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Protein

COUP transcription factor 2

Gene

NR2F2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-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

HGNCiHGNC:7976. NR2F2.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: BHF-UCL
Complete GO annotation...

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 rs587777372dbSNPEnsembl.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 rs587777371dbSNPEnsembl.1
Natural variantiVAR_071771412A → S in CHTD4. 1 PublicationCorresponds to variant rs201527820dbSNPEnsembl.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.

Organism-specific databases

HPAiCAB004260.

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

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi112884. 53 interactors.
DIPiDIP-29713N.
IntActiP24468. 12 interactors.
MINTiMINT-1183332.
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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni117 – 414Interaction with ZFPM2By similarityAdd BLAST298
Regioni183 – 414Ligand-bindingBy similarityAdd BLAST232
Regioni337 – 414Important for dimerizationAdd BLAST78

Compositional bias

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

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

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.
OMAiPPNNAQS.
OrthoDBiEOG091G0YX6.
PhylomeDBiP24468.
TreeFamiTF352097.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. COUP_TF.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

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 rs587777372dbSNPEnsembl.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 rs587777371dbSNPEnsembl.1
Natural variantiVAR_071771412A → S in CHTD4. 1 PublicationCorresponds to variant rs201527820dbSNPEnsembl.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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi112884. 53 interactors.
DIPiDIP-29713N.
IntActiP24468. 12 interactors.
MINTiMINT-1183332.
STRINGi9606.ENSP00000377721.

Chemistry databases

BindingDBiP24468.
ChEMBLiCHEMBL1961790.

PTM databases

iPTMnetiP24468.
PhosphoSitePlusiP24468.

Polymorphism and mutation databases

BioMutaiNR2F2.
DMDMi114203.

Proteomic databases

EPDiP24468.
MaxQBiP24468.
PaxDbiP24468.
PeptideAtlasiP24468.
PRIDEiP24468.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi7026.
DisGeNETi7026.
GeneCardsiNR2F2.
HGNCiHGNC:7976. NR2F2.
HPAiCAB004260.
MalaCardsiNR2F2.
MIMi107773. gene.
615779. phenotype.
neXtProtiNX_P24468.
OpenTargetsiENSG00000185551.
Orphaneti1329. Complete atrioventricular canal.
1330. Partial atrioventricular canal.
PharmGKBiPA31759.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiNR2F2. human.
EvolutionaryTraceiP24468.
GeneWikiiCOUP-TFII.
GenomeRNAii7026.
PROiP24468.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185551.
CleanExiHS_NR2F2.
ExpressionAtlasiP24468. baseline and differential.
GenevisibleiP24468. HS.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. COUP_TF.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCOT2_HUMAN
AccessioniPrimary (citable) accession number: P24468
Secondary accession number(s): B4DQJ2
, B6ZGU1, Q03754, Q3KQR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: November 2, 2016
This is version 173 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.