Reviewed, UniProtKB/Swiss-Prot P10276 (RARA_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	462 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression.
Subunit structure	Interacts with CDK7 By similarity. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with NOCA7 in a ligand-inducible manner.
Subcellular location	Nucleus.
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal steroid-binding domain.
Post-translational modification	Phosphorylated. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for transcriptional activity By similarity.
Involvement in disease	Chromosomal aberrations involving RARA may be a cause of acute promyelocytic leukemia (APL). 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.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	estrogen receptor signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of interferon-gamma production Inferred from direct assay. Source: UniProtKB negative regulation of tumor necrosis factor production Inferred from direct assay. Source: UniProtKB positive regulation of T-helper 2 cell differentiation Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-13 production Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-4 production Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-5 production Inferred from direct assay. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro response to estradiol stimulus Inferred from direct assay. Source: UniProtKB response to retinoic acid Inferred from mutant phenotype. Source: UniProtKB retinoic acid receptor signaling pathway Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cell surface Ref.6 Inferred by curator. Source: UniProtKB nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	retinoic acid binding Ref.6 Inferred from direct assay. Source: UniProtKB retinoic acid receptor activity Ref.6 Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Ref.6 Inferred from direct assay. Source: UniProtKB transcription factor 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
EZH2	Q15910	2	EBI-413374,EBI-530054
MBD1	Q9UIS9	1	EBI-413374,EBI-867196
Ncoa6	Q9JLI4	1	EBI-413374,EBI-286271	From a different organism.

Alternative products

This entry describes 2 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

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

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

449

1

Phosphoserine By similarity

Modified residue

456

1

Phosphoserine By similarity

Modified residue

461

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 60

60

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

VSP_003629

Experimental info

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 – 198

16

Helix

202 – 204

3

Helix

222 – 245

24

Turn

247 – 251

5

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 – 315

10

Helix

317 – 319

3

Helix

323 – 334

12

Helix

345 – 366

22

Helix

373 – 378

6

Helix

380 – 401

22

Helix

410 – 415

6

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		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

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: 2825036] [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: 8302850] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (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: 10337631] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA-1).
[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] (ISOFORMS ALPHA-1 AND ALPHA-2). Tissue: Blood and Brain.
[5]	"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: 2175878] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-80 (ISOFORM ALPHA-1).
[6]	"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: 2825025] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-462.
[7]	Chambon P. Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[8]	"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: 8562957] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-462, CHROMOSOMAL TRANSLOCATION WITH NPM. Tissue: Bone marrow.
[9]	"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 OF 1-54 (ISOFORM ALPHA-2).
[10]	"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: 12691149] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-68, CHROMOSOMAL TRANSLOCATION WITH PML.
[11]	"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: 9267036] [Abstract] Cited for: INTERACTION WITH NCOA3.
[12]	"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: 10567404] [Abstract] Cited for: INTERACTION WITH NCOA6.
[13]	"ERAP140, a conserved tissue-specific nuclear receptor coactivator." Shao W., Halachmi S., Brown M. Mol. Cell. Biol. 22:3358-3372(2002) [PubMed: 11971969] [Abstract] Cited for: INTERACTION WITH NOCA7.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

Retinoic acid receptor entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X06614 mRNA. Translation: CAA29829.1.
X06538 mRNA. Translation: CAA29787.1.
AF088895 , AF088889, AF088890, AF088891, AF088892, AF088893, AF088894 Genomic DNA. Translation: AAD05222.1.
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.

PIR

A29491.

RefSeq

NP_000955.1.
NP_001019980.1.

UniGene

Hs.654583

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DKF	X-ray	2.50	B	182-416	[»]
1DSZ	X-ray	1.70	A	82-167	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:34N.

IntAct

P10276.

PTM databases

PhosphoSite

P10276.

Genome annotation databases

Ensembl

ENSG00000131759. Homo sapiens. [Contig view]

GeneID

5914.

KEGG

hsa:5914.

Organism-specific databases

H-InvDB

HIX0017867.

HGNC

HGNC:9864. RARA.

MIM

180240. gene.

Orphanet

520. Acute promyelocytic leukaemia.

PharmGKB

PA34225.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P10276.

Gene expression databases

ArrayExpress

P10276.

CleanEx

HS_RARA.

GermOnline

ENSG00000131759. 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.
[Graphical view]

Gene3D

G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit.

PANTHER

PTHR11865:SF169. Rtnoid_rcpt. 1 hit.

Pfam

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

PRINTS

PR01292. RETNOICACIDR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

ProDom

PD000035. Znf_C4steroid. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NU