ID   NR1I2_MOUSE             Reviewed;         431 AA.
AC   O54915;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   24-JAN-2024, entry version 179.
DE   RecName: Full=Nuclear receptor subfamily 1 group I member 2;
DE   AltName: Full=Orphan nuclear receptor PXR;
DE   AltName: Full=Pregnane X receptor;
GN   Name=Nr1i2; Synonyms=Pxr;
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 [MRNA], AND ALTERNATIVE SPLICING.
RC   TISSUE=Liver;
RX   PubMed=9489701; DOI=10.1016/s0092-8674(00)80900-9;
RA   Kliewer S.A., Moore J.T., Wade L., Staudinger J.L., Watson M.A.,
RA   Jones S.A., McKee D.D., Oliver B.B., Willson T.M., Zetterstrom R.H.,
RA   Perlmann T., Lehmann J.M.;
RT   "An orphan nuclear receptor activated by pregnanes defines a novel steroid
RT   signaling pathway.";
RL   Cell 92:73-82(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=C57BL/6J; TISSUE=Cecum;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   SUBCELLULAR LOCATION.
RX   PubMed=12606758; DOI=10.1124/mol.63.3.524;
RA   Kawana K., Ikuta T., Kobayashi Y., Gotoh O., Takeda K., Kawajiri K.;
RT   "Molecular mechanism of nuclear translocation of an orphan nuclear
RT   receptor, SXR.";
RL   Mol. Pharmacol. 63:524-531(2003).
RN   [4]
RP   FUNCTION.
RX   PubMed=12569201; DOI=10.1073/pnas.0336235100;
RA   Dussault I., Yoo H.-D., Lin M., Wang E., Fan M., Batta A.K., Salen G.,
RA   Erickson S.K., Forman B.M.;
RT   "Identification of an endogenous ligand that activates pregnane X receptor-
RT   mediated sterol clearance.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:833-838(2003).
RN   [5]
RP   FUNCTION.
RX   PubMed=19297428; DOI=10.3945/jn.108.103572;
RA   Li Y., Ross-Viola J.S., Shay N.F., Moore D.D., Ricketts M.L.;
RT   "Human CYP3A4 and murine Cyp3A11 are regulated by equol and genistein via
RT   the pregnane X receptor in a species-specific manner.";
RL   J. Nutr. 139:898-904(2009).
RN   [6]
RP   INTERACTION WITH CRY1 AND CRY2.
RX   PubMed=28751364; DOI=10.1073/pnas.1704955114;
RA   Kriebs A., Jordan S.D., Soto E., Henriksson E., Sandate C.R., Vaughan M.E.,
RA   Chan A.B., Duglan D., Papp S.J., Huber A.L., Afetian M.E., Yu R.T.,
RA   Zhao X., Downes M., Evans R.M., Lamia K.A.;
RT   "Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors
RT   and modulate transcriptional activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 114:8776-8781(2017).
CC   -!- FUNCTION: Nuclear receptor that binds and is activated by a variety of
CC       endogenous and xenobiotic compounds. Transcription factor that
CC       activates the transcription of multiple genes involved in the
CC       metabolism and secretion of potentially harmful xenobiotics, endogenous
CC       compounds and drugs. Response to specific ligands is species-specific,
CC       due to differences in the ligand-binding domain. Binds to a response
CC       element in the promoters of the CYP3A4 and ABCB1/MDR1 genes (By
CC       similarity). Activated by naturally occurring steroids such as
CC       pregnenolone and progesterone, the cholesterol metabolite 5-beta-
CC       cholestane-3-alpha,7-alpha,12-alpha-triol, synthetic glucocorticoids
CC       and antiglucocorticoids and 16-alpha-carbonitrile (PCN). {ECO:0000250,
CC       ECO:0000269|PubMed:12569201, ECO:0000269|PubMed:19297428}.
CC   -!- SUBUNIT: Heterodimer with RXRA (By similarity). Interacts with NCOA1
CC       (By similarity). Interacts (via domain NR LBD) with CRY1 and CRY2 in a
CC       ligand-dependent manner (PubMed:28751364).
CC       {ECO:0000250|UniProtKB:O75469, ECO:0000269|PubMed:28751364}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=PXR.1;
CC         IsoId=O54915-1; Sequence=Displayed;
CC       Name=2; Synonyms=PXR.2;
CC         IsoId=O54915-2; Sequence=VSP_003670;
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AF031814; AAC39964.1; -; mRNA.
DR   EMBL; AK018630; BAB31316.1; -; mRNA.
DR   CCDS; CCDS28164.1; -. [O54915-1]
DR   RefSeq; NP_001091874.1; NM_001098404.1. [O54915-2]
DR   RefSeq; NP_035066.1; NM_010936.3. [O54915-1]
DR   RefSeq; XP_006521909.1; XM_006521846.3. [O54915-1]
DR   RefSeq; XP_006521911.1; XM_006521848.3. [O54915-1]
DR   AlphaFoldDB; O54915; -.
DR   SMR; O54915; -.
DR   BioGRID; 201839; 5.
DR   ComplexPortal; CPX-505; RXRalpha-PXR nuclear receptor complex.
DR   ComplexPortal; CPX-644; PXR-NCOA1 activated nuclear receptor complex.
DR   IntAct; O54915; 2.
DR   STRING; 10090.ENSMUSP00000023504; -.
DR   ChEMBL; CHEMBL1743244; -.
DR   DrugCentral; O54915; -.
DR   GuidetoPHARMACOLOGY; 606; -.
DR   iPTMnet; O54915; -.
DR   PhosphoSitePlus; O54915; -.
DR   PaxDb; 10090-ENSMUSP00000023504; -.
DR   ProteomicsDB; 293717; -. [O54915-1]
DR   ProteomicsDB; 293718; -. [O54915-2]
DR   Antibodypedia; 16619; 482 antibodies from 42 providers.
DR   DNASU; 18171; -.
DR   Ensembl; ENSMUST00000023504.5; ENSMUSP00000023504.5; ENSMUSG00000022809.5. [O54915-1]
DR   GeneID; 18171; -.
DR   KEGG; mmu:18171; -.
DR   UCSC; uc007zep.1; mouse. [O54915-2]
DR   UCSC; uc007zeq.1; mouse. [O54915-1]
DR   AGR; MGI:1337040; -.
DR   CTD; 8856; -.
DR   MGI; MGI:1337040; Nr1i2.
DR   VEuPathDB; HostDB:ENSMUSG00000022809; -.
DR   eggNOG; KOG3575; Eukaryota.
DR   GeneTree; ENSGT00940000161118; -.
DR   HOGENOM; CLU_007368_12_0_1; -.
DR   InParanoid; O54915; -.
DR   OMA; GTCEITQ; -.
DR   OrthoDB; 5359733at2759; -.
DR   PhylomeDB; O54915; -.
DR   TreeFam; TF316304; -.
DR   Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR   Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR   BioGRID-ORCS; 18171; 1 hit in 81 CRISPR screens.
DR   ChiTaRS; Nr1i2; mouse.
DR   PRO; PR:O54915; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; O54915; Protein.
DR   Bgee; ENSMUSG00000022809; Expressed in duodenum and 53 other cell types or tissues.
DR   ExpressionAtlas; O54915; baseline and differential.
DR   GO; GO:0045111; C:intermediate filament cytoskeleton; ISO:MGI.
DR   GO; GO:0016604; C:nuclear body; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005667; C:transcription regulator complex; EXP:ComplexPortal.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR   GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR   GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:MGI.
DR   GO; GO:0042178; P:xenobiotic catabolic process; ISS:UniProtKB.
DR   GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR   GO; GO:0042908; P:xenobiotic transport; ISS:UniProtKB.
DR   Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR   Gene3D; 1.10.565.10; Retinoid X Receptor; 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   PANTHER; PTHR24082; NUCLEAR HORMONE RECEPTOR; 1.
DR   PANTHER; PTHR24082:SF39; NUCLEAR RECEPTOR SUBFAMILY 1 GROUP I MEMBER 2; 1.
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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR   PROSITE; PS51843; NR_LBD; 1.
DR   PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR   PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR   Genevisible; O54915; MM.
PE   1: Evidence at protein level;
KW   Activator; Alternative splicing; DNA-binding; Metal-binding; Nucleus;
KW   Receptor; Reference proteome; Transcription; Transcription regulation;
KW   Zinc; Zinc-finger.
FT   CHAIN           1..431
FT                   /note="Nuclear receptor subfamily 1 group I member 2"
FT                   /id="PRO_0000053549"
FT   DOMAIN          143..430
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        35..104
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         38..58
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         74..99
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          105..142
FT                   /note="Hinge"
FT   MOTIF           63..89
FT                   /note="Bipartite nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   BINDING         244
FT                   /ligand="hyperforin"
FT                   /ligand_id="ChEBI:CHEBI:5834"
FT                   /ligand_note="agonist"
FT                   /evidence="ECO:0000250|UniProtKB:O75469"
FT   BINDING         282..285
FT                   /ligand="hyperforin"
FT                   /ligand_id="ChEBI:CHEBI:5834"
FT                   /ligand_note="agonist"
FT                   /evidence="ECO:0000250|UniProtKB:O75469"
FT   VAR_SEQ         171..211
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_003670"
SQ   SEQUENCE   431 AA;  49567 MW;  F592AF91F689329E CRC64;
     MRPEESWSRV GLVQCEEADS ALEEPINVEE EDGGLQICRV CGDKANGYHF NVMTCEGCKG
     FFRRAMKRNV RLRCPFRKGT CEITRKTRRQ CQACRLRKCL ESGMKKEMIM SDAAVEQRRA
     LIKRKKREKI EAPPPGGQGL TEEQQALIQE LMDAQMQTFD TTFSHFKDFR LPAVFHSGCE
     LPEFLQASLL EDPATWSQIM KDRVPMKISL QLRGEDGSIW NYQPPSKSDG KEIIPLLPHL
     ADVSTYMFKG VINFAKVISY FRDLPIEDQI SLLKGATFEM CILRFNTMFD TETGTWECGR
     LAYCFEDPNG GFQKLLLDPL MKFHCMLKKL QLHKEEYVLM QAISLFSPDR PGVVQRSVVD
     QLQERFALTL KAYIECSRPY PAHRFLFLKI MAVLTELRSI NAQQTQQLLR IQDSHPFATP
     LMQELFSSTD G
//