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Protein

Nuclear receptor subfamily 2 group C member 2

Gene

Nr2c2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene 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)DescriptionActionsGraphical viewLength
DNA bindingi114 – 189Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri117 – 137NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri153 – 177NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • cerebellum development Source: UniProtKB
  • meiotic cell cycle Source: MGI
  • mitophagy in response to mitochondrial depolarization Source: Ensembl
  • p38MAPK cascade Source: CACAO
  • positive regulation of behavior Source: UniProtKB
  • positive regulation of embryonic development Source: UniProtKB
  • positive regulation of myoblast differentiation Source: CACAO
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • spermatogenesis Source: MGI
  • 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

Enzyme and pathway databases

ReactomeiR-MMU-383280. Nuclear Receptor transcription pathway.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1352466. Nr2c2.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Mutagenesisi15S → A: Enhanced transcriptional activation; Greatly enhanced transcriptional activation; when associated with A-68. 1
Mutagenesisi19S → E: Some repression of transcriptional activation; Repressed transcriptional activity by about 10-fold; when associated with E-68. 1 Publication1
Mutagenesisi55S → A: No effect on transcriptional activation. 1 Publication1
Mutagenesisi68S → A: Enhanced transcriptional activation; Greatly enhanced transcriptional activation; when associated with A-15. 1 Publication1
Mutagenesisi68S → E: Some repression of transcriptional activation; Repressed transcriptional activity by about 10-fold; when associated with E-19. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535891 – 596Nuclear receptor subfamily 2 group C member 2Add BLAST596

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Phosphoserine; by MAPK1 Publication1
Modified residuei46PhosphoserineBy similarity1
Modified residuei55Phosphoserine; by MAPK1 Publication1
Modified residuei68Phosphoserine; by MAPK1 Publication1
Modified residuei98PhosphoserineBy similarity1
Modified residuei219PhosphoserineBy similarity1
Modified residuei224PhosphothreonineBy similarity1
Modified residuei231N6-acetyllysineCombined sources1

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

EPDiP49117.
PaxDbiP49117.
PRIDEiP49117.

PTM databases

iPTMnetiP49117.
PhosphoSitePlusiP49117.

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

BgeeiENSMUSG00000005893.
CleanExiMM_NR2C2.
ExpressionAtlasiP49117. baseline and differential.
GenevisibleiP49117. MM.

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 (PubMed:16887930). Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity (PubMed:16887930). Interacts with NLRP10. Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2-mediated transcriptional repression (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiP49117. 1 interactor.
MINTiMINT-6797261.
STRINGi10090.ENSMUSP00000109087.

Structurei

3D structure databases

ProteinModelPortaliP49117.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni388 – 554Ligand-bindingBy similarityAdd BLAST167

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri117 – 137NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri153 – 177NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000013058.
HOVERGENiHBG008596.
InParanoidiP49117.
KOiK08544.
PhylomeDBiP49117.
TreeFamiTF316650.

Family and domain databases

Gene3Di1.10.565.10. 3 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_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 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAC18408 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60G → E in AAC18408 (PubMed:7841789).Curated1
Sequence conflicti106A → Q in AAC18408 (PubMed:7841789).Curated1
Sequence conflicti122D → V in AAC18408 (PubMed:7841789).Curated1
Sequence conflicti247N → K in AAC18408 (PubMed:7841789).Curated1
Sequence conflicti263A → T in AAC18408 (PubMed:7841789).Curated1
Sequence conflicti323T → I in AAC18408 (PubMed:7841789).Curated1
Sequence conflicti327 – 328SP → CF in AAC18408 (PubMed:7841789).Curated2
Sequence conflicti337A → T in AAC18408 (PubMed:7841789).Curated1
Sequence conflicti484 – 485KL → NW in AAC18408 (PubMed:7841789).Curated2
Sequence conflicti510G → S in AAC18408 (PubMed:7841789).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006505904.3.
XP_006505968.1. XM_006505905.3.
XP_006505969.1. XM_006505906.3.
UniGeneiMm.442385.
Mm.87062.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006505904.3.
XP_006505968.1. XM_006505905.3.
XP_006505969.1. XM_006505906.3.
UniGeneiMm.442385.
Mm.87062.

3D structure databases

ProteinModelPortaliP49117.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP49117. 1 interactor.
MINTiMINT-6797261.
STRINGi10090.ENSMUSP00000109087.

PTM databases

iPTMnetiP49117.
PhosphoSitePlusiP49117.

Proteomic databases

EPDiP49117.
PaxDbiP49117.
PRIDEiP49117.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7182.
MGIiMGI:1352466. Nr2c2.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000013058.
HOVERGENiHBG008596.
InParanoidiP49117.
KOiK08544.
PhylomeDBiP49117.
TreeFamiTF316650.

Enzyme and pathway databases

ReactomeiR-MMU-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

PROiP49117.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000005893.
CleanExiMM_NR2C2.
ExpressionAtlasiP49117. baseline and differential.
GenevisibleiP49117. MM.

Family and domain databases

Gene3Di1.10.565.10. 3 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_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]
ProtoNetiSearch...

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: November 30, 2016
This is version 149 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

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 one 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.