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 24-JAN-2024, entry version 175. 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 transcriptionally 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}. 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; 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; 10090-ENSMUSP00000039175; -. DR ProteomicsDB; 253008; -. DR Antibodypedia; 16231; 484 antibodies from 35 providers. DR DNASU; 23957; -. DR Ensembl; ENSMUST00000042706.3; ENSMUSP00000039175.3; ENSMUSG00000037583.3. DR GeneID; 23957; -. DR KEGG; mmu:23957; -. DR UCSC; uc008vcz.1; mouse. DR AGR; MGI:1346344; -. 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; 5393882at2759; -. DR PhylomeDB; Q62227; -. DR TreeFam; TF332386; -. DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway. DR BioGRID-ORCS; 23957; 2 hits in 80 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 48 other cell types or tissues. 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:0045892; P:negative regulation of DNA-templated transcription; IMP: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:0007219; P:Notch signaling pathway; IDA:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO: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: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; Retinoid X Receptor; 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; NUCLEAR RECEPTOR SUBFAMILY 0 GROUP B; 1. DR PANTHER; PTHR24081:SF0; NUCLEAR RECEPTOR SUBFAMILY 0 GROUP B MEMBER 2; 1. DR Pfam; PF00104; Hormone_recep; 1. DR PRINTS; PR00398; STRDHORMONER. DR SMART; SM00430; HOLI; 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR Genevisible; Q62227; MM. 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 //