NR0B2_MOUSE
ID NR0B2_MOUSE Reviewed; 260 AA.
AC Q62227; Q53Z53;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Nuclear receptor subfamily 0 group B member 2;
DE AltName: Full=Orphan nuclear receptor SHP;
DE AltName: Full=Small heterodimer partner;
GN Name=Nr0b2; Synonyms=Shp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INTERACTION WITH RARA;
RP RXRA; THRB; NR5A2 AND NR1I3.
RC TISSUE=Liver;
RX PubMed=8650544; DOI=10.1126/science.272.5266.1336;
RA Seol W., Choi H.-S., Moore D.D.;
RT "An orphan nuclear hormone receptor that lacks a DNA binding domain and
RT heterodimerizes with other receptors.";
RL Science 272:1336-1339(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=I/LnJ, and PERA/Ei;
RX PubMed=12949731; DOI=10.1016/s0016-5085(03)01053-9;
RA Wittenburg H., Lyons M.A., Li R., Churchill G.A., Carey M.C., Paigen B.;
RT "FXR and ABCG5/ABCG8 as determinants of cholesterol gallstone formation
RT from quantitative trait locus mapping in mice.";
RL Gastroenterology 125:868-881(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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).
RN [4]
RP INTERACTION WITH EID1.
RX PubMed=11964378; DOI=10.1093/embo-reports/kvf087;
RA Bavner A., Johansson L., Toresson G., Gustafsson J.-A., Treuter E.;
RT "A transcriptional inhibitor targeted by the atypical orphan nuclear
RT receptor SHP.";
RL EMBO Rep. 3:478-484(2002).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=14752053; DOI=10.1210/me.2003-0311;
RA Kim J.Y., Chu K., Kim H.J., Seong H.A., Park K.C., Sanyal S., Takeda J.,
RA Ha H., Shong M., Tsai M.J., Choi H.S.;
RT "Orphan nuclear receptor small heterodimer partner, a novel corepressor for
RT a basic helix-loop-helix transcription factor BETA2/neuroD.";
RL Mol. Endocrinol. 18:776-790(2004).
RN [6]
RP METHYLATION AT ARG-57.
RX PubMed=21262773; DOI=10.1128/mcb.01212-10;
RA Kanamaluru D., Xiao Z., Fang S., Choi S.E., Kim D.H., Veenstra T.D.,
RA Kemper J.K.;
RT "Arginine methylation by PRMT5 at a naturally occurring mutation site is
RT critical for liver metabolic regulation by small heterodimer partner.";
RL Mol. Cell. Biol. 31:1540-1550(2011).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH NR1D1 AND RORG, AND TISSUE
RP SPECIFICITY.
RX PubMed=25212631; DOI=10.1002/hep.27437;
RA Lee S.M., Zhang Y., Tsuchiya H., Smalling R., Jetten A.M., Wang L.;
RT "Small heterodimer partner/neuronal PAS domain protein 2 axis regulates the
RT oscillation of liver lipid metabolism.";
RL Hepatology 61:497-505(2015).
RN [8]
RP FUNCTION, AND INTERACTION WITH NFIL3; NR1D1 AND BHLHE41.
RX PubMed=30555544; DOI=10.7150/thno.28676;
RA Zhang T., Yu F., Guo L., Chen M., Yuan X., Wu B.;
RT "Small heterodimer partner regulates circadian cytochromes p450 and drug-
RT induced hepatotoxicity.";
RL Theranostics 8:5246-5258(2018).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 17-30 IN COMPLEX WITH NR5A1.
RX PubMed=15707893; DOI=10.1016/j.cell.2005.01.024;
RA Krylova I.N., Sablin E.P., Moore J., Xu R.X., Waitt G.M., MacKay J.A.,
RA Juzumiene D., Bynum J.M., Madauss K., Montana V., Lebedeva L., Suzawa M.,
RA Williams J.D., Williams S.P., Guy R.K., Thornton J.W., Fletterick R.J.,
RA Willson T.M., Ingraham H.A.;
RT "Structural analyses reveal phosphatidyl inositols as ligands for the NR5
RT orphan receptors SF-1 and LRH-1.";
RL Cell 120:343-355(2005).
CC -!- FUNCTION: Transcriptional regulator that acts as a negative regulator
CC of receptor-dependent signaling pathways (PubMed:8650544). Specifically
CC inhibits transactivation of the nuclear receptor with which it
CC interacts (PubMed:8650544). Inhibits transcriptional activity of
CC NEUROD1 on E-box-containing promoter by interfering with the
CC coactivation function of the p300/CBP-mediated transcription complex
CC for NEUROD1 (By similarity). Essential component of the liver circadian
CC clock which via its interaction with NR1D1 and RORG regulates NPAS2-
CC mediated hepatic lipid metabolism (PubMed:25212631). Regulates the
CC circadian expression of cytochrome P450 (CYP) enzymes
CC (PubMed:30555544). Represses: NR5A2 and HNF4A to down-regulate CYP2C38,
CC NFLI3 to up-regulate CYP2A5, BHLHE41/HNF1A axis to up-regulate CYP1A2,
CC CYP2E1 and CYP3A11, and NR1D1 to up-regulate CYP2B10, CYP4A10 and
CC CYP4A14 (PubMed:30555544). {ECO:0000250|UniProtKB:Q15466,
CC ECO:0000269|PubMed:25212631, ECO:0000269|PubMed:30555544,
CC ECO:0000269|PubMed:8650544}.
CC -!- SUBUNIT: Heterodimer; efficient DNA binding requires dimerization with
CC another bHLH protein (By similarity). Interacts (via N-terminus) with
CC NEUROD1 (via N-terminus and C-terminus) (By similarity). Interacts with
CC ID2 (By similarity). Interacts with NR5A2, PPARA and PPARG (By
CC similarity). Interacts with RARA, RXRA, THRB, NR5A1 and NR1I3
CC (PubMed:8650544). Interacts with EID1 (PubMed:11964378). Interacts with
CC NR1D1 (PubMed:25212631, PubMed:30555544). Interacts with RORG
CC (PubMed:25212631). Interacts with NFIL3 and BHLHE41 (PubMed:30555544).
CC Interacts with HNF4A; the resulting heterodimer is transcriptionnally
CC inactive (By similarity). Interacts with DDX3X; this interaction
CC disrupts the interaction between HNF4 and NR0B2/SHP that forms inactive
CC heterodimers and enhances the formation of active HNF4 homodimers (By
CC similarity). {ECO:0000250|UniProtKB:P97947,
CC ECO:0000250|UniProtKB:Q15466, ECO:0000269|PubMed:11964378,
CC ECO:0000269|PubMed:15707893, ECO:0000269|PubMed:25212631,
CC ECO:0000269|PubMed:30555544, ECO:0000269|PubMed:8650544}.
CC -!- INTERACTION:
CC Q62227; Q04207: Rela; NbExp=3; IntAct=EBI-4310440, EBI-644400;
CC Q62227; Q923E4: Sirt1; NbExp=2; IntAct=EBI-4310440, EBI-1802585;
CC Q62227; P70196: Traf6; NbExp=5; IntAct=EBI-4310440, EBI-448028;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15466}. Nucleus
CC {ECO:0000250|UniProtKB:Q15466}. Note=Colocalizes with NEUROD1 in the
CC nucleus. {ECO:0000250|UniProtKB:Q15466}.
CC -!- TISSUE SPECIFICITY: Expressed in islets of Langerhans (at protein
CC level) (PubMed:14752053). Expressed in a circadian manner in the liver
CC (PubMed:25212631). {ECO:0000269|PubMed:14752053,
CC ECO:0000269|PubMed:25212631}.
CC -!- PTM: Arginine methylation by PRMT5 enhances repression activity of
CC metabolic genes in liver in response to bile acid signaling, by
CC increasing interaction with cofactors. {ECO:0000269|PubMed:21262773}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit a significant disruption in the
CC circadian rhythm of several important hepatic genes involved in the
CC metabolism of lipid, cholesterol, fatty acid and bile acid.
CC {ECO:0000269|PubMed:25212631}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR0
CC subfamily. {ECO:0000305}.
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DR EMBL; L76567; AAB59732.1; -; Genomic_DNA.
DR EMBL; AY360323; AAQ55057.1; -; mRNA.
DR EMBL; AY360324; AAQ55058.1; -; mRNA.
DR EMBL; BC019540; AAH19540.1; -; mRNA.
DR CCDS; CCDS18751.1; -.
DR RefSeq; NP_035980.1; NM_011850.3.
DR PDB; 1YMT; X-ray; 1.20 A; B=17-30.
DR PDB; 4NUF; X-ray; 2.80 A; A=53-260.
DR PDBsum; 1YMT; -.
DR PDBsum; 4NUF; -.
DR AlphaFoldDB; Q62227; -.
DR SMR; Q62227; -.
DR BioGRID; 204818; 19.
DR IntAct; Q62227; 4.
DR STRING; 10090.ENSMUSP00000039175; -.
DR iPTMnet; Q62227; -.
DR PhosphoSitePlus; Q62227; -.
DR PaxDb; Q62227; -.
DR PRIDE; Q62227; -.
DR ProteomicsDB; 253008; -.
DR Antibodypedia; 16231; 433 antibodies from 35 providers.
DR DNASU; 23957; -.
DR Ensembl; ENSMUST00000042706; ENSMUSP00000039175; ENSMUSG00000037583.
DR GeneID; 23957; -.
DR KEGG; mmu:23957; -.
DR UCSC; uc008vcz.1; mouse.
DR CTD; 8431; -.
DR MGI; MGI:1346344; Nr0b2.
DR VEuPathDB; HostDB:ENSMUSG00000037583; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00390000015719; -.
DR HOGENOM; CLU_093194_0_0_1; -.
DR InParanoid; Q62227; -.
DR OMA; FFRPIVG; -.
DR OrthoDB; 955476at2759; -.
DR PhylomeDB; Q62227; -.
DR TreeFam; TF332386; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 23957; 2 hits in 75 CRISPR screens.
DR EvolutionaryTrace; Q62227; -.
DR PRO; PR:Q62227; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q62227; protein.
DR Bgee; ENSMUSG00000037583; Expressed in left lobe of liver and 46 other tissues.
DR Genevisible; Q62227; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; ISO:MGI.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; ISO:MGI.
DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; ISO:MGI.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISO:MGI.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0015721; P:bile acid and bile salt transport; IEA:Ensembl.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR Gene3D; 1.10.565.10; -; 1.
DR IDEAL; IID50230; -.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR033544; NR0B1/2.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR PANTHER; PTHR24081; PTHR24081; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR SMART; SM00430; HOLI; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Biological rhythms; Cytoplasm; Methylation; Nucleus;
KW Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..260
FT /note="Nuclear receptor subfamily 0 group B member 2"
FT /id="PRO_0000053753"
FT DOMAIN 16..260
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT MOD_RES 57
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000269|PubMed:21262773"
FT VARIANT 241
FT /note="R -> C"
FT HELIX 20..25
FT /evidence="ECO:0007829|PDB:1YMT"
FT HELIX 57..74
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 84..92
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 146..162
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 166..177
FT /evidence="ECO:0007829|PDB:4NUF"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 188..204
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 213..228
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 232..239
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 241..244
FT /evidence="ECO:0007829|PDB:4NUF"
FT HELIX 249..256
FT /evidence="ECO:0007829|PDB:4NUF"
SQ SEQUENCE 260 AA; 28763 MW; 7B859325AA73DCA1 CRC64;
MSSGQSGVCP CQGSAGRPTI LYALLSPSPR TRPVAPASHS HCLCQQQRPV RLCAPHRTCR
EALDVLAKTV AFLRNLPSFC HLPHEDQRRL LECCWGPLFL LGLAQDAVTF EVAEAPVPSI
LKKILLEEAS SGTQGAQPSD RPQPSLAAVQ WLQRCLESFW SLELGPKEYA YLKGTILFNP
DVPGLRASCH IAHLQQEAHW ALCEVLEPWY PASQGRLARI LLMASTLKNI PGTLLVDLFF
RPIMGDVDIT ELLEDMLLLR
