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P10588

- NR2F6_HUMAN

UniProt

P10588 - NR2F6_HUMAN

Protein

Nuclear receptor subfamily 2 group F member 6

Gene

NR2F6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 2 (19 Sep 2002)
      Previous versions | rss
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    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

    1. DNA binding Source: ProtInc
    2. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: ProtInc
    3. protein binding Source: IntAct
    4. sequence-specific DNA binding Source: UniProtKB
    5. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    6. steroid hormone receptor activity Source: ProtInc
    7. thyroid hormone receptor activity Source: ProtInc
    8. zinc ion binding Source: InterPro

    GO - Biological processi

    1. detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
    2. entrainment of circadian clock by photoperiod Source: Ensembl
    3. gene expression Source: Reactome
    4. intracellular receptor signaling pathway Source: GOC
    5. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    6. neuron development Source: Ensembl
    7. signal transduction Source: ProtInc
    8. transcription initiation from RNA polymerase II promoter Source: Reactome

    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: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:7977. NR2F6.

    Subcellular locationi

    Nucleus 2 PublicationsPROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleoplasm Source: Reactome
    2. nucleus Source: UniProtKB

    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.

    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 – 401Phosphoserine1 Publication
    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

    ArrayExpressiP10588.
    BgeeiP10588.
    CleanExiHS_NR2F6.
    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. 11 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.
    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

    MAMVTGGWGG PGGDTNGVDK AGGYPRAAED DSASPPGAAS DAEPGDEERP    50
    GLQVDCVVCG DKSSGKHYGV FTCEGCKSFF KRSIRRNLSY TCRSNRDCQI 100
    DQHHRNQCQY CRLKKCFRVG MRKEAVQRGR IPHSLPGAVA ASSGSPPGSA 150
    LAAVASGGDL FPGQPVSELI AQLLRAEPYP AAAGRFGAGG GAAGAVLGID 200
    NVCELAARLL FSTVEWARHA PFFPELPVAD QVALLRLSWS ELFVLNAAQA 250
    ALPLHTAPLL AAAGLHAAPM AAERAVAFMD QVRAFQEQVD KLGRLQVDSA 300
    EYGCLKAIAL FTPDACGLSD PAHVESLQEK AQVALTEYVR AQYPSQPQRF 350
    GRLLLRLPAL RAVPASLISQ LFFMRLVGKT PIETLIRDML LSGSTFNWPY 400
    GSGQ 404
    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:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi23503053.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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. Positions 54-397.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108375. 11 interactions.
    IntActi P10588. 15 interactions.
    MINTi MINT-7944366.
    STRINGi 9606.ENSP00000291442.

    Chemistry

    ChEMBLi CHEMBL1961791.

    PTM databases

    PhosphoSitei P10588.

    Polymorphism databases

    DMDMi 23503053.

    Proteomic databases

    MaxQBi P10588.
    PaxDbi P10588.
    PRIDEi P10588.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000291442 ; ENSP00000291442 ; ENSG00000160113 .
    GeneIDi 2063.
    KEGGi hsa:2063.
    UCSCi uc002nfq.3. human.

    Organism-specific databases

    CTDi 2063.
    GeneCardsi GC19M017342.
    HGNCi HGNC:7977. NR2F6.
    MIMi 132880. gene.
    neXtProti NX_P10588.
    PharmGKBi PA31760.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG277317.
    HOGENOMi HOG000260820.
    HOVERGENi HBG005606.
    InParanoidi P10588.
    KOi K08549.
    OMAi SDMEAGD.
    OrthoDBi EOG72RMZ5.
    PhylomeDBi P10588.
    TreeFami TF352097.

    Enzyme and pathway databases

    Reactomei REACT_15525. Nuclear Receptor transcription pathway.
    SignaLinki P10588.

    Miscellaneous databases

    GeneWikii V-erbA-related_gene.
    GenomeRNAii 2063.
    NextBioi 8381.
    PROi P10588.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P10588.
    Bgeei P10588.
    CleanExi HS_NR2F6.
    Genevestigatori P10588.

    Family and domain databases

    Gene3Di 1.10.565.10. 1 hit.
    3.30.50.10. 1 hit.
    InterProi IPR003068. 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 ]
    Pfami PF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view ]
    PRINTSi PR01282. COUPTNFACTOR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTi SM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48508. SSF48508. 1 hit.
    PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    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: October 1, 2014
    This is version 160 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