protein that in humans is encoded by the NR2F2 gene.^[1]^[2] The COUP acronym stands for chicken ovalbumin upstream promoter.

Function

COUP-TFII plays a critical role in controlling the development of a number of tissues and organs including heart, blood vessels, muscles and limbs.^[3]^[4]

The glucocorticoid receptor (GR) stimulates COUP-TFII-induced transactivation while COUP-TFII represses the GR transcriptional activity.^[5]^[6] COUP-TFII interacts with GATA2 to inhibit adipocyte differentiation.^[7]

Interactions

COUP-TFII has been shown to interact with:

References

↑ "Entrez Gene: NR2F2 nuclear receptor subfamily 2, group F, member 2".
↑ Qiu Y, Krishnan V, Zeng Z, Gilbert DJ, Copeland NG, Gibson L, Yang-Feng T, Jenkins NA, Tsai MJ, Tsai SY (September 1995). "Isolation, characterization, and chromosomal localization of mouse and human COUP-TF I and II genes". Genomics 29 (1): 240–6. doi:10.1006/geno.1995.1237. PMID 8530078.
↑ Pereira FA, Qiu Y, Zhou G, Tsai MJ, Tsai SY (April 1999). "The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development". Genes Dev. 13 (8): 1037–49. doi:10.1101/gad.13.8.1037. PMC 316637. PMID 10215630.
↑ Lee CT, Li L, Takamoto N, Martin JF, Demayo FJ, Tsai MJ, Tsai SY (December 2004). "The Nuclear Orphan Receptor COUP-TFII Is Required for Limb and Skeletal Muscle Development". Mol. Cell. Biol. 24 (24): 10835–43. doi:10.1128/MCB.24.24.10835-10843.2004. PMC 533959. PMID 15572686.
↑ De Martino MU, Bhattachryya N, Alesci S, Ichijo T, Chrousos GP, Kino T (April 2004). "The glucocorticoid receptor and the orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II interact with and mutually affect each other's transcriptional activities: implications for intermediary metabolism". Mol. Endocrinol. 18 (4): 820–33. doi:10.1210/me.2003-0341. PMID 14739255.
↑ De Martino MU, Alesci S, Chrousos GP, Kino T (June 2004). "Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII): implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism". Ann. N. Y. Acad. Sci. 1024: 72–85. doi:10.1196/annals.1321.006. PMID 15265774.
↑ Xu Z, Yu S, Hsu CH, Eguchi J, Rosen ED (February 2008). "The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis". Proc. Natl. Acad. Sci. U.S.A. 105 (7): 2421–6. doi:10.1073/pnas.0707082105. PMC 2268152. PMID 18250317.
↑ Smirnov DA, Hou S, Ricciardi RP (March 2000). "Association of histone deacetylase with COUP-TF in tumorigenic Ad12-transformed cells and its potential role in shut-off of MHC class I transcription". Virology 268 (2): 319–28. doi:10.1006/viro.1999.0181. PMID 10704340.
↑ Marcus SL, Winrow CJ, Capone JP, Rachubinski RA (November 1996). "A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor". J. Biol. Chem. 271 (44): 27197–200. doi:10.1074/jbc.271.44.27197. PMID 8910285.
↑ Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M (May 1999). "Heterodimeric Interactions between Chicken Ovalbumin Upstream Promoter-Transcription Factor Family Members ARP1 and Ear2". J. Biol. Chem. 274 (20): 14331–6. doi:10.1074/jbc.274.20.14331. PMC 2823254. PMID 10318855.
↑ Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, Pierce WM, Ivanova MM, Bates PJ, Appana SN, Datta S, Kulesza P, McBryan J, Young LS, Klinge CM (May 2012). "Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells.". PLOS ONE 7 (5): e38278. doi:10.1371/journal.pone.0038278. PMC 3365040. PMID 22693611.

De Martino MU, Alesci S, Chrousos GP, Kino T (2004). "Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII): implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism". Ann. N. Y. Acad. Sci. 1024: 72–85. doi:10.1196/annals.1321.006. PMID 15265774.
Mietus-Snyder M, Sladek FM, Ginsburg GS, Kuo CF, Ladias JA, Darnell JE, Karathanasis SK (1992). "Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells". Mol. Cell. Biol. 12 (4): 1708–18. PMC 369614. PMID 1312668.
Wang LH, Ing NH, Tsai SY, O'Malley BW, Tsai MJ (1992). "The COUP-TFs compose a family of functionally related transcription factors". Gene Expr. 1 (3): 207–16. PMID 1820218.
Ladias JA, Karathanasis SK (1991). "Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily". Science 251 (4993): 561–5. doi:10.1126/science.1899293. PMID 1899293.
Marcus SL, Winrow CJ, Capone JP, Rachubinski RA (1996). "A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor". J. Biol. Chem. 271 (44): 27197–200. doi:10.1074/jbc.271.44.27197. PMID 8910285.
Thénot S, Henriquet C, Rochefort H, Cavaillès V (1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". J. Biol. Chem. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.
Chu K, Zingg HH (1998). "The nuclear orphan receptors COUP-TFII and Ear-2 act as silencers of the human oxytocin gene promoter". J. Mol. Endocrinol. 19 (2): 163–72. doi:10.1677/jme.0.0190163. PMID 9343308.
Bailey P, Sartorelli V, Hamamori Y, Muscat GE (1999). "The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD". Nucleic Acids Res. 26 (23): 5501–10. doi:10.1093/nar/26.23.5501. PMC 147985. PMID 9826778.
Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M (1999). "Heterodimeric Interactions between Chicken Ovalbumin Upstream Promoter-Transcription Factor Family Members ARP1 and Ear2". J. Biol. Chem. 274 (20): 14331–6. doi:10.1074/jbc.274.20.14331. PMC 2823254. PMID 10318855.
Smirnov DA, Hou S, Ricciardi RP (2000). "Association of histone deacetylase with COUP-TF in tumorigenic Ad12-transformed cells and its potential role in shut-off of MHC class I transcription". Virology 268 (2): 319–28. doi:10.1006/viro.1999.0181. PMID 10704340.
Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, Leid M (2000). "Isolation of a Novel Family of C2H2 Zinc Finger Proteins Implicated in Transcriptional Repression Mediated by Chicken Ovalbumin Upstream Promoter Transcription Factor (COUP-TF) Orphan Nuclear Receptors". J. Biol. Chem. 275 (14): 10315–22. doi:10.1074/jbc.275.14.10315. PMC 2819356. PMID 10744719.
Jordan EM, Worley T, Breen GA (2003). "Transcriptional regulation of the nuclear gene encoding the alpha-subunit of the mammalian mitochondrial F1F0 ATP synthase complex: role for the orphan nuclear receptor, COUP-TFII/ARP-1". Biochemistry 42 (9): 2656–63. doi:10.1021/bi0268347. PMID 12614160.
Sato Y, Suzuki T, Hidaka K, Sato H, Ito K, Ito S, Sasano H (2003). "Immunolocalization of nuclear transcription factors, DAX-1 and COUP-TF II, in the normal human ovary: correlation with adrenal 4 binding protein/steroidogenic factor-1 immunolocalization during the menstrual cycle". J. Clin. Endocrinol. Metab. 88 (7): 3415–20. doi:10.1210/jc.2002-021723. PMID 12843196.
Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (2004). "Functional Proteomics Mapping of a Human Signaling Pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
Kurihara I, Shibata H, Kobayashi S, Suda N, Ikeda Y, Yokota K, Murai A, Saito I, Rainey WE, Saruta T (2005). "Ubc9 and Protein Inhibitor of Activated STAT 1 Activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated Human CYP11B2 Gene Transcription". J. Biol. Chem. 280 (8): 6721–30. doi:10.1074/jbc.M411820200. PMID 15611122.
Shibata H, Kobayashi S, Kurihara I, Suda N, Yokota K, Murai A, Ikeda Y, Saito I, Rainey WE, Saruta T (2005). "COUP-TF and transcriptional co-regulators in adrenal steroidogenesis". Endocr. Res. 30 (4): 795–801. doi:10.1081/ERC-200044042. PMID 15666827.

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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COUP-TFII

Function

Interactions

References

Further reading