RARA (retinoic acid receptor alpha)

Gene

• Entrez ID: 5914
• Gene name: Retinoic acid receptor alpha
• Gene symbol: RARA
• Synonyms: NR1B1, RAR
• Chromosome: 17
• Chromosome location: 17q21.2
• Summary: This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs786205678	C>T	Drug-response	Missense variant, coding sequence variant
rs1555574254	TCATCCAGGAAATGTTGGAGAACTCAGAGGGCCTGGACACTCTGAGCGGACAGCCGGGGGGTGGGGGGCGGGACGGGGGTGGCCTGGCCCCCCCGCCAGGCAGCTGTAGCCCCAGCCTCAGCCCCAGCTCCAACAGAAGCAGCCCGGCCACCCACTCCCCGTGAC>-	Drug-response	Terminator codon variant, 3 prime UTR variant, stop lost, inframe indel

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004389	hsa-miR-125a-5p	Microarray, Northern blot	16331254
MIRT024237	hsa-miR-218-5p	Sequencing	20371350
MIRT039873	hsa-miR-615-3p	CLASH	23622248
MIRT045829	hsa-miR-138-5p	CLASH	23622248
MIRT045829	hsa-miR-138-5p	Luciferase reporter assay, Western blot	25680531
MIRT469545	hsa-miR-6780a-5p	PAR-CLIP	23592263
MIRT469546	hsa-miR-6779-5p	PAR-CLIP	23592263
MIRT469547	hsa-miR-3689c	PAR-CLIP	23592263
MIRT469548	hsa-miR-3689b-3p	PAR-CLIP	23592263
MIRT469549	hsa-miR-3689a-3p	PAR-CLIP	23592263
MIRT469550	hsa-miR-30b-3p	PAR-CLIP	23592263
MIRT469551	hsa-miR-1273h-5p	PAR-CLIP	23592263
MIRT469552	hsa-miR-519e-5p	PAR-CLIP	23592263
MIRT469553	hsa-miR-515-5p	PAR-CLIP	23592263
MIRT469554	hsa-miR-6778-5p	PAR-CLIP	23592263
MIRT469555	hsa-miR-1233-5p	PAR-CLIP	23592263
MIRT469556	hsa-miR-6780b-5p	PAR-CLIP	23592263
MIRT469557	hsa-miR-4725-3p	PAR-CLIP	23592263
MIRT469558	hsa-miR-4271	PAR-CLIP	23592263
MIRT469559	hsa-miR-6799-5p	PAR-CLIP	23592263
MIRT469560	hsa-miR-5196-5p	PAR-CLIP	23592263
MIRT469561	hsa-miR-7106-5p	PAR-CLIP	23592263
MIRT469562	hsa-miR-4747-5p	PAR-CLIP	23592263
MIRT469563	hsa-miR-6797-5p	PAR-CLIP	23592263
MIRT469564	hsa-miR-1249-5p	PAR-CLIP	23592263
MIRT469565	hsa-miR-6133	PAR-CLIP	23592263
MIRT469566	hsa-miR-6130	PAR-CLIP	23592263
MIRT469567	hsa-miR-6129	PAR-CLIP	23592263
MIRT469568	hsa-miR-6127	PAR-CLIP	23592263
MIRT469569	hsa-miR-4510	PAR-CLIP	23592263
MIRT469570	hsa-miR-4419a	PAR-CLIP	23592263
MIRT469571	hsa-miR-605-3p	PAR-CLIP	23592263
MIRT469572	hsa-miR-3925-3p	PAR-CLIP	23592263
MIRT469573	hsa-miR-766-3p	PAR-CLIP	23592263
MIRT469574	hsa-miR-194-3p	PAR-CLIP	23592263
MIRT469575	hsa-miR-6783-5p	PAR-CLIP	23592263
MIRT469576	hsa-miR-4756-5p	PAR-CLIP	23592263
MIRT469577	hsa-miR-4739	PAR-CLIP	23592263
MIRT469578	hsa-miR-1321	PAR-CLIP	23592263
MIRT469579	hsa-miR-940	PAR-CLIP	23592263
MIRT469580	hsa-miR-6893-5p	PAR-CLIP	23592263
MIRT469581	hsa-miR-3714	PAR-CLIP	23592263
MIRT469582	hsa-miR-6808-5p	PAR-CLIP	23592263
MIRT733217	hsa-miR-27a-3p	Luciferase reporter assay, Microarray, qRT-PCR	25915942

Transcription factors

Transcription factor	Regulation	Reference
CRABP2	Activation	16166294
CREBBP	Unknown	21110951
ESR1	Activation	9626663
JUN	Repression	9377582
KLF4	Repression	19531492
SP1	Activation	9626663

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IBA	21873635
GO:0000785	Component	Chromatin	IDA	17363140, 21131358
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	19917671, 21131358
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	20080953
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001972	Function	Retinoic acid binding	IDA	2825025
GO:0003682	Function	Chromatin binding	IDA	20080953
GO:0003700	Function	DNA-binding transcription factor activity	IDA	18922886, 20413580
GO:0004879	Function	Nuclear receptor activity	IBA	21873635
GO:0004879	Function	Nuclear receptor activity	IDA	2825025, 21131358
GO:0005102	Function	Signaling receptor binding	IDA	19628791
GO:0005515	Function	Protein binding	IPI	9653119, 16189514, 16456540, 16606617, 16769902, 17363140, 17560333, 17641689, 18048326, 19345331, 19850744, 19917671, 19934264, 20080953, 20133701, 20543827, 21478865, 21516116, 21988832, 22056876, 22351778, 23518351, 24819975, 25036637, 25241761, 25303530, 25416956, 26871637, 2989
GO:0005634	Component	Nucleus	IDA	18845237, 19917671, 20080953
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005730	Component	Nucleolus	IDA
GO:0005737	Component	Cytoplasm	IDA	19850744
GO:0005829	Component	Cytosol	IDA
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
GO:0006468	Process	Protein phosphorylation	IMP	16456540
GO:0007165	Process	Signal transduction	IDA	2825025
GO:0008134	Function	Transcription factor binding	IPI	17641689
GO:0008270	Function	Zinc ion binding	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	20080953
GO:0009755	Process	Hormone-mediated signaling pathway	IBA	21873635
GO:0009986	Component	Cell surface	IC	2825025
GO:0015629	Component	Actin cytoskeleton	IDA
GO:0019899	Function	Enzyme binding	IPI	9628876, 12039952
GO:0019904	Function	Protein domain specific binding	IPI	20413580
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030853	Process	Negative regulation of granulocyte differentiation	IDA	19917671
GO:0031490	Function	Chromatin DNA binding	IDA	19917671
GO:0032526	Process	Response to retinoic acid	IMP	17538076
GO:0032689	Process	Negative regulation of interferon-gamma production	IDA	18416830
GO:0032720	Process	Negative regulation of tumor necrosis factor production	IDA	18416830
GO:0032736	Process	Positive regulation of interleukin-13 production	IDA	18416830
GO:0032753	Process	Positive regulation of interleukin-4 production	IDA	18416830
GO:0032754	Process	Positive regulation of interleukin-5 production	IDA	18416830
GO:0032991	Component	Protein-containing complex	IDA	19917671, 20080953
GO:0043277	Process	Apoptotic cell clearance	IMP	19628791
GO:0043422	Function	Protein kinase B binding	IPI	16417524
GO:0044323	Function	Retinoic acid-responsive element binding	IDA	19917671
GO:0045630	Process	Positive regulation of T-helper 2 cell differentiation	IDA	18416830
GO:0045787	Process	Positive regulation of cell cycle	IMP	20080953
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	20080953
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	18845237, 19850744, 20080953
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	19628791
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	19850744, 19917671, 21131358
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	20080953
GO:0048384	Process	Retinoic acid receptor signaling pathway	IBA	21873635
GO:0048384	Process	Retinoic acid receptor signaling pathway	IDA	19917671
GO:0048384	Process	Retinoic acid receptor signaling pathway	IMP	17538076
GO:0051018	Function	Protein kinase A binding	IDA	20215566
GO:0051099	Process	Positive regulation of binding	IMP	20080953
GO:0051393	Function	Alpha-actinin binding	IPI	22351778
GO:0071391	Process	Cellular response to estrogen stimulus	IDA	20080953
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 180240
• HGNC: 9864
• e!Ensembl: ENSG00000131759

Protein

• UniProt ID: P10276
• Protein name: Retinoic acid receptor alpha (RAR-alpha) (Nuclear receptor subfamily 1 group B member 1)
• Protein function: Receptor for retinoic acid (PubMed:19850744, PubMed:16417524, PubMed:20215566). 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 (PubMed:28167758). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:28167758). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:9267036, PubMed:19850744, PubMed:20215566). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758).
• PDB: 1DKF, 1DSZ, 3A9E, 3KMR, 3KMZ, 4DQM, 5K13, 6XWG
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00105	zf-C4	86 → 155	Zinc finger, C4 type (two domains)	Domain
  PF00104	Hormone_recep	224 → 401	Ligand-binding domain of nuclear hormone receptor	Domain

• Sequence:

  MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT
  IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM
  VYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL
  TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTV
  EFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA
  GFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK
  VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGL
  DTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP

• Sequence length: 462