NR2C2_RAT
ID NR2C2_RAT Reviewed; 596 AA.
AC P55094;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 25-MAY-2022, entry version 147.
DE RecName: Full=Nuclear receptor subfamily 2 group C member 2;
DE AltName: Full=Orphan nuclear receptor TR4;
DE AltName: Full=Testicular receptor 4;
GN Name=Nr2c2; Synonyms=Tr4;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Hypothalamus, and Prostate;
RX PubMed=8016112; DOI=10.1073/pnas.91.13.6040;
RA Chang C., da Silva S.L., Ideta R., Lee Y., Yeh S., Burbach J.P.;
RT "Human and rat TR4 orphan receptors specify a subclass of the steroid
RT receptor superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6040-6044(1994).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=9556573; DOI=10.1074/jbc.273.18.10948;
RA Yan Z.H., Karam W.G., Staudinger J.L., Medvedev A., Ghanayem B.I.,
RA Jetten A.M.;
RT "Regulation of peroxisome proliferator-activated receptor alpha-induced
RT transactivation by the nuclear orphan receptor TAK1/TR4.";
RL J. Biol. Chem. 273:10948-10957(1998).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Orphan nuclear receptor that can act as a repressor or
CC activator of transcription. An important repressor of nuclear receptor
CC signaling pathways such as retinoic acid receptor, retinoid X, vitamin
CC D3 receptor, thyroid hormone receptor and estrogen receptor pathways.
CC May regulate gene expression during the late phase of spermatogenesis.
CC Activates transcriptional activity of LHCG and is antagonist of PPARA-
CC mediated transactivation. Together with NR2C1, forms the core of the
CC DRED (direct repeat erythroid-definitive) complex that represses
CC embryonic and fetal globin transcription including that of GATA1. Binds
CC to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half
CC site direct repeat consensus sequences. Plays a fundamental role in
CC early embryonic development and embryonic stem cells. Required for
CC normal spermatogenesis and cerebellum development. Appears to be
CC important for neurodevelopmentally regulated behavior (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; can bind DNA as homodimer. Heterodimer; binds DNA
CC as a heterodimer with NR2C1 required for chromatin remodeling and for
CC binding to promoter regions such as globin DR1 repeats. Interacts with
CC NR2C2AP; the interaction represses selective NR2C2-mediated
CC transcriptional activity. Interacts with PCAF; the interaction
CC preferentially occurs on the non-phosphorylated form and induces NR2C2-
CC mediated transactivation activity and does not require the ligand-
CC binding domain. Interacts (MAPK-mediated phosphorylated form) with
CC NRIP1; the interaction promotes repression of NR2C2-mediated activity.
CC Interacts with NLRP10. Interacts (via ligand-binding region) with
CC transcriptional corepressor JAZF1; the interaction promotes NR2C2-
CC mediated transcriptional repression. {ECO:0000250|UniProtKB:P49116,
CC ECO:0000250|UniProtKB:P49117}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- TISSUE SPECIFICITY: Expressed in hepatocytes. Also expressed in granule
CC cells of the hippocampus and the cerebellum.
CC {ECO:0000269|PubMed:8016112, ECO:0000269|PubMed:9556573}.
CC -!- PTM: Phosphorylation on Ser-19 and Ser-68 is an important regulator of
CC NR2C2-mediated transcriptional activity. Phosphorylation on these
CC residues recruits the corepressor, NRIP1, leading to transcripional
CC repression, whereas the non-phosphorylated form preferentially recruits
CC the coactivator, PCAF (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L27513; AAA21475.1; -; mRNA.
DR PIR; I80177; I80177.
DR RefSeq; NP_059019.1; NM_017323.1.
DR AlphaFoldDB; P55094; -.
DR STRING; 10116.ENSRNOP00000014354; -.
DR iPTMnet; P55094; -.
DR PhosphoSitePlus; P55094; -.
DR PaxDb; P55094; -.
DR GeneID; 50659; -.
DR KEGG; rno:50659; -.
DR UCSC; RGD:3201; rat.
DR CTD; 7182; -.
DR RGD; 3201; Nr2c2.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; P55094; -.
DR OrthoDB; 278171at2759; -.
DR PhylomeDB; P55094; -.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR PRO; PR:P55094; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F: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:0021549; P:cerebellum development; ISO:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0051321; P:meiotic cell cycle; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0038066; P:p38MAPK cascade; ISO:RGD.
DR GO; GO:0048520; P:positive regulation of behavior; ISO:RGD.
DR GO; GO:0040019; P:positive regulation of embryonic development; ISO:RGD.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
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 1: Evidence at protein level;
KW Acetylation; Activator; Differentiation; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Repressor; Spermatogenesis; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..596
FT /note="Nuclear receptor subfamily 2 group C member 2"
FT /id="PRO_0000053590"
FT DOMAIN 341..583
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 114..189
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 117..137
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 153..177
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT MOD_RES 19
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P49116"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49116"
FT MOD_RES 55
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P49117"
FT MOD_RES 68
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P49116"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49116"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 231
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49117"
FT CROSSLNK 192
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P49116"
SQ SEQUENCE 596 AA; 65344 MW; A5A7E7C1FFBB6B70 CRC64;
MTSPSPRIQI ISTDSAVRSP QRIQIVTDQQ TGQKLQIVTA VDASGSSKQQ FILTSPDGAG
TGKVILASPE TSSAKQLIFT TSDNLVPGRI QIVTDSASVE RLLGKADVQR PQVVEYCVVC
GDKASGRHYG AVSCEGCKGF FKRSVRKNLT YSCRSSQDCI INKHHRNRCQ FCRLKKCLEM
GMKMESVQSE RKPFDVQREK PSNCAASTEK IYIRKDLRSP LIATPTFVAD KDGSRQTGLL
DPGMLVNIQQ PLIREDGTVL LATDSKAETS QGALGTLANV VTSLANLSES LNNGDASEMQ
PEDQSASEIT RAFDTLAKAL NTTDSASPPS LADGIDASGG GSIHVISRDQ STPIIEVEGP
LLSDTHVTFK LTMPSPMPEY LNVHYICESA SRLLFLSMHW ARSIPAFQAL GQDCNTSLVR
ACWNELFTLG LAQCAQVMSL STILAAIVNH LQNSIQEDKL SGDRIKQVME HIWKLQEFCN
SMAKLDIDGH EYAYLKAIVL FSPDHPGLTG TSQIEKFQEK AQMELQDYVQ KTYSEDTYRL
ARILVRLPAL RLMSSNITEE LFFTGLIGNV SIDSIIPYIL KMETAEYNGQ ITGASL
