RARB_MOUSE
ID RARB_MOUSE Reviewed; 482 AA.
AC P22605; P11417; P22604;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Retinoic acid receptor beta;
DE Short=RAR-beta;
DE AltName: Full=Nuclear receptor subfamily 1 group B member 2;
GN Name=Rarb; Synonyms=Nr1b2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA-1; BETA-2 AND BETA-3).
RC STRAIN=C57BL/C;
RX PubMed=1846599; DOI=10.1002/j.1460-2075.1991.tb07922.x;
RA Zelent A., Mendelsohn C., Kastner P., Krust A., Garnier J.-M.,
RA Ruffenach F., Leroy P., Chambon P.;
RT "Differentially expressed isoforms of the mouse retinoic acid receptor beta
RT generated by usage of two promoters and alternative splicing.";
RL EMBO J. 10:71-81(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2).
RX PubMed=2544807; DOI=10.1038/339714a0;
RA Zelent A., Krust A., Petkovich M., Kastner P., Chambon P.;
RT "Cloning of murine alpha and beta retinoic acid receptors and a novel
RT receptor gamma predominantly expressed in skin.";
RL Nature 339:714-717(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2).
RX PubMed=8383767; DOI=10.3109/10799899309073687;
RA Heiermann R., Rentrop M., Lang E., Maelicke A.;
RT "Cloning of several genes coding for retinoic acid nuclear receptors in the
RT mouse embryonal carcinoma cell line PCC7-MZ1.";
RL J. Recept. Res. 13:693-709(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-4).
RX PubMed=1313565; DOI=10.1073/pnas.89.7.2718;
RA Nagpal S., Zelent A., Chambon P.;
RT "RAR-beta 4, a retinoic acid receptor isoform is generated from RAR-beta 2
RT by alternative splicing and usage of a CUG initiator codon.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2718-2722(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-48 (ISOFORM BETA-2).
RX PubMed=1663808; DOI=10.3109/10425179109039679;
RA Shen S., Kruyt F.A., den Hertog J., van der Saag P.T., Kruijer W.;
RT "Mouse and human retinoic acid receptor beta 2 promoters: sequence
RT comparison and localization of retinoic acid responsiveness.";
RL DNA Seq. 2:111-119(1991).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19389355; DOI=10.1016/j.ydbio.2009.01.031;
RA Williams J.A., Kondo N., Okabe T., Takeshita N., Pilchak D.M., Koyama E.,
RA Ochiai T., Jensen D., Chu M.L., Kane M.A., Napoli J.L., Enomoto-Iwamoto M.,
RA Ghyselinck N., Chambon P., Pacifici M., Iwamoto M.;
RT "Retinoic acid receptors are required for skeletal growth, matrix
RT homeostasis and growth plate function in postnatal mouse.";
RL Dev. Biol. 328:315-327(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 180-482 IN COMPLEX WITH RXRA AND
RP MED1.
RX PubMed=15528208; DOI=10.1074/jbc.m409302200;
RA Pogenberg V., Guichou J.F., Vivat-Hannah V., Kammerer S., Perez E.,
RA Germain P., de Lera A.R., Gronemeyer H., Royer C.A., Bourguet W.;
RT "Characterization of the interaction between retinoic acid
RT receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional
RT coactivators through structural and fluorescence anisotropy studies.";
RL J. Biol. Chem. 280:1625-1633(2005).
CC -!- FUNCTION: Receptor for retinoic acid. Retinoic acid receptors bind as
CC heterodimers to their target response elements in response to their
CC ligands, all-trans or 9-cis retinoic acid, and regulate gene expression
CC in various biological processes. The RAR/RXR heterodimers bind to the
CC retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3'
CC sites known as DR1-DR5. In the absence of ligand, acts mainly as an
CC activator of gene expression due to weak binding to corepressors (By
CC similarity). The RXRA/RARB heterodimer can act as a repressor on the
CC DR1 element and as an activator on the DR5 element (By similarity). In
CC concert with RARG, required for skeletal growth, matrix homeostasis and
CC growth plate function (PubMed:19389355). {ECO:0000250|UniProtKB:P10826,
CC ECO:0000269|PubMed:19389355}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer; with a RXR molecule
CC (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By
CC similarity). Heterodimerizes (via NR LBD) with RXRA (By similarity).
CC Interacts weakly with NCOR2 (By similarity).
CC {ECO:0000250|UniProtKB:P10826, ECO:0000250|UniProtKB:P28702}.
CC -!- INTERACTION:
CC P22605; Q8C0D7: Ing4; NbExp=3; IntAct=EBI-2903247, EBI-645598;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P10826}. Cytoplasm
CC {ECO:0000250|UniProtKB:P10826}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=Beta-3;
CC IsoId=P22605-1; Sequence=Displayed;
CC Name=Beta-1;
CC IsoId=P22605-2; Sequence=VSP_003639, VSP_003640;
CC Name=Beta-2;
CC IsoId=P22605-3; Sequence=VSP_003636;
CC Name=Beta-4;
CC IsoId=P22605-4; Sequence=VSP_003637, VSP_003638;
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- DOMAIN: The DNA-binding nuclear receptor domain and the NR LBD domain
CC are required for binding of the RARB/RXRA heterodimer to both DR1 and
CC DR5 DNA elements. {ECO:0000250|UniProtKB:P10826}.
CC -!- DISRUPTION PHENOTYPE: Rarb and Rarg, but not Rarb and Rara, double null
CC mice exhibit growth retardation 3 weeks after birth. Defects are found
CC in the growth plates with deficiency in cartilage. Growth retardation
CC was noticable in limb sketal elements such as femurs. Early lethality
CC and male sterility due to squamous metaplasia of the seminal vesicles
CC and prostate are also observed. Isoform 2 mutants appear normal.
CC {ECO:0000269|PubMed:19389355}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X56574; CAA39921.1; -; mRNA.
DR EMBL; X56569; CAA39918.1; -; mRNA.
DR EMBL; X56573; CAA39920.1; -; mRNA.
DR EMBL; S56660; AAB25784.2; -; mRNA.
DR EMBL; S92180; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS26834.1; -. [P22605-3]
DR PIR; S05051; S05051.
DR RefSeq; NP_001276689.1; NM_001289760.1. [P22605-1]
DR RefSeq; NP_001276690.1; NM_001289761.1. [P22605-2]
DR RefSeq; NP_001276691.1; NM_001289762.1. [P22605-4]
DR RefSeq; NP_035373.1; NM_011243.2. [P22605-3]
DR PDB; 1XDK; X-ray; 2.90 A; B/F=180-482.
DR PDBsum; 1XDK; -.
DR AlphaFoldDB; P22605; -.
DR SMR; P22605; -.
DR BioGRID; 230063; 3.
DR IntAct; P22605; 4.
DR MINT; P22605; -.
DR STRING; 10090.ENSMUSP00000067694; -.
DR BindingDB; P22605; -.
DR ChEMBL; CHEMBL3266; -.
DR DrugCentral; P22605; -.
DR GuidetoPHARMACOLOGY; 591; -.
DR iPTMnet; P22605; -.
DR PhosphoSitePlus; P22605; -.
DR PaxDb; P22605; -.
DR PRIDE; P22605; -.
DR ProteomicsDB; 255096; -. [P22605-1]
DR ProteomicsDB; 255097; -. [P22605-2]
DR ProteomicsDB; 255098; -. [P22605-3]
DR ProteomicsDB; 255099; -. [P22605-4]
DR Antibodypedia; 934; 531 antibodies from 44 providers.
DR DNASU; 218772; -.
DR Ensembl; ENSMUST00000063750; ENSMUSP00000067694; ENSMUSG00000017491. [P22605-3]
DR GeneID; 218772; -.
DR KEGG; mmu:218772; -.
DR UCSC; uc007shh.2; mouse. [P22605-4]
DR UCSC; uc007shi.2; mouse. [P22605-2]
DR UCSC; uc007shj.2; mouse. [P22605-1]
DR CTD; 5915; -.
DR MGI; MGI:97857; Rarb.
DR VEuPathDB; HostDB:ENSMUSG00000017491; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000156196; -.
DR HOGENOM; CLU_007368_18_2_1; -.
DR InParanoid; P22605; -.
DR OMA; PFHATRN; -.
DR PhylomeDB; P22605; -.
DR TreeFam; TF328382; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-5362517; Signaling by Retinoic Acid.
DR BioGRID-ORCS; 218772; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Rarb; mouse.
DR EvolutionaryTrace; P22605; -.
DR PRO; PR:P22605; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P22605; protein.
DR Bgee; ENSMUSG00000017491; Expressed in caudate-putamen and 262 other tissues.
DR ExpressionAtlas; P22605; baseline and differential.
DR Genevisible; P22605; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:1901363; F:heterocyclic compound binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IGI:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IGI:MGI.
DR GO; GO:0060348; P:bone development; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0048566; P:embryonic digestive tract development; ISO:MGI.
DR GO; GO:0048048; P:embryonic eye morphogenesis; IGI:MGI.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IGI:MGI.
DR GO; GO:0002068; P:glandular epithelial cell development; IGI:MGI.
DR GO; GO:0003417; P:growth plate cartilage development; IGI:MGI.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0035264; P:multicellular organism growth; IGI:MGI.
DR GO; GO:0061037; P:negative regulation of cartilage development; IMP:MGI.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IMP:MGI.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0061351; P:neural precursor cell proliferation; ISO:MGI.
DR GO; GO:0022008; P:neurogenesis; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:MGI.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0012501; P:programmed cell death; IGI:MGI.
DR GO; GO:0031641; P:regulation of myelination; ISO:MGI.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0072089; P:stem cell proliferation; IGI:MGI.
DR GO; GO:0021756; P:striatum development; IMP:MGI.
DR GO; GO:0001657; P:ureteric bud development; IMP:MGI.
DR GO; GO:0055012; P:ventricular cardiac muscle cell differentiation; IMP:MGI.
DR DisProt; DP02633; -.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR003078; Retinoic_acid_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR01292; RETNOICACIDR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; DNA-binding; Metal-binding;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..482
FT /note="Retinoic acid receptor beta"
FT /id="PRO_0000053468"
FT DOMAIN 210..444
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 115..180
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 115..135
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 151..175
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..114
FT /note="Modulating"
FT REGION 181..209
FT /note="Hinge"
FT REGION 443..482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10826"
FT VAR_SEQ 1..87
FT /note="MSTSSHACPVPAVRGHMTHYPAAPYPLLFPPVIRGLSLPPLHGLHGHPPPSG
FT CSTPSPASVGQACQRTTGGSQFAASTKWTPSLNAA -> MFDCMDVLSVSPGQILDFYT
FT ASPSSCMLQEKALKACLSGFTQAEWQHRHTAQS (in isoform Beta-2)"
FT /evidence="ECO:0000303|PubMed:1663808,
FT ECO:0000303|PubMed:1846599, ECO:0000303|PubMed:2544807,
FT ECO:0000303|PubMed:8383767"
FT /id="VSP_003636"
FT VAR_SEQ 1..83
FT /note="Missing (in isoform Beta-4)"
FT /evidence="ECO:0000303|PubMed:1313565"
FT /id="VSP_003637"
FT VAR_SEQ 60
FT /note="S -> T (in isoform Beta-1)"
FT /evidence="ECO:0000303|PubMed:1846599"
FT /id="VSP_003639"
FT VAR_SEQ 61..87
FT /note="Missing (in isoform Beta-1)"
FT /evidence="ECO:0000303|PubMed:1846599"
FT /id="VSP_003640"
FT VAR_SEQ 84..86
FT /note="LNA -> MEN (in isoform Beta-4)"
FT /evidence="ECO:0000303|PubMed:1313565"
FT /id="VSP_003638"
FT HELIX 212..225
FT /evidence="ECO:0007829|PDB:1XDK"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 249..271
FT /evidence="ECO:0007829|PDB:1XDK"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:1XDK"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 281..301
FT /evidence="ECO:0007829|PDB:1XDK"
FT TURN 306..309
FT /evidence="ECO:0007829|PDB:1XDK"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:1XDK"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 321..326
FT /evidence="ECO:0007829|PDB:1XDK"
FT TURN 327..329
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 333..343
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 350..361
FT /evidence="ECO:0007829|PDB:1XDK"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 372..378
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 380..393
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 400..405
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 407..425
FT /evidence="ECO:0007829|PDB:1XDK"
FT TURN 426..428
FT /evidence="ECO:0007829|PDB:1XDK"
FT HELIX 435..441
FT /evidence="ECO:0007829|PDB:1XDK"
SQ SEQUENCE 482 AA; 53331 MW; 48E78E6C7D012515 CRC64;
MSTSSHACPV PAVRGHMTHY PAAPYPLLFP PVIRGLSLPP LHGLHGHPPP SGCSTPSPAS
VGQACQRTTG GSQFAASTKW TPSLNAAIET QSTSSEELVP SPPSPLPPPR VYKPCFVCQD
KSSGYHYGVS ACEGCKGFFR RSIQKNMIYT CHRDKNCVIN KVTRNRCQYC RLQKCFEVGM
SKESVRNDRN KKKKEPSKQE CTESYEMTAE LDDLTEKIRK AHQETFPSLC QLGKYTTNSS
ADHRVRLDLG LWDKFSELAT KCIIKIVEFA KRLPGFTGLT IADQITLLKA ACLDILILRI
CTRYTPEQDT MTFSDGLTLN RTQMHNAGFG PLTDLVFTFA NQLLPLEMDD TETGLLSAIC
LICGDRQDLE EPTKVDKLQE PLLEALKIYI RKRRPSKPHM FPKILMKITD LRSISAKGAE
RVITLKMEIP GSMPPLIQEM LENSEGHEPL TPSSSGNIAE HSPSVSPSSV ENSGVSQSPL
LQ
