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Protein

Nuclear receptor subfamily 2 group F member 6

Gene

NR2F6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi53 – 12876Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri56 – 7621NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri92 – 11625NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: ProtInc
  • ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: ProtInc
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: Ensembl
  • RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: Ensembl
  • sequence-specific DNA binding Source: UniProtKB
  • sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • steroid hormone receptor activity Source: ProtInc
  • thyroid hormone receptor activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_15525. Nuclear Receptor transcription pathway.
SignaLinkiP10588.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:7977. NR2F6.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi74 – 785EGCKS → GSCKV: Loss of DNA (TRE) binding. Reduces the corepressor activity towards THRB. 1 Publication

Organism-specific databases

PharmGKBiPA31760.

Polymorphism and mutation databases

BioMutaiNR2F6.
DMDMi23503053.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 404404Nuclear receptor subfamily 2 group F member 6PRO_0000053613Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei40 – 401Phosphoserine2 Publications
Modified residuei83 – 831Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP10588.
PaxDbiP10588.
PRIDEiP10588.

PTM databases

PhosphoSiteiP10588.

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

BgeeiP10588.
CleanExiHS_NR2F6.
ExpressionAtlasiP10588. baseline and differential.
GenevestigatoriP10588.

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

WithEntry#Exp.IntActNotes
CBX1P839162EBI-2681496,EBI-78129
NAP1L1P552092EBI-2681496,EBI-356392

Protein-protein interaction databases

BioGridi108375. 16 interactions.
IntActiP10588. 15 interactions.
MINTiMINT-7944366.
STRINGi9606.ENSP00000291442.

Structurei

3D structure databases

ProteinModelPortaliP10588.
SMRiP10588. Positions 54-397.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni171 – 404234Ligand-bindingBy similarityAdd
BLAST
Regioni327 – 40478Important for dimerizationBy similarityAdd
BLAST

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri56 – 7621NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri92 – 11625NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG277317.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000260820.
HOVERGENiHBG005606.
InParanoidiP10588.
KOiK08549.
OMAiSDMEAGD.
OrthoDBiEOG72RMZ5.
PhylomeDBiP10588.
TreeFamiTF352097.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. 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]
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]

Sequencei

Sequence statusi: Complete.

P10588-1 [UniParc]FASTAAdd 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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti83 – 831S → T in CAA31282 (PubMed:2905047).Curated
Sequence conflicti220 – 2212AP → G in CAA31282 (PubMed:2905047).Curated
Sequence conflicti237 – 2371L → M in CAA31282 (PubMed:2905047).Curated

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.
CCDSiCCDS12352.1.
PIRiS02709.
RefSeqiNP_005225.2. NM_005234.3.
UniGeneiHs.466148.

Genome annotation databases

EnsembliENST00000291442; ENSP00000291442; ENSG00000160113.
GeneIDi2063.
KEGGihsa:2063.
UCSCiuc002nfq.3. human.

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.
CCDSiCCDS12352.1.
PIRiS02709.
RefSeqiNP_005225.2. NM_005234.3.
UniGeneiHs.466148.

3D structure databases

ProteinModelPortaliP10588.
SMRiP10588. Positions 54-397.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108375. 16 interactions.
IntActiP10588. 15 interactions.
MINTiMINT-7944366.
STRINGi9606.ENSP00000291442.

Chemistry

ChEMBLiCHEMBL1961791.

PTM databases

PhosphoSiteiP10588.

Polymorphism and mutation databases

BioMutaiNR2F6.
DMDMi23503053.

Proteomic databases

MaxQBiP10588.
PaxDbiP10588.
PRIDEiP10588.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000291442; ENSP00000291442; ENSG00000160113.
GeneIDi2063.
KEGGihsa:2063.
UCSCiuc002nfq.3. human.

Organism-specific databases

CTDi2063.
GeneCardsiGC19M017342.
HGNCiHGNC:7977. NR2F6.
MIMi132880. gene.
neXtProtiNX_P10588.
PharmGKBiPA31760.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG277317.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000260820.
HOVERGENiHBG005606.
InParanoidiP10588.
KOiK08549.
OMAiSDMEAGD.
OrthoDBiEOG72RMZ5.
PhylomeDBiP10588.
TreeFamiTF352097.

Enzyme and pathway databases

ReactomeiREACT_15525. Nuclear Receptor transcription pathway.
SignaLinkiP10588.

Miscellaneous databases

ChiTaRSiNR2F6. human.
GeneWikiiV-erbA-related_gene.
GenomeRNAii2063.
NextBioi8381.
PROiP10588.
SOURCEiSearch...

Gene expression databases

BgeeiP10588.
CleanExiHS_NR2F6.
ExpressionAtlasiP10588. baseline and differential.
GenevestigatoriP10588.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. 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]
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...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.
  12. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiNR2F6_HUMAN
AccessioniPrimary (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: April 29, 2015
This is version 165 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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 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.