NR2F6

Functionⁱ

Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4⁺ T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC).4 Publications

Regions

Feature key	Position(s)	DescriptionActions	Length
DNA bindingⁱ	53 – 128	Nuclear receptorPROSITE-ProRule annotationAdd BLAST	76
Zinc fingerⁱ	56 – 76	NR C4-typePROSITE-ProRule annotationAdd BLAST	21
Zinc fingerⁱ	92 – 116	NR C4-typePROSITE-ProRule annotationAdd BLAST	25

GO - Molecular functionⁱ

DNA binding
Source: ProtInc
Traceable author statementⁱ
- 2905047
DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 10644740
DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
DNA-binding transcription repressor activity, RNA polymerase II-specific Source: Ensembl
nuclear receptor activity
Source: ProtInc
Traceable author statementⁱ
- 2905047
RNA polymerase II distal enhancer sequence-specific DNA binding Source: Ensembl
sequence-specific DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 10644740
steroid hormone receptor activity
Source: ProtInc
Traceable author statementⁱ
- 2905047
thyroid hormone receptor activity
Source: ProtInc
Traceable author statementⁱ
- 2905047
zinc ion binding Source: InterPro

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
entrainment of circadian clock by photoperiod Source: Ensembl
negative regulation of transcription by RNA polymerase II
Source: UniProtKB
Inferred from direct assayⁱ
- 10644740
neuron development Source: Ensembl
signal transduction
Source: ProtInc
Traceable author statementⁱ
- 2905047
transcription initiation from RNA polymerase II promoter Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	DNA-binding, Receptor, Repressor
Biological process	Transcription, Transcription regulation
Ligand	Metal-binding, Zinc

Enzyme and pathway databases

Reactomeⁱ	R-HSA-383280 Nuclear Receptor transcription pathway
SignaLinkⁱ	P10588
SIGNORⁱ	P10588

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Nuclear receptor subfamily 2 group F member 6 Alternative name(s): V-erbA-related protein 2 Short name: EAR-2
Gene namesⁱ	Name:NR2F6 Synonyms:EAR2, ERBAL2
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 19

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000160113.5
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:7977 NR2F6
MIMⁱ	132880 gene
neXtProtⁱ	NX_P10588

Keywords - Cellular componentⁱ

Nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	74 – 78	EGCKS → GSCKV: Loss of DNA (TRE) binding. Reduces the corepressor activity towards THRB. 1 Publication		5

Organism-specific databases

DisGeNET More...DisGeNETⁱ	2063
Open Targets More...OpenTargetsⁱ	ENSG00000160113
PharmGKBⁱ	PA31760

Chemistry databases

ChEMBLⁱ	CHEMBL1961791

ChEMBLⁱ

CHEMBL1961791

Polymorphism and mutation databases

BioMutaⁱ	NR2F6
DMDMⁱ	23503053

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000053613	1 – 404	Nuclear receptor subfamily 2 group F member 6Add BLAST		404

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	34	PhosphoserineBy similarity	1
Modified residueⁱ	40	PhosphoserineCombined sources	1
Modified residueⁱ	83	Phosphoserine1 Publication	1

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

EPDⁱ	P10588
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P10588
PaxDbⁱ	P10588
PeptideAtlas More...PeptideAtlasⁱ	P10588
PRIDEⁱ	P10588
ProteomicsDBⁱ	52614

PTM databases

iPTMnetⁱ	P10588
PhosphoSitePlusⁱ	P10588

Expressionⁱ

Tissue specificityⁱ

Expressed in heart, placenta, liver, skeletal muscle, kidney and pancreas.1 Publication

Inductionⁱ

Inhibited by gonadotropin in granulosa cells.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000160113 Expressed in 224 organ(s), highest expression level in vagina
CleanExⁱ	HS_NR2F6
ExpressionAtlasⁱ	P10588 baseline and differential
Genevisibleⁱ	P10588 HS

Interactionⁱ

Subunit structureⁱ

Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1 (By similarity). Interacts with THRB.By similarity2 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
CBX1	P83916	2	EBI-2681496,EBI-78129
NAP1L1	P55209	2	EBI-2681496,EBI-356392

Protein-protein interaction databases

BioGridⁱ	108375, 26 interactors
IntActⁱ	P10588, 18 interactors
Molecular INTeraction database More...MINTⁱ	P10588
STRINGⁱ	9606.ENSP00000291442

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	P10588
SMRⁱ	P10588
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	165 – 393	NR LBDPROSITE-ProRule annotationAdd BLAST		229

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	327 – 404	Important for dimerizationBy similarityAdd BLAST		78

Sequence similaritiesⁱ

Belongs to the nuclear hormone receptor family. NR2 subfamily.Curated

Zinc finger

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	56 – 76	NR C4-typePROSITE-ProRule annotationAdd BLAST		21
Zinc fingerⁱ	92 – 116	NR C4-typePROSITE-ProRule annotationAdd BLAST		25

Keywords - Domainⁱ

Zinc-finger

Phylogenomic databases

eggNOGⁱ	KOG3575 Eukaryota ENOG410XRZC LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000118948
HOGENOMⁱ	HOG000260820
HOVERGENⁱ	HBG005606
InParanoidⁱ	P10588
KEGG Orthology (KO) More...KOⁱ	K08549
OMAⁱ	NAMGIDN
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0YX6
PhylomeDBⁱ	P10588
TreeFamⁱ	TF352097

Family and domain databases

Gene3Dⁱ	3.30.50.10, 1 hit
InterProⁱ	View 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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00104 Hormone_recep, 1 hit PF00105 zf-C4, 1 hit
PRINTSⁱ	PR01282 COUPTNFACTOR PR00398 STRDHORMONER PR00047 STROIDFINGER
SMARTⁱ	View protein in SMART SM00430 HOLI, 1 hit SM00399 ZnF_C4, 1 hit
SUPFAMⁱ	SSF48508 SSF48508, 1 hit
PROSITEⁱ	View protein in PROSITE PS51843 NR_LBD, 1 hit PS00031 NUCLEAR_REC_DBD_1, 1 hit PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show all Align All

P10588-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MAMVTGGWGG PGGDTNGVDK AGGYPRAAED DSASPPGAAS DAEPGDEERP 
        60         70         80         90        100
GLQVDCVVCG DKSSGKHYGV FTCEGCKSFF KRSIRRNLSY TCRSNRDCQI 
       110        120        130        140        150
DQHHRNQCQY CRLKKCFRVG MRKEAVQRGR IPHSLPGAVA ASSGSPPGSA 
       160        170        180        190        200
LAAVASGGDL FPGQPVSELI AQLLRAEPYP AAAGRFGAGG GAAGAVLGID 
       210        220        230        240        250
NVCELAARLL FSTVEWARHA PFFPELPVAD QVALLRLSWS ELFVLNAAQA 
       260        270        280        290        300
ALPLHTAPLL AAAGLHAAPM AAERAVAFMD QVRAFQEQVD KLGRLQVDSA 
       310        320        330        340        350
EYGCLKAIAL FTPDACGLSD PAHVESLQEK AQVALTEYVR AQYPSQPQRF 
       360        370        380        390        400
GRLLLRLPAL RAVPASLISQ LFFMRLVGKT PIETLIRDML LSGSTFNWPY 

GSGQ

Length:404

Mass (Da):42,979

Last modified:September 19, 2002 - v2

Checksum:ⁱD1FFE523E782E969

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	M0R175	M0R175_HUMAN		Nuclear receptor subfamily 2 group ... Nuclear receptor subfamily 2 group F member 6	NR2F6	125	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	83	S → T in CAA31282 (PubMed:2905047).Curated	1
Sequence conflictⁱ	220 – 221	AP → G in CAA31282 (PubMed:2905047).Curated	2
Sequence conflictⁱ	237	L → M in CAA31282 (PubMed:2905047).Curated	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X12794 Genomic DNA Translation: CAA31282.1 AK314961 mRNA Translation: BAG37465.1 CH471106 Genomic DNA Translation: EAW84580.1 BC002669 mRNA Translation: AAH02669.3 BC063018 mRNA Translation: AAH63018.2 BC084544 mRNA Translation: AAH84544.2
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12352.1
PIRⁱ	S02709
NCBI Reference Sequences More...RefSeqⁱ	NP_005225.2, NM_005234.3
UniGeneⁱ	Hs.466148

Genome annotation databases

Ensemblⁱ	ENST00000291442; ENSP00000291442; ENSG00000160113
GeneIDⁱ	2063
KEGGⁱ	hsa:2063
UCSC genome browser More...UCSCⁱ	uc002nfq.4 human

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P10588	Nuclear receptor V-erbA-related		HUMAN		404	UniRef100_P10588
NR2F6 isoform 1		PONAB		404
Uncharacterized protein (Fragment)		HUMAN		46
Nuclear receptor subfamily 2 group F member 6 (Fragment)		HUMAN		125
NR2F6 isoform 2 (Fragment)		PONAB		125

Protein	Similar proteins		Species	Score	Length	Source
P10588	Nuclear receptor V-erbA-related		HUMAN		404	UniRef90_P10588
NR2F6 isoform 1		PONAB		404
nuclear receptor subfamily 2 group F member 6		Florida manatee		409
Uncharacterized protein		MYOLU		407
Uncharacterized protein		FELCA		406
+60

Protein	Similar proteins		Species	Score	Length	Source
P10588	Nuclear receptor subfamily 2 group F member 6		MOUSE		390	UniRef50_P10588
Nuclear receptor subfamily 2 group F member 6		RAT		390
Nuclear receptor subfamily 2 group F member 1-B		DANRE		389
Nuclear receptor V-erbA-related		HUMAN		404
NR2F6 isoform 1		PONAB		404
+358

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X12794 Genomic DNA Translation: CAA31282.1 AK314961 mRNA Translation: BAG37465.1 CH471106 Genomic DNA Translation: EAW84580.1 BC002669 mRNA Translation: AAH02669.3 BC063018 mRNA Translation: AAH63018.2 BC084544 mRNA Translation: AAH84544.2
CCDSⁱ	CCDS12352.1
PIRⁱ	S02709
RefSeqⁱ	NP_005225.2, NM_005234.3
UniGeneⁱ	Hs.466148

3D structure databases

ProteinModelPortalⁱ	P10588
SMRⁱ	P10588
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	108375, 26 interactors
IntActⁱ	P10588, 18 interactors
MINTⁱ	P10588
STRINGⁱ	9606.ENSP00000291442

Chemistry databases

ChEMBLⁱ	CHEMBL1961791

ChEMBLⁱ

CHEMBL1961791

PTM databases

iPTMnetⁱ	P10588
PhosphoSitePlusⁱ	P10588

Polymorphism and mutation databases

BioMutaⁱ	NR2F6
DMDMⁱ	23503053

Proteomic databases

EPDⁱ	P10588
MaxQBⁱ	P10588
PaxDbⁱ	P10588
PeptideAtlasⁱ	P10588
PRIDEⁱ	P10588
ProteomicsDBⁱ	52614

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000291442; ENSP00000291442; ENSG00000160113
GeneIDⁱ	2063
KEGGⁱ	hsa:2063
UCSCⁱ	uc002nfq.4 human

Organism-specific databases

CTDⁱ	2063
DisGeNETⁱ	2063
EuPathDBⁱ	HostDB:ENSG00000160113.5
GeneCardsⁱ	NR2F6
HGNCⁱ	HGNC:7977 NR2F6
MIMⁱ	132880 gene
neXtProtⁱ	NX_P10588
OpenTargetsⁱ	ENSG00000160113
PharmGKBⁱ	PA31760
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3575 Eukaryota ENOG410XRZC LUCA
GeneTreeⁱ	ENSGT00760000118948
HOGENOMⁱ	HOG000260820
HOVERGENⁱ	HBG005606
InParanoidⁱ	P10588
KOⁱ	K08549
OMAⁱ	NAMGIDN
OrthoDBⁱ	EOG091G0YX6
PhylomeDBⁱ	P10588
TreeFamⁱ	TF352097

Enzyme and pathway databases

Reactomeⁱ	R-HSA-383280 Nuclear Receptor transcription pathway
SignaLinkⁱ	P10588
SIGNORⁱ	P10588

Miscellaneous databases

ChiTaRSⁱ	NR2F6 human
GeneWikiⁱ	V-erbA-related_gene
GenomeRNAiⁱ	2063
Protein Ontology More...PROⁱ	PR:P10588
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000160113 Expressed in 224 organ(s), highest expression level in vagina
CleanExⁱ	HS_NR2F6
ExpressionAtlasⁱ	P10588 baseline and differential
Genevisibleⁱ	P10588 HS

Family and domain databases

Gene3Dⁱ	3.30.50.10, 1 hit
InterProⁱ	View 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
Pfamⁱ	View protein in Pfam PF00104 Hormone_recep, 1 hit PF00105 zf-C4, 1 hit
PRINTSⁱ	PR01282 COUPTNFACTOR PR00398 STRDHORMONER PR00047 STROIDFINGER
SMARTⁱ	View protein in SMART SM00430 HOLI, 1 hit SM00399 ZnF_C4, 1 hit
SUPFAMⁱ	SSF48508 SSF48508, 1 hit
PROSITEⁱ	View protein in PROSITE PS51843 NR_LBD, 1 hit PS00031 NUCLEAR_REC_DBD_1, 1 hit PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	NR2F6_HUMAN
Accessionⁱ	P10588Primary (citable) accession number: P10588 Secondary accession number(s): B2RC68 , Q5XGA0, Q6P586, Q9BUE8
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
	Last sequence update:	September 19, 2002
	Last modified:	November 7, 2018
	This is version 195 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM

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UniProtKB - P10588 (NR2F6_HUMAN)

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Nuclear receptor subfamily 2 group F member 6

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Nucleus

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ