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Protein

COUP transcription factor 2

Gene

NR2F2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Ligand-activated transcription factor. Activated by high concentrations of 9-cis-retinoic acid and all-trans-retinoic acid, but not by dexamethasone, cortisol or progesterone (in vitro). Regulation of the apolipoprotein A-I gene transcription. Binds to DNA site A.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi76 – 151Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri79 – 99NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri115 – 139NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • DNA binding transcription factor activity Source: UniProtKB
  • nuclear receptor activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • retinoic acid binding Source: UniProtKB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: UniProtKB
  • steroid hormone receptor activity Source: InterPro
  • transcription corepressor activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • anterior/posterior pattern specification Source: Ensembl
  • blood vessel morphogenesis Source: Ensembl
  • fertilization Source: Ensembl
  • forebrain development Source: Ensembl
  • limb development Source: Ensembl
  • lipid metabolic process Source: ProtInc
  • maternal placenta development Source: Ensembl
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • negative regulation of endothelial cell migration Source: BHF-UCL
  • negative regulation of endothelial cell proliferation Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • neuron migration Source: Ensembl
  • placenta blood vessel development Source: Ensembl
  • positive regulation of systemic arterial blood pressure Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • radial pattern formation Source: Ensembl
  • regulation of transcription by RNA polymerase II Source: ProtInc
  • regulation of transcription involved in lymphatic endothelial cell fate commitment Source: BHF-UCL
  • response to estradiol Source: Ensembl
  • signal transduction Source: ProtInc
  • skeletal muscle tissue development Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
  • trophoblast giant cell differentiation Source: Ensembl

Keywordsi

Molecular functionActivator, DNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-381340 Transcriptional regulation of white adipocyte differentiation
SignaLinkiP24468
SIGNORiP24468

Names & Taxonomyi

Protein namesi
Recommended name:
COUP transcription factor 2
Short name:
COUP-TF2
Alternative name(s):
Apolipoprotein A-I regulatory protein 1
Short name:
ARP-1
COUP transcription factor II
Short name:
COUP-TF II
Nuclear receptor subfamily 2 group F member 2
Gene namesi
Name:NR2F2
Synonyms:ARP1, TFCOUP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000185551.12
HGNCiHGNC:7976 NR2F2
MIMi107773 gene
neXtProtiNX_P24468

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Congenital heart defects, multiple types, 4 (CHTD4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. Some patients also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions.
See also OMIM:615779
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07176675Q → QQ in CHTD4; the mutation results in reduced transcription activation of the EGR1 promoter; does not affect transcription activation of the APOB FT promoter. 1 Publication1
Natural variantiVAR_071767170D → V in CHTD4. 1 Publication1
Natural variantiVAR_071768205N → I in CHTD4; the mutation results in increased transcription activation of the EGR1 promoter; transcription activation of the APOB promoter is decreased. 1 PublicationCorresponds to variant dbSNP:rs587777372Ensembl.1
Natural variantiVAR_071769251E → D in CHTD4. 1 Publication1
Natural variantiVAR_071770341S → Y in CHTD4; the mutation results in reduced transcriptional activity. 1 PublicationCorresponds to variant dbSNP:rs587777371EnsemblClinVar.1
Natural variantiVAR_071771412A → S in CHTD4. 1 PublicationCorresponds to variant dbSNP:rs201527820Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi228R → E: Reduces transcription activation by 40%; when associated with R-398. 1 Publication1
Mutagenesisi249W → A: Reduces transcription activation by 50%; when associated with A-250. 1 Publication1
Mutagenesisi250S → A: Reduces transcription activation by 50%; when associated with A-249. 1 Publication1
Mutagenesisi250S → W: Reduces transcription activation by 50%. 1 Publication1
Mutagenesisi253 – 254FV → AA: Reduces transcription activation by 50%. 1 Publication2
Mutagenesisi269 – 270LL → AA: Reduces transcription activation by 50%. 2
Mutagenesisi364 – 365LL → AA: Reduces transcription activation by 80%. 1 Publication2
Mutagenesisi398D → R: Reduces transcription activation by 40%; when associated with E-228. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7026
MalaCardsiNR2F2
MIMi615779 phenotype
OpenTargetsiENSG00000185551
Orphaneti1329 Complete atrioventricular canal
1330 Partial atrioventricular canal
PharmGKBiPA31759

Chemistry databases

ChEMBLiCHEMBL1961790

Polymorphism and mutation databases

BioMutaiNR2F2
DMDMi114203

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536061 – 414COUP transcription factor 2Add BLAST414

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei51PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP24468
MaxQBiP24468
PaxDbiP24468
PeptideAtlasiP24468
PRIDEiP24468

PTM databases

iPTMnetiP24468
PhosphoSitePlusiP24468

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000185551
CleanExiHS_NR2F2
ExpressionAtlasiP24468 baseline and differential
GenevisibleiP24468 HS

Interactioni

Subunit structurei

Interacts with SQSTM1 (By similarity). Binds DNA as a dimer; homodimer or heterodimer with NR2F6. Interacts with NCOA1, NCOA2, NCOA3 and PPARGC1A. Interacts with ZFPM2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SMAD4Q134854EBI-2795198,EBI-347263

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi112884, 73 interactors
CORUMiP24468
DIPiDIP-29713N
IntActiP24468, 15 interactors
MINTiP24468
STRINGi9606.ENSP00000377721

Chemistry databases

BindingDBiP24468

Structurei

Secondary structure

1414
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi175 – 187Combined sources13
Helixi212 – 229Combined sources18
Beta strandi230 – 232Combined sources3
Helixi233 – 235Combined sources3
Helixi238 – 260Combined sources23
Helixi290 – 304Combined sources15
Helixi309 – 320Combined sources12
Helixi331 – 352Combined sources22
Helixi359 – 364Combined sources6
Helixi367 – 372Combined sources6
Helixi375 – 382Combined sources8
Helixi384 – 387Combined sources4
Helixi392 – 394Combined sources3
Helixi396 – 400Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3CJWX-ray1.48A175-414[»]
ProteinModelPortaliP24468
SMRiP24468
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24468

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini177 – 403NR LBDPROSITE-ProRule annotationAdd BLAST227

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni117 – 414Interaction with ZFPM2By similarityAdd BLAST298
Regioni337 – 414Important for dimerizationAdd BLAST78

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi71 – 75Poly-Gln5

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri79 – 99NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri115 – 139NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118948
HOGENOMiHOG000260820
HOVERGENiHBG005606
InParanoidiP24468
KOiK08548
OMAiGNQGTQP
OrthoDBiEOG091G0YX6
PhylomeDBiP24468
TreeFamiTF352097

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR003068 COUP_TF
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR01282 COUPTNFACTOR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P24468-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAMVVSTWRD PQDEVPGSQG SQASQAPPVP GPPPGAPHTP QTPGQGGPAS
60 70 80 90 100
TPAQTAAGGQ GGPGGPGSDK QQQQQHIECV VCGDKSSGKH YGQFTCEGCK
110 120 130 140 150
SFFKRSVRRN LSYTCRANRN CPIDQHHRNQ CQYCRLKKCL KVGMRREAVQ
160 170 180 190 200
RGRMPPTQPT HGQFALTNGD PLNCHSYLSG YISLLLRAEP YPTSRFGSQC
210 220 230 240 250
MQPNNIMGIE NICELAARML FSAVEWARNI PFFPDLQITD QVALLRLTWS
260 270 280 290 300
ELFVLNAAQC SMPLHVAPLL AAAGLHASPM SADRVVAFMD HIRIFQEQVE
310 320 330 340 350
KLKALHVDSA EYSCLKAIVL FTSDACGLSD VAHVESLQEK SQCALEEYVR
360 370 380 390 400
SQYPNQPTRF GKLLLRLPSL RTVSSSVIEQ LFFVRLVGKT PIETLIRDML
410
LSGSSFNWPY MAIQ
Length:414
Mass (Da):45,571
Last modified:March 1, 1992 - v1
Checksum:iC24CB2E8C8A27E8C
GO
Isoform 2 (identifier: P24468-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-147: MAMVVSTWRD...KCLKVGMRRE → MQAVWDLEQGKYGF

Show »
Length:281
Mass (Da):31,484
Checksum:i038DD27B80868BB5
GO
Isoform 3 (identifier: P24468-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-153: Missing.

Show »
Length:261
Mass (Da):29,163
Checksum:i5526AD057E2A639E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07176675Q → QQ in CHTD4; the mutation results in reduced transcription activation of the EGR1 promoter; does not affect transcription activation of the APOB FT promoter. 1 Publication1
Natural variantiVAR_071767170D → V in CHTD4. 1 Publication1
Natural variantiVAR_071768205N → I in CHTD4; the mutation results in increased transcription activation of the EGR1 promoter; transcription activation of the APOB promoter is decreased. 1 PublicationCorresponds to variant dbSNP:rs587777372Ensembl.1
Natural variantiVAR_071769251E → D in CHTD4. 1 Publication1
Natural variantiVAR_071770341S → Y in CHTD4; the mutation results in reduced transcriptional activity. 1 PublicationCorresponds to variant dbSNP:rs587777371EnsemblClinVar.1
Natural variantiVAR_071771412A → S in CHTD4. 1 PublicationCorresponds to variant dbSNP:rs201527820Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0438971 – 153Missing in isoform 3. 2 PublicationsAdd BLAST153
Alternative sequenceiVSP_0426301 – 147MAMVV…GMRRE → MQAVWDLEQGKYGF in isoform 2. 4 PublicationsAdd BLAST147

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64497 mRNA Translation: AAA86429.1
U60477 Genomic DNA Translation: AAB09475.1
AB307711 mRNA Translation: BAH02302.1
FM208183 mRNA Translation: CAR63888.1
AK298824 mRNA Translation: BAG60954.1
AK301595 mRNA Translation: BAG63083.1
AK316086 mRNA Translation: BAH14457.1
HQ692849 mRNA Translation: ADZ17360.1
HQ692850 mRNA Translation: ADZ17361.1
AC016251 Genomic DNA No translation available.
CH471101 Genomic DNA Translation: EAX02195.1
CH471101 Genomic DNA Translation: EAX02196.1
CH471101 Genomic DNA Translation: EAX02197.1
BC014664 mRNA Translation: AAH14664.1
BC042897 mRNA Translation: AAH42897.1
BC106083 mRNA Translation: AAI06084.1
M62760 mRNA Translation: AAA21479.1
CCDSiCCDS10375.1 [P24468-1]
CCDS45358.1 [P24468-2]
CCDS45359.1 [P24468-3]
PIRiA37133
RefSeqiNP_001138627.1, NM_001145155.1 [P24468-2]
NP_001138628.1, NM_001145156.1 [P24468-3]
NP_001138629.1, NM_001145157.1 [P24468-3]
NP_066285.1, NM_021005.3 [P24468-1]
UniGeneiHs.347991

Genome annotation databases

EnsembliENST00000394166; ENSP00000377721; ENSG00000185551 [P24468-1]
ENST00000394171; ENSP00000377726; ENSG00000185551 [P24468-3]
ENST00000421109; ENSP00000401674; ENSG00000185551 [P24468-2]
ENST00000453270; ENSP00000389853; ENSG00000185551 [P24468-3]
GeneIDi7026
KEGGihsa:7026
UCSCiuc002btp.4 human [P24468-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCOT2_HUMAN
AccessioniPrimary (citable) accession number: P24468
Secondary accession number(s): B4DQJ2
, B6ZGU1, Q03754, Q3KQR7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: April 25, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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