NR2C1_RAT
ID NR2C1_RAT Reviewed; 590 AA.
AC Q8VIJ4;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Nuclear receptor subfamily 2 group C member 1;
DE AltName: Full=Orphan nuclear receptor TR2;
DE AltName: Full=Testicular receptor 2;
GN Name=Nr2c1; Synonyms=Tr2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RA Ideta R., Adachi K., Takeda H., Chang C., Yeh S., Lee Y., Su C.;
RT "Gene expression of the androgen repressed rat TR2 orphan receptor: a
RT member of steroid receptor superfamily.";
RL Endocr. J. 3:277-283(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Orphan nuclear receptor. Binds the IR7 element in the
CC promoter of its own gene in an autoregulatory negative feedback
CC mechanism. Primarily repressor of a broad range of genes including ESR1
CC and RARB. Together with NR2C2, forms the core of the DRED (direct
CC repeat erythroid-definitive) complex that represses embryonic and fetal
CC globin transcription. Binds to hormone response elements (HREs)
CC consisting of two 5'-AGGTCA-3' half site direct repeat consensus
CC sequences. Also activator of OCT4 gene expression. Plays a fundamental
CC role in early embryogenesis and regulates embryonic stem cell
CC proliferation and differentiation. Mediator of retinoic acid-regulated
CC preadipocyte proliferation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer; with NR2C2 which is
CC required for chromatin remodeling and for binding to promoter regions
CC such as globin DR1 repeats (By similarity). Interacts with ESR1; the
CC interaction prevents homodimerization of ESR1 and suppresses its
CC transcriptional activity and cell growth. Interacts with NRIP1 (via its
CC LXXLL motifs); the interaction provides corepressor activity. Interacts
CC with HDAC3 (via the DNA-binding domain); the interaction recruits
CC phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with
CC HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the
CC interaction is required for sumoylation of NR2C1. Interacts with UBE2I;
CC the interaction is required for sumoylation of NR2C1. Interacts with
CC KAT2B; the interaction acts as a corepressor of gene expression (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC Nucleus, PML body {ECO:0000250}. Note=Recruited by HDAC3, after all-
CC trans retinoic acid stimulated MAPK1-mediated Thr-210 phosphorylation,
CC to PML bodies for subsequent sumoylation. {ECO:0000250}.
CC -!- PTM: Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to
CC dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction
CC with NRIP1 but inhibits interaction with KAT2B. In proliferating cells,
CC stimulation by all-trans retinoic acid, activation of MAPK1-mediated
CC phosphorylation and recruitment to PML bodies with subsequent
CC sumoylation, suppresses OCT4 expression (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on several serine and threonine residues.
CC Phosphorylation on Thr-210, stimulated by all-trans retinoic acid
CC (atRA) mediates PML location and sumoylation in proliferating cells
CC which then modulates its association with effector molecules, KAT2B and
CC NRIP1. Phosphorylation on Ser-568 by PKC is important for protein
CC stability and function as activator of RARB (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
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DR EMBL; L26398; AAL31316.1; -; mRNA.
DR EMBL; CH473960; EDM16889.1; -; Genomic_DNA.
DR EMBL; BC061822; AAH61822.1; -; mRNA.
DR RefSeq; NP_665723.1; NM_145780.1.
DR RefSeq; XP_008763438.1; XM_008765216.2.
DR RefSeq; XP_017450160.1; XM_017594671.1.
DR AlphaFoldDB; Q8VIJ4; -.
DR STRING; 10116.ENSRNOP00000009578; -.
DR BindingDB; Q8VIJ4; -.
DR PhosphoSitePlus; Q8VIJ4; -.
DR PaxDb; Q8VIJ4; -.
DR PRIDE; Q8VIJ4; -.
DR Ensembl; ENSRNOT00000009578; ENSRNOP00000009578; ENSRNOG00000006983.
DR GeneID; 252924; -.
DR KEGG; rno:252924; -.
DR UCSC; RGD:3200; rat.
DR CTD; 7181; -.
DR RGD; 3200; Nr2c1.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000158165; -.
DR InParanoid; Q8VIJ4; -.
DR OMA; RKPIEMS; -.
DR OrthoDB; 278171at2759; -.
DR PhylomeDB; Q8VIJ4; -.
DR TreeFam; TF316650; -.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR PRO; PR:Q8VIJ4; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Proteomes; UP000234681; Chromosome 7.
DR Bgee; ENSRNOG00000006983; Expressed in testis and 19 other tissues.
DR Genevisible; Q8VIJ4; RN.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0016605; C:PML body; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 2: Evidence at transcript level;
KW Activator; DNA-binding; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..590
FT /note="Nuclear receptor subfamily 2 group C member 1"
FT /id="PRO_0000369405"
FT DOMAIN 333..577
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 98..173
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 101..121
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 137..156
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..166
FT /note="Required for interaction with KAT2B"
FT /evidence="ECO:0000250"
FT REGION 571..590
FT /note="Required for interaction with NRIP1"
FT /evidence="ECO:0000250"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q505F1"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT MOD_RES 208
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT MOD_RES 210
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q505F1"
FT MOD_RES 568
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q505F1"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT CROSSLNK 575
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P13056"
SQ SEQUENCE 590 AA; 65528 MW; 000311C5FB6BA86F CRC64;
MATIEEIAHQ IIDQQMGEIV TEQQTGQKIQ IVTALDHSTQ GKQFILANHE GSTPGKVFLT
TPDAAGVNQL FFASPDLSTP HLQLLTENSP DQGPNKVFDL CVVCGDKASG RHYGAITCEG
CKGFFKRSIR KNLVYSCRGS KDCIINKHHR NRCQYCRLQR CIAFGMKQDS VQCERKPIEV
SREKSSNCAA STEKIYIRKD LRSPLAATPT FVTDSETARS TGLLDSGMFV NIHPSGIKTE
PALLMTPDKA ESCQGDLGTL ASVVTSLANL GKAKDLSHCG GDLPVVQSLR NGDTSFGAFH
QDIQTNGDVS RAFDNLAKAL TPGENPACQS PGESMEGSTH LIAGEPSCME REGPLLSDSH
VVFRLTMPSP MPEYLNVHYI GESASRLLFL SMHWALSIPS FQALGQENSI SLVKAYWNEL
FTLGLAQCWQ VMNVATILAT FVNCLHNSLQ QDKMSPERRK LLMEHIFKLQ EFCNSMVKLC
IDGHEYAYLK AIVLFSPDHP GLENMELIEK FQEKAYVEFQ DYITRTYPDD TYRLSRLLLR
LPALRLMNAT ITEELFFKGL IGNVRIDSVI PHILKMEPAD YNSQIIGHSL
