O35627 (NR1I3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	358 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Cytoplasm › cytoskeleton 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 11891224. Source: MGI
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay PubMed 12885400. Source: MGI nucleus Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	DNA binding Inferred from direct assay PubMed 11891224. Source: MGI sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro thyroid hormone receptor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 358

358

Nuclear receptor subfamily 1 group I member 3

PRO_0000053554

Regions

DNA binding

18 – 93

76

Nuclear receptor

Zinc finger

21 – 41

21

NR C4-type

Zinc finger

57 – 81

25

NR C4-type

Sites

Site

171

1

Important for TCPOBOP recognition

Site

175

1

Important for TCPOBOP recognition

Site

216

1

Important for TCPOBOP recognition

Site

227

1

Important for TCPOBOP recognition

Site

244

1

Important for TCPOBOP recognition

Site

336

1

Important for TCPOBOP recognition

Amino acid modifications

Modified residue

48

1

Phosphothreonine; by PKC By similarity

Natural variations

Alternative sequence

281 – 286

6

DRPGVT → GFCMQS in isoform CAR2.

VSP_003671

Alternative sequence

287 – 358

72

Missing in isoform CAR2.

VSP_003672

Experimental info

Mutagenesis

171

1

F → W: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Mutagenesis

175

1

N → F: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Mutagenesis

216

1

L → F: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Mutagenesis

227

1

F → W: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Mutagenesis

234

1

Y → A: No effect on binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Mutagenesis

244

1

F → A: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Mutagenesis

336

1

Y → A: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Mutagenesis

346

1

L → F: Dramatic increase in binding NCOA2. Little effect on binding of coactivator NCOA2 in the presence of TCPOBOP. Ref.8

Sequence conflict

138

1

M → L in AAC53349. Ref.1

Sequence conflict

138

1

M → L in AAC53350. Ref.1

Secondary structure

1

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358

Helix Strand Turn

Details...

Helix

118 – 134

17

Turn

135 – 137

3

Helix

138 – 144

7

Helix

149 – 152

4

Beta strand

160 – 162

3

Helix

164 – 187

24

Helix

190 – 193

4

Helix

197 – 216

20

Helix

217 – 219

3

Turn

222 – 225

4

Beta strand

226 – 229

4

Beta strand

232 – 234

3

Helix

236 – 241

6

Helix

246 – 260

15

Helix

266 – 277

12

Helix

288 – 308

21

Turn

309 – 312

4

Helix

318 – 335

18

Helix

337 – 343

7

Helix

345 – 349

5

Helix

351 – 357

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform CAR1 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: A11C92B1EC2C06A7	FASTA	358	40,913
	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
	Isoform CAR2 [UniParc]. Checksum: DAEF17A3369F529E	FASTA	286	32,544
	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 HAGFQYEFLE SILHFHKNLK GLHLQEPEYV LMAATALFSP GFCMQS

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00132688.
IPI00678716.

RefSeq

NP_001229991.1. NM_001243062.1.
NP_001229992.1. NM_001243063.1.
NP_033933.2. NM_009803.5.

UniGene

Mm.486506.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XLS	X-ray	2.96	E/F/G/H	117-358	[»]
1XNX	X-ray	2.90	A/B	109-358	[»]

ProteinModelPortal

O35627.

SMR

O35627. Positions 21-356.

ModBase

Search...

PTM databases

PhosphoSite

O35627.

Proteomic databases

PRIDE

O35627.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000005820; ENSMUSP00000005820; ENSMUSG00000005677.
ENSMUST00000075469; ENSMUSP00000074915; ENSMUSG00000005677.

GeneID

12355.

KEGG

mmu:12355.

UCSC

uc007dnf.2. mouse.
uc007dng.2. mouse.

Organism-specific databases

CTD

9970.

MGI

MGI:1346307. Nr1i3.

Phylogenomic databases

eggNOG

NOG251788.

GeneTree

ENSGT00680000099585.

HOGENOM

HOG000220844.

HOVERGEN

HBG108655.

InParanoid

Q3V008.

KO

K08541.

OMA

PRDRFLY.

OrthoDB

EOG4CVG7C.

Gene expression databases

ArrayExpress

O35627.

Bgee

O35627.

CleanEx

MM_NR1I3.

Genevestigator

O35627.

GermOnline

ENSMUSG00000005677. Mus musculus.

Family and domain databases

Gene3D

1.10.565.10. 2 hits.
3.30.50.10. 1 hit.

InterPro

IPR008946. 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]

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O35627.

ChEMBL

CHEMBL3069.

ChiTaRS

NR1I3. mouse.

EvolutionaryTrace

O35627.

NextBio

281020.

SOURCE

Search...

Entry information

Entry name

NR1I3_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program