P10276 (RARA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:	RARA
Synonyms:	NR1B1

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	462 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 of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function By similarity. Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis. Ref.19 Ref.22 Ref.23 Ref.24
Subunit structure	Heterodimer; with RXRA. Binds DNA preferentially as a heterodimer. Interacts with CDK7 By similarity. Interacts with coactivators NCOA3 and NCOA6. Interacts with NCOA7; the interaction requires ligand-binding. Interacts with MLL5. Interacts (via the ligand-binding domain) with PRAME; the interaction is ligand (retinoic acid)-dependent. Interacts with AKT1; the interaction phosphorylates RARA and represses transactivation. Interacts with PRKAR1A; the interaction negatively regulates RARA transcriptional activity. Interacts with NCOR1 and NCOR2. Interacts with PRMT2. Interacts with LRIF1. Interacts with ASXL1 and NCOA1. Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.27
Subcellular location	Nucleus. Cytoplasm. Note: Nuclear localization depends on ligand binding, phosphorylation and sumoylation. Transloaction to the nucleus in the absence of ligand is dependent on activation of PKC and the downstream MAPK phosphorylation. Ref.17 Ref.22
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Post-translational modification	Phosphorylated on serine and threonine residues. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for transcriptional activity By similarity. Phosphorylation by AKT1 is required for the repressor activity but has no effect on DNA binding, protein stability nor subcellular localization. Phosphorylated by PKA in vitro. This phosphorylation on Ser-219 and Ser-369 is critical for ligand binding, nuclear localization and transcriptional activity in response to FSH signaling. Ref.19 Ref.24 Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding. On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171. Probably desumoylated by SENP6. Sumoylation levels determine nuclear localization and regulate ATRA-mediated transcriptional activity. Ref.17 Ref.22 Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation. Ubiquitinated.
Involvement in disease	Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence AAB00112.1 differs from that shown. Reason: Erroneous initiation. The sequence AAB00113.1 differs from that shown. Reason: Erroneous initiation. The sequence BAB62809.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell fate commitment Inferred from electronic annotation. Source: Compara apoptotic cell clearance Inferred from mutant phenotype PubMed 19628791. Source: UniProtKB cellular response to estrogen stimulus Inferred from direct assay PubMed 20080953. Source: UniProtKB cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara cellular response to retinoic acid Inferred from direct assay PubMed 19917671. Source: UniProtKB chondroblast differentiation Inferred from electronic annotation. Source: Compara germ cell development Inferred from electronic annotation. Source: Compara growth plate cartilage development Inferred from electronic annotation. Source: Compara intracellular estrogen receptor signaling pathway Inferred from direct assay PubMed 15831516. Source: BHF-UCL multicellular organism growth Inferred from electronic annotation. Source: Compara negative regulation of cartilage development Inferred from electronic annotation. Source: Compara negative regulation of granulocyte differentiation Inferred from direct assay PubMed 19917671. Source: UniProtKB negative regulation of interferon-gamma production Inferred from direct assay PubMed 18416830. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 20080953. Source: UniProtKB negative regulation of translational initiation Inferred from electronic annotation. Source: Compara negative regulation of tumor necrosis factor production Inferred from direct assay PubMed 18416830. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of T-helper 2 cell differentiation Inferred from direct assay PubMed 18416830. Source: BHF-UCL positive regulation of binding Inferred from mutant phenotype PubMed 20080953. Source: UniProtKB positive regulation of cell cycle Inferred from mutant phenotype PubMed 20080953. Source: UniProtKB positive regulation of cell proliferation Inferred from mutant phenotype PubMed 20080953. Source: UniProtKB positive regulation of interleukin-13 production Inferred from direct assay PubMed 18416830. Source: BHF-UCL positive regulation of interleukin-4 production Inferred from direct assay PubMed 18416830. Source: BHF-UCL positive regulation of interleukin-5 production Inferred from direct assay PubMed 18416830. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.22. Source: UniProtKB protein phosphorylation Inferred from mutant phenotype PubMed 16456540. Source: UniProtKB response to estradiol stimulus Inferred from direct assay PubMed 15831516. Source: BHF-UCL spermatogenesis Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome ureteric bud development Inferred from electronic annotation. Source: Compara ventricular cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred by curator Ref.8. Source: BHF-UCL cytoplasm Inferred from direct assay Ref.22. Source: UniProtKB dendrite Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from direct assay PubMed 17363140. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	chromatin DNA binding Inferred from direct assay PubMed 19917671. Source: UniProtKB phosphatidylinositol 3-kinase regulator activity Inferred from electronic annotation. Source: Compara protein heterodimerization activity Inferred from direct assay PubMed 19917671. Source: UniProtKB protein kinase A binding Inferred from direct assay Ref.24. Source: UniProtKB receptor binding Inferred from direct assay PubMed 19628791. Source: UniProtKB retinoic acid binding Inferred from direct assay Ref.8. Source: BHF-UCL retinoic acid receptor activity Inferred from direct assay Ref.8. Source: BHF-UCL retinoic acid-responsive element binding Inferred from direct assay PubMed 19917671. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Inferred from direct assay PubMed 20080953. Source: UniProtKB transcription corepressor activity Inferred from direct assay PubMed 20080953. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASXL1	Q8IXJ9	3	EBI-413374,EBI-1646500
Asxl1	P59598	4	EBI-413374,EBI-5743705	From a different organism.
EZH2	Q15910	2	EBI-413374,EBI-530054
GNAQ	P50148	4	EBI-413374,EBI-3909604
MED1	Q15648	2	EBI-413374,EBI-394459
MLL5	Q8IZD2	3	EBI-413374,EBI-2689959
NCOR1	O75376	3	EBI-413374,EBI-347233
RXRA	P19793	3	EBI-413374,EBI-78598
SIRT1	Q96EB6	3	EBI-413374,EBI-1802965
ZNF423	Q2M1K9	2	EBI-413374,EBI-950016

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha-1 (identifier: P10276-1)

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 Alpha-2 (identifier: P10276-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: MASNSSSCPT...SGYSTPSPAT → MYESVEVGGP...TPLWNGSNHS

Isoform Alpha-1-deltaBC (identifier: P10276-3)

The sequence of this isoform differs from the canonical sequence as follows:
     61-157: Missing.

Note: Does not bind nor transactivate RARE on its own but may do so as a heterodimer with Alpha-1.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 462

462

Retinoic acid receptor alpha

PRO_0000053461

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

Region

404 – 419

16

Required for binding corepressor NCOR1

Sites

Site

60 – 61

2

Breakpoint for translocation to form PLZF-RAR-alpha, RAR-alpha1-PLZF and PML-RAR-alpha oncogenes

Amino acid modifications

Modified residue

77

1

Phosphoserine; by CDK7 By similarity

Modified residue

96

1

Phosphoserine; by PKB/AKT1 Ref.19

Modified residue

219

1

Phosphoserine; by PKA Ref.24

Modified residue

369

1

Phosphoserine; by PKA Ref.24

Cross-link

166

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22

Cross-link

171

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22

Cross-link

399

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22

Natural variations

Alternative sequence

1 – 60

60

MASNS…PSPAT → MYESVEVGGPTPNPFLVVDF YNQNRACLLPEKGLPAPGPY STPLRTPLWNGSNHS in isoform Alpha-2.

VSP_003629

Alternative sequence

61 – 157

97

Missing in isoform Alpha-1-deltaBC.

VSP_043143

Experimental info

Mutagenesis

95

1

S → A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation. Ref.19

Mutagenesis

96

1

S → A: Abolishes PKB/AKT1-mediated phosphorylation. Repressed transactivation. Ref.19

Mutagenesis

147

1

K → R: Abrogates sumoylation in the presence or absence of ATRA and primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-166; R-171 and R-399. Ref.22

Mutagenesis

154

1

S → A: No effect on PKB/AKT1-mediated phosphorylation. No repression of transactivation. Ref.19

Mutagenesis

157

1

S → A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation. Ref.19

Mutagenesis

166

1

K → R: Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-171 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-171 and R-399. Ref.22

Mutagenesis

171

1

K → R: Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-166 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-399. Ref.22

Mutagenesis

219

1

S → A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-369. Ref.24

Mutagenesis

219

1

S → E: No effect on heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, no increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-369. Ref.24

Mutagenesis

369

1

S → A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-219. Ref.24

Mutagenesis

369

1

S → E: Some inhibition of heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-219. Ref.24

Mutagenesis

396

1

I → E: Abrogates interaction with NCOR1 or NCOR2. Increased affinity for NCOR1 and NCOR2 in the presence of BMS493. Increased transcriptional activity in the presence of agonist and decreased activity in the presence of neutral antagonist. Ref.27

Mutagenesis

399

1

K → R in the absence of ATRA, abolishes sumoylation and is mainly nuclear. In the presence of ATRA, some sumoylation, cytoplasmic location, reduced transcriptional activity and no SENP6 binding. Low sumoylation levels in the presence of ATRA and nuclear location in the absence of ATRA; when associated with R-166 or with R-171. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-171. Ref.22

Mutagenesis

409 – 410

2

LI → AA: Abolishes interaction with ASXL1 and NCOA1.

Mutagenesis

412

1

E → Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-415. Ref.20

Mutagenesis

413 – 414

2

ML → AA: Abolishes interaction with ASXL1 and NCOA1.

Mutagenesis

415

1

E → Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-412. Ref.20

Sequence conflict

241

1

E → D in AAD05222. Ref.3

Secondary structure

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462

Helix Strand Turn

Details...

Turn

89 – 91

3

Beta strand

97 – 99

3

Helix

106 – 117

12

Turn

134 – 136

3

Helix

137 – 139

3

Helix

141 – 150

10

Helix

155 – 157

3

Helix

183 – 196

14

Helix

202 – 204

3

Beta strand

214 – 216

3

Helix

222 – 244

23

Helix

249 – 251

3

Helix

254 – 275

22

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 – 401

29

Beta strand

402 – 404

3

Helix

408 – 414

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-1 [UniParc]. Last modified October 1, 1989. Version 2. Checksum: E8D1CF9A1E57CB99	FASTA	462	50,771
	10 20 30 40 50 60 MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTTLQHQLPV SGYSTPSPAT 70 80 90 100 110 120 IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY GVSACEGCKG FFRRSIQKNM 130 140 150 160 170 180 VYTCHRDKNC IINKVTRNRC QYCRLQKCFE VGMSKESVRN DRNKKKKEVP KPECSESYTL 190 200 210 220 230 240 TPEVGELIEK VRKAHQETFP ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV 250 260 270 280 290 300 EFAKQLPGFT TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA 310 320 330 340 350 360 GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDRVDM LQEPLLEALK 370 380 390 400 410 420 VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM EIPGSMPPLI QEMLENSEGL 430 440 450 460 DTLSGQPGGG GRDGGGLAPP PGSCSPSLSP SSNRSSPATH SP
	Isoform Alpha-2 [UniParc]. Checksum: 1E328ED7945D1F95	FASTA	457	50,742
	10 20 30 40 50 60 MYESVEVGGP TPNPFLVVDF YNQNRACLLP EKGLPAPGPY STPLRTPLWN GSNHSIETQS 70 80 90 100 110 120 SSSEEIVPSP PSPPPLPRIY KPCFVCQDKS SGYHYGVSAC EGCKGFFRRS IQKNMVYTCH 130 140 150 160 170 180 RDKNCIINKV TRNRCQYCRL QKCFEVGMSK ESVRNDRNKK KKEVPKPECS ESYTLTPEVG 190 200 210 220 230 240 ELIEKVRKAH QETFPALCQL GKYTTNNSSE QRVSLDIDLW DKFSELSTKC IIKTVEFAKQ 250 260 270 280 290 300 LPGFTTLTIA DQITLLKAAC LDILILRICT RYTPEQDTMT FSDGLTLNRT QMHNAGFGPL 310 320 330 340 350 360 TDLVFAFANQ LLPLEMDDAE TGLLSAICLI CGDRQDLEQP DRVDMLQEPL LEALKVYVRK 370 380 390 400 410 420 RRPSRPHMFP KMLMKITDLR SISAKGAERV ITLKMEIPGS MPPLIQEMLE NSEGLDTLSG 430 440 450 QPGGGGRDGG GLAPPPGSCS PSLSPSSNRS SPATHSP
	Isoform Alpha-1-deltaBC [UniParc]. Checksum: D24F282D50E9953E	FASTA	365	39,700
	10 20 30 40 50 60 MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTTLQHQLPV SGYSTPSPAT 70 80 90 100 110 120 VRNDRNKKKK EVPKPECSES YTLTPEVGEL IEKVRKAHQE TFPALCQLGK YTTNNSSEQR 130 140 150 160 170 180 VSLDIDLWDK FSELSTKCII KTVEFAKQLP GFTTLTIADQ ITLLKAACLD ILILRICTRY 190 200 210 220 230 240 TPEQDTMTFS DGLTLNRTQM HNAGFGPLTD LVFAFANQLL PLEMDDAETG LLSAICLICG 250 260 270 280 290 300 DRQDLEQPDR VDMLQEPLLE ALKVYVRKRR PSRPHMFPKM LMKITDLRSI SAKGAERVIT 310 320 330 340 350 360 LKMEIPGSMP PLIQEMLENS EGLDTLSGQP GGGGRDGGGL APPPGSCSPS LSPSSNRSSP ATHSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a receptor for the morphogen retinoic acid." Giguere V., Ong E.S., Segui P., Evans R.M. Nature 330:624-629(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
[2]	"PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors." Chen Z., Guidez F., Rousselot P., Agadir A., Chen S.-J., Wang Z.-Y., Degos L., Zelent A., Waxman S., Chomienne C. Proc. Natl. Acad. Sci. U.S.A. 91:1178-1182(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1), CHROMOSOMAL TRANSLOCATION WITH PML.
[3]	"Genomic structure of the human retinoic acid receptor-alpha1 gene." Hjalt T.A.H., Murray J.C. Mamm. Genome 10:528-529(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA-1).
[4]	"Retinoic acid receptor alpha1 variants, RARalpha1DeltaB and RARalpha1DeltaBC, define a new class of nuclear receptor isoforms." Parrado A., Despouy G., Kraiba R., Le Pogam C., Dupas S., Choquette M., Robledo M., Larghero J., Bui H., Le Gall I., Rochette-Egly C., Chomienne C., Padua R.A. Nucleic Acids Res. 29:4901-4908(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1-DELTABC).
[5]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2). Tissue: Blood and Brain.
[7]	"Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha)." Brand N.J., Petkovich M., Chambon P. Nucleic Acids Res. 18:6799-6806(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-80 (ISOFORM ALPHA-1).
[8]	"A human retinoic acid receptor which belongs to the family of nuclear receptors." Petkovich M., Brand N.J., Krust A., Chambon P. Nature 330:444-450(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-462.
[9]	Chambon P. Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[10]	"The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion." Redner R.L., Rush E.A., Faas S., Rudert W.A., Corey S.J. Blood 87:882-886(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-462, CHROMOSOMAL TRANSLOCATION WITH NPM. Tissue: Bone marrow.
[11]	"Homo sapiens retinoic acid receptor alpha (RAR-alpha) gene, promoter and 5' region of RAR-alpha 2 isoform." Chen A., Petrie K., Waxman S., Zelent A. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54 (ISOFORM ALPHA-2).
[12]	"Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia: structure of the fusion point in a case lacking classic t(15;17) translocation." Fujita K., Oba R., Harada H., Mori H., Niikura H., Isoyama K., Omine M. Leuk. Lymphoma 44:111-115(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-68, CHROMOSOMAL TRANSLOCATION WITH PML.
[13]	"Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300." Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L., Privalsky M.L., Nakatani Y., Evans R.M. Cell 90:569-580(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA3.
[14]	"A nuclear factor ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo." Lee S.-K., Anzick S.L., Choi J.-E., Bubendorf L., Guan X.-Y., Jung Y.-K., Kallioniemi O.-P., Kononen J., Trent J.M., Azorsa D., Jhun B.-H., Cheong J.H., Lee Y.C., Meltzer P.S., Lee J.W. J. Biol. Chem. 274:34283-34293(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA6.
[15]	"Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha." Qi C., Chang J., Zhu Y., Yeldandi A.V., Rao S.M., Zhu Y.-J. J. Biol. Chem. 277:28624-28630(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRMT2.
[16]	"ERAP140, a conserved tissue-specific nuclear receptor coactivator." Shao W., Halachmi S., Brown M. Mol. Cell. Biol. 22:3358-3372(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA7.
[17]	"Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation." Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H. Biochem. Biophys. Res. Commun. 330:746-754(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION OF THE PML-RARALPHA ONCOPROTEIN WITH UBE2I, SUMOYLATION, SUBCELLULAR LOCATION.
[18]	"The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling." Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R. Cell 122:835-847(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRAME.
[19]	"Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha." Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L., Weigel N.L., Brown P.H., Kurie J.M. Biochem. J. 395:653-662(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-96, FUNCTION, INTERACTION WITH AKT1, MUTAGENESIS OF SER-95; SER-96; SER-154 AND SER-157.
[20]	"Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor." Cho Y.S., Kim E.J., Park U.H., Sin H.S., Um S.J. J. Biol. Chem. 281:17588-17598(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASXL1 AND NCOA1, MUTAGENESIS OF 409-ILE-LEU-410; GLU-412; 413-MET-LEU-414 AND GLU-415.
[21]	"RIF-1, a novel nuclear receptor corepressor that associates with the nuclear matrix." Li H.J., Haque Z.K., Chen A., Mendelsohn M. J. Cell. Biochem. 102:1021-1035(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRIF1.
[22]	"Small ubiquitin-like modifier-2 modification of retinoic acid receptor-alpha regulates its subcellular localization and transcriptional activity." Zhu L., Santos N.C., Kim K.H. Endocrinology 150:5586-5595(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-166; LYS-171 AND LYS-399, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-147; LYS-166; LYS-171 AND LYS-399.
[23]	"GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis." Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G., Kitagawa H., Kato S. Nature 459:455-459(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MLL5.
[24]	"Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling." Santos N.C., Kim K.H. Endocrinology 151:2361-2372(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-219 AND SER-369, INTERACTION WITH RXRA AND PRKAR1A, FUNCTION, MUTAGENESIS OF SER-219 AND SER-369.
[25]	"Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1." Rastinejad F., Wagner T., Zhao Q., Khorasanizadeh S. EMBO J. 19:1045-1054(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 82-167 IN COMPLEX WITH RXRA AND DNA.
[26]	"Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains." Bourguet W., Vivat V., Wurtz J.M., Chambon P., Gronemeyer H., Moras D. Mol. Cell 5:289-298(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 182-416 IN COMPLEX WITH M.MUSCULUS RXRA.
[27]	"A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor." le Maire A., Teyssier C., Erb C., Grimaldi M., Alvarez S., de Lera A.R., Balaguer P., Gronemeyer H., Royer C.A., Germain P., Bourguet W. Nat. Struct. Mol. Biol. 17:801-807(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 176-421 IN COMPLEXES WITH AGONIST AM580 AND NCOA1 AND WITH INVERSE AGONIST BMS493 AND NCOR1, INTERACTION WITH NCOR1 AND NCOR2, MUTAGENESIS OF ILE-396.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

Retinoic acid receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X06614 mRNA. Translation: CAA29829.1.
X06538 mRNA. Translation: CAA29787.1.
AF088895 , AF088889, AF088890, AF088891, AF088892, AF088893, AF088894 Genomic DNA. Translation: AAD05222.1.
FJ487576 mRNA. Translation: ACK86665.1.
AC080112 Genomic DNA. No translation available.
BC008727 mRNA. Translation: AAH08727.1.
BC071733 mRNA. Translation: AAH71733.1.
X56058, X58685 mRNA. Translation: CAA39533.1.
X58685 mRNA. Translation: CAA41532.1.
U41742 mRNA. Translation: AAB00112.1. Different initiation.
U41743 mRNA. Translation: AAB00113.1. Different initiation.
AF283809 Genomic DNA. Translation: AAF87249.1.
AB067754 mRNA. Translation: BAB62809.1. Different initiation.

IPI

IPI00020071.
IPI00218375.
IPI00922641.

PIR

A29491.

RefSeq

NP_000955.1. NM_000964.3.
NP_001019980.1. NM_001024809.3.
NP_001138773.1. NM_001145301.2.
NP_001138774.1. NM_001145302.2.

UniGene

Hs.654583.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DKF	X-ray	2.50	B	182-416	[»]
1DSZ	X-ray	1.70	A	82-167	[»]
3A9E	X-ray	2.75	B	153-421	[»]
3KMR	X-ray	1.80	A	176-421	[»]
3KMZ	X-ray	2.10	A/B	176-421	[»]
4DQM	X-ray	2.75	A/C	182-415	[»]

ProteinModelPortal

P10276.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34N.

IntAct

P10276. 56 interactions.

MINT

MINT-123081.

STRING

9606.ENSP00000254066.

PTM databases

PhosphoSite

P10276.

Polymorphism databases

DMDM

133483.

Proteomic databases

PaxDb

P10276.

PRIDE

P10276.

Protocols and materials databases

DNASU

5914.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000254066; ENSP00000254066; ENSG00000131759.
ENST00000394081; ENSP00000377643; ENSG00000131759.
ENST00000394089; ENSP00000377649; ENSG00000131759.
ENST00000425707; ENSP00000389993; ENSG00000131759.

GeneID

5914.

KEGG

hsa:5914.

UCSC

uc002huk.2. human.
uc010wfe.2. human.

Organism-specific databases

CTD

5914.

GeneCards

GC17P038465.

HGNC

HGNC:9864. RARA.

MIM

180240. gene.
612376. phenotype.

neXtProt

NX_P10276.

Orphanet

520. Acute promyelocytic leukemia.

PharmGKB

PA34225.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG297448.

HOGENOM

HOG000010312.

HOVERGEN

HBG005606.

KO

K08527.

OMA

RTENVCI.

PhylomeDB

P10276.

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.

SignaLink

P10276.

Gene expression databases

ArrayExpress

P10276.

Bgee

P10276.

CleanEx

HS_RARA.

Genevestigator

P10276.

GermOnline

ENSG00000131759. 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.
IPR003078. Retinoic_acid_rcpt.
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

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

BindingDB

P10276.

ChEMBL

CHEMBL2055.

ChiTaRS

RARA. human.

DrugBank

DB00459. Acitretin.
DB00210. Adapalene.
DB00523. Alitretinoin.
DB00926. Etretinate.
DB00982. Isotretinoin.
DB04942. Tamibarotene.
DB00799. Tazarotene.

EvolutionaryTrace

P10276.

GenomeRNAi

5914.

NextBio

23018.

SOURCE

Search...

Entry information

Entry name

RARA_HUMAN

Accession

Primary (citable) accession number: P10276
Secondary accession number(s): B8Y636 , P78456, Q13440, Q13441, Q96S41, Q9NQS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 1, 1989
Last modified:	May 29, 2013
This is version 175 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.