P28702 (RXRB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Retinoic acid receptor RXR-beta

Alternative name(s):
Nuclear receptor subfamily 2 group B member 2
Retinoid X receptor beta

Gene names

Name:	RXRB
Synonyms:	NR2B2

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

General annotation (Comments)

Function	Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 By similarity. Specifically binds 9-cis retinoic acid (9C-RA).
Subunit structure	Homodimer By similarity. Heterodimer with a RAR molecule. Binds DNA preferentially as a RAR/RXR heterodimer. Ref.1
Subcellular location	Nucleus.
Tissue specificity	Expressed in a variety of tumor cell lines. Ref.10
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR2 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence BAD92481.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
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	cardiac muscle cell proliferation Inferred from electronic annotation. Source: Compara cellular response to retinoic acid Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara maternal placenta development Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome ventricular cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	9-cis retinoic acid receptor activity Traceable author statement PubMed 1662118. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: Compara steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Traceable author statement PubMed 1662118. Source: ProtInc transcription regulatory region DNA binding Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CACNA1B	Q00975	3	EBI-748576,EBI-1055161

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P28702-1)

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: P28702-3)

The sequence of this isoform differs from the canonical sequence as follows:
     418-418: D → DRSLS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 533

533

Retinoic acid receptor RXR-beta

PRO_0000053572

Regions

DNA binding

205 – 270

66

Nuclear receptor

Zinc finger

205 – 225

21

NR C4-type

Zinc finger

241 – 265

25

NR C4-type

Region

1 – 204

204

Modulating By similarity

Region

271 – 330

60

Hinge

Region

331 – 533

203

Ligand-binding By similarity

Compositional bias

61 – 198

138

Pro-rich

Natural variations

Alternative sequence

418

1

D → DRSLS in isoform 2.

VSP_045587

Experimental info

Sequence conflict

112

1

S → T in AAA60293. Ref.1

Secondary structure

1

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533

Helix Strand Turn

Details...

Helix

301 – 309

9

Helix

336 – 347

12

Helix

350 – 355

6

Helix

360 – 362

3

Helix

365 – 387

23

Turn

388 – 390

3

Beta strand

394 – 396

3

Beta strand

402 – 404

3

Helix

405 – 411

7

Helix

414 – 423

10

Helix

425 – 431

7

Helix

435 – 446

12

Helix

457 – 478

22

Helix

485 – 490

6

Helix

493 – 513

21

Helix

517 – 521

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: D0069FE93AC16A04	FASTA	533	56,922
	10 20 30 40 50 60 MSWAARPPFL PQRHAAGQCG PVGVRKEMHC GVASRWRRRR PWLDPAAAAA AAVAGGEQQT 70 80 90 100 110 120 PEPEPGEAGR DGMGDSGRDS RSPDSSSPNP LPQGVPPPSP PGPPLPPSTA PSLGGSGAPP 130 140 150 160 170 180 PPPMPPPPLG SPFPVISSSM GSPGLPPPAP PGFSGPVSSP QINSTVSLPG GGSGPPEDVK 190 200 210 220 230 240 PPVLGVRGLH CPPPPGGPGA GKRLCAICGD RSSGKHYGVY SCEGCKGFFK RTIRKDLTYS 250 260 270 280 290 300 CRDNKDCTVD KRQRNRCQYC RYQKCLATGM KREAVQEERQ RGKDKDGDGE GAGGAPEEMP 310 320 330 340 350 360 VDRILEAELA VEQKSDQGVE GPGGTGGSGS SPNDPVTNIC QAADKQLFTL VEWAKRIPHF 370 380 390 400 410 420 SSLPLDDQVI LLRAGWNELL IASFSHRSID VRDGILLATG LHVHRNSAHS AGVGAIFDRV 430 440 450 460 470 480 LTELVSKMRD MRMDKTELGC LRAIILFNPD AKGLSNPSEV EVLREKVYAS LETYCKQKYP 490 500 510 520 530 EQQGRFAKLL LRLPALRSIG LKCLEHLFFF KLIGDTPIDT FLMEMLEAPH QLA
	Isoform 2 [UniParc]. Checksum: E6789FB00428DA2C	FASTA	537	57,365
	10 20 30 40 50 60 MSWAARPPFL PQRHAAGQCG PVGVRKEMHC GVASRWRRRR PWLDPAAAAA AAVAGGEQQT 70 80 90 100 110 120 PEPEPGEAGR DGMGDSGRDS RSPDSSSPNP LPQGVPPPSP PGPPLPPSTA PSLGGSGAPP 130 140 150 160 170 180 PPPMPPPPLG SPFPVISSSM GSPGLPPPAP PGFSGPVSSP QINSTVSLPG GGSGPPEDVK 190 200 210 220 230 240 PPVLGVRGLH CPPPPGGPGA GKRLCAICGD RSSGKHYGVY SCEGCKGFFK RTIRKDLTYS 250 260 270 280 290 300 CRDNKDCTVD KRQRNRCQYC RYQKCLATGM KREAVQEERQ RGKDKDGDGE GAGGAPEEMP 310 320 330 340 350 360 VDRILEAELA VEQKSDQGVE GPGGTGGSGS SPNDPVTNIC QAADKQLFTL VEWAKRIPHF 370 380 390 400 410 420 SSLPLDDQVI LLRAGWNELL IASFSHRSID VRDGILLATG LHVHRNSAHS AGVGAIFDRS 430 440 450 460 470 480 LSRVLTELVS KMRDMRMDKT ELGCLRAIIL FNPDAKGLSN PSEVEVLREK VYASLETYCK 490 500 510 520 530 QKYPEQQGRF AKLLLRLPAL RSIGLKCLEH LFFFKLIGDT PIDTFLMEML EAPHQLA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently." Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewsi T., Chen J.Y., Staub A., Garnier J.-M., Mader S., Chambon P. Cell 68:377-395(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), HETERODIMERIZATION. Tissue: Mammary carcinoma.
[2]	Erratum Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewsi T., Chen J.Y., Staub A., Garnier J.-M., Mader S., Chambon P. Cell 71:887-887(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"Isolation of a full-length cDNA clone encoding a N-terminally variant form of the human retinoid X receptor beta." Fleischhauer K., Park J.H., Disanto J.P., Marks M.S., Ozato K., Yang S.Y. Nucleic Acids Res. 20:1801-1801(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	Numasawa T., Koga H., Ueyama K., Maeda S., Sakou T., Harata S., Leppert M., Inoue I. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Isolation of cDNA coding for putatively new variants of multiple human nuclear receptors." Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Liver.
[6]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[7]	"Molecular cloning and characterization of the human HRXRB gene and 5' flanking region." Corella A., Vergara A., Paez G., de Miguel C., Encio I. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] (ISOFORM 1). Tissue: Brain.
[10]	"Cloning and chromosome mapping of human retinoid X receptor beta: selective amino acid sequence conservation of a nuclear hormone receptor in mammals." Fleischhauer K., McBride O.W., DiSanto J.P., Ozato K., Yang S.Y. Hum. Genet. 90:505-510(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 161-331 (ISOFORM 1), TISSUE SPECIFICITY.
[11]	"The structural basis for the specificity of retinoid-X receptor-selective agonists: new insights into the role of helix H12." Love J.D., Gooch J.T., Benko S., Li C., Nagy L., Chatterjee V.K., Evans R.M., Schwabe J.W. J. Biol. Chem. 277:11385-11391(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 299-522 IN COMPLEX WITH THE RXR-SPECIFIC AGONIST LG100268.
[12]	"Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation." Svensson S., Ostberg T., Jacobsson M., Norstrom C., Stefansson K., Hallen D., Johansson I.C., Zachrisson K., Ogg D., Jendeberg L. EMBO J. 22:4625-4633(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 298-533 IN COMPLEX WITH NR1H3.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M84820 mRNA. Translation: AAA60293.1.
X63522 mRNA. Translation: CAA45087.1.
AF065396 Genomic DNA. Translation: AAC18599.1.
AF120161 Genomic DNA. Translation: AAD13794.1.
HQ709179 mRNA. Translation: ADZ17386.1.
AB209244 mRNA. Translation: BAD92481.1. Different initiation.
AL031228 Genomic DNA. Translation: CAA20239.1.
AL844527 Genomic DNA. Translation: CAI41836.2.
CR936877 Genomic DNA. Translation: CAQ09065.1.
CR759733 Genomic DNA. Translation: CAQ10299.1.
CR354565 Genomic DNA. Translation: CAQ11083.1.
AL645940 Genomic DNA. No translation available.
AL662824 Genomic DNA. No translation available.
BC001167 mRNA. Translation: AAH01167.1.
X66424 mRNA. No translation available.

IPI

IPI00426305.
IPI00607575.

PIR

S37781.

RefSeq

NP_001257330.1. NM_001270401.1.
NP_068811.1. NM_021976.4.

UniGene

Hs.388034.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H9U	X-ray	2.70	A/B/C/D	299-522	[»]
1UHL	X-ray	2.90	A	298-533	[»]

ProteinModelPortal

P28702.

ModBase

Search...

Protein-protein interaction databases

IntAct

P28702. 30 interactions.

MINT

MINT-1365658.

STRING

9606.ENSP00000363812.

PTM databases

PhosphoSite

P28702.

Polymorphism databases

DMDM

1350911.

Proteomic databases

PaxDb

P28702.

PRIDE

P28702.

Protocols and materials databases

DNASU

6257.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374680; ENSP00000363812; ENSG00000204231.
ENST00000374685; ENSP00000363817; ENSG00000204231.
ENST00000383216; ENSP00000372703; ENSG00000206289.
ENST00000383217; ENSP00000372704; ENSG00000206289.
ENST00000415157; ENSP00000402506; ENSG00000228333.
ENST00000415909; ENSP00000410468; ENSG00000235712.
ENST00000431161; ENSP00000393286; ENSG00000235712.
ENST00000431820; ENSP00000411238; ENSG00000231321.
ENST00000436753; ENSP00000415199; ENSG00000227322.
ENST00000443603; ENSP00000402590; ENSG00000227322.
ENST00000455462; ENSP00000400104; ENSG00000228333.
ENST00000456244; ENSP00000393870; ENSG00000231321.

GeneID

6257.

KEGG

hsa:6257.

UCSC

uc003odb.3. human.

Organism-specific databases

CTD

6257.

GeneCards

GC06M033161.

HGNC

HGNC:10478. RXRB.

HPA

CAB002003.

MIM

180246. gene.

neXtProt

NX_P28702.

PharmGKB

PA34891.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG327099.

HOGENOM

HOG000260821.

HOVERGEN

HBG005606.

KO

K08525.

OrthoDB

EOG4SJ5DV.

PhylomeDB

P28702.

Enzyme and pathway databases

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
ar_tf_pathway. Regulation of Androgen receptor activity.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.
rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P28702.

Bgee

P28702.

CleanEx

HS_RXRB.

Genevestigator

P28702.

GermOnline

ENSG00000204231. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.
3.30.50.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR000003. Retinoid-X_rcpt/HNF4.
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

PR00545. RETINOIDXR.
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

P28702.

ChEMBL

CHEMBL1870.

ChiTaRS

RXRB. human.

DrugBank

DB00459. Acitretin.
DB00210. Adapalene.
DB00523. Alitretinoin.
DB00307. Bexarotene.
DB00926. Etretinate.
DB00799. Tazarotene.
DB00755. Tretinoin.

EvolutionaryTrace

P28702.

GenomeRNAi

6257.

NextBio

24299.

SOURCE

Search...

Entry information

Entry name

RXRB_HUMAN

Accession

Primary (citable) accession number: P28702
Secondary accession number(s): P28703 , Q59G65, Q5JP92, Q5STQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 151 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.