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P49117

- NR2C2_MOUSE

UniProt

P49117 - NR2C2_MOUSE

Protein

Nuclear receptor subfamily 2 group C member 2

Gene

Nr2c2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    Functioni

    Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear recptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during expression during the late phase of spermatogenesis. Activates transcriptional activity of LHCG and is antagonist of PPARA-mediated transactivation By similarity. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior.By similarity7 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi114 – 18976Nuclear receptorPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri117 – 13721NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri153 – 17725NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. sequence-specific DNA binding Source: Ensembl
    3. sequence-specific DNA binding transcription factor activity Source: Ensembl
    4. steroid hormone receptor activity Source: InterPro
    5. zinc ion binding Source: InterPro

    GO - Biological processi

    1. cell differentiation Source: UniProtKB-KW
    2. cerebellum development Source: UniProtKB
    3. meiotic cell cycle Source: MGI
    4. positive regulation of behavior Source: UniProtKB
    5. positive regulation of embryonic development Source: UniProtKB
    6. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    7. spermatogenesis Source: MGI
    8. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Receptor, Repressor

    Keywords - Biological processi

    Differentiation, Spermatogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nuclear receptor subfamily 2 group C member 2
    Alternative name(s):
    Orphan nuclear receptor TAK1
    Orphan nuclear receptor TR4
    Testicular receptor 4
    Gene namesi
    Name:Nr2c2
    Synonyms:Mtr2r1, Tak1, Tr4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 6

    Organism-specific databases

    MGIiMGI:1352466. Nr2c2.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Impaired spermatogenesis. Mutant animals have smaller cerebellums with disruption of lobes VI-VII. They exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells 7 days after birth. Deficiencies in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Also responses to novel environmental situations are inhibited. NR2C1 and NR2C2 double knockout results in embryonic lethality around 7.5 dpc and increased apoptosis.4 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi15 – 151S → A: Enhanced transcriptional activation; Greatly enhanced transcriptional activation; when associated with A-68.
    Mutagenesisi19 – 191S → E: Some repression of transcriptional activation; Repressed transcriptional activity by about 10-fold; when associated with E-68. 1 Publication
    Mutagenesisi55 – 551S → A: No effect on transcriptional activation. 1 Publication
    Mutagenesisi68 – 681S → A: Enhanced transcriptional activation; Greatly enhanced transcriptional activation; when associated with A-15. 1 Publication
    Mutagenesisi68 – 681S → E: Some repression of transcriptional activation; Repressed transcriptional activity by about 10-fold; when associated with E-19. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 596596Nuclear receptor subfamily 2 group C member 2PRO_0000053589Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei19 – 191Phosphoserine; by MAPK1 Publication
    Modified residuei46 – 461PhosphoserineBy similarity
    Modified residuei55 – 551Phosphoserine; by MAPK1 Publication
    Modified residuei68 – 681Phosphoserine; by MAPK1 Publication
    Modified residuei98 – 981PhosphoserineBy similarity
    Modified residuei219 – 2191PhosphoserineBy similarity
    Modified residuei231 – 2311N6-acetyllysine1 Publication

    Post-translational modificationi

    Phosphorylation on Ser-19 and Ser-68 is an important regulator of NR2C2-mediated transcriptional activity. Phosphorylation on these residues recruits the corepressor, NRIP1, leading to transcripional repression, whereas the non-phosphorylated form preferentially recruits the coactivator, PCAF.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP49117.
    PRIDEiP49117.

    PTM databases

    PhosphoSiteiP49117.

    Expressioni

    Tissue specificityi

    Expressed, during embryogenesis, in perichondrium, developing glomeruli structures and tubules of kidney, as well as in intestiinal villi. Also expressed in lung and hair follicles.3 Publications

    Inductioni

    Induced by retinoic acid.1 Publication

    Gene expression databases

    ArrayExpressiP49117.
    BgeeiP49117.
    CleanExiMM_NR2C2.
    GenevestigatoriP49117.

    Interactioni

    Subunit structurei

    Homodimer; can bind DNA as homodimer By similarity. Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity By similarity. Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain. Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity. Interacts with NLRP10.By similarity1 Publication

    Protein-protein interaction databases

    IntActiP49117. 1 interaction.
    MINTiMINT-6797261.

    Structurei

    3D structure databases

    ProteinModelPortaliP49117.
    SMRiP49117. Positions 115-582.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni388 – 554167Ligand-bindingBy similarityAdd
    BLAST

    Sequence similaritiesi

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

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri117 – 13721NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri153 – 17725NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG297520.
    HOGENOMiHOG000013058.
    HOVERGENiHBG008596.
    InParanoidiP49117.
    KOiK08544.
    OrthoDBiEOG7FJH0K.
    PhylomeDBiP49117.
    TreeFamiTF316650.

    Family and domain databases

    Gene3Di1.10.565.10. 3 hits.
    3.30.50.10. 1 hit.
    InterProiIPR008946. 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]
    PRINTSiPR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTiSM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view]
    SUPFAMiSSF48508. SSF48508. 2 hits.
    PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P49117-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTSPSPRIQI ISTDSAVASP QRIQIVTDQQ TGQKIQIVTA VDASGSSKQQ    50
    FILTSPDGAG TGKVILASPE TSSAKQLIFT TSDNLVPGRI QIVTDSASVE 100
    RLLGKADVQR PQVVEYCVVC GDKASGRHYG AVSCEGCKGF FKRSVRKNLT 150
    YSCRSSQDCI INKHHRNRCQ FCRLKKCLEM GMKMESVQSE RKPFDVQREK 200
    PSNCAASTEK IYIRKDLRSP LIATPTFVAD KDGARQTGLL DPGMLVNIQQ 250
    PLIREDGTVL LAADSKAETS QGALGTLANV VTSLANLSES LNNGDASEMQ 300
    PEDQSASEIT RAFDTLAKAL NTTDSASPPS LADGIDASGG GSIHVISRDQ 350
    STPIIEVEGP LLSDTHVTFK LTMPSPMPEY LNVHYICESA SRLLFLSMHW 400
    ARSIPAFQAL GQDCNTSLVR ACWNELFTLG LAQCAQVMSL STILAAIVNH 450
    LQNSIQEDKL SGDRIKQVME HIWKLQEFCN SMAKLDIDGY EYAYLKAIVL 500
    FSPDHPGLTG TSQIEKFQEK AQMELQDYVQ KTYSEDTYRL ARILVRLPAL 550
    RLMSSNITEE LFFTGLIGNV SIDSIIPYIL KMETAEYNGQ ITGASL 596
    Length:596
    Mass (Da):65,239
    Last modified:February 1, 1996 - v1
    Checksum:iDE93C438A9CF1ED7
    GO

    Sequence cautioni

    The sequence AAB33314.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
    The sequence AAC18408.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti60 – 601G → E in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti106 – 1061A → Q in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti122 – 1221D → V in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti247 – 2471N → K in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti263 – 2631A → T in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti323 – 3231T → I in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti327 – 3282SP → CF in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti337 – 3371A → T in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti484 – 4852KL → NW in AAC18408. (PubMed:7841789)Curated
    Sequence conflicti510 – 5101G → S in AAC18408. (PubMed:7841789)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U11688 mRNA. Translation: AAA93150.1.
    S75970 mRNA. Translation: AAB33314.1. Different initiation.
    U32939 mRNA. Translation: AAC18408.1. Different initiation.
    CCDSiCCDS20372.1.
    PIRiI54075.
    JC4299.
    RefSeqiNP_035760.1. NM_011630.3.
    XP_006505967.1. XM_006505904.1.
    XP_006505968.1. XM_006505905.1.
    XP_006505969.1. XM_006505906.1.
    UniGeneiMm.442385.
    Mm.87062.

    Genome annotation databases

    EnsembliENSMUST00000113460; ENSMUSP00000109087; ENSMUSG00000005893.
    GeneIDi22026.
    KEGGimmu:22026.
    UCSCiuc009cyp.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U11688 mRNA. Translation: AAA93150.1 .
    S75970 mRNA. Translation: AAB33314.1 . Different initiation.
    U32939 mRNA. Translation: AAC18408.1 . Different initiation.
    CCDSi CCDS20372.1.
    PIRi I54075.
    JC4299.
    RefSeqi NP_035760.1. NM_011630.3.
    XP_006505967.1. XM_006505904.1.
    XP_006505968.1. XM_006505905.1.
    XP_006505969.1. XM_006505906.1.
    UniGenei Mm.442385.
    Mm.87062.

    3D structure databases

    ProteinModelPortali P49117.
    SMRi P49117. Positions 115-582.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P49117. 1 interaction.
    MINTi MINT-6797261.

    PTM databases

    PhosphoSitei P49117.

    Proteomic databases

    PaxDbi P49117.
    PRIDEi P49117.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000113460 ; ENSMUSP00000109087 ; ENSMUSG00000005893 .
    GeneIDi 22026.
    KEGGi mmu:22026.
    UCSCi uc009cyp.2. mouse.

    Organism-specific databases

    CTDi 7182.
    MGIi MGI:1352466. Nr2c2.

    Phylogenomic databases

    eggNOGi NOG297520.
    HOGENOMi HOG000013058.
    HOVERGENi HBG008596.
    InParanoidi P49117.
    KOi K08544.
    OrthoDBi EOG7FJH0K.
    PhylomeDBi P49117.
    TreeFami TF316650.

    Miscellaneous databases

    ChiTaRSi NR2C2. mouse.
    NextBioi 301768.
    PROi P49117.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49117.
    Bgeei P49117.
    CleanExi MM_NR2C2.
    Genevestigatori P49117.

    Family and domain databases

    Gene3Di 1.10.565.10. 3 hits.
    3.30.50.10. 1 hit.
    InterProi 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 PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTi SM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48508. SSF48508. 2 hits.
    PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of the gene encoding the murine orphan receptor TAK1 and cell-type-specific expression in testis."
      Hirose T., O'Brien D.A., Jetten A.M.
      Gene 163:239-242(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: CD-1.
    2. "Molecular cloning of a novel member of the nuclear receptor superfamily related to the orphan receptor, TR2."
      Law S.W., Conneely O.M., O'Malley B.W.
      Gene Expr. 4:77-84(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. Young W.J., Smith S., Chang C.
      Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6J.
      Tissue: Testis.
    4. "Differential regulation of direct repeat 3 vitamin D3 and direct repeat 4 thyroid hormone signaling pathways by the human TR4 orphan receptor."
      Lee Y.F., Young W.J., Lin W.J., Shyr C.R., Chang C.
      J. Biol. Chem. 274:16198-16205(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    5. "An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer."
      Tanabe O., Katsuoka F., Campbell A.D., Song W., Yamamoto M., Tanimoto K., Engel J.D.
      EMBO J. 21:3434-3442(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY AS A COMPONENT OF THE DRED COMPLEX, FUNCTION, SUBCELLULAR LOCATION, HETERODIMERIZATION, DEVELOPMENTAL STAGE.
    6. "Targeted inactivation of testicular nuclear orphan receptor 4 delays and disrupts late meiotic prophase and subsequent meiotic divisions of spermatogenesis."
      Mu X., Lee Y.F., Liu N.C., Chen Y.T., Kim E., Shyr C.R., Chang C.
      Mol. Cell. Biol. 24:5887-5899(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, FUNCTION.
    7. "Modulation of testicular receptor 4 activity by mitogen-activated protein kinase-mediated phosphorylation."
      Huq M.D., Gupta P., Tsai N.P., Wei L.N.
      Mol. Cell. Proteomics 5:2072-2082(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-19; SER-55 AND SER-68, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH NRIP1 AND PCAF, MUTAGENESIS OF SER-19; SER-55 AND SER-68.
    8. "Abnormal cerebellar cytoarchitecture and impaired inhibitory signaling in adult mice lacking TR4 orphan nuclear receptor."
      Chen Y.T., Collins L.L., Uno H., Chou S.M., Meshul C.K., Chang S.S., Chang C.
      Brain Res. 1168:72-82(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, FUNCTION.
    9. "The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription."
      Tanabe O., Shen Y., Liu Q., Campbell A.D., Kuroha T., Yamamoto M., Engel J.D.
      Genes Dev. 21:2832-2844(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: HETERODIMERIZATION, FUNCTION.
    10. "Roles of testicular orphan nuclear receptors 2 and 4 in early embryonic development and embryonic stem cells."
      Shyr C.R., Kang H.Y., Tsai M.Y., Liu N.C., Ku P.Y., Huang K.E., Chang C.
      Endocrinology 150:2454-2462(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, INDUCTION, FUNCTION.
    11. "Altered cerebellar development in nuclear receptor TAK1/ TR4 null mice is associated with deficits in GLAST(+) glia, alterations in social behavior, motor learning, startle reactivity, and microglia."
      Kim Y.S., Harry G.J., Kang H.S., Goulding D., Wine R.N., Kissling G.E., Liao G., Jetten A.M.
      Cerebellum 9:310-323(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    12. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-231, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiNR2C2_MOUSE
    AccessioniPrimary (citable) accession number: P49117
    Secondary accession number(s): P55093
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 127 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3