P55055 (NR1H2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Oxysterols receptor LXR-beta

Alternative name(s):
Liver X receptor beta
Nuclear receptor NER
Nuclear receptor subfamily 1 group H member 2
Ubiquitously-expressed nuclear receptor

Gene names

Name:	NR1H2
Synonyms:	LXRB, NER, UNR

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	460 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 By similarity.
Subunit structure	Forms a heterodimer with RXR.
Subcellular location	Nucleus Potential.
Tissue specificity	Ubiquitous.
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	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	cellular lipid metabolic process Inferred from electronic annotation. Source: Compara cholesterol homeostasis Inferred from electronic annotation. Source: Compara negative regulation of cholesterol storage Inferred from mutant phenotype PubMed 17693624. 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 derived foam cell differentiation Inferred by curator PubMed 17693624. 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 transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 12393874. Source: HGNC positive regulation of cellular protein metabolic process Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL positive regulation of cholesterol efflux Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL positive regulation of fatty acid biosynthetic process Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL positive regulation of high-density lipoprotein particle assembly Inferred from electronic annotation. Source: Compara positive regulation of lipid storage Inferred from electronic annotation. Source: Compara positive regulation of lipoprotein lipase activity Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL positive regulation of pancreatic juice secretion Inferred from electronic annotation. Source: Compara positive regulation of secretion of lysosomal enzymes Inferred from electronic annotation. Source: Compara 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 17186944. Source: BHF-UCL retinoic acid receptor signaling pathway Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	cytoplasm Inferred from direct assay PubMed 12393874. Source: HGNC nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Traceable author statement Ref.1. Source: ProtInc 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 sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity Inferred from electronic annotation. Source: Compara steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDFI	Q99750	3	EBI-745354,EBI-724076

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 460

460

Oxysterols receptor LXR-beta

PRO_0000053532

Regions

DNA binding

84 – 161

78

Nuclear receptor

Zinc finger

87 – 107

21

NR C4-type

Zinc finger

125 – 149

25

NR C4-type

Region

230 – 460

231

Ligand-binding Potential

Compositional bias

190 – 195

6

Poly-Ser

Natural variations

Natural variant

2

1

S → F.
Corresponds to variant rs41379547 [ dbSNP | Ensembl ].

VAR_050579

Experimental info

Sequence conflict

175

1

Q → QQ in AAA61783. Ref.1

Sequence conflict

175

1

Q → QQ in BAF83544. Ref.2

Sequence conflict

175

1

Q → QQ in AAH07790. Ref.4

Sequence conflict

175

1

Q → QQ in AAH33500. Ref.4

Sequence conflict

175

1

Q → QQ in AAH47750. Ref.4

Sequence conflict

175

1

Q → QQ in AAH74500. Ref.4

Sequence conflict

175

1

Q → QQ in AAA58594. Ref.5

Secondary structure

1

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460

Helix Strand Turn

Details...

Helix

221 – 242

22

Helix

245 – 247

3

Helix

261 – 286

26

Helix

291 – 293

3

Helix

296 – 317

22

Turn

321 – 324

4

Beta strand

325 – 329

5

Beta strand

332 – 334

3

Helix

336 – 341

6

Helix

346 – 362

17

Helix

366 – 377

12

Helix

388 – 409

22

Beta strand

410 – 412

3

Helix

416 – 442

27

Turn

443 – 445

3

Helix

450 – 456

7

Sequences

	Sequence		Length	Mass (Da)
	P55055 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 9465A6FFB7FCFD2F	FASTA	460	50,974
	10 20 30 40 50 60 MSSPTTSSLD TPLPGNGPPQ PGAPSSSPTV KEEGPEPWPG GPDPDVPGTD EASSACSTDW 70 80 90 100 110 120 VIPDPEEEPE RKRKKGPAPK MLGHELCRVC GDKASGFHYN VLSCEGCKGF FRRSVVRGGA 130 140 150 160 170 180 RRYACRGGGT CQMDAFMRRK CQQCRLRKCK EAGMREQCVL SEEQIRKKKI RKQQQESQSQ 190 200 210 220 230 240 SQSPVGPQGS SSSASGPGAS PGGSEAGSQG SGEGEGVQLT AAQELMIQQL VAAQLQCNKR 250 260 270 280 290 300 SFSDQPKVTP WPLGADPQSR DARQQRFAHF TELAIISVQE IVDFAKQVPG FLQLGREDQI 310 320 330 340 350 360 ALLKASTIEI MLLETARRYN HETECITFLK DFTYSKDDFH RAGLQVEFIN PIFEFSRAMR 370 380 390 400 410 420 RLGLDDAEYA LLIAINIFSA DRPNVQEPGR VEALQQPYVE ALLSYTRIKR PQDQLRFPRM 430 440 450 460 LMKLVSLRTL SSVHSEQVFA LRLQDKKLPP LLSEIWDVHE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NER, a new member of the gene family encoding the human steroid hormone nuclear receptor." Shinar D.M., Endo N., Rutledge S.J., Vogel R., Rodan G.A., Schmidt A. Gene 147:273-276(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Osteosarcoma.
[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]. Tissue: Mammary gland.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood, Brain, Placenta and Uterus.
[5]	"Ubiquitous receptor: a novel receptor that modulates gene activation by retinoic acid and thyroid hormone receptors." Song C., Konkontis J.M., Hiipakka R.A., Liao S. Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-460.
[6]	"The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands." Farnegardh M., Bonn T., Sun S., Ljunggren J., Ahola H., Wilhelmsson A., Gustafsson J.-A., Carlquist M. J. Biol. Chem. 278:38821-38828(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 208-460 IN COMPLEX WITH SYNTHETIC LIGANDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U07132 mRNA. Translation: AAA61783.1.
AK290855 mRNA. Translation: BAF83544.1.
AC008655 Genomic DNA. No translation available.
BC007790 mRNA. Translation: AAH07790.1.
BC033500 mRNA. Translation: AAH33500.1.
BC047750 mRNA. Translation: AAH47750.1.
BC074500 mRNA. Translation: AAH74500.1.
U14534 mRNA. Translation: AAA58594.1.

IPI

IPI00022730.

PIR

JC4014.

RefSeq

NP_001243576.1. NM_001256647.1.
NP_009052.3. NM_007121.5.

UniGene

Hs.432976.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P8D	X-ray	2.80	A/B	213-460	[»]
1PQ6	X-ray	2.40	A/B/C/D	212-460	[»]
1PQ9	X-ray	2.10	A/B/C/D	212-460	[»]
1PQC	X-ray	2.80	A/B/C/D	212-460	[»]
1UPV	X-ray	2.10	A	208-460	[»]
1UPW	X-ray	2.40	A	208-460	[»]
3KFC	X-ray	2.40	A/B/C/D	212-460	[»]
3L0E	X-ray	2.30	A	212-460	[»]
4DK7	X-ray	2.45	A/C	218-460	[»]
4DK8	X-ray	2.75	A/C	218-460	[»]

ProteinModelPortal

P55055.

SMR

P55055. Positions 85-459.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-53004N.

IntAct

P55055. 7 interactions.

MINT

MINT-1444220.

STRING

9606.ENSP00000253727.

PTM databases

PhosphoSite

P55055.

Polymorphism databases

DMDM

296439251.

Proteomic databases

PaxDb

P55055.

PRIDE

P55055.

Protocols and materials databases

DNASU

7376.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253727; ENSP00000253727; ENSG00000131408.
ENST00000593926; ENSP00000471194; ENSG00000131408.

GeneID

7376.

KEGG

hsa:7376.

Organism-specific databases

CTD

7376.

GeneCards

GC19P050879.

HGNC

HGNC:7965. NR1H2.

MIM

600380. gene.

neXtProt

NX_P55055.

PharmGKB

PA31750.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG285805.

HOVERGEN

HBG108655.

InParanoid

P55055.

KO

K08535.

OMA

DEASSAC.

OrthoDB

EOG4DV5M7.

PhylomeDB

P55055.

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

P55055.

Bgee

P55055.

CleanEx

HS_NR1H2.

Genevestigator

P55055.

GermOnline

ENSG00000131408. 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

P55055.

ChEMBL

CHEMBL4093.

ChiTaRS

NR1H2. human.

EvolutionaryTrace

P55055.

GenomeRNAi

7376.

NextBio

28886.

SOURCE

Search...

Entry information

Entry name

NR1H2_HUMAN

Accession

Primary (citable) accession number: P55055
Secondary accession number(s): A8K490, Q12970, Q5I0Y1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 145 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.