Q14994 (NR1I3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor subfamily 1 group I member 3

Alternative name(s):
Constitutive activator of retinoid response
Short name=Constitutive active response
Constitutive androstane receptor
Short name=CAR
Orphan nuclear receptor MB67

Gene names

Name:	NR1I3
Synonyms:	CAR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	352 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.
Subunit structure	Interacts with ECT2 By similarity. Heterodimer of NR1I3 and RXR. Interacts with PSMC4. Directly interacts with DNAJC7. The DNAJC7-NR1I3 complex may also include HSP90 By similarity. Ref.5 Ref.6
Subcellular location	Nucleus By similarity. Cytoplasm. Cytoplasm › cytoskeleton. Note: Recruited to the cytoplasm by DNAJC7 By similarity. Ref.6
Tissue specificity	Predominantly expressed in liver.
Induction	By dexamethasone.
Domain	Composed by a short N-terminal domain followed by the DNA binding, hinge, and ligand binding/dimerization domains.
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 Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Uncategorized	regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor Traceable author statement. Source: Reactome
Biological process	transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Molecular function	androgen receptor activity Traceable author statement. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement. Source: ProtInc thyroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Traceable author statement. Source: ProtInc 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 1 (identifier: Q14994-1)

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 2 (identifier: Q14994-2)

The sequence of this isoform differs from the canonical sequence as follows:
     233-236: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 352

352

Nuclear receptor subfamily 1 group I member 3

PRO_0000053552

Regions

DNA binding

8 – 83

76

Nuclear receptor

Zinc finger

11 – 31

21

NR C4-type

Zinc finger

47 – 71

25

NR C4-type

Natural variations

Alternative sequence

233 – 236

4

Missing in isoform 2.

VSP_010634

Natural variant

133

1

V → G. Ref.8

VAR_018344

Secondary structure

1

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352

Helix Strand Turn

Details...

Helix

108 – 124

17

Beta strand

125 – 127

3

Helix

128 – 134

7

Helix

139 – 142

4

Helix

155 – 177

23

Helix

180 – 183

4

Helix

187 – 206

20

Turn

207 – 209

3

Turn

212 – 215

4

Beta strand

216 – 219

4

Beta strand

222 – 224

3

Helix

226 – 231

6

Helix

240 – 255

16

Helix

260 – 271

12

Helix

282 – 301

20

Helix

312 – 336

25

Helix

340 – 343

4

Helix

345 – 350

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 21, 2004. Version 2. Checksum: 73B060FE4950D519	FASTA	352	39,942
	10 20 30 40 50 60 MASREDELRN CVVCGDQATG YHFNALTCEG CKGFFRRTVS KSIGPTCPFA GSCEVSKTQR 70 80 90 100 110 120 RHCPACRLQK CLDAGMRKDM ILSAEALALR RAKQAQRRAQ QTPVQLSKEQ EELIRTLLGA 130 140 150 160 170 180 HTRHMGTMFE QFVQFRPPAH LFIHHQPLPT LAPVLPLVTH FADINTFMVL QVIKFTKDLP 190 200 210 220 230 240 VFRSLPIEDQ ISLLKGAAVE ICHIVLNTTF CLQTQNFLCG PLRYTIEDGA RVSPTVGFQV 250 260 270 280 290 300 EFLELLFHFH GTLRKLQLQE PEYVLLAAMA LFSPDRPGVT QRDEIDQLQE EMALTLQSYI 310 320 330 340 350 KGQQRRPRDR FLYAKLLGLL AELRSINEAY GYQIQHIQGL SAMMPLLQEI CS
	Isoform 2 [UniParc]. Checksum: 92EAAD07D7DCB9DA	FASTA	348	39,558
	10 20 30 40 50 60 MASREDELRN CVVCGDQATG YHFNALTCEG CKGFFRRTVS KSIGPTCPFA GSCEVSKTQR 70 80 90 100 110 120 RHCPACRLQK CLDAGMRKDM ILSAEALALR RAKQAQRRAQ QTPVQLSKEQ EELIRTLLGA 130 140 150 160 170 180 HTRHMGTMFE QFVQFRPPAH LFIHHQPLPT LAPVLPLVTH FADINTFMVL QVIKFTKDLP 190 200 210 220 230 240 VFRSLPIEDQ ISLLKGAAVE ICHIVLNTTF CLQTQNFLCG PLRYTIEDGA RVGFQVEFLE 250 260 270 280 290 300 LLFHFHGTLR KLQLQEPEYV LLAAMALFSP DRPGVTQRDE IDQLQEEMAL TLQSYIKGQQ 310 320 330 340 RRPRDRFLYA KLLGLLAELR SINEAYGYQI QHIQGLSAMM PLLQEICS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements." Baes M., Gulick T., Choi H.S., Martinoli M.G., Simha D., Moore D.D. Mol. Cell. Biol. 14:1544-1552(1994) [PubMed: 8114692] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Liver.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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: 8603043] [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: 14573755] [Abstract] Cited for: INTERACTION WITH DNAJC7, SUBCELLULAR LOCATION.
[7]	"A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer." Xu R.X., Lambert M.H., Wisely B.B., Warren E.N., Weinert E.E., Waitt G.M., Williams J.D., Collins J.L., Moore L.B., Willson T.M., Moore J.T. Mol. Cell 16:919-928(2004) [PubMed: 15610735] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 103-352.
[8]	"Twenty-six novel single nucleotide polymorphisms and their frequencies of the NR1I3 (CAR) gene in a Japanese population." Ikeda S., Kurose K., Ozawa S., Sai K., Hasegawa R., Komamura K., Ueno K., Kamakura S., Kitakaze M., Tomoike H., Nakajima T., Matsumoto K., Saito H., Goto Y., Kimura H., Katoh M., Sugai K., Minami N. , Shirao K., Tamura T., Yamamoto N., Minami H., Ohtsu A., Yoshida T., Saijo N., Saito Y., Sawada J. Drug Metab. Pharmacokinet. 18:413-418(2003) [PubMed: 15618763] [Abstract] Cited for: VARIANT GLY-133.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z30425 mRNA. Translation: CAA83016.1.
AL590714 Genomic DNA. Translation: CAH72153.1.
AL590714 Genomic DNA. Translation: CAH72154.1.
CH471121 Genomic DNA. Translation: EAW52608.1.
CH471121 Genomic DNA. Translation: EAW52609.1.
BC069626 mRNA. Translation: AAH69626.1.

IPI

IPI00001687.
IPI00418379.

PIR

A56197.

RefSeq

NP_001070948.1. NM_001077480.2.
NP_005113.1. NM_005122.4.

UniGene

Hs.349642.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XV9	X-ray	2.70	B/D	103-352	[»]
1XVP	X-ray	2.60	B/D	103-352	[»]

ProteinModelPortal

Q14994.

SMR

Q14994. Positions 8-352.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14994. 5 interactions.

STRING

Q14994.

PTM databases

PhosphoSite

Q14994.

Polymorphism databases

DMDM

49066046.

Proteomic databases

PRIDE

Q14994.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367979; ENSP00000356958; ENSG00000143257.
ENST00000367983; ENSP00000356962; ENSG00000143257.

GeneID

9970.

KEGG

hsa:9970.

UCSC

uc001fzx.1. human.

Organism-specific databases

CTD

9970.

GeneCards

GC01M161199.

HGNC

HGNC:7969. NR1I3.

MIM

603881. gene.

neXtProt

NX_Q14994.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00570000079102.

HOVERGEN

HBG108655.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q14994.

Bgee

Q14994.

CleanEx

HS_NR1I3.

Genevestigator

Q14994.

GermOnline

ENSG00000143257. Homo sapiens.

Family and domain databases

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]

Gene3D

G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit.
G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.

KO

K08541.

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

NextBio

37626.

SOURCE

Search...

Entry information

Entry name

NR1I3_HUMAN

Accession

Primary (citable) accession number: Q14994
Secondary accession number(s): Q5VTW5, Q5VTW6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 21, 2004
Last modified:	January 25, 2012
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.