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O35627

- NR1I3_MOUSE

UniProt

O35627 - NR1I3_MOUSE

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Protein

Nuclear receptor subfamily 1 group I member 3

Gene

Nr1i3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei171 – 1711Important for TCPOBOP recognition
Sitei175 – 1751Important for TCPOBOP recognition
Sitei216 – 2161Important for TCPOBOP recognition
Sitei227 – 2271Important for TCPOBOP recognition
Sitei244 – 2441Important for TCPOBOP recognition
Sitei336 – 3361Important for TCPOBOP recognition

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi18 – 9376Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri21 – 4121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri57 – 8125NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. RNA polymerase II regulatory region sequence-specific DNA binding Source: Ensembl
  3. RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  4. steroid hormone receptor activity Source: InterPro
  5. thyroid hormone receptor activity Source: InterPro
  6. zinc ion binding Source: InterPro

GO - Biological processi

  1. negative regulation of transcription, DNA-templated Source: MGI
  2. regulation of transcription, DNA-templated Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 1 group I member 3
Alternative name(s):
Constitutive androstane receptor
Short name:
CAR
Orphan nuclear receptor MB67
Gene namesi
Name:Nr1i3
Synonyms:Car
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:1346307. Nr1i3.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoskeleton Source: UniProtKB-KW
  3. cytosol Source: MGI
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi171 – 1711F → W: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication
Mutagenesisi175 – 1751N → F: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication
Mutagenesisi216 – 2161L → F: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication
Mutagenesisi227 – 2271F → W: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication
Mutagenesisi234 – 2341Y → A: No effect on binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication
Mutagenesisi244 – 2441F → A: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication
Mutagenesisi336 – 3361Y → A: Diminished binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication
Mutagenesisi346 – 3461L → F: Dramatic increase in binding NCOA2. Little effect on binding of coactivator NCOA2 in the presence of TCPOBOP. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 358358Nuclear receptor subfamily 1 group I member 3PRO_0000053554Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei48 – 481Phosphothreonine; by PKCBy similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiO35627.

PTM databases

PhosphoSiteiO35627.

Expressioni

Tissue specificityi

Predominantly expressed in liver.

Gene expression databases

BgeeiO35627.
CleanExiMM_NR1I3.
ExpressionAtlasiO35627. baseline and differential.
GenevestigatoriO35627.

Interactioni

Subunit structurei

Heterodimer of NR1I3 and RXR. Interacts with PSMC4. Interacts with ECT2. Directly interacts with DNAJC7; this complex may also include HSP90.4 Publications

Protein-protein interaction databases

BioGridi198489. 12 interactions.

Structurei

Secondary structure

1
358
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi118 – 13417
Turni135 – 1373
Helixi138 – 1447
Helixi149 – 1524
Beta strandi160 – 1623
Helixi164 – 18724
Helixi190 – 1934
Helixi197 – 21620
Helixi217 – 2193
Turni222 – 2254
Beta strandi226 – 2294
Beta strandi232 – 2343
Helixi236 – 2416
Helixi246 – 26015
Helixi266 – 27712
Helixi288 – 30821
Turni309 – 3124
Helixi318 – 33518
Helixi337 – 3437
Helixi345 – 3495
Helixi351 – 3577

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1XLSX-ray2.96E/F/G/H117-358[»]
1XNXX-ray2.90A/B109-358[»]
ProteinModelPortaliO35627.
SMRiO35627. Positions 21-356.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO35627.

Family & Domainsi

Domaini

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

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri21 – 4121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri57 – 8125NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG251788.
GeneTreeiENSGT00760000118837.
HOGENOMiHOG000220844.
HOVERGENiHBG108655.
InParanoidiO35627.
KOiK08541.
OMAiPRDRFLY.
OrthoDBiEOG7SXW4K.
TreeFamiTF316304.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR008946. 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]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform CAR1 (identifier: O35627-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MTAMLTLETM ASEEEYGPRN CVVCGDRATG YHFHALTCEG CKGFFRRTVS
60 70 80 90 100
KTIGPICPFA GRCEVSKAQR RHCPACRLQK CLNVGMRKDM ILSAEALALR
110 120 130 140 150
RARQAQRRAE KASLQLNQQQ KELVQILLGA HTRHVGPMFD QFVQFKPPAY
160 170 180 190 200
LFMHHRPFQP RGPVLPLLTH FADINTFMVQ QIIKFTKDLP LFRSLTMEDQ
210 220 230 240 250
ISLLKGAAVE ILHISLNTTF CLQTENFFCG PLCYKMEDAV HAGFQYEFLE
260 270 280 290 300
SILHFHKNLK GLHLQEPEYV LMAATALFSP DRPGVTQREE IDQLQEEMAL
310 320 330 340 350
ILNNHIMEQQ SRLQSRFLYA KLMGLLADLR SINNAYSYEL QRLEELSAMT

PLLGEICS
Length:358
Mass (Da):40,913
Last modified:July 27, 2011 - v2
Checksum:iA11C92B1EC2C06A7
GO
Isoform CAR2 (identifier: O35627-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:286
Mass (Da):32,544
Checksum:iDAEF17A3369F529E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti138 – 1381M → L in AAC53349. (PubMed:9295294)Curated
Sequence conflicti138 – 1381M → L in AAC53350. (PubMed:9295294)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei281 – 2866DRPGVT → GFCMQS in isoform CAR2. 1 PublicationVSP_003671
Alternative sequencei287 – 35872Missing in isoform CAR2. 1 PublicationVSP_003672Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF009327 mRNA. Translation: AAC53349.1.
AF009328 mRNA. Translation: AAC53350.1.
AK133515 mRNA. Translation: BAE21697.1.
CH466520 Genomic DNA. Translation: EDL39126.1.
CCDSiCCDS15480.1. [O35627-1]
CCDS56654.1. [O35627-2]
RefSeqiNP_001229991.1. NM_001243062.1. [O35627-2]
NP_001229992.1. NM_001243063.1.
NP_033933.2. NM_009803.5. [O35627-1]
UniGeneiMm.486506.

Genome annotation databases

EnsembliENSMUST00000005820; ENSMUSP00000005820; ENSMUSG00000005677. [O35627-1]
ENSMUST00000075469; ENSMUSP00000074915; ENSMUSG00000005677. [O35627-2]
GeneIDi12355.
KEGGimmu:12355.
UCSCiuc007dnf.2. mouse. [O35627-1]
uc007dng.2. mouse. [O35627-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF009327 mRNA. Translation: AAC53349.1 .
AF009328 mRNA. Translation: AAC53350.1 .
AK133515 mRNA. Translation: BAE21697.1 .
CH466520 Genomic DNA. Translation: EDL39126.1 .
CCDSi CCDS15480.1. [O35627-1 ]
CCDS56654.1. [O35627-2 ]
RefSeqi NP_001229991.1. NM_001243062.1. [O35627-2 ]
NP_001229992.1. NM_001243063.1.
NP_033933.2. NM_009803.5. [O35627-1 ]
UniGenei Mm.486506.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali O35627.
SMRi O35627. Positions 21-356.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198489. 12 interactions.

Chemistry

BindingDBi O35627.
ChEMBLi CHEMBL3069.
GuidetoPHARMACOLOGYi 607.

PTM databases

PhosphoSitei O35627.

Proteomic databases

PRIDEi O35627.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000005820 ; ENSMUSP00000005820 ; ENSMUSG00000005677 . [O35627-1 ]
ENSMUST00000075469 ; ENSMUSP00000074915 ; ENSMUSG00000005677 . [O35627-2 ]
GeneIDi 12355.
KEGGi mmu:12355.
UCSCi uc007dnf.2. mouse. [O35627-1 ]
uc007dng.2. mouse. [O35627-2 ]

Organism-specific databases

CTDi 9970.
MGIi MGI:1346307. Nr1i3.

Phylogenomic databases

eggNOGi NOG251788.
GeneTreei ENSGT00760000118837.
HOGENOMi HOG000220844.
HOVERGENi HBG108655.
InParanoidi O35627.
KOi K08541.
OMAi PRDRFLY.
OrthoDBi EOG7SXW4K.
TreeFami TF316304.

Miscellaneous databases

ChiTaRSi NR1I3. mouse.
EvolutionaryTracei O35627.
NextBioi 281020.
PROi O35627.
SOURCEi Search...

Gene expression databases

Bgeei O35627.
CleanExi MM_NR1I3.
ExpressionAtlasi O35627. baseline and differential.
Genevestigatori O35627.

Family and domain databases

Gene3Di 1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProi 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 ]
Pfami PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PRINTSi PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 1 hit.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiNR1I3_MOUSE
AccessioniPrimary (citable) accession number: O35627
Secondary accession number(s): O35628, Q3V008
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3