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P49117

- NR2C2_MOUSE

UniProt

P49117 - NR2C2_MOUSE

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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

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. sequence-specific DNA binding Source: InterPro
  2. sequence-specific DNA binding transcription factor activity Source: InterPro
  3. steroid hormone receptor activity Source: InterPro
  4. 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. spermatogenesis Source: MGI
  7. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

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-KW
Complete GO annotation...

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

MaxQBiP49117.
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

BgeeiP49117.
CleanExiMM_NR2C2.
ExpressionAtlasiP49117. baseline and differential.
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 117-225, 348-582.
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

        10         20         30         40         50
MTSPSPRIQI ISTDSAVASP QRIQIVTDQQ TGQKIQIVTA VDASGSSKQQ
60 70 80 90 100
FILTSPDGAG TGKVILASPE TSSAKQLIFT TSDNLVPGRI QIVTDSASVE
110 120 130 140 150
RLLGKADVQR PQVVEYCVVC GDKASGRHYG AVSCEGCKGF FKRSVRKNLT
160 170 180 190 200
YSCRSSQDCI INKHHRNRCQ FCRLKKCLEM GMKMESVQSE RKPFDVQREK
210 220 230 240 250
PSNCAASTEK IYIRKDLRSP LIATPTFVAD KDGARQTGLL DPGMLVNIQQ
260 270 280 290 300
PLIREDGTVL LAADSKAETS QGALGTLANV VTSLANLSES LNNGDASEMQ
310 320 330 340 350
PEDQSASEIT RAFDTLAKAL NTTDSASPPS LADGIDASGG GSIHVISRDQ
360 370 380 390 400
STPIIEVEGP LLSDTHVTFK LTMPSPMPEY LNVHYICESA SRLLFLSMHW
410 420 430 440 450
ARSIPAFQAL GQDCNTSLVR ACWNELFTLG LAQCAQVMSL STILAAIVNH
460 470 480 490 500
LQNSIQEDKL SGDRIKQVME HIWKLQEFCN SMAKLDIDGY EYAYLKAIVL
510 520 530 540 550
FSPDHPGLTG TSQIEKFQEK AQMELQDYVQ KTYSEDTYRL ARILVRLPAL
560 570 580 590
RLMSSNITEE LFFTGLIGNV SIDSIIPYIL KMETAEYNGQ ITGASL
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 117-225, 348-582.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P49117. 1 interaction.
MINTi MINT-6797261.

PTM databases

PhosphoSitei P49117.

Proteomic databases

MaxQBi P49117.
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

Bgeei P49117.
CleanExi MM_NR2C2.
ExpressionAtlasi P49117. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 128 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