NR1I3_MOUSE
ID NR1I3_MOUSE Reviewed; 358 AA.
AC O35627; O35628; Q3V008;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Nuclear receptor subfamily 1 group I member 3;
DE AltName: Full=Constitutive androstane receptor;
DE Short=CAR;
DE AltName: Full=Orphan nuclear receptor MB67;
GN Name=Nr1i3; Synonyms=Car;
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] (ISOFORMS CAR1 AND CAR2).
RC TISSUE=Liver;
RX PubMed=9295294; DOI=10.1074/jbc.272.38.23565;
RA Choi H.-S., Chung M., Tzameli I., Simha D., Lee Y.-K., Seol W., Moore D.D.;
RT "Differential transactivation by two isoforms of the orphan nuclear hormone
RT receptor CAR.";
RL J. Biol. Chem. 272:23565-23571(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CAR1).
RC STRAIN=C57BL/6J; TISSUE=Ovary, and Uterus;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [4]
RP FUNCTION.
RX PubMed=10462436; DOI=10.1006/abbi.1999.1351;
RA Waxman D.J.;
RT "P450 gene induction by structurally diverse xenochemicals: central role of
RT nuclear receptors CAR, PXR, and PPAR.";
RL Arch. Biochem. Biophys. 369:11-23(1999).
RN [5]
RP INTERACTION WITH PSMC4.
RX PubMed=8603043; DOI=10.1016/0960-0760(95)00220-0;
RA Choi H.S., Seol W., Moore D.D.;
RT "A component of the 26S proteasome binds on orphan member of the nuclear
RT hormone receptor superfamily.";
RL J. Steroid Biochem. Mol. Biol. 56:23-30(1996).
RN [6]
RP INTERACTION WITH DNAJC7 AND HSP90, AND SUBCELLULAR LOCATION.
RX PubMed=14573755; DOI=10.1124/mol.64.5.1069;
RA Kobayashi K., Sueyoshi T., Inoue K., Moore R., Negishi M.;
RT "Cytoplasmic accumulation of the nuclear receptor CAR by a
RT tetratricopeptide repeat protein in HepG2 cells.";
RL Mol. Pharmacol. 64:1069-1075(2003).
RN [7]
RP INTERACTION WITH ECT2, AND SUBCELLULAR LOCATION.
RX PubMed=17904126; DOI=10.1016/j.febslet.2007.09.024;
RA Hosseinpour F., Timsit Y., Koike C., Matsui K., Yamamoto Y., Moore R.,
RA Negishi M.;
RT "Overexpression of the Rho-guanine nucleotide exchange factor ECT2 inhibits
RT nuclear translocation of nuclear receptor CAR in the mouse liver.";
RL FEBS Lett. 581:4937-4942(2007).
RN [8]
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 227-458 IN COMPLEX WITH H.SAPIENS
RP RXRA; R.NORVEGICUS NCOA2 AND AGONIST INSECTICIDE CONTAMINANT TCPOBOP, AND
RP MUTAGENESIS OF PHE-171; ASN-175; LEU-216; PHE-227; TYR-234; PHE-244;
RP TYR-336 AND LEU-346.
RX PubMed=15610733; DOI=10.1016/j.molcel.2004.11.036;
RA Suino K., Peng L., Reynolds R., Li Y., Cha J.Y., Repa J.J., Kliewer S.A.,
RA Xu H.E.;
RT "The nuclear xenobiotic receptor CAR: structural determinants of
RT constitutive activation and heterodimerization.";
RL Mol. Cell 16:893-905(2004).
CC -!- FUNCTION: Binds and transactivates the retinoic acid response elements
CC that control expression of the retinoic acid receptor beta 2 and
CC alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital
CC responsive element module of the human CYP2B6 gene and the CYP3A4
CC xenobiotic response element (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:10462436}.
CC -!- SUBUNIT: Heterodimer of NR1I3 and RXR. Interacts with PSMC4. Interacts
CC with ECT2. Directly interacts with DNAJC7; this complex may also
CC include HSP90. Interacts with CRY1 (PubMed:28751364). Interacts with
CC CRY2 in a ligand-dependent manner (PubMed:28751364).
CC {ECO:0000269|PubMed:14573755, ECO:0000269|PubMed:15610733,
CC ECO:0000269|PubMed:17904126, ECO:0000269|PubMed:28751364,
CC ECO:0000269|PubMed:8603043}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton
CC {ECO:0000250}. Note=Recruited to the cytoplasm by DNAJC7.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=CAR1;
CC IsoId=O35627-1; Sequence=Displayed;
CC Name=CAR2;
CC IsoId=O35627-2; Sequence=VSP_003671, VSP_003672;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver.
CC -!- DOMAIN: Composed by a short N-terminal domain followed by the DNA
CC binding, hinge, and ligand binding/dimerization domains.
CC -!- PTM: Phosphorylated at Thr-48 by PKC, dephosphorylation of Thr-48 is
CC required for nuclear translocation and activation. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform CAR2]: Does not seem to act as a
CC transactivator. Lacks the C-terminal portion of the ligand
CC binding/dimerization domain. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; AF009327; AAC53349.1; -; mRNA.
DR EMBL; AF009328; AAC53350.1; -; mRNA.
DR EMBL; AK133515; BAE21697.1; -; mRNA.
DR EMBL; CH466520; EDL39126.1; -; Genomic_DNA.
DR CCDS; CCDS15480.1; -. [O35627-1]
DR CCDS; CCDS56654.1; -. [O35627-2]
DR RefSeq; NP_001229991.1; NM_001243062.1. [O35627-2]
DR RefSeq; NP_001229992.1; NM_001243063.1.
DR RefSeq; NP_033933.2; NM_009803.5. [O35627-1]
DR PDB; 1XLS; X-ray; 2.96 A; E/F/G/H=117-358.
DR PDB; 1XNX; X-ray; 2.90 A; A/B=109-358.
DR PDBsum; 1XLS; -.
DR PDBsum; 1XNX; -.
DR AlphaFoldDB; O35627; -.
DR SMR; O35627; -.
DR BioGRID; 198489; 13.
DR IntAct; O35627; 1.
DR STRING; 10090.ENSMUSP00000005820; -.
DR BindingDB; O35627; -.
DR ChEMBL; CHEMBL3069; -.
DR DrugCentral; O35627; -.
DR GuidetoPHARMACOLOGY; 607; -.
DR iPTMnet; O35627; -.
DR PhosphoSitePlus; O35627; -.
DR PaxDb; O35627; -.
DR PRIDE; O35627; -.
DR ProteomicsDB; 295523; -. [O35627-1]
DR ProteomicsDB; 295524; -. [O35627-2]
DR Antibodypedia; 20508; 473 antibodies from 32 providers.
DR DNASU; 12355; -.
DR Ensembl; ENSMUST00000005820; ENSMUSP00000005820; ENSMUSG00000005677. [O35627-1]
DR Ensembl; ENSMUST00000075469; ENSMUSP00000074915; ENSMUSG00000005677. [O35627-2]
DR GeneID; 12355; -.
DR KEGG; mmu:12355; -.
DR UCSC; uc007dnf.2; mouse. [O35627-1]
DR UCSC; uc007dng.2; mouse. [O35627-2]
DR CTD; 9970; -.
DR MGI; MGI:1346307; Nr1i3.
DR VEuPathDB; HostDB:ENSMUSG00000005677; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000160641; -.
DR HOGENOM; CLU_007368_12_0_1; -.
DR InParanoid; O35627; -.
DR OMA; VHAGFQE; -.
DR OrthoDB; 297114at2759; -.
DR PhylomeDB; O35627; -.
DR TreeFam; TF316304; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 12355; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Nr1i3; mouse.
DR EvolutionaryTrace; O35627; -.
DR PRO; PR:O35627; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; O35627; protein.
DR Bgee; ENSMUSG00000005677; Expressed in left lobe of liver and 60 other tissues.
DR ExpressionAtlas; O35627; baseline and differential.
DR Genevisible; O35627; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; 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:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID50248; -.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001728; ThyrH_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 PRINTS; PR00546; THYROIDHORMR.
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 3D-structure; Activator; Alternative splicing; Cytoplasm; Cytoskeleton;
KW DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..358
FT /note="Nuclear receptor subfamily 1 group I member 3"
FT /id="PRO_0000053554"
FT DOMAIN 119..358
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 18..93
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 21..41
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 57..81
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT SITE 171
FT /note="Important for TCPOBOP recognition"
FT SITE 175
FT /note="Important for TCPOBOP recognition"
FT SITE 216
FT /note="Important for TCPOBOP recognition"
FT SITE 227
FT /note="Important for TCPOBOP recognition"
FT SITE 244
FT /note="Important for TCPOBOP recognition"
FT SITE 336
FT /note="Important for TCPOBOP recognition"
FT MOD_RES 48
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q14994"
FT VAR_SEQ 281..286
FT /note="DRPGVT -> GFCMQS (in isoform CAR2)"
FT /evidence="ECO:0000303|PubMed:9295294"
FT /id="VSP_003671"
FT VAR_SEQ 287..358
FT /note="Missing (in isoform CAR2)"
FT /evidence="ECO:0000303|PubMed:9295294"
FT /id="VSP_003672"
FT MUTAGEN 171
FT /note="F->W: Diminished binding of coactivator NCOA2 in the
FT presence of TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT MUTAGEN 175
FT /note="N->F: Diminished binding of coactivator NCOA2 in the
FT presence of TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT MUTAGEN 216
FT /note="L->F: Diminished binding of coactivator NCOA2 in the
FT presence of TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT MUTAGEN 227
FT /note="F->W: Diminished binding of coactivator NCOA2 in the
FT presence of TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT MUTAGEN 234
FT /note="Y->A: No effect on binding of coactivator NCOA2 in
FT the presence of TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT MUTAGEN 244
FT /note="F->A: Diminished binding of coactivator NCOA2 in the
FT presence of TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT MUTAGEN 336
FT /note="Y->A: Diminished binding of coactivator NCOA2 in the
FT presence of TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT MUTAGEN 346
FT /note="L->F: Dramatic increase in binding NCOA2. Little
FT effect on binding of coactivator NCOA2 in the presence of
FT TCPOBOP."
FT /evidence="ECO:0000269|PubMed:15610733"
FT CONFLICT 138
FT /note="M -> L (in Ref. 1; AAC53349/AAC53350)"
FT /evidence="ECO:0000305"
FT HELIX 118..134
FT /evidence="ECO:0007829|PDB:1XNX"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 138..144
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:1XNX"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:1XLS"
FT HELIX 164..187
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 197..216
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:1XNX"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:1XNX"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:1XNX"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 236..241
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 246..260
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 266..277
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 288..308
FT /evidence="ECO:0007829|PDB:1XNX"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 318..335
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 337..343
FT /evidence="ECO:0007829|PDB:1XNX"
FT HELIX 345..349
FT /evidence="ECO:0007829|PDB:1XLS"
FT HELIX 351..357
FT /evidence="ECO:0007829|PDB:1XLS"
SQ SEQUENCE 358 AA; 40913 MW; A11C92B1EC2C06A7 CRC64;
MTAMLTLETM ASEEEYGPRN CVVCGDRATG YHFHALTCEG CKGFFRRTVS KTIGPICPFA
GRCEVSKAQR RHCPACRLQK CLNVGMRKDM ILSAEALALR RARQAQRRAE KASLQLNQQQ
KELVQILLGA HTRHVGPMFD QFVQFKPPAY LFMHHRPFQP RGPVLPLLTH FADINTFMVQ
QIIKFTKDLP LFRSLTMEDQ ISLLKGAAVE ILHISLNTTF CLQTENFFCG PLCYKMEDAV
HAGFQYEFLE SILHFHKNLK GLHLQEPEYV LMAATALFSP DRPGVTQREE IDQLQEEMAL
ILNNHIMEQQ SRLQSRFLYA KLMGLLADLR SINNAYSYEL QRLEELSAMT PLLGEICS
