P10826 (RARB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	455 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 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.
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 process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Proto-oncogene
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	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	embryonic digestive tract development Inferred from mutant phenotype. Source: DFLAT transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Molecular function	retinoic acid receptor activity Traceable author statement. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 455

455

Retinoic acid receptor beta

PRO_0000053467

Regions

DNA binding

88 – 153

66

Nuclear receptor

Zinc finger

88 – 108

21

NR C4-type

Zinc finger

124 – 148

25

NR C4-type

Region

1 – 87

87

Modulating

Region

154 – 199

46

Hinge

Region

200 – 419

220

Ligand-binding

Natural variations

Alternative sequence

1 – 119

119

Missing in isoform Beta-4.

VSP_003635

Alternative sequence

1 – 60

60

MTTSG…PSPAT → MFDCMDVLSVSPGQILDFYT ASPSSCMLQEKALKACFSGL TQTEWQHRHTAQS in isoform Beta-2.

VSP_003634

Natural variant

90

1

V → I in a colorectal cancer sample; somatic mutation. Ref.13

VAR_036060

Experimental info

Mutagenesis

188

1

T → I: No effect on transcriptional activation in the absence of hormone. Ref.10

Mutagenesis

191

1

I → V: No effect on transcriptional activation in the absence of hormone. Ref.10

Mutagenesis

222

1

L → I: Reduced transcriptional activation in the absence of hormone. Even gretaer 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

Mutagenesis

223

1

G → D: Greatly reduced transcriptional activation in the absence of hormone. Even gretaer 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

Mutagenesis

232

1

A → 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 conflict

206

1

G → A in CAA68398. Ref.2

Sequence conflict

317

1

L → Q in CAA30262. Ref.1

Sequence conflict

414

1

L → M in CAA68398. Ref.2

Sequence conflict

454

1

V → L in CAA30262. Ref.1

Secondary structure

1

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455

Helix Strand Turn

Details...

Beta strand

87 – 91

5

Beta strand

100 – 102

3

Helix

107 – 118

12

Beta strand

133 – 135

3

Helix

141 – 148

8

Helix

149 – 151

3

Helix

183 – 198

16

Helix

202 – 204

3

Helix

222 – 245

24

Helix

249 – 251

3

Helix

254 – 274

21

Turn

279 – 282

4

Beta strand

283 – 285

3

Beta strand

289 – 293

5

Helix

294 – 300

7

Helix

303 – 305

3

Helix

306 – 316

11

Helix

317 – 319

3

Helix

323 – 334

12

Helix

345 – 366

22

Helix

373 – 389

17

Helix

391 – 401

11

Helix

408 – 414

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Beta-1 [UniParc]. Last modified November 16, 2001. Version 2. Checksum: 8813263AD0495D5A	FASTA	455	50,489
	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
	Isoform Beta-2 [UniParc]. Checksum: 844A298AD32F46A8	FASTA	448	50,344
	10 20 30 40 50 60 MFDCMDVLSV SPGQILDFYT ASPSSCMLQE KALKACFSGL TQTEWQHRHT AQSIETQSTS 70 80 90 100 110 120 SEELVPSPPS PLPPPRVYKP CFVCQDKSSG YHYGVSACEG CKGFFRRSIQ KNMIYTCHRD 130 140 150 160 170 180 KNCVINKVTR NRCQYCRLQK CFEVGMSKES VRNDRNKKKK ETSKQECTES YEMTAELDDL 190 200 210 220 230 240 TEKIRKAHQE TFPSLCQLGK YTTNSSADHR VRLDLGLWDK FSELATKCII KIVEFAKRLP 250 260 270 280 290 300 GFTGLTIADQ ITLLKAACLD ILILRICTRY TPEQDTMTFS DGLTLNRTQM HNAGFGPLTD 310 320 330 340 350 360 LVFTFANQLL PLEMDDTETG LLSAICLICG DRQDLEEPTK VDKLQEPLLE ALKIYIRKRR 370 380 390 400 410 420 PSKPHMFPKI LMKITDLRSI SAKGAERVIT LKMEIPGSMP PLIQEMLENS EGHEPLTPSS 430 440 SGNTAEHSPS ISPSSVENSG VSQSPLVQ
	Isoform Beta-3 (Sequence not available).		–	–
	Isoform Beta-4 [UniParc]. Checksum: D248E5CAB87DA44E	FASTA	336	37,932
	10 20 30 40 50 60 MIYTCHRDKN CVINKVTRNR CQYCRLQKCF EVGMSKESVR NDRNKKKKET SKQECTESYE 70 80 90 100 110 120 MTAELDDLTE KIRKAHQETF PSLCQLGKYT TNSSADHRVR LDLGLWDKFS ELATKCIIKI 130 140 150 160 170 180 VEFAKRLPGF TGLTIADQIT LLKAACLDIL ILRICTRYTP EQDTMTFSDG LTLNRTQMHN 190 200 210 220 230 240 AGFGPLTDLV FTFANQLLPL EMDDTETGLL SAICLICGDR QDLEEPTKVD KLQEPLLEAL 250 260 270 280 290 300 KIYIRKRRPS KPHMFPKILM KITDLRSISA KGAERVITLK MEIPGSMPPL IQEMLENSEG 310 320 330 HEPLTPSSSG NTAEHSPSIS PSSVENSGVS QSPLVQ

References

	« Hide 'large scale' referencesShow '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: 2836738] [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: 2825037] [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: 10411930] [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: 15489334] [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: 1663808] [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: 8275470] [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: 3014347] [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: 2170809] [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: 2833708] [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: 12554770] [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: 1321662] [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: 8383553] [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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-90.
+	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.

IPI

IPI00022989.
IPI00219014.
IPI00745428.

PIR

S02827.
S49021.

RefSeq

NP_000956.2. NM_000965.3.
NP_057236.1. NM_016152.3.

UniGene

Hs.654490.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HRA	NMR	-	A	82-160	[»]
1XAP	X-ray	2.10	A	176-421	[»]

ProteinModelPortal

P10826.

SMR

P10826. Positions 82-426.

ModBase

Search...

Protein-protein interaction databases

IntAct

P10826. 3 interactions.

MINT

MINT-1180428.

STRING

P10826.

Polymorphism databases

DMDM

17380507.

Proteomic databases

PRIDE

P10826.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000404969; ENSP00000385865; ENSG00000077092.

GeneID

5915.

KEGG

hsa:5915.

Organism-specific databases

CTD

5915.

GeneCards

GC03P025194.

HGNC

HGNC:9865. RARB.

HPA

CAB002617.
HPA004174.

MIM

180220. gene.

neXtProt

NX_P10826.

PharmGKB

PA34226.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04425.

HOGENOM

HBG713785.

HOVERGEN

HBG005606.

OMA

QEVFVCI.

OrthoDB

EOG4F7NK7.

PhylomeDB

P10826.

Enzyme and pathway databases

Pathway_Interaction_DB

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

P10826.

Bgee

P10826.

CleanEx

HS_RARB.

Genevestigator

P10826.

GermOnline

ENSG00000077092. Homo sapiens.

Family and domain databases

InterPro

IPR008946. 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]

Gene3D

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

KO

K08528.

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR01292. RETNOICACIDR.
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

DrugBank

DB00459. Acitretin.
DB00210. Adapalene.
DB00523. Alitretinoin.
DB00926. Etretinate.
DB04942. Tamibarotene.
DB00799. Tazarotene.

NextBio

23024.

SOURCE

Search...

Entry information

Entry name

RARB_HUMAN

Accession

Primary (citable) accession number: P10826
Secondary accession number(s): P12891 , Q00989, Q15298, Q9UN48

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	November 16, 2001
Last modified:	December 14, 2011
This is version 153 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.