P13631 (RARG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Retinoic acid receptor gamma
Short name=RAR-gamma

Alternative name(s):
Nuclear receptor subfamily 1 group B member 3

Gene names

Name:	RARG
Synonyms:	NR1B3

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	454 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. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function By similarity.
Subunit structure	Homodimer By similarity. Heterodimer with a RXR molecule By similarity. Binds DNA preferentially as a RAR/RXR heterodimer By similarity. Forms a complex with PUS1 and the SRA1 RNA in the nucleus By similarity.
Subcellular location	Nucleus.
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 CAA40548.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
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	canonical Wnt receptor signaling pathway Traceable author statement. Source: BHF-UCL embryonic eye morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL embryonic hindlimb morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL regulation of cell size Traceable author statement. Source: BHF-UCL response to retinoic acid Inferred from direct assay. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Non-traceable author statement. Source: BHF-UCL transcription factor complex Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	retinoic acid receptor activity Inferred from electronic annotation. Source: InterPro retinoid X receptor binding Inferred from sequence or structural similarity. Source: BHF-UCL sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL 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 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoforms differ only in their N-terminal regions.

Isoform 1 (identifier: P13631-1)

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: P13631-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MATNKERLFA...PDLPKEMASL → MYDCMETFAP...FAWPQPASLQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 454

454

Retinoic acid receptor gamma

PRO_0000053472

Regions

DNA binding

90 – 155

66

Nuclear receptor

Zinc finger

90 – 110

21

NR C4-type

Zinc finger

126 – 150

25

NR C4-type

Region

1 – 89

89

Modulating

Region

156 – 201

46

Hinge

Region

202 – 421

220

Ligand-binding

Natural variations

Alternative sequence

1 – 61

61

MATNK…EMASL → MYDCMETFAPGPRRLYGAAG PGAGLLRRATGGSCFAGLES FAWPQPASLQ in isoform 2.

VSP_031080

Natural variant

427

1

S → L.
Corresponds to variant rs2229774 [ dbSNP | Ensembl ].

VAR_038554

Natural variant

430

1

G → S in a breast cancer sample; somatic mutation. Ref.13

VAR_036061

Experimental info

Sequence conflict

118

1

I → T in CAB60726. Ref.9

Sequence conflict

172

1

K → R in AAG41594. Ref.10

Sequence conflict

252

1

T → A in CAB60726. Ref.9

Sequence conflict

421

1

M → L in CAB60726. Ref.9

Secondary structure

1

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454

Helix Strand Turn

Details...

Helix

184 – 200

17

Helix

204 – 206

3

Helix

224 – 246

23

Helix

251 – 253

3

Helix

256 – 276

21

Turn

281 – 284

4

Beta strand

285 – 287

3

Beta strand

292 – 295

4

Helix

296 – 302

7

Helix

305 – 307

3

Helix

308 – 318

11

Helix

319 – 321

3

Helix

325 – 336

12

Helix

347 – 368

22

Helix

375 – 403

29

Beta strand

404 – 406

3

Helix

410 – 416

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 1EE27B22772D4AFD	FASTA	454	50,342
	10 20 30 40 50 60 MATNKERLFA AGALGPGSGY PGAGFPFAFP GALRGSPPFE MLSPSFRGLG QPDLPKEMAS 70 80 90 100 110 120 LSVETQSTSS EEMVPSSPSP PPPPRVYKPC FVCNDKSSGY HYGVSSCEGC KGFFRRSIQK 130 140 150 160 170 180 NMVYTCHRDK NCIINKVTRN RCQYCRLQKC FEVGMSKEAV RNDRNKKKKE VKEEGSPDSY 190 200 210 220 230 240 ELSPQLEELI TKVSKAHQET FPSLCQLGKY TTNSSADHRV QLDLGLWDKF SELATKCIIK 250 260 270 280 290 300 IVEFAKRLPG FTGLSIADQI TLLKAACLDI LMLRICTRYT PEQDTMTFSD GLTLNRTQMH 310 320 330 340 350 360 NAGFGPLTDL VFAFAGQLLP LEMDDTETGL LSAICLICGD RMDLEEPEKV DKLQEPLLEA 370 380 390 400 410 420 LRLYARRRRP SQPYMFPRML MKITDLRGIS TKGAERAITL KMEIPGPMPP LIREMLENPE 430 440 450 MFEDDSSQPG PHPNASSEDE VPGGQGKGGL KSPA
	Isoform 2 [UniParc]. Checksum: 4D709194F5111E86	FASTA	443	49,308
	10 20 30 40 50 60 MYDCMETFAP GPRRLYGAAG PGAGLLRRAT GGSCFAGLES FAWPQPASLQ SVETQSTSSE 70 80 90 100 110 120 EMVPSSPSPP PPPRVYKPCF VCNDKSSGYH YGVSSCEGCK GFFRRSIQKN MVYTCHRDKN 130 140 150 160 170 180 CIINKVTRNR CQYCRLQKCF EVGMSKEAVR NDRNKKKKEV KEEGSPDSYE LSPQLEELIT 190 200 210 220 230 240 KVSKAHQETF PSLCQLGKYT TNSSADHRVQ LDLGLWDKFS ELATKCIIKI VEFAKRLPGF 250 260 270 280 290 300 TGLSIADQIT LLKAACLDIL MLRICTRYTP EQDTMTFSDG LTLNRTQMHN AGFGPLTDLV 310 320 330 340 350 360 FAFAGQLLPL EMDDTETGLL SAICLICGDR MDLEEPEKVD KLQEPLLEAL RLYARRRRPS 370 380 390 400 410 420 QPYMFPRMLM KITDLRGIST KGAERAITLK MEIPGPMPPL IREMLENPEM FEDDSSQPGP 430 440 HPNASSEDEV PGGQGKGGLK SPA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A third human retinoic acid receptor, hRAR-gamma." Krust A., Kastner P., Petkovich M., Zelent A., Chambon P. Proc. Natl. Acad. Sci. U.S.A. 86:5310-5314(1989) [PubMed: 2546152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"A functional retinoic acid receptor encoded by the gene on human chromosome 12." Ishikawa T., Umesono K., Mangelsdorf D.J., Aburatani H., Stanger B.Z., Shibasaki Y., Imawari M., Evans R.M., Takaku F. Mol. Endocrinol. 4:837-844(1990) [PubMed: 2172793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Genomic organization of the retinoic acid receptor gamma gene." Lehmann J.M., Hoffmann B., Pfahl M. Nucleic Acids Res. 19:573-578(1991) [PubMed: 1849262] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING. Tissue: Placenta.
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Tongue.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 1). Tissue: Colon.
[7]	"Murine isoforms of retinoic acid receptor gamma with specific patterns of expression." Kastner P., Krust A., Mendelsohn C., Garnier J.-M., Zelent A., Leroy P., Staub A., Chambon P. Proc. Natl. Acad. Sci. U.S.A. 87:2700-2704(1990) [PubMed: 2157210] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-63 (ISOFORM 2).
[8]	"RAR-gamma-2 expression is regulated through a retinoic acid response element embedded in Sp1 sites." Lehmann J.M., Zhang X.K., Pfahl M. Mol. Cell. Biol. 12:2976-2985(1992) [PubMed: 1320193] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-55, ALTERNATIVE SPLICING. Tissue: Placenta.
[9]	Gebhard W. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 74-454. Tissue: Lung carcinoma.
[10]	"Genomic organization of the human retinoic acid receptor gamma gene." Xu H., Clifford J.L. Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-191 AND 394-411.
[11]	"Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid." Renaud J.-P., Rochel N., Ruff M., Vivat V., Chambon P., Gronemeyer H., Moras D. Nature 378:681-689(1995) [PubMed: 7501014] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 178-423.
[12]	"Conformational adaptation of agonists to the human nuclear receptor RAR gamma." Klaholz B.P., Renaud J.-P., Mitschler A., Zusi C., Chambon P., Gronemeyer H., Moras D. Nat. Struct. Biol. 5:199-202(1998) [PubMed: 9501913] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 178-423.
[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] SER-430.
+	Additional computationally mapped references.

Web resources

Wikipedia

Retinoic acid receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M24857 mRNA. Translation: AAA52692.1.
M57707 mRNA. Translation: AAA63254.1.
M38258 mRNA. Translation: AAA60254.1.
AK316259 mRNA. Translation: BAH14630.1.
CH471054 Genomic DNA. Translation: EAW96676.1.
BC093727 mRNA. Translation: AAH93727.1.
BC093729 mRNA. Translation: AAH93729.1.
M32074 mRNA. Translation: AAA60253.1.
X57280 Genomic DNA. Translation: CAA40548.1. Sequence problems.
AJ250835 Genomic DNA. Translation: CAB60726.1.
AY013703 Genomic DNA. Translation: AAG41594.2.
AY013704 Genomic DNA. Translation: AAG41595.1.

IPI

IPI00427809.
IPI00465344.

PIR

A33903.
C35991.

RefSeq

NP_000957.1. NM_000966.5.
NP_001036193.1. NM_001042728.2.

UniGene

Hs.1497.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EXA	X-ray	1.59	A	178-423	[»]
1EXX	X-ray	1.67	A	178-423	[»]
1FCX	X-ray	1.47	A	183-417	[»]
1FCY	X-ray	1.30	A	183-417	[»]
1FCZ	X-ray	1.38	A	183-417	[»]
1FD0	X-ray	1.38	A	183-417	[»]
2LBD	X-ray	2.06	A	178-423	[»]
3LBD	X-ray	2.40	A	178-423	[»]
4LBD	X-ray	2.50	A	178-423	[»]

ProteinModelPortal

P13631.

SMR

P13631. Positions 88-417.

ModBase

Search...

Protein-protein interaction databases

IntAct

P13631. 10 interactions.

STRING

P13631.

PTM databases

PhosphoSite

P13631.

Polymorphism databases

DMDM

133498.

Proteomic databases

PRIDE

P13631.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327550; ENSP00000332695; ENSG00000172819.
ENST00000394426; ENSP00000377947; ENSG00000172819.

GeneID

5916.

KEGG

hsa:5916.

UCSC

uc001scd.1. human.
uc001sce.1. human.

Organism-specific databases

CTD

5916.

GeneCards

GC12M053604.

H-InvDB

HIX0036789.

HGNC

HGNC:9866. RARG.

MIM

180190. gene.

neXtProt

NX_P13631.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG005606.

InParanoid

P13631.

OMA

DQTESND.

OrthoDB

EOG4F7NK7.

PhylomeDB

P13631.

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

P13631.

Bgee

P13631.

CleanEx

HS_RARG.

Genevestigator

P13631.

GermOnline

ENSG00000172819. 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

K08529.

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.
DB00799. Tazarotene.
DB00755. Tretinoin.

NextBio

23030.

SOURCE

Search...

Entry information

Entry name

RARG_HUMAN

Accession

Primary (citable) accession number: P13631
Secondary accession number(s): B7ZAE4 , P22932, Q15281, Q52LZ8, Q9BYX8, Q9H1I3, Q9UJ38

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	January 25, 2012
This is version 148 of the entry and version 1 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.