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P10826 (RARB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 180. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Retinoic acid receptor beta

Short name=RAR-beta
Alternative name(s):
HBV-activated protein
Nuclear receptor subfamily 1 group B member 2
RAR-epsilon
Gene names
Name:RARB
Synonyms:HAP, NR1B2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length455 AA.
Sequence statusComplete.
Protein existenceEvidence 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 RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. Ref.10

Subunit structure

Homodimer By similarity. Heterodimer; with a RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer By similarity. Interacts weakly with NCOR2. Ref.10

Subcellular location

Isoform Beta-1: Nucleus.

Isoform Beta-2: Nucleus.

Isoform Beta-4: Cytoplasm.

Domain

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Involvement in disease

Microphthalmia, syndromic, 12 (MCOPS12) [MIM:615524]: A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS12 patients manifest variable features, including diaphragmatic hernia, pulmonary hypoplasia, and cardiac abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Sequence similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

The sequence CAA27637.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Microphthalmia
Proto-oncogene
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processembryonic digestive tract development

Inferred from mutant phenotype PubMed 19443732. Source: DFLAT

embryonic eye morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic hindlimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

growth plate cartilage development

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of cartilage development

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of myelination

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.9. Source: ProtInc

striatum development

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

ventricular cardiac muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 18845237. Source: UniProtKB

   Molecular_functionDNA binding

Traceable author statement PubMed 2153268. Source: ProtInc

drug binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 7565739. Source: IntAct

retinoic acid receptor activity

Traceable author statement Ref.9. Source: ProtInc

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

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

P032552EBI-8583223,EBI-2603114From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform Beta-1 (identifier: P10826-1)

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 Beta-2 (identifier: P10826-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: MTTSGHACPV...SGCSTPSPAT → MFDCMDVLSV...EWQHRHTAQS
Isoform Beta-3 (identifier: P10826-4)

The sequence of this isoform is not available.
Isoform Beta-4 (identifier: P10826-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 455455Retinoic acid receptor beta
PRO_0000053467

Regions

DNA binding88 – 15366Nuclear receptor
Zinc finger88 – 10821NR C4-type
Zinc finger124 – 14825NR C4-type
Region1 – 8787Modulating
Region154 – 19946Hinge
Region200 – 419220Ligand-binding

Natural variations

Alternative sequence1 – 119119Missing in isoform Beta-4.
VSP_003635
Alternative sequence1 – 6060MTTSG…PSPAT → MFDCMDVLSVSPGQILDFYT ASPSSCMLQEKALKACFSGL TQTEWQHRHTAQS in isoform Beta-2.
VSP_003634
Natural variant901V → I in a colorectal cancer sample; somatic mutation. Ref.13
VAR_036060
Natural variant3941R → C in MCOPS12; increases transcriptional response to retinoic acid. Ref.14
VAR_070780
Natural variant3941R → S in MCOPS12; increases transcriptional response to retinoic acid. Ref.14
VAR_070781

Experimental info

Mutagenesis1881T → I: No effect on transcriptional activation in the absence of hormone. Ref.10
Mutagenesis1911I → V: No effect on transcriptional activation in the absence of hormone. Ref.10
Mutagenesis2221L → I: Reduced transcriptional activation in the absence of hormone. Even greater reduction in transcriptional activation in the absence of hormone; when associated with D-223 or S-232. Great reduction in transcriptional activation in the absence of hormone; when associated with D-223 and S-232. Ref.10
Mutagenesis2231G → D: Greatly reduced transcriptional activation in the absence of hormone. Even greater reduction in transcriptional activation in the absence of hormone; when associated with I-222 or S-232. Great reduction in transcriptional activation in the absence of hormone; when associated with I-222 and S-232. Ref.10
Mutagenesis2321A → S: Reduced transcriptional activation in the absence of hormone. Some further reduction of transcriptional activity in the absence of hormone; when associated with I-222 or D-223. Great reduction in transcriptional activation in the absence of hormone; when associated with I-222 and D-223. Ref.10
Sequence conflict2061G → A in CAA68398. Ref.2
Sequence conflict3171L → Q in CAA30262. Ref.1
Sequence conflict4141L → M in CAA68398. Ref.2
Sequence conflict4541V → L in CAA30262. Ref.1

Secondary structure

............................................ 455
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Beta-1 [UniParc].

Last modified November 16, 2001. Version 2.
Checksum: 8813263AD0495D5A

FASTA45550,489
        10         20         30         40         50         60 
MTTSGHACPV PAVNGHMTHY PATPYPLLFP PVIGGLSLPP LHGLHGHPPP SGCSTPSPAT 

        70         80         90        100        110        120 
IETQSTSSEE LVPSPPSPLP PPRVYKPCFV CQDKSSGYHY GVSACEGCKG FFRRSIQKNM 

       130        140        150        160        170        180 
IYTCHRDKNC VINKVTRNRC QYCRLQKCFE VGMSKESVRN DRNKKKKETS KQECTESYEM 

       190        200        210        220        230        240 
TAELDDLTEK IRKAHQETFP SLCQLGKYTT NSSADHRVRL DLGLWDKFSE LATKCIIKIV 

       250        260        270        280        290        300 
EFAKRLPGFT GLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA 

       310        320        330        340        350        360 
GFGPLTDLVF TFANQLLPLE MDDTETGLLS AICLICGDRQ DLEEPTKVDK LQEPLLEALK 

       370        380        390        400        410        420 
IYIRKRRPSK PHMFPKILMK ITDLRSISAK GAERVITLKM EIPGSMPPLI QEMLENSEGH 

       430        440        450 
EPLTPSSSGN TAEHSPSISP SSVENSGVSQ SPLVQ 

« Hide

Isoform Beta-2 [UniParc].

Checksum: 844A298AD32F46A8
Show »

FASTA44850,344
Isoform Beta-3 (Sequence not available).
Isoform Beta-4 [UniParc].

Checksum: D248E5CAB87DA44E
Show »

FASTA33637,932

References

« Hide 'large scale' references
[1]"A new retinoic acid receptor identified from a hepatocellular carcinoma."
Benbrook D., Lernherdt E., Pfahl M.
Nature 333:669-672(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2).
Tissue: Placenta.
[2]"A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma."
de The H., Marchio A., Tiollais P., Dejean A.
Nature 330:667-670(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2).
[3]"Elevated retinoic acid receptor beta(4) protein in human breast tumor cells with nuclear and cytoplasmic localization."
Sommer K.M., Chen L.I., Treuting P.M., Smith L.T., Swisshelm K.
Proc. Natl. Acad. Sci. U.S.A. 96:8651-8656(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-4).
Tissue: Mammary tumor.
[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] (ISOFORM BETA-2).
Tissue: Placenta.
[5]"Mouse and human retinoic acid receptor beta 2 promoters: sequence comparison and localization of retinoic acid responsiveness."
Shen S., Kruyt F.A., den Hertog J., van der Saag P.T., Kruijer W.
DNA Seq. 2:111-119(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52 (ISOFORM BETA-2).
[6]"Fetal isoform of human retinoic acid receptor beta expressed in small cell lung cancer lines."
Houle B., Pelletier M., Wu J., Goodyer C., Bradley W.E.
Cancer Res. 54:365-369(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72 (ISOFORM BETA-1).
[7]"Hepatitis B virus DNA integration in a sequence homologous to v-erb-A and steroid receptor genes in a hepatocellular carcinoma."
Dejean A., Bougueleret L., Grzeschik K.-H., Tiollais P.
Nature 322:70-72(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 61-109.
[8]"Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma."
Dejean A., de The H.
Mol. Biol. Med. 7:213-222(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 61-109.
Tissue: Liver.
[9]"Identification of a second human retinoic acid receptor."
Brand N., Petkovitch M., Krust A., Chambon P., de The H., Marchio A., Tiollais P., Dejean A.
Nature 332:850-853(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF LIGAND.
[10]"Retinoic acid receptors beta and gamma do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand."
Hauksdottir H., Farboud B., Privalsky M.L.
Mol. Endocrinol. 17:373-385(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HETERODIMERIZATION, INTERACTION WITH NCOR2, MUTAGENESIS OF THR-188; ILE-191; LEU-222; GLY-223 AND ALA-232.
[11]"Homo- and heteronuclear NMR studies of the human retinoic acid receptor beta DNA-binding domain: sequential assignments and identification of secondary structure elements."
Kathira M., Knegtel R.M.A., Boelens R., Eib D., Schilthuis J.G., van der Saag P.T., Kaptein R.
Biochemistry 31:6474-6480(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 82-160.
[12]"The solution structure of the human retinoic acid receptor-beta DNA-binding domain."
Knegtel R.M.A., Katahira M., Schilthuis J.G., Bonvin A.M., Boelens R., Eib D., van der Saag P.T., Kaptein R.
J. Biomol. NMR 3:1-17(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 82-160.
[13]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-90.
[14]"Recessive and dominant mutations in retinoic acid receptor beta in cases with microphthalmia and diaphragmatic hernia."
Srour M., Chitayat D., Caron V., Chassaing N., Bitoun P., Patry L., Cordier M.P., Capo-Chichi J.M., Francannet C., Calvas P., Ragge N., Dobrzeniecka S., Hamdan F.F., Rouleau G.A., Tremblay A., Michaud J.L.
Am. J. Hum. Genet. 93:765-772(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCOPS12 SER-394 AND CYS-394, CHARACTERIZATION OF VARIANTS MCOPS12 SER-394 AND CYS-394.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X07282 mRNA. Translation: CAA30262.1.
Y00291 mRNA. Translation: CAA68398.1.
AF157483 mRNA. Translation: AAD45688.1.
BC060794 mRNA. Translation: AAH60794.1.
X56849 Genomic DNA. No translation available.
X77664 Genomic DNA. Translation: CAA54740.1.
X04014 Genomic DNA. Translation: CAA27637.1. Sequence problems.
M57445 Genomic DNA. Translation: AAA58728.1.
CCDSCCDS2642.1. [P10826-2]
CCDS46775.1. [P10826-3]
PIRS02827.
S49021.
RefSeqNP_000956.2. NM_000965.4. [P10826-2]
NP_001277145.1. NM_001290216.1. [P10826-1]
NP_001277146.1. NM_001290217.1. [P10826-3]
NP_001277195.1. NM_001290266.1.
NP_001277205.1. NM_001290276.1. [P10826-3]
NP_057236.1. NM_016152.3. [P10826-3]
UniGeneHs.654490.
Hs.733004.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HRANMR-A82-160[»]
1XAPX-ray2.10A176-421[»]
4DM6X-ray1.90A/B176-421[»]
4DM8X-ray2.30A/B176-421[»]
4JYGX-ray2.35A/B176-421[»]
4JYHX-ray2.60A/B176-421[»]
4JYIX-ray1.90A/B176-421[»]
ProteinModelPortalP10826.
SMRP10826. Positions 82-415.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111850. 19 interactions.
IntActP10826. 8 interactions.
MINTMINT-1180428.
STRING9606.ENSP00000332296.

Chemistry

BindingDBP10826.
ChEMBLCHEMBL2008.
DrugBankDB00459. Acitretin.
DB00210. Adapalene.
DB00523. Alitretinoin.
DB00926. Etretinate.
DB04942. Tamibarotene.
DB00799. Tazarotene.
GuidetoPHARMACOLOGY591.

Polymorphism databases

DMDM17380507.

Proteomic databases

MaxQBP10826.
PaxDbP10826.
PRIDEP10826.

Protocols and materials databases

DNASU5915.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330688; ENSP00000332296; ENSG00000077092. [P10826-2]
ENST00000404969; ENSP00000385865; ENSG00000077092. [P10826-1]
ENST00000437042; ENSP00000398840; ENSG00000077092. [P10826-3]
ENST00000458646; ENSP00000391391; ENSG00000077092. [P10826-3]
GeneID5915.
KEGGhsa:5915.
UCSCuc003cdi.2. human. [P10826-1]

Organism-specific databases

CTD5915.
GeneCardsGC03P025194.
HGNCHGNC:9865. RARB.
HPACAB002617.
HPA004174.
MIM180220. gene.
615524. phenotype.
neXtProtNX_P10826.
Orphanet2470. Matthew-Wood syndrome.
PharmGKBPA34226.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297448.
HOGENOMHOG000010312.
HOVERGENHBG005606.
KOK08528.
OMACINIPHC.
PhylomeDBP10826.
TreeFamTF328382.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkP10826.

Gene expression databases

ArrayExpressP10826.
BgeeP10826.
CleanExHS_RARB.
GenevestigatorP10826.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR003078. Retinoic_acid_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01292. RETNOICACIDR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10826.
GeneWikiRetinoic_acid_receptor_beta.
GenomeRNAi5915.
NextBio23024.
PROP10826.
SOURCESearch...

Entry information

Entry nameRARB_HUMAN
AccessionPrimary (citable) accession number: P10826
Secondary accession number(s): P12891 expand/collapse secondary AC list , Q00989, Q15298, Q9UN48
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 16, 2001
Last modified: July 9, 2014
This is version 180 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM