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... See more...

Aliases for RARA Gene

Aliases for RARA Gene

  • Retinoic Acid Receptor Alpha 2 3 4 5
  • NR1B1 2 3 4
  • Nuclear Receptor Subfamily 1 Group B Member 1 3 4
  • RAR-Alpha 3 4
  • RAR 2 3
  • Nucleophosmin-Retinoic Acid Receptor Alpha Fusion Protein NPM-RAR Long Form 3
  • Retinoic Acid Nuclear Receptor Alpha Variant 1 3
  • Retinoic Acid Nuclear Receptor Alpha Variant 2 3
  • Retinoic Acid Receptor, Alpha Polypeptide 3
  • Retinoic Acid Receptor, Alpha 2
  • RARA 5

External Ids for RARA Gene

Previous GeneCards Identifiers for RARA Gene

  • GC17P037961
  • GC17P040640
  • GC17P038374
  • GC17P038838
  • GC17P038860
  • GC17P035718
  • GC17P038465
  • GC17P034259

Summaries for RARA Gene

Entrez Gene Summary for RARA Gene

  • 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]

GeneCards Summary for RARA Gene

RARA (Retinoic Acid Receptor Alpha) is a Protein Coding gene. Diseases associated with RARA include Acute Promyelocytic Leukemia and Leukemia. Among its related pathways are Transcriptional misregulation in cancer and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is RARB.

UniProtKB/Swiss-Prot Summary for RARA Gene

  • 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).

Tocris Summary for RARA Gene

  • Retinoic acid receptors (RARs) are nuclear hormone receptors of the NR1B class, which function as heterodimers with retinoid X receptors (RXRs). There are three distinct RAR subtypes: RARalpha, present in most tissue types; and RARbeta and RARgamma, with more selective expression.

Gene Wiki entry for RARA Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RARA Gene

Genomics for RARA Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RARA Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RARA on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RARA

Top Transcription factor binding sites by QIAGEN in the RARA gene promoter:
  • C/EBPalpha
  • p53
  • Sp1
  • STAT1

Genomic Locations for RARA Gene

Genomic Locations for RARA Gene
chr17:40,309,180-40,357,643
(GRCh38/hg38)
Size:
48,464 bases
Orientation:
Plus strand
chr17:38,465,423-38,513,895
(GRCh37/hg19)
Size:
48,473 bases
Orientation:
Plus strand

Genomic View for RARA Gene

Genes around RARA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RARA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RARA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RARA Gene

Proteins for RARA Gene

  • Protein details for RARA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P10276-RARA_HUMAN
    Recommended name:
    Retinoic acid receptor alpha
    Protein Accession:
    P10276
    Secondary Accessions:
    • B8Y636
    • P78456
    • Q13440
    • Q13441
    • Q96S41
    • Q9NQS0

    Protein attributes for RARA Gene

    Size:
    462 amino acids
    Molecular mass:
    50771 Da
    Quaternary structure:
    • Heterodimer; with RXRA (via C-terminus); association with RXRA is enhanced by pulsatile shear stress (PubMed:28167758, PubMed:10698945, PubMed:10882070, PubMed:20215566, PubMed:15509776). Binds DNA preferentially as a heterodimer (PubMed:10698945, PubMed:28167758). RXRA serves as enhancer to induce RARA binding to RARE (PubMed:30468856). Interacts with RXRG (PubMed:28167758). Interacts with coactivators NCOA3 and NCOA6 (PubMed:9267036, PubMed:10567404). Interacts with NCOA7; the interaction requires ligand-binding (PubMed:11971969). Interacts (via the ligand-binding domain) with PRAME; the interaction is ligand (retinoic acid)-dependent (PubMed:16179254). Interacts with AKT1; the interaction phosphorylates RARA and represses transactivation (PubMed:16417524). Interacts with PRKAR1A; the interaction negatively regulates RARA transcriptional activity (PubMed:20215566). Interacts with NCOR1 and NCOR2 (PubMed:20543827). Interacts with PRMT2 (PubMed:12039952). Interacts with LRIF1 (PubMed:17455211). Interacts with ASXL1 and NCOA1 (PubMed:16606617). Interacts with ACTN4 (PubMed:22351778). In a complex with HDAC3, HDAC5 and HDAC7; the HDACs serve as corepressors of RARA, causing its deacetylation and inhibition of RARE DNA element binding; association with HDAC3, HDAC5 and HDAC7 is increased upon oscillatory shear stress (PubMed:28167758). Interacts with CDK7 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).
    SequenceCaution:
    • Sequence=AAB00112.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAB00113.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB62809.1; Type=Erroneous initiation; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform Alpha-1-deltaBC]: Does not bind nor transactivate RARE on its own but may do so as a heterodimer with Alpha-1.

    Three dimensional structures from OCA and Proteopedia for RARA Gene

    Alternative splice isoforms for RARA Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RARA Gene

Post-translational modifications for RARA Gene

  • 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.
  • 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.
  • Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation.
  • Ubiquitinated.
  • Acetylated; acetylation is increased upon pulsatile shear stress and decreased upon oscillatory shear stress.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

No data available for DME Specific Peptides for RARA Gene

Domains & Families for RARA Gene

Gene Families for RARA Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • FDA approved drug targets
  • Nuclear receptors
  • Plasma proteins
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for RARA Gene

InterPro:
Blocks:
  • Steroid hormone receptor signature
  • Retinoic acid receptor (1B nuclear receptor) signature
ProtoNet:

Suggested Antigen Peptide Sequences for RARA Gene

GenScript: Design optimal peptide antigens:
  • Retinoic acid receptor, alpha, isoform CRA_b (F1D8N9_HUMAN)
  • RARA protein (Q15997_HUMAN)
  • cDNA, FLJ92939, Homo sapiens retinoic acid receptor, alpha (RARA), mRNA (Q6I9R7_HUMAN)
  • Nuclear receptor subfamily 1 group B member 1 (RARA_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P10276

UniProtKB/Swiss-Prot:

RARA_HUMAN :
  • Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
Domain:
  • Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
  • The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Family:
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
genes like me logo Genes that share domains with RARA: view

Function for RARA Gene

Molecular function for RARA Gene

UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Induction:
Down-regulated by aging (PubMed:26463675). Induced by pulsatile shear stress (PubMed:28167758).
GENATLAS Biochemistry:
retinoic acid receptor binding and activated by both all-trans (T-RA) and its 9-cis isomer (9-cis-RA) retinoic acids,alpha subunit,steroid/thyroid hormone receptor superfamily

Phenotypes From GWAS Catalog for RARA Gene

Gene Ontology (GO) - Molecular Function for RARA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000900 translation repressor activity, mRNA regulatory element binding IEA --
GO:0000976 transcription regulatory region sequence-specific DNA binding IBA --
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 21131358
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0001012 RNA polymerase II regulatory region DNA binding IEA --
genes like me logo Genes that share ontologies with RARA: view
genes like me logo Genes that share phenotypes with RARA: view

Human Phenotype Ontology for RARA Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RARA Gene

MGI Knock Outs for RARA:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RARA

Clone Products

  • Addgene plasmids for RARA

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for RARA Gene

Localization for RARA Gene

Subcellular locations from UniProtKB/Swiss-Prot for RARA Gene

Nucleus. Cytoplasm. Note=Nuclear localization depends on ligand binding, phosphorylation and sumoylation (PubMed:19850744). Translocation to the nucleus in the absence of ligand is dependent on activation of PKC and the downstream MAPK phosphorylation (By similarity). Increased nuclear localization upon pulsatile shear stress (PubMed:28167758). {ECO:0000250 UniProtKB:P11416, ECO:0000269 PubMed:19850744, ECO:0000269 PubMed:28167758}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RARA gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
mitochondrion 2
peroxisome 2
lysosome 2
endoplasmic reticulum 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RARA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA,ISA --
GO:0005634 nucleus IEA,IDA 18845237
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,IDA 19850744
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with RARA: view

Pathways & Interactions for RARA Gene

genes like me logo Genes that share pathways with RARA: view

Pathways by source for RARA Gene

3 GeneGo (Thomson Reuters) pathways for RARA Gene
  • Transcription Ligand-dependent activation of the ESR1/SP pathway
  • Transcription Ligand-Dependent Transcription of Retinoid-Target genes
  • Transcription Sin3 and NuRD in transcription regulation
4 Qiagen pathways for RARA Gene
  • all-trans-Retinoic Acid Mediated Apoptosis
  • all-trans-Retinoic Acid Signaling in Brain
  • Molecular Mechanisms of Cancer
  • Nuclear Receptor Activation by Vitamin-A

SIGNOR curated interactions for RARA Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for RARA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IBA 21873635
GO:0001657 ureteric bud development IEA --
GO:0001843 neural tube closure IEA --
GO:0001889 liver development IBA --
GO:0002068 glandular epithelial cell development IEA --
genes like me logo Genes that share ontologies with RARA: view

Drugs & Compounds for RARA Gene

(86) Drugs for RARA Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tretinoin Approved, Investigational Nutra Agonist, Full agonist, Antagonist, Target, binder 273
Acitretin Approved Pharma Target, agonist, inhibitor Metabolite of etretinate 33
Adapalene Approved Pharma Target, binder RAR尾 and RAR纬 agonist 90
Tazarotene Approved, Investigational Pharma Target, agonist, binder Topical retinoid;antiproliferative;inducer of TIG3 tumor suppressor 48
Isotretinoin Approved Pharma Target, other/unknown, agonist Endogenous agonist for retinoic acid receptors; inducer of neuronal differentiation 151

(45) Additional Compounds for RARA Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
retinoic acid
302-79-4
EC 23
104561-41-3
Liarozole dihydrochloride

(5) Tocris Compounds for RARA Gene

Compound Action Cas Number
EC 23 Synthetic retinoid; induces differentiation of stem cells 104561-41-3
Isotretinoin Endogenous agonist for retinoic acid receptors; inducer of neuronal differentiation 4759-48-2
Liarozole dihydrochloride Blocks retinoic acid metabolism
Retinoic acid Endogenous retinoic acid receptor agonist 302-79-4
TTNPB Retinoic acid analog; RAR agonist 71441-28-6

(22) ApexBio Compounds for RARA Gene

Compound Action Cas Number
Acitretin Metabolite of etretinate 55079-83-9
Acitretin sodium 925701-88-8
Adapalene RAR尾 and RAR纬 agonist 106685-40-9
Adarotene Apoptosis inducer/DNA damage agent 496868-77-0
AGN 194310 pan-RAR antagonist 229961-45-9
AM580 Selective RARα agonist 102121-60-8
BMS 195614 Neutral RARα selective antagonist 253310-42-8
BMS 453 RAR agonist 166977-43-1
BMS 493 Pan-RAR inverse agonist 215030-90-3
BMS 753 RARα-selective agonist 215307-86-1
Ch 55 110368-33-7
ER 50891 187400-85-7
Fenretinide Synthetic retinoid agonist 65646-68-6
LE 135 155877-83-1
MM 11253 345952-44-5
Palovarotene 410528-02-8
Talarozole Cytochrome P450 inhibitor 201410-53-9
Tamibarotene RARα agonist 94497-51-5
Tazarotene Topical retinoid;antiproliferative;inducer of TIG3 tumor suppressor 118292-40-3
Tretinoin (Aberela) 302-79-4
TTNPB (Arotinoid Acid) Potent RAR agonist 71441-28-6
Vitamin A Acetate Unsaturated nutritional hydrocarbons 127-47-9
genes like me logo Genes that share compounds with RARA: view

Drug Products

Transcripts for RARA Gene

mRNA/cDNA for RARA Gene

5 REFSEQ mRNAs :
24 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RARA

Clone Products

  • Addgene plasmids for RARA

Alternative Splicing Database (ASD) splice patterns (SP) for RARA Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15
SP1: - - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - -
SP4: -
SP5: - - - -
SP6:
SP7: -
SP8: -

Relevant External Links for RARA Gene

GeneLoc Exon Structure for
RARA

Expression for RARA Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RARA Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RARA Gene

This gene is overexpressed in Whole Blood (x9.5).

Protein differential expression in normal tissues from HIPED for RARA Gene

This gene is overexpressed in Heart (54.1) and Cerebrospinal fluid (14.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for RARA Gene



Protein tissue co-expression partners for RARA Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RARA

SOURCE GeneReport for Unigene cluster for RARA Gene:

Hs.654583

mRNA Expression by UniProt/SwissProt for RARA Gene:

P10276-RARA_HUMAN
Tissue specificity: Expressed in monocytes.

Evidence on tissue expression from TISSUES for RARA Gene

  • Nervous system(4.7)
  • Bone marrow(4.7)
  • Blood(4.6)
  • Kidney(2.9)
  • Intestine(2.7)
  • Liver(2.7)
  • Skin(2.6)
  • Spleen(2.6)
  • Lung(2.6)
  • Heart(2.5)
  • Muscle(2.4)
  • Thyroid gland(2.4)
  • Lymph node(2.4)
  • Adrenal gland(2.1)
  • Stomach(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RARA Gene

Germ Layers:
  • mesoderm
Systems:
  • immune
  • lymphatic
Regions:
General:
  • blood
  • bone marrow
  • white blood cell
genes like me logo Genes that share expression patterns with RARA: view

Orthologs for RARA Gene

This gene was present in the common ancestor of animals.

Orthologs for RARA Gene

Organism Taxonomy Gene Similarity Type Details
Oppossum
(Monodelphis domestica)
Mammalia RARA 31
  • 97 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia RARA 30 31
  • 94.66 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RARA 30 31
  • 94.59 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Rara 30 17 31
  • 91.56 (n)
OneToOne
Chimpanzee
(Pan troglodytes)
Mammalia RARA 31
  • 91 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rara 30
  • 90.27 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia RARA