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Protein

Nuclear receptor subfamily 2 group C member 1

Gene

Nr2c1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes including ESR1 and RARB. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences (By similarity). Also activator of OCT4 gene expression. Plays a fundamental role in early embryogenesis and regulates embryonic stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation.By similarity13 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi98 – 173Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri101 – 121NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri137 – 156NR C4-typePROSITE-ProRule annotationAdd BLAST20

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Receptor, Repressor
Biological processTranscription, Transcription regulation
LigandMetal-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 1
Alternative name(s):
Orphan nuclear receptor TR2
Testicular receptor 2
Short name:
mTR2
Gene namesi
Name:Nr2c1Imported
Synonyms:Tr2, Tr2-11Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1352465 Nr2c1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice exhibit normal spermatogenesis and testis development, as well as normal central nervous system development. NR2C1 and NR2C2 double null mutants result in early embryonic lethality and increased apoptosis. Embryos die around 7.5 dpc.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi167K → A: No effect on sumoylation. 1 Publication1
Mutagenesisi170S → A: No effect on sumoylation nor on DNA-binding and little effect on binding KAT2B. Greatly reduced DNA-binding, binding to KAT2B and activation of the RARB promoter; when associated with A-185. 2 Publications1
Mutagenesisi185S → A: No effect on sumoylation and little effect on binding KAT2B. Some reduced DNA-binding. Greatly reduced DNA-binding, binding to KAT2B and activation of the RARB promoter; when associated with A-170. 2 Publications1
Mutagenesisi203S → A: No effect on sumoylation. 1 Publication1
Mutagenesisi208T → A: No effect on sumoylation. 1 Publication1
Mutagenesisi210T → A: Abolishes sumoylation. No repression of OCT4 gene expression with or without retinoic acid and enhanced interaction with KAT2B and HDAC3. Abolishes interaction with HDAC3 and PML association; when associated with R-238. 1 Publication1
Mutagenesisi210T → E: Sumoylated. Repressed OCT4 gene expression. Enhanced interaction with KAT2B; when associated with R-238. 1 Publication1
Mutagenesisi238K → A: Abolishes sumoylation. Strongly associated with PML nuclear bodies. No effect on activation of OCT4 but activation not suppressed by additional SUMO1. Increased binding to KAT2B and reduced binding to NRIP1. Abolishes PML association; when associated with A-210. 2 Publications1
Mutagenesisi238K → R: Abolishes sumoylation. No effect on activation of OCT4 but activation not suppressed by additional SUMO1. Enhanced interaction with KAT2B; when associated with A-210 or E-210. 2 Publications1
Mutagenesisi240E → A: Abolishes sumoylation. 1 Publication1
Mutagenesisi461S → A: Little effect on PKC-stimulated protein stability nor on activation of RARB reporter. 1 Publication1
Mutagenesisi461S → A: No effect on sumoylation. 1 Publication1
Mutagenesisi568S → A: Greatly reduced PKC-stimulated protein stability and activation of RARB reporter. 1 Publication1
Mutagenesisi568S → A: No effect on sumoylation. 1 Publication1
Mutagenesisi575K → R: No effect on sumoylation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535871 – 590Nuclear receptor subfamily 2 group C member 1Add BLAST590

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei185Phosphoserine1 Publication1
Modified residuei203Phosphoserine1 Publication1
Modified residuei208Phosphothreonine1 Publication1
Modified residuei210Phosphothreonine; by MAPK11 Publication1
Cross-linki238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei461Phosphoserine; by PKC1 Publication1
Modified residuei568Phosphoserine; by PKC1 Publication1
Cross-linki575Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction with NRIP1 but inhibits interaction with KAT2B. In proliferating cells, stimulation by all-trans retinoic acid, activation of MAPK1-mediated phosphorylation and recruitment to PML bodies with subsequent sumoylation, suppresses OCT4 expression.
Phosphorylated on several serine and threonine residues. Phosphorylation on Thr-210, stimulated by all-trans retinoic acid (atRA) mediates PML location and sumoylation in proliferating cells which then modulates its association with effector molecules, KAT2B and NRIP1. Phosphorylation on Ser-568 by PKC is important for protein stability and function as activator of RARB.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ505F1
PeptideAtlasiQ505F1
PRIDEiQ505F1

PTM databases

iPTMnetiQ505F1
PhosphoSitePlusiQ505F1

Expressioni

Tissue specificityi

Isoform 1 is highly expressed in the adlumenal compartment of the seminiferous tubule of adult testes (at protein level) and in the eyes of newborn animals. Weakly expressed in other adult organs including the seminal vesicle, prostate, ovary, adrenal gland, heart, thymus, placenta and brain. Expressed during embryonic stages in developing eyes, brain and cartilage primordia (at protein level). Also expressed in the developing spinal motor neurons and in the sympathetic-, parasympathetic- and sensory ganglia of the embryonic PNS. Expressed in the developing neural epithelia of the inner ear, nasal cavity, tongue and retina. At day 16.5, expressed in various tissues including kidney and intestine. In contrast, isoform 2 is widely expressed at a low level throughout the adult testis.7 Publications

Developmental stagei

Isoform 1 is highly expressed in early to midgestation embryos, with expression leveling off at 15 dpc. Expressed in yolk sac erythrocytes at 9.5 dpc. After birth, expression in the testes remains at a basal level until puberty, begins to increase at postnatal day 16 (P16) and peaks at P20 to P24. Expression is maintained at a high level throughout adulthood. Isoform 2 peaks transiently at P24.4 Publications

Inductioni

By ciliary neurotrophic factor (CNTF). Repressed by vitamin A. Induced by retinoic acid.2 Publications

Gene expression databases

BgeeiENSMUSG00000005897 Expressed in 255 organ(s), highest expression level in retina
CleanExiMM_NR2C1
GenevisibleiQ505F1 MM

Interactioni

Subunit structurei

Homodimer. Heterodimer; with NR2C2 which is required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth (By similarity). Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain); the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression.By similarity6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204299, 2 interactors
DIPiDIP-29275N
IntActiQ505F1, 7 interactors
STRINGi10090.ENSMUSP00000089858

Structurei

3D structure databases

ProteinModelPortaliQ505F1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini333 – 577NR LBDPROSITE-ProRule annotationAdd BLAST245

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 166Required for interaction with KAT2BAdd BLAST166
Regioni571 – 590Required for interaction with NRIP1Add BLAST20

Sequence similaritiesi

Belongs to the nuclear hormone receptor family. NR2 subfamily.Sequence analysis

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri101 – 121NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri137 – 156NR C4-typePROSITE-ProRule annotationAdd BLAST20

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118948
HOVERGENiHBG008596
InParanoidiQ505F1
KOiK08543
OMAiKAYMEFQ
OrthoDBiEOG091G099H
TreeFamiTF316650

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 13 Publications (identifier: Q505F1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MATIEEIAHQ IIDQQMGEIV TEQQTGQKIQ IVTALDHSTQ GKQFILANHE
60 70 80 90 100
GSTPGKVFLT TPDAAGVNQL FFTSPDLSAP HLQLLTEKSP DQGPNKVFDL
110 120 130 140 150
CVVCGDKASG RHYGAITCEG CKGFFKRSIR KNLVYSCRGS KDCVINKHHR
160 170 180 190 200
NRCQYCRLQR CIAFGMKQDS VQCERKPIEV SREKSSNCAA STEKIYIRKD
210 220 230 240 250
LRSPLAATPT FVTDSETARS AGLLDSGMFV NIHPSGIKTE PAMLMAPDKA
260 270 280 290 300
ESCQGDLSTL ASVVTSLANL GKAKDLSHCG GDMPVVQSLR NGDTSFGAFH
310 320 330 340 350
HDIQTNGDVS RAFDTLAKAL TPGESSACQS PEEGMEGSPH LIAGEPSFVE
360 370 380 390 400
KEGPLLSESH VAFRLTMPSP MPEYLNVHYI GESASRLLFL SMHWALSIPS
410 420 430 440 450
FQALGQENSI SLVKAYWNEL FTLGLAQCWQ VMNVATILAT FVNCLHSSLQ
460 470 480 490 500
QDKMSPERRK SLMEHIFKLQ EFCNSMVKLC IDGHEYAYLK AIVLFSPDHP
510 520 530 540 550
GLENMELIER FQEKAYVEFQ DYITRTYPDD TYRLSRLLLR LPALRLMNAT
560 570 580 590
ITEELFFKGL IGNVRIDSVI PHILKMEPAD YNSQIIGHSL
Length:590
Mass (Da):65,476
Last modified:July 27, 2011 - v3
Checksum:iE639AF3E5312918D
GO
Isoform 21 Publication (identifier: Q505F1-2) [UniParc]FASTAAdd to basket
Also known as: TR2-11-t1 Publication, TR2-11-truncated1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     220-256: SAGLLDSGMFVNIHPSGIKTEPAMLMAPDKAESCQGD → CPAAISASFASLPRSTETKTCASFVAGQLDCWIQECL
     257-590: Missing.

Note: Due to intron retention.1 Publication
Show »
Length:256
Mass (Da):28,225
Checksum:i53064D53EEB1C54A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88K → N in CAA72244 (PubMed:9504722).Curated1
Sequence conflicti88K → N in AAC29502 (PubMed:9694834).Curated1
Sequence conflicti88K → N in AAL31315 (Ref. 6) Curated1
Sequence conflicti200D → N in AAC29502 (PubMed:9694834).Curated1
Sequence conflicti200D → N in AAL31315 (Ref. 6) Curated1
Sequence conflicti273A → T in AAC29502 (PubMed:9694834).Curated1
Sequence conflicti273A → T in AAL31315 (Ref. 6) Curated1
Sequence conflicti326 – 327SA → TS in AAC52787 (PubMed:8595902).Curated2
Sequence conflicti326 – 327SA → TS in AAC53253 (PubMed:8595902).Curated2
Sequence conflicti326 – 327SA → TS in CAA72244 (PubMed:9504722).Curated2
Sequence conflicti326 – 327SA → TS in AAL31315 (Ref. 6) Curated2
Sequence conflicti331P → S in AAC29502 (PubMed:9694834).Curated1
Sequence conflicti331P → S in AAL31315 (Ref. 6) Curated1
Sequence conflicti529D → N in BAE27509 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti29I → M in strain: CD-1. 2 Publications1
Natural varianti145I → M in strain: CD-1. 2 Publications1
Natural varianti296 – 304FGAFHHDIQ → SVLFIMIFK in strain: CD-1. 2 Publications9
Natural varianti361V → I in strain: CD-1. 2 Publications1
Natural varianti377V → A in strain: CD-1. 2 Publications1
Natural varianti456P → A in strain: CD-1. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_051921220 – 256SAGLL…SCQGD → CPAAISASFASLPRSTETKT CASFVAGQLDCWIQECL in isoform 2. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_051922257 – 590Missing in isoform 2. 1 PublicationAdd BLAST334

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28280
, U28269, U28270, U28271, U28272, U28273, U28274, U28275, U28276, U28277, U28278, U28279 Genomic DNA Translation: AAC53253.1
U28265 mRNA Translation: AAC52787.1
Y11436 mRNA Translation: CAA72244.1
U30482 mRNA Translation: AAC29502.1
L26957 mRNA Translation: AAL31315.1
AK146891 mRNA Translation: BAE27509.1
AK149374 mRNA Translation: BAE28842.1
AC127596 Genomic DNA No translation available.
AC138026 Genomic DNA No translation available.
BC090662 mRNA Translation: AAH90662.1
BC094580 mRNA Translation: AAH94580.1
CCDSiCCDS24131.1 [Q505F1-1]
RefSeqiNP_035759.3, NM_011629.3 [Q505F1-1]
XP_006513655.1, XM_006513592.2 [Q505F1-1]
UniGeneiMm.107483

Genome annotation databases

EnsembliENSMUST00000092213; ENSMUSP00000089858; ENSMUSG00000005897 [Q505F1-1]
ENSMUST00000099343; ENSMUSP00000096945; ENSMUSG00000005897 [Q505F1-1]
ENSMUST00000105290; ENSMUSP00000100927; ENSMUSG00000005897 [Q505F1-1]
GeneIDi22025
KEGGimmu:22025
UCSCiuc007gvo.2 mouse [Q505F1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28280
, U28269, U28270, U28271, U28272, U28273, U28274, U28275, U28276, U28277, U28278, U28279 Genomic DNA Translation: AAC53253.1
U28265 mRNA Translation: AAC52787.1
Y11436 mRNA Translation: CAA72244.1
U30482 mRNA Translation: AAC29502.1
L26957 mRNA Translation: AAL31315.1
AK146891 mRNA Translation: BAE27509.1
AK149374 mRNA Translation: BAE28842.1
AC127596 Genomic DNA No translation available.
AC138026 Genomic DNA No translation available.
BC090662 mRNA Translation: AAH90662.1
BC094580 mRNA Translation: AAH94580.1
CCDSiCCDS24131.1 [Q505F1-1]
RefSeqiNP_035759.3, NM_011629.3 [Q505F1-1]
XP_006513655.1, XM_006513592.2 [Q505F1-1]
UniGeneiMm.107483

3D structure databases

ProteinModelPortaliQ505F1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204299, 2 interactors
DIPiDIP-29275N
IntActiQ505F1, 7 interactors
STRINGi10090.ENSMUSP00000089858

PTM databases

iPTMnetiQ505F1
PhosphoSitePlusiQ505F1

Proteomic databases

PaxDbiQ505F1
PeptideAtlasiQ505F1
PRIDEiQ505F1

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000092213; ENSMUSP00000089858; ENSMUSG00000005897 [Q505F1-1]
ENSMUST00000099343; ENSMUSP00000096945; ENSMUSG00000005897 [Q505F1-1]
ENSMUST00000105290; ENSMUSP00000100927; ENSMUSG00000005897 [Q505F1-1]
GeneIDi22025
KEGGimmu:22025
UCSCiuc007gvo.2 mouse [Q505F1-1]

Organism-specific databases

CTDi7181
MGIiMGI:1352465 Nr2c1

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118948
HOVERGENiHBG008596
InParanoidiQ505F1
KOiK08543
OMAiKAYMEFQ
OrthoDBiEOG091G099H
TreeFamiTF316650

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway

Miscellaneous databases

ChiTaRSiNr2c1 mouse
PROiPR:Q505F1
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000005897 Expressed in 255 organ(s), highest expression level in retina
CleanExiMM_NR2C1
GenevisibleiQ505F1 MM

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNR2C1_MOUSE
AccessioniPrimary (citable) accession number: Q505F1
Secondary accession number(s): P97763
, Q0VGP8, Q3UIJ7, Q4U1Z4, Q60927, Q62152, Q8VIJ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 125 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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