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Protein

Nuclear receptor subfamily 2 group C member 1

Gene

Nr2c1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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. 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 similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi98 – 17376Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri101 – 12121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri137 – 15620NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-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
Gene namesi
Name:Nr2c1
Synonyms:Tr2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi3200. Nr2c1.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation
  • NucleusPML body By similarity

  • Note: Recruited by HDAC3, after all-trans retinoic acid stimulated MAPK1-mediated Thr-210 phosphorylation, to PML bodies for subsequent sumoylation.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 590590Nuclear receptor subfamily 2 group C member 1PRO_0000369405Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei185 – 1851PhosphoserineBy similarity
Modified residuei203 – 2031PhosphoserineBy similarity
Modified residuei208 – 2081PhosphothreonineBy similarity
Modified residuei210 – 2101Phosphothreonine; by MAPK1By similarity
Cross-linki238 – 238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei568 – 5681Phosphoserine; by PKCBy 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 (By similarity).By similarity
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 (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8VIJ4.
PRIDEiQ8VIJ4.

PTM databases

PhosphoSiteiQ8VIJ4.

Expressioni

Gene expression databases

BgeeiENSRNOG00000006983.
GenevisibleiQ8VIJ4. RN.

Interactioni

Subunit structurei

Homodimer (By similarity). Heterodimer; with NR2C2 which is required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats (By similarity). Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. 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 similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009578.

Structurei

3D structure databases

ProteinModelPortaliQ8VIJ4.
SMRiQ8VIJ4. Positions 100-176.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 166166Required for interaction with KAT2BBy similarityAdd
BLAST
Regioni571 – 59020Required for interaction with NRIP1By similarityAdd
BLAST

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri101 – 12121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri137 – 15620NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000013058.
InParanoidiQ8VIJ4.
KOiK08543.
OMAiQEMQTNG.
OrthoDBiEOG091G099H.
PhylomeDBiQ8VIJ4.
TreeFamiTF316650.

Family and domain databases

Gene3Di1.10.565.10. 2 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.

Q8VIJ4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATIEEIAHQ IIDQQMGEIV TEQQTGQKIQ IVTALDHSTQ GKQFILANHE
60 70 80 90 100
GSTPGKVFLT TPDAAGVNQL FFASPDLSTP HLQLLTENSP DQGPNKVFDL
110 120 130 140 150
CVVCGDKASG RHYGAITCEG CKGFFKRSIR KNLVYSCRGS KDCIINKHHR
160 170 180 190 200
NRCQYCRLQR CIAFGMKQDS VQCERKPIEV SREKSSNCAA STEKIYIRKD
210 220 230 240 250
LRSPLAATPT FVTDSETARS TGLLDSGMFV NIHPSGIKTE PALLMTPDKA
260 270 280 290 300
ESCQGDLGTL ASVVTSLANL GKAKDLSHCG GDLPVVQSLR NGDTSFGAFH
310 320 330 340 350
QDIQTNGDVS RAFDNLAKAL TPGENPACQS PGESMEGSTH LIAGEPSCME
360 370 380 390 400
REGPLLSDSH VVFRLTMPSP MPEYLNVHYI GESASRLLFL SMHWALSIPS
410 420 430 440 450
FQALGQENSI SLVKAYWNEL FTLGLAQCWQ VMNVATILAT FVNCLHNSLQ
460 470 480 490 500
QDKMSPERRK LLMEHIFKLQ EFCNSMVKLC IDGHEYAYLK AIVLFSPDHP
510 520 530 540 550
GLENMELIEK FQEKAYVEFQ DYITRTYPDD TYRLSRLLLR LPALRLMNAT
560 570 580 590
ITEELFFKGL IGNVRIDSVI PHILKMEPAD YNSQIIGHSL
Length:590
Mass (Da):65,528
Last modified:March 1, 2002 - v1
Checksum:i000311C5FB6BA86F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L26398 mRNA. Translation: AAL31316.1.
CH473960 Genomic DNA. Translation: EDM16889.1.
BC061822 mRNA. Translation: AAH61822.1.
RefSeqiNP_665723.1. NM_145780.1.
XP_008763438.1. XM_008765216.1.
XP_008763439.1. XM_008765217.1.
UniGeneiRn.79894.

Genome annotation databases

EnsembliENSRNOT00000009578; ENSRNOP00000009578; ENSRNOG00000006983.
ENSRNOT00000089228; ENSRNOP00000071901; ENSRNOG00000006983.
GeneIDi252924.
KEGGirno:252924.
UCSCiRGD:3200. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L26398 mRNA. Translation: AAL31316.1.
CH473960 Genomic DNA. Translation: EDM16889.1.
BC061822 mRNA. Translation: AAH61822.1.
RefSeqiNP_665723.1. NM_145780.1.
XP_008763438.1. XM_008765216.1.
XP_008763439.1. XM_008765217.1.
UniGeneiRn.79894.

3D structure databases

ProteinModelPortaliQ8VIJ4.
SMRiQ8VIJ4. Positions 100-176.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009578.

PTM databases

PhosphoSiteiQ8VIJ4.

Proteomic databases

PaxDbiQ8VIJ4.
PRIDEiQ8VIJ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000009578; ENSRNOP00000009578; ENSRNOG00000006983.
ENSRNOT00000089228; ENSRNOP00000071901; ENSRNOG00000006983.
GeneIDi252924.
KEGGirno:252924.
UCSCiRGD:3200. rat.

Organism-specific databases

CTDi7181.
RGDi3200. Nr2c1.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000013058.
InParanoidiQ8VIJ4.
KOiK08543.
OMAiQEMQTNG.
OrthoDBiEOG091G099H.
PhylomeDBiQ8VIJ4.
TreeFamiTF316650.

Enzyme and pathway databases

ReactomeiR-RNO-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

PROiQ8VIJ4.

Gene expression databases

BgeeiENSRNOG00000006983.
GenevisibleiQ8VIJ4. RN.

Family and domain databases

Gene3Di1.10.565.10. 2 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 nameiNR2C1_RAT
AccessioniPrimary (citable) accession number: Q8VIJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: March 1, 2002
Last modified: September 7, 2016
This is version 109 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. 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.