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P49117 (NR2C2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 2 group C member 2
Alternative name(s):
Orphan nuclear receptor TAK1
Orphan nuclear receptor TR4
Testicular receptor 4
Gene names
Name:Nr2c2
Synonyms:Mtr2r1, Tak1, Tr4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length596 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subunit structure

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. Ref.5 Ref.7 Ref.9

Subcellular location

Nucleus By similarity Ref.5.

Tissue specificity

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. Ref.4 Ref.6 Ref.8

Induction

Induced by retinoic acid. Ref.10

Post-translational modification

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. Ref.7

Disruption phenotype

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. Ref.6 Ref.8 Ref.10 Ref.11

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

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.

Ontologies

Keywords
   Biological processDifferentiation
Spermatogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Receptor
Repressor
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

cerebellum development

Inferred from mutant phenotype Ref.11. Source: UniProtKB

meiotic cell cycle

Inferred from mutant phenotype Ref.6. Source: MGI

positive regulation of behavior

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of embryonic development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from mutant phenotype Ref.6. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 19268530. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 596596Nuclear receptor subfamily 2 group C member 2
PRO_0000053589

Regions

DNA binding114 – 18976Nuclear receptor
Zinc finger117 – 13721NR C4-type
Zinc finger153 – 17725NR C4-type
Region388 – 554167Ligand-binding By similarity

Amino acid modifications

Modified residue191Phosphoserine; by MAPK Ref.7
Modified residue461Phosphoserine By similarity
Modified residue551Phosphoserine; by MAPK Ref.7
Modified residue681Phosphoserine; by MAPK Ref.7
Modified residue981Phosphoserine By similarity
Modified residue2191Phosphoserine By similarity
Modified residue2311N6-acetyllysine Ref.12

Experimental info

Mutagenesis151S → A: Enhanced transcriptional activation; Greatly enhanced transcriptional activation; when associated with A-68.
Mutagenesis191S → E: Some repression of transcriptional activation; Repressed transcriptional activity by about 10-fold; when associated with E-68. Ref.7
Mutagenesis551S → A: No effect on transcriptional activation. Ref.7
Mutagenesis681S → A: Enhanced transcriptional activation; Greatly enhanced transcriptional activation; when associated with A-15. Ref.7
Mutagenesis681S → E: Some repression of transcriptional activation; Repressed transcriptional activity by about 10-fold; when associated with E-19. Ref.7
Sequence conflict601G → E in AAC18408. Ref.2
Sequence conflict1061A → Q in AAC18408. Ref.2
Sequence conflict1221D → V in AAC18408. Ref.2
Sequence conflict2471N → K in AAC18408. Ref.2
Sequence conflict2631A → T in AAC18408. Ref.2
Sequence conflict3231T → I in AAC18408. Ref.2
Sequence conflict327 – 3282SP → CF in AAC18408. Ref.2
Sequence conflict3371A → T in AAC18408. Ref.2
Sequence conflict484 – 4852KL → NW in AAC18408. Ref.2
Sequence conflict5101G → S in AAC18408. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P49117 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: DE93C438A9CF1ED7

FASTA59665,239
        10         20         30         40         50         60 
MTSPSPRIQI ISTDSAVASP QRIQIVTDQQ TGQKIQIVTA VDASGSSKQQ FILTSPDGAG 

        70         80         90        100        110        120 
TGKVILASPE TSSAKQLIFT TSDNLVPGRI QIVTDSASVE RLLGKADVQR PQVVEYCVVC 

       130        140        150        160        170        180 
GDKASGRHYG AVSCEGCKGF FKRSVRKNLT YSCRSSQDCI INKHHRNRCQ FCRLKKCLEM 

       190        200        210        220        230        240 
GMKMESVQSE RKPFDVQREK PSNCAASTEK IYIRKDLRSP LIATPTFVAD KDGARQTGLL 

       250        260        270        280        290        300 
DPGMLVNIQQ PLIREDGTVL LAADSKAETS QGALGTLANV VTSLANLSES LNNGDASEMQ 

       310        320        330        340        350        360 
PEDQSASEIT RAFDTLAKAL NTTDSASPPS LADGIDASGG GSIHVISRDQ STPIIEVEGP 

       370        380        390        400        410        420 
LLSDTHVTFK LTMPSPMPEY LNVHYICESA SRLLFLSMHW ARSIPAFQAL GQDCNTSLVR 

       430        440        450        460        470        480 
ACWNELFTLG LAQCAQVMSL STILAAIVNH LQNSIQEDKL SGDRIKQVME HIWKLQEFCN 

       490        500        510        520        530        540 
SMAKLDIDGY EYAYLKAIVL FSPDHPGLTG TSQIEKFQEK AQMELQDYVQ KTYSEDTYRL 

       550        560        570        580        590 
ARILVRLPAL RLMSSNITEE LFFTGLIGNV SIDSIIPYIL KMETAEYNGQ ITGASL 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U11688 mRNA. Translation: AAA93150.1.
S75970 mRNA. Translation: AAB33314.1. Different initiation.
U32939 mRNA. Translation: AAC18408.1. Different initiation.
CCDSCCDS20372.1.
PIRI54075.
JC4299.
RefSeqNP_035760.1. NM_011630.3.
XP_006505967.1. XM_006505904.1.
XP_006505968.1. XM_006505905.1.
XP_006505969.1. XM_006505906.1.
UniGeneMm.442385.
Mm.87062.

3D structure databases

ProteinModelPortalP49117.
SMRP49117. Positions 115-582.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP49117. 1 interaction.
MINTMINT-6797261.

PTM databases

PhosphoSiteP49117.

Proteomic databases

PaxDbP49117.
PRIDEP49117.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000113460; ENSMUSP00000109087; ENSMUSG00000005893.
GeneID22026.
KEGGmmu:22026.
UCSCuc009cyp.2. mouse.

Organism-specific databases

CTD7182.
MGIMGI:1352466. Nr2c2.

Phylogenomic databases

eggNOGNOG297520.
HOGENOMHOG000013058.
HOVERGENHBG008596.
InParanoidP49117.
KOK08544.
OrthoDBEOG7FJH0K.
PhylomeDBP49117.
TreeFamTF316650.

Gene expression databases

ArrayExpressP49117.
BgeeP49117.
CleanExMM_NR2C2.
GenevestigatorP49117.

Family and domain databases

Gene3D1.10.565.10. 3 hits.
3.30.50.10. 1 hit.
InterProIPR008946. 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]
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 2 hits.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNR2C2. mouse.
NextBio301768.
PROP49117.
SOURCESearch...

Entry information

Entry nameNR2C2_MOUSE
AccessionPrimary (citable) accession number: P49117
Secondary accession number(s): P55093
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot