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P10588 (NR2F6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 2 group F member 6
Alternative name(s):
V-erbA-related protein 2
Short name=EAR-2
Gene names
Name:NR2F6
Synonyms:EAR2, ERBAL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length404 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.5 Ref.6 Ref.7 Ref.8

Subunit structure

Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1 By similarity. Interacts with THRB. Ref.6 Ref.7

Subcellular location

Nucleus Ref.5 Ref.8.

Tissue specificity

Expressed in heart, placenta, liver, skeletal muscle, kidney and pancreas. Ref.6

Induction

Inhibited by gonadotropin in granulosa cells. Ref.7

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
Repressor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdetection of temperature stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

entrainment of circadian clock by photoperiod

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

intracellular receptor signaling pathway

Traceable author statement Ref.1. Source: GOC

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.5. Source: UniProtKB

neuron development

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functionDNA binding

Traceable author statement Ref.1. Source: ProtInc

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

sequence-specific DNA binding

Inferred from direct assay Ref.5. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.5. Source: UniProtKB

steroid hormone receptor activity

Traceable author statement Ref.1. Source: ProtInc

thyroid hormone receptor activity

Traceable author statement Ref.1. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CBX1P839162EBI-2681496,EBI-78129
NAP1L1P552092EBI-2681496,EBI-356392

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 404404Nuclear receptor subfamily 2 group F member 6
PRO_0000053613

Regions

DNA binding53 – 12876Nuclear receptor Ref.6
Zinc finger56 – 7621NR C4-type
Zinc finger92 – 11625NR C4-type
Region171 – 404234Ligand-binding By similarity
Region327 – 40478Important for dimerization By similarity

Amino acid modifications

Modified residue401Phosphoserine Ref.9
Modified residue831Phosphoserine Ref.8

Experimental info

Mutagenesis74 – 785EGCKS → GSCKV: Loss of DNA (TRE) binding. Reduces the corepressor activity towards THRB. Ref.6
Sequence conflict831S → T in CAA31282. Ref.1
Sequence conflict220 – 2212AP → G in CAA31282. Ref.1
Sequence conflict2371L → M in CAA31282. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P10588 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: D1FFE523E782E969

FASTA40442,979
        10         20         30         40         50         60 
MAMVTGGWGG PGGDTNGVDK AGGYPRAAED DSASPPGAAS DAEPGDEERP GLQVDCVVCG 

        70         80         90        100        110        120 
DKSSGKHYGV FTCEGCKSFF KRSIRRNLSY TCRSNRDCQI DQHHRNQCQY CRLKKCFRVG 

       130        140        150        160        170        180 
MRKEAVQRGR IPHSLPGAVA ASSGSPPGSA LAAVASGGDL FPGQPVSELI AQLLRAEPYP 

       190        200        210        220        230        240 
AAAGRFGAGG GAAGAVLGID NVCELAARLL FSTVEWARHA PFFPELPVAD QVALLRLSWS 

       250        260        270        280        290        300 
ELFVLNAAQA ALPLHTAPLL AAAGLHAAPM AAERAVAFMD QVRAFQEQVD KLGRLQVDSA 

       310        320        330        340        350        360 
EYGCLKAIAL FTPDACGLSD PAHVESLQEK AQVALTEYVR AQYPSQPQRF GRLLLRLPAL 

       370        380        390        400 
RAVPASLISQ LFFMRLVGKT PIETLIRDML LSGSTFNWPY GSGQ 

« Hide

References

« Hide 'large scale' references
[1]"Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other."
Miyajima N., Kadowaki Y., Fukushige S., Shimizu S., Semba K., Yamanashi Y., Matsubara K., Toyoshima K., Yamamoto T.
Nucleic Acids Res. 16:11057-11074(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Fetal lung.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney, Pancreas and Uterus.
[5]"Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor."
Zhang Y., Dufau M.L.
J. Biol. Chem. 275:2763-2770(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]"The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function."
Zhu X.G., Park K.S., Kaneshige M., Bhat M.K., Zhu Q., Mariash C.N., McPhie P., Cheng S.Y.
Mol. Cell. Biol. 20:2604-2618(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DNA-BINDING, INTERACTION WITH THRB, MUTAGENESIS OF 74-GLU--SER-78.
[7]"EAR2 and EAR3/COUP-TFI regulate transcription of the rat LH receptor."
Zhang Y., Dufau M.L.
Mol. Endocrinol. 15:1891-1905(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INDUCTION BY GONADOTROPIN.
[8]"The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity."
Hermann-Kleiter N., Gruber T., Lutz-Nicoladoni C., Thuille N., Fresser F., Labi V., Schiefermeier N., Warnecke M., Huber L., Villunger A., Eichele G., Kaminski S., Baier G.
Immunity 29:205-216(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-83.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS02709.
RefSeqNP_005225.2. NM_005234.3.
UniGeneHs.466148.

3D structure databases

ProteinModelPortalP10588.
SMRP10588. Positions 54-397.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108375. 11 interactions.
IntActP10588. 15 interactions.
MINTMINT-7944366.
STRING9606.ENSP00000291442.

Chemistry

ChEMBLCHEMBL1961791.

PTM databases

PhosphoSiteP10588.

Polymorphism databases

DMDM23503053.

Proteomic databases

PaxDbP10588.
PRIDEP10588.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000291442; ENSP00000291442; ENSG00000160113.
GeneID2063.
KEGGhsa:2063.
UCSCuc002nfq.3. human.

Organism-specific databases

CTD2063.
GeneCardsGC19M017342.
HGNCHGNC:7977. NR2F6.
MIM132880. gene.
neXtProtNX_P10588.
PharmGKBPA31760.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG277317.
HOGENOMHOG000260820.
HOVERGENHBG005606.
InParanoidP10588.
KOK08549.
OMASDMEAGD.
OrthoDBEOG72RMZ5.
PhylomeDBP10588.
TreeFamTF352097.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkP10588.

Gene expression databases

ArrayExpressP10588.
BgeeP10588.
CleanExHS_NR2F6.
GenevestigatorP10588.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR003068. COUP_TF.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiV-erbA-related_gene.
GenomeRNAi2063.
NextBio8381.
PROP10588.
SOURCESearch...

Entry information

Entry nameNR2F6_HUMAN
AccessionPrimary (citable) accession number: P10588
Secondary accession number(s): B2RC68 expand/collapse secondary AC list , Q5XGA0, Q6P586, Q9BUE8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: September 19, 2002
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant 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