Q13133 (NR1H3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Oxysterols receptor LXR-alpha

Alternative name(s):
Liver X receptor alpha
Nuclear receptor subfamily 1 group H member 3

Gene names

Name:	NR1H3
Synonyms:	LXRA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	447 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Orphan receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 By similarity.
Subunit structure	Heterodimer of LXRA and RXR.
Subcellular location	Nucleus Potential.
Tissue specificity	Visceral organs specific expression. Strong expression was found in liver, kidney and intestine followed by spleen and to a lesser extent the adrenals.
Induction	By 9-cis retinoic acid (9CRA).
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	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic cell clearance Inferred from mutant phenotype PubMed 19628791. Source: UniProtKB cellular lipid metabolic process Inferred from electronic annotation. Source: Compara cellular response to lipopolysaccharide Inferred from direct assay PubMed 18511497. Source: BHF-UCL cholesterol homeostasis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of cholesterol storage Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL negative regulation of inflammatory response Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of interferon-gamma-mediated signaling pathway Non-traceable author statement PubMed 21268089. Source: BHF-UCL negative regulation of lipid transport Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL negative regulation of macrophage activation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of macrophage derived foam cell differentiation Inferred by curator PubMed 17693624. Source: BHF-UCL negative regulation of pancreatic juice secretion Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of pinocytosis Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL negative regulation of proteolysis Inferred from electronic annotation. Source: Compara negative regulation of secretion of lysosomal enzymes Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cellular protein metabolic process Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL positive regulation of cholesterol efflux Inferred from direct assay PubMed 16141411. Source: BHF-UCL positive regulation of cholesterol homeostasis Inferred from direct assay PubMed 18511497. Source: BHF-UCL positive regulation of fatty acid biosynthetic process Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL positive regulation of lipoprotein lipase activity Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL positive regulation of receptor biosynthetic process Inferred from direct assay PubMed 18511497. Source: BHF-UCL positive regulation of toll-like receptor 4 signaling pathway Inferred from direct assay PubMed 18511497. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20219900. Source: UniProtKB positive regulation of triglyceride biosynthetic process Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL regulation of circadian rhythm Traceable author statement PubMed 18511497. Source: BHF-UCL response to progesterone stimulus Inferred from direct assay PubMed 16141411. Source: BHF-UCL transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome triglyceride homeostasis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	nuclear chromatin Inferred from direct assay PubMed 18511497. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	cholesterol binding Traceable author statement PubMed 11090131. Source: BHF-UCL ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Traceable author statement Ref.1. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro sterol response element binding Inferred from direct assay PubMed 19628791. Source: UniProtKB transcription coactivator activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EDF1	O60869	4	EBI-781356,EBI-781301

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13133-1)

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: Q13133-2)

The sequence of this isoform differs from the canonical sequence as follows:
     237-296: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q13133-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 447

447

Oxysterols receptor LXR-alpha

PRO_0000053535

Regions

DNA binding

95 – 170

76

Nuclear receptor

Zinc finger

98 – 118

21

NR C4-type

Zinc finger

134 – 158

25

NR C4-type

Region

215 – 434

220

Ligand-binding Potential

Natural variations

Alternative sequence

1 – 45

45

Missing in isoform 3.

VSP_044960

Alternative sequence

237 – 296

60

Missing in isoform 2.

VSP_003664

Natural variant

52

1

G → V.
Corresponds to variant rs41481445 [ dbSNP | Ensembl ].

VAR_050580

Experimental info

Sequence conflict

196

1

A → R in AAA85856. Ref.1

Secondary structure

1

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447

Helix Strand Turn

Details...

Helix

208 – 221

14

Helix

229 – 233

5

Helix

250 – 274

25

Helix

278 – 280

3

Helix

283 – 304

22

Turn

308 – 311

4

Beta strand

312 – 315

4

Turn

316 – 318

3

Beta strand

319 – 321

3

Helix

323 – 328

6

Helix

333 – 349

17

Helix

353 – 364

12

Beta strand

369 – 371

3

Helix

375 – 396

22

Helix

403 – 430

28

Helix

437 – 443

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 0D27B237440F8C9C	FASTA	447	50,396
	10 20 30 40 50 60 MSLWLGAPVP DIPPDSAVEL WKPGAQDASS QAQGGSSCIL REEARMPHSA GGTAGVGLEA 70 80 90 100 110 120 AEPTALLTRA EPPSEPTEIR PQKRKKGPAP KMLGNELCSV CGDKASGFHY NVLSCEGCKG 130 140 150 160 170 180 FFRRSVIKGA HYICHSGGHC PMDTYMRRKC QECRLRKCRQ AGMREECVLS EEQIRLKKLK 190 200 210 220 230 240 RQEEEQAHAT SLPPRASSPP QILPQLSPEQ LGMIEKLVAA QQQCNRRSFS DRLRVTPWPM 250 260 270 280 290 300 APDPHSREAR QQRFAHFTEL AIVSVQEIVD FAKQLPGFLQ LSREDQIALL KTSAIEVMLL 310 320 330 340 350 360 ETSRRYNPGS ESITFLKDFS YNREDFAKAG LQVEFINPIF EFSRAMNELQ LNDAEFALLI 370 380 390 400 410 420 AISIFSADRP NVQDQLQVER LQHTYVEALH AYVSIHHPHD RLMFPRMLMK LVSLRTLSSV 430 440 HSEQVFALRL QDKKLPPLLS EIWDVHE
	Isoform 2 [UniParc]. Checksum: 9C96CF2BBE66403C	FASTA	387	43,555
	10 20 30 40 50 60 MSLWLGAPVP DIPPDSAVEL WKPGAQDASS QAQGGSSCIL REEARMPHSA GGTAGVGLEA 70 80 90 100 110 120 AEPTALLTRA EPPSEPTEIR PQKRKKGPAP KMLGNELCSV CGDKASGFHY NVLSCEGCKG 130 140 150 160 170 180 FFRRSVIKGA HYICHSGGHC PMDTYMRRKC QECRLRKCRQ AGMREECVLS EEQIRLKKLK 190 200 210 220 230 240 RQEEEQAHAT SLPPRASSPP QILPQLSPEQ LGMIEKLVAA QQQCNRRSFS DRLRVTVMLL 250 260 270 280 290 300 ETSRRYNPGS ESITFLKDFS YNREDFAKAG LQVEFINPIF EFSRAMNELQ LNDAEFALLI 310 320 330 340 350 360 AISIFSADRP NVQDQLQVER LQHTYVEALH AYVSIHHPHD RLMFPRMLMK LVSLRTLSSV 370 380 HSEQVFALRL QDKKLPPLLS EIWDVHE
	Isoform 3 [UniParc]. Checksum: 78EAE53CFB2358E7	FASTA	402	45,692
	10 20 30 40 50 60 MPHSAGGTAG VGLEAAEPTA LLTRAEPPSE PTEIRPQKRK KGPAPKMLGN ELCSVCGDKA 70 80 90 100 110 120 SGFHYNVLSC EGCKGFFRRS VIKGAHYICH SGGHCPMDTY MRRKCQECRL RKCRQAGMRE 130 140 150 160 170 180 ECVLSEEQIR LKKLKRQEEE QAHATSLPPR ASSPPQILPQ LSPEQLGMIE KLVAAQQQCN 190 200 210 220 230 240 RRSFSDRLRV TPWPMAPDPH SREARQQRFA HFTELAIVSV QEIVDFAKQL PGFLQLSRED 250 260 270 280 290 300 QIALLKTSAI EVMLLETSRR YNPGSESITF LKDFSYNRED FAKAGLQVEF INPIFEFSRA 310 320 330 340 350 360 MNELQLNDAE FALLIAISIF SADRPNVQDQ LQVERLQHTY VEALHAYVSI HHPHDRLMFP 370 380 390 400 RMLMKLVSLR TLSSVHSEQV FALRLQDKKL PPLLSEIWDV HE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LXR, a nuclear receptor that defines a distinct retinoid response pathway." Willy P.J., Umesono K., Ong E.S., Evans R.M., Heyman R.A., Mangelsdorf D.J. Genes Dev. 9:1033-1045(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Heart.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Brain and Placenta.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U22662 mRNA. Translation: AAA85856.1.
AK290614 mRNA. Translation: BAF83303.1.
AC018410 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW67949.1.
CH471064 Genomic DNA. Translation: EAW67942.1.
CH471064 Genomic DNA. Translation: EAW67943.1.
CH471064 Genomic DNA. Translation: EAW67944.1.
CH471064 Genomic DNA. Translation: EAW67947.1.
CH471064 Genomic DNA. Translation: EAW67948.1.
BC008819 mRNA. Translation: AAH08819.1.
BC041172 mRNA. Translation: AAH41172.1.

IPI

IPI00220134.
IPI00301894.
IPI00796145.

PIR

I38975.

RefSeq

NP_001123573.1. NM_001130101.2.
NP_001123574.1. NM_001130102.2.
NP_005684.2. NM_005693.3.

UniGene

Hs.438863.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UHL	X-ray	2.90	B	207-447	[»]
3IPQ	X-ray	2.00	A	182-447	[»]
3IPS	X-ray	2.26	A/B	182-447	[»]
3IPU	X-ray	2.40	A/B	182-447	[»]

ProteinModelPortal

Q13133.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13133. 4 interactions.

STRING

9606.ENSP00000342470.

PTM databases

PhosphoSite

Q13133.

Polymorphism databases

DMDM

23503089.

Proteomic databases

PaxDb

Q13133.

PRIDE

Q13133.

Protocols and materials databases

DNASU

10062.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000395397; ENSP00000378793; ENSG00000025434.
ENST00000405853; ENSP00000384745; ENSG00000025434.
ENST00000407404; ENSP00000385801; ENSG00000025434.
ENST00000441012; ENSP00000387946; ENSG00000025434.
ENST00000467728; ENSP00000420656; ENSG00000025434.

GeneID

10062.

KEGG

hsa:10062.

UCSC

uc001nek.3. human.
uc001nen.4. human.

Organism-specific databases

CTD

10062.

GeneCards

GC11P047269.

HGNC

HGNC:7966. NR1H3.

HPA

CAB037109.
HPA036443.

MIM

602423. gene.

neXtProt

NX_Q13133.

Orphanet

803. Amyotrophic lateral sclerosis.

PharmGKB

PA31751.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG285805.

HOGENOM

HOG000220845.

HOVERGEN

HBG108655.

InParanoid

Q13133.

KO

K08536.

OMA

CILREEA.

PhylomeDB

Q13133.

Enzyme and pathway databases

Pathway_Interaction_DB

rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q13133.

Bgee

Q13133.

CleanEx

HS_NR1H3.

Genevestigator

Q13133.

GermOnline

ENSG00000025434. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 2 hits.
3.30.50.10. 1 hit.

InterPro

IPR023257. Liver_X_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_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

PR02034. LIVERXRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

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

Q13133.

ChEMBL

CHEMBL2808.

EvolutionaryTrace

Q13133.

GenomeRNAi

10062.

NextBio

38029.

SOURCE

Search...

Entry information

Entry name

NR1H3_HUMAN

Accession

Primary (citable) accession number: Q13133
Secondary accession number(s): A8K3J9 , D3DQR1, Q8IW13, Q96H87

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	September 19, 2002
Last modified:	May 1, 2013
This is version 140 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.