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O35627 (NR1I3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 1 group I member 3
Alternative name(s):
Constitutive androstane receptor
Short name=CAR
Orphan nuclear receptor MB67
Gene names
Name:Nr1i3
Synonyms:Car
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length358 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element By similarity. Ref.4

Subunit structure

Heterodimer of NR1I3 and RXR. Interacts with PSMC4. Interacts with ECT2. Directly interacts with DNAJC7; this complex may also include HSP90. Ref.5 Ref.6 Ref.7

Subcellular location

Nucleus. Cytoplasm. Cytoplasmcytoskeleton By similarity. Note: Recruited to the cytoplasm by DNAJC7. Ref.6 Ref.7

Tissue specificity

Predominantly expressed in liver.

Domain

Composed by a short N-terminal domain followed by the DNA binding, hinge, and ligand binding/dimerization domains.

Post-translational modification

Phosphorylated at Thr-48 by PKC, dephosphorylation of Thr-48 is required for nuclear translocation and activation By similarity.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform CAR1 (identifier: O35627-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform CAR2 (identifier: O35627-2)

The sequence of this isoform differs from the canonical sequence as follows:
     281-286: DRPGVT → GFCMQS
     287-358: Missing.
Note: Does not seem to act as a transactivator. Lacks the C-terminal portion of the ligand binding/dimerization domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 358358Nuclear receptor subfamily 1 group I member 3
PRO_0000053554

Regions

DNA binding18 – 9376Nuclear receptor
Zinc finger21 – 4121NR C4-type
Zinc finger57 – 8125NR C4-type

Sites

Site1711Important for TCPOBOP recognition
Site1751Important for TCPOBOP recognition
Site2161Important for TCPOBOP recognition
Site2271Important for TCPOBOP recognition
Site2441Important for TCPOBOP recognition
Site3361Important for TCPOBOP recognition

Amino acid modifications

Modified residue481Phosphothreonine; by PKC By similarity

Natural variations

Alternative sequence281 – 2866DRPGVT → GFCMQS in isoform CAR2.
VSP_003671
Alternative sequence287 – 35872Missing in isoform CAR2.
VSP_003672

Experimental info

Mutagenesis1711F → W: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Mutagenesis1751N → F: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Mutagenesis2161L → F: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Mutagenesis2271F → W: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Mutagenesis2341Y → A: No effect on binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Mutagenesis2441F → A: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Mutagenesis3361Y → A: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Mutagenesis3461L → F: Dramatic increase in binding NCOA2. Little effect on binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8
Sequence conflict1381M → L in AAC53349. Ref.1
Sequence conflict1381M → L in AAC53350. Ref.1

Secondary structure

...................................... 358
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform CAR1 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: A11C92B1EC2C06A7

FASTA35840,913
        10         20         30         40         50         60 
MTAMLTLETM ASEEEYGPRN CVVCGDRATG YHFHALTCEG CKGFFRRTVS KTIGPICPFA 

        70         80         90        100        110        120 
GRCEVSKAQR RHCPACRLQK CLNVGMRKDM ILSAEALALR RARQAQRRAE KASLQLNQQQ 

       130        140        150        160        170        180 
KELVQILLGA HTRHVGPMFD QFVQFKPPAY LFMHHRPFQP RGPVLPLLTH FADINTFMVQ 

       190        200        210        220        230        240 
QIIKFTKDLP LFRSLTMEDQ ISLLKGAAVE ILHISLNTTF CLQTENFFCG PLCYKMEDAV 

       250        260        270        280        290        300 
HAGFQYEFLE SILHFHKNLK GLHLQEPEYV LMAATALFSP DRPGVTQREE IDQLQEEMAL 

       310        320        330        340        350 
ILNNHIMEQQ SRLQSRFLYA KLMGLLADLR SINNAYSYEL QRLEELSAMT PLLGEICS 

« Hide

Isoform CAR2 [UniParc].

Checksum: DAEF17A3369F529E
Show »

FASTA28632,544

References

« Hide 'large scale' references
[1]"Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR."
Choi H.-S., Chung M., Tzameli I., Simha D., Lee Y.-K., Seol W., Moore D.D.
J. Biol. Chem. 272:23565-23571(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CAR1 AND CAR2).
Tissue: Liver.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CAR1).
Strain: C57BL/6J.
Tissue: Ovary and Uterus.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR."
Waxman D.J.
Arch. Biochem. Biophys. 369:11-23(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily."
Choi H.S., Seol W., Moore D.D.
J. Steroid Biochem. Mol. Biol. 56:23-30(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PSMC4.
[6]"Cytoplasmic accumulation of the nuclear receptor CAR by a tetratricopeptide repeat protein in HepG2 cells."
Kobayashi K., Sueyoshi T., Inoue K., Moore R., Negishi M.
Mol. Pharmacol. 64:1069-1075(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNAJC7 AND HSP90, SUBCELLULAR LOCATION.
[7]"Overexpression of the Rho-guanine nucleotide exchange factor ECT2 inhibits nuclear translocation of nuclear receptor CAR in the mouse liver."
Hosseinpour F., Timsit Y., Koike C., Matsui K., Yamamoto Y., Moore R., Negishi M.
FEBS Lett. 581:4937-4942(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ECT2, SUBCELLULAR LOCATION.
[8]"The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization."
Suino K., Peng L., Reynolds R., Li Y., Cha J.Y., Repa J.J., Kliewer S.A., Xu H.E.
Mol. Cell 16:893-905(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 227-458 IN COMPLEX WITH H.SAPIENS RXRA; R.NORVEGICUS NCOA2 AND AGONIST INSECTICIDE CONTAMINANT TCPOBOP, MUTAGENESIS OF PHE-171; ASN-175; LEU-216; PHE-227; TYR-234; PHE-244; TYR-336 AND LEU-346.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF009327 mRNA. Translation: AAC53349.1.
AF009328 mRNA. Translation: AAC53350.1.
AK133515 mRNA. Translation: BAE21697.1.
CH466520 Genomic DNA. Translation: EDL39126.1.
RefSeqNP_001229991.1. NM_001243062.1.
NP_001229992.1. NM_001243063.1.
NP_033933.2. NM_009803.5.
UniGeneMm.486506.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XLSX-ray2.96E/F/G/H117-358[»]
1XNXX-ray2.90A/B109-358[»]
ProteinModelPortalO35627.
SMRO35627. Positions 21-356.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198489. 12 interactions.

Chemistry

BindingDBO35627.
ChEMBLCHEMBL3069.
GuidetoPHARMACOLOGY607.

PTM databases

PhosphoSiteO35627.

Proteomic databases

PRIDEO35627.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000005820; ENSMUSP00000005820; ENSMUSG00000005677. [O35627-1]
ENSMUST00000075469; ENSMUSP00000074915; ENSMUSG00000005677. [O35627-2]
GeneID12355.
KEGGmmu:12355.
UCSCuc007dnf.2. mouse. [O35627-1]
uc007dng.2. mouse. [O35627-2]

Organism-specific databases

CTD9970.
MGIMGI:1346307. Nr1i3.

Phylogenomic databases

eggNOGNOG251788.
GeneTreeENSGT00720000108423.
HOGENOMHOG000220844.
HOVERGENHBG108655.
InParanoidQ3V008.
KOK08541.
OMAPRDRFLY.
OrthoDBEOG7SXW4K.
TreeFamTF316304.

Gene expression databases

BgeeO35627.
CleanExMM_NR1I3.
GenevestigatorO35627.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001728. ThyrH_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNR1I3. mouse.
EvolutionaryTraceO35627.
NextBio281020.
PROO35627.
SOURCESearch...

Entry information

Entry nameNR1I3_MOUSE
AccessionPrimary (citable) accession number: O35627
Secondary accession number(s): O35628, Q3V008
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot