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RARA Gene

protein-coding   GIFtS: 73
GCID: GC17P038465

Retinoic Acid Receptor, Alpha

  See RARA-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Retinoic Acid Receptor, Alpha1 2     Nucleophosmin-Retinoic Acid Receptor Alpha Fusion Protein NPM-RAR Long
Form2
Nuclear Receptor Subfamily 1 Group B Member 12 3     Retinoic Acid Nuclear Receptor Alpha Variant 12
NR1B12 3     Retinoic Acid Nuclear Receptor Alpha Variant 22
RAR-alpha2 3     Retinoic Acid Receptor Alpha2
RAR2     Retinoic Acid Receptor, Alpha Polypeptide2

External Ids:    HGNC: 98641   Entrez Gene: 59142   Ensembl: ENSG000001317597   OMIM: 1802405   UniProtKB: P102763   

Export aliases for RARA gene to outside databases

Previous GC identifers: GC17P037961 GC17P040640 GC17P038374 GC17P038838 GC17P038860 GC17P035718 GC17P034259


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 aleukemic leukemia cutis. GO annotations related to this gene include protein heterodimerization activity and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is VDR.

UniProtKB/Swiss-Prot: RARA_HUMAN, P10276
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 KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis

summary for RARA Gene:
Retinoic acid receptors (RARs) are nuclear hormone receptors of the NRB1 class, which function as
heterodimers with retinoid X receptors (RXRs). There are three distinct RAR subtypes; RARalpha, RARbeta and
RARgamma. RARalpha is present in most tissue types, whereas RARbeta and RARgamma expression is more
selective. RXR-RAR heterodimers act as ligand-dependent transcriptional regulators by binding to the
specific retinoic acid response element (RARE) found in the promoter regions of target genes. In the absence
of an RAR agonist, RXR-RAR recruits co-repressor proteins such as NCoR and associated factors such as
histone deacetylase to maintain a condensed chromatin structure. RAR agonist binding stimulates co-repressor
release and co-activator complexes, such as histone acetyltransferase, are recruited to activate
transcription. RARs transduce retinoid signals in vivo, which mediates proper embryogenesis, differentiation
and growth arrest. Specifically, RXRalpha-RARgamma heterodimers are necessary for growth arrest and viseral
and primitive endodermal differentiation, whereas RXRalpha-RARalpha is required for cAMP-dependent parietal
endodermal differentiation. In vitro it has been difficult to elucidate the roles of individual subtypes as
functional RAR knockouts generate artificial redundancies that are thought not to exist under normal
conditions.

Gene Wiki entry for RARA (Retinoic acid receptor alpha) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000017.10  NT_010783.16  NC_018928.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the RARA gene promoter:
         STAT1   Sp1   p53   C/EBPalpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): RARA promoter sequence
   Search Chromatin IP Primers for RARA

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RARA


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q21   Ensembl cytogenetic band:  17q21.2   HGNC cytogenetic band: 17q21.1

RARA Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RARA gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P038465:  view genomic region     (about GC identifiers)

Start:
38,465,423 bp from pter      End:
38,513,895 bp from pter
Size:
48,473 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: RARA_HUMAN, P10276 (See protein sequence)
Recommended Name: Retinoic acid receptor alpha  
Size: 462 amino acids; 50771 Da
Subunit: 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 KMT2E/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
Sequence caution: Sequence=AAB00112.1; Type=Erroneous initiation; Sequence=AAB00113.1; Type=Erroneous initiation;
Sequence=BAB62809.1; Type=Erroneous initiation;
6 PDB 3D structures from and Proteopedia for RARA:
1DKF (3D)        1DSZ (3D)        3A9E (3D)        3KMR (3D)        3KMZ (3D)        4DQM (3D)    
Secondary accessions: B8Y636 P78456 Q13440 Q13441 Q96S41 Q9NQS0
Alternative splicing: 3 isoforms:  P10276-1   P10276-2   P10276-3   (Does not bind nor transactivate RARE on its own but may do so as a heterodimer with Alpha-1)

Explore the universe of human proteins at neXtProt for RARA: NX_P10276

Explore proteomics data for RARA at MOPED

Post-translational modifications: 

  • 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 signaling1
  • 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 activity1
  • Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation1
  • Ubiquitinated1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See RARA Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_000955.1  NP_001019980.1  NP_001138773.1  NP_001138774.1  

    ENSEMBL proteins: 
     ENSP00000464287   ENSP00000254066   ENSP00000377649   ENSP00000389993   ENSP00000377648  
     ENSP00000377643   ENSP00000462514  
    Reactome Protein details: P10276

    RARA Human Recombinant Protein Products:

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    Novus Biologicals RARA Proteins
    Novus Biologicals RARA Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for RARA
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for RARA 

     
    antibodies-online proteins for RARA (18 products) 

     
    antibodies-online peptides for RARA

    RARA Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of RARA
    R&D Systems Antibodies for RARA (RAR alpha/NR1B1)
    Cell Signaling Technology (CST) Antibodies for RARA 
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    Novus Biologicals RARA Antibodies
    Abcam antibodies for RARA
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for RARA
    antibodies-online antibodies for RARA (114 products) 

    RARA Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript Custom Assay Services for RARA
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for RARA 
    antibodies-online kits for RARA (19 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    NR: Nuclear hormone receptors

    IUPHAR Guide to PHARMACOLOGY protein family classification: Retinoic acid receptor-alpha
    1B. Retinoic acid receptors

    Selected InterPro protein domains (see all 6):
     IPR008946 Nucl_hormone_rcpt_ligand-bd
     IPR001723 Str_hrmn_rcpt
     IPR003078 Retinoic_acid_rcpt
     IPR013088 Znf_NHR/GATA
     IPR000536 Nucl_hrmn_rcpt_lig-bd_core

    Graphical View of Domain Structure for InterPro Entry P10276

    ProtoNet protein and cluster: P10276

    2 Blocks protein domains:
    IPB001723 Steroid hormone receptor signature
    IPB003078 Retinoic acid receptor (1B nuclear receptor) signature


    UniProtKB/Swiss-Prot: RARA_HUMAN, P10276
    Domain: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal
    ligand-binding domain
    Similarity: Belongs to the nuclear hormone receptor family. NR1 subfamily
    Similarity: Contains 1 nuclear receptor DNA-binding domain


    Find genes that share domains with RARA           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: RARA_HUMAN, P10276
    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 KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis

         Genatlas biochemistry entry for RARA:
    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

         Gene Ontology (GO): Selected molecular function terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000900translation repressor activity, nucleic acid binding IEA--
    GO:0001972retinoic acid binding IDA2825025
    GO:0003677DNA binding ----
    GO:0003700sequence-specific DNA binding transcription factor activity IDA18922886
    GO:0003707steroid hormone receptor activity IEA--
         
    Find genes that share ontologies with RARA           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for RARA:
     Increased cell death HMECs cel  Synthetic lethal with imatinib  Wnt reporter downregulated 

         Selected MGI mutant phenotypes (inferred from 5 alleles(MGI details for Rara) (see all 22):
     cardiovascular system  cellular  craniofacial  digestive/alimentary  embryogenesis 
     endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system  immune system 
     limbs/digits/tail  liver/biliary system  mortality/aging  muscle  nervous system 

    Find genes that share phenotypes with RARA           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for RARA: Raratm2Ipc Raratm1Ipc Raratm3.1Ipc Raratm1Rev

       genOway: Develop your customized and physiologically relevant rodent model for RARA

    miRNA
    Products:
        
    miRTarBase miRNAs that target RARA:
    hsa-mir-615-3p (MIRT039873), hsa-mir-138-5p (MIRT045829), hsa-mir-125a-5p (MIRT004389), hsa-mir-218-5p (MIRT024237)

    Block miRNA regulation of human, mouse, rat RARA using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate RARA (see all 41):
    hsa-miR-513a-5p hsa-miR-128 hsa-miR-16-1* hsa-let-7a-2* hsa-miR-218 hsa-miR-4267 hsa-miR-3613-3p hsa-miR-548am
    SwitchGear 3'UTR luciferase reporter plasmidRARA 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for RARA
    Predesigned siRNA for gene silencing in human, mouse, rat RARA

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for RARA

    Clone
    Products:
         
    OriGene clones in human, mouse for RARA (see all 22)
    OriGene ORF clones in mouse, rat for RARA
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 4): RARA (NM_001024809)
    Sino Biological Human cDNA Clone for RARA
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for RARA
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat RARA
    Addgene plasmids for RARA 

    Cell Line
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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RARA


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    RARA_HUMAN, P10276: 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
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    extracellular3
    cytoskeleton1
    mitochondrion1
    peroxisome1
    plasma membrane1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000790nuclear chromatin IDA17363140
    GO:0005634nucleus IDA18845237
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm IDA19850744
    GO:0009986cell surface IC2825025

    Find genes that share ontologies with RARA           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for RARA About   (see all 19)  
    See pathways by source

    SuperPathContained pathways About
    1Nuclear Receptor transcription pathway
    Nuclear Receptor transcription pathway0.67
    Nuclear Receptors0.67
    2Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40
    3PEDF Induced Signaling
    all-trans-Retinoic Acid Signaling in Brain0.71
    4Apoptotic Pathways in Synovial Fibroblasts
    Nuclear Receptor Activation by Vitamin-A0.57
    5ERK Signaling
    Molecular Mechanisms of Cancer0.51


    Find genes that share SuperPaths with RARA           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    4 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for RARA
        Nuclear Receptor Activation by Vitamin-A
    Molecular Mechanisms of Cancer
    all-trans-Retinoic Acid Signaling in Brain
    all-trans-Retinoic Acid Mediated Apoptosis

    3 GeneGo (Thomson Reuters) Pathways for RARA
        Transcription Ligand-dependent activation of the ESR1/SP pathway
    Transcription Sin3 and NuRD in transcription regulation
    Transcription Ligand-Dependent Transcription of Retinoid-Target genes

    Selected BioSystems Pathways for RARA (see all 7)
        Adipogenesis
    Nuclear Receptors
    Vitamin A and carotenoid metabolism
    IL-3 Signaling Pathway
    Nuclear receptors in lipid metabolism and toxicity


    1 Reactome Pathway for RARA
        Nuclear Receptor transcription pathway


    3 Kegg Pathways  (Kegg details for RARA):
        Pathways in cancer
    Transcriptional misregulation in cancer
    Acute myeloid leukemia

        Pathway & Disease-focused RT2 Profiler PCR Arrays including RARA: 
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Estrogen Receptor Signaling in human mouse rat
              TGFB Signaling Targets in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Cancer Drug Resistance in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for RARA

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for RARA (P102761, 2, 3 ENSP000002540664) via UniProtKB, MINT, STRING, and/or I2D (see all 207)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MED25Q71SY51, 2, 3, ENSP000003267674EBI-413374,EBI-394558 MINT-5210199 MINT-5210070 MINT-5210046 MINT-5209882 MINT-5210176 MINT-5209983 MINT-5210334 MINT-5209938 MINT-5210212 MINT-5210090 I2D: score=4 STRING: ENSP00000326767
    NCOA1Q157881, 2, 3, ENSP000003209404EBI-413374,EBI-455189 MINT-2834489 MINT-5209864 I2D: score=6 STRING: ENSP00000320940
    RXRAP197931, 2, 3, ENSP000004196924EBI-413374,EBI-78598 MINT-24895 I2D: score=7 STRING: ENSP00000419692
    RXRGP484431, 2, 3, ENSP000003529004EBI-413374,EBI-712405 MINT-67080 I2D: score=6 STRING: ENSP00000352900
    MED1Q156481, 2, 3, ENSP000003006514EBI-413374,EBI-394459 MINT-5209905 I2D: score=4 STRING: ENSP00000300651
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 59):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IEA--
    GO:0001657ureteric bud development IEA--
    GO:0001889liver development IEA--
    GO:0003417growth plate cartilage development IEA--
    GO:0006355regulation of transcription, DNA-templated ----

    Find genes that share ontologies with RARA           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for RARA available from Tocris Bioscience    About this table
    CompoundAction CAS #
    Liarozole hydrochlorideBlocks retinoic acid metabolism[145858-50-0]
    BMS 195614Selective RARalpha antagonist[253310-42-8]
    FenretinideSynthetic retinoid. Potent anticancer agent[65646-68-6]
    BMS 493Pan-RAR inverse agonist[215030-90-3]
    CD 1530Potent and selective RARgamma agonist[107430-66-0]

    1 HMDB Compound for RARA    About this table
    CompoundSynonyms CAS #PubMed Ids
    Retinoic acidRetinoate (see all 21)302-79-4--

    7 DrugBank Compounds for RARA    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Alitretinoin9-cis-Retinoic acid (see all 4)5300-03-8targetagonist18321241 16253547 16144296 11752352 16420438 16424870 16339527
    Tazarotene-- 118292-40-3targetagonist16144296 15383624 10828316 11519864 9035701 14675762
    AdapaleneAdapaleno [INN-Spanish] (see all 2)106685-40-9targetagonist9990415 10651997 9990413 9557255 9204085
    Etretinate-- 54350-48-0targetagonist9298126 1965892 10459139 8301142 9074840
    Isotretinoin-- 4759-48-2targetother/unknown16983322 7601910 9691099 10955779 9204085
    TamibaroteneAm 80 (see all 2)94497-51-5targetagonist17611697 17925887 11752352 15563242 15843826
    Acitretin-- 55079-83-9targetagonist9153406 19144697 10459139 9074840

    Selected IUPHAR Ligands for RARA (Retinoic acid receptor-alpha) (see all 12)    About this table
    LigandTypeActionAffinityPubmed IDs
    9-cis-retinoic acid
    AgonistAgonist9.53184125 7791761
    all-trans-retinoic acid
    AgonistAgonist9.48380496 8264595 10964567 7791761 10637371
    BMS614
    AntagonistAntagonist8.710882070 11805839 10421757
    AGN193109
    AntagonistInverse agonist8.710777502 10637371 8798442
    BMS753
    AgonistAgonist8.710421757
    BMS493
    AntagonistInverse agonist8.411805839
    AGN193836
    AgonistAgonist8.412372520
    TTNPB
    AgonistAgonist7.4410637371 8264595 10964567 7791761
    Ro 40-6055
    AgonistAgonist7.443184125 10637371
    Ro 41-5253
    AntagonistAntagonist6.34 - 7.228264595 1323127

    Selected Novoseek inferred chemical compound relationships for RARA gene (see all 94)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    retinoic acid 97.7 3241 9506453 (10), 11278809 (8), 15520197 (7), 9852056 (6) (see all 99)
    retinoid 95.8 290 11034091 (5), 9205071 (5), 7671258 (5), 15956352 (3) (see all 99)
    ttnpb 91.2 37 9528950 (2), 8668150 (2), 9006080 (2), 9009084 (2) (see all 24)
    am 580 89.5 45 8608243 (4), 8216300 (3), 11302942 (2), 16636311 (2) (see all 20)
    alpha-retinoic acid 86.2 11 2171781 (2), 1715692 (1), 8396481 (1), 8207983 (1) (see all 8)
    ch 55 85.5 8 10704935 (2), 9720716 (1), 2154975 (1), 1652063 (1) (see all 5)
    am80 84.9 22 19292987 (3), 9720716 (2), 11034091 (1), 11945126 (1) (see all 14)
    cd 2019 84.7 8 8216300 (3), 11302942 (1), 9639510 (1), 10374844 (1) (see all 5)
    cd 437 82.1 14 8216300 (3), 10942519 (2), 10037194 (1), 11302942 (1) (see all 9)
    vitamin a 79.5 53 12901928 (3), 12606456 (2), 8384711 (2), 15632377 (2) (see all 33)

    2 PharmGKB related drug/compound annotations for RARA gene    About this table
    Drug/compound PharmGKB Annotation
    arsenic trioxide
    tretinoin



    Find genes that share compounds with RARA           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
    About This Section

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    REFSEQ mRNAs for RARA gene (5 alternative transcripts): 
    NM_000964.3  NM_001024809.3  NM_001145301.2  NM_001145302.2  NM_001033603.1  

    Unigene Cluster for RARA:

    Retinoic acid receptor, alpha
    Hs.654583  [show with all ESTs]
    Unigene Representative Sequence: NM_001024809
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000577646 ENST00000254066(uc002huk.2 uc002hul.4) ENST00000394089(uc021txb.1)
    ENST00000425707(uc010wfe.2) ENST00000582914 ENST00000394086 ENST00000394081(uc002hun.2)
    ENST00000579727 ENST00000475125 ENST00000420042
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate RARA (see all 41):
    hsa-miR-513a-5p hsa-miR-128 hsa-miR-16-1* hsa-let-7a-2* hsa-miR-218 hsa-miR-4267 hsa-miR-3613-3p hsa-miR-548am
    SwitchGear 3'UTR luciferase reporter plasmidRARA 3' UTR sequence
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    GenScript: all cDNA clones in your preferred vector (see all 4): RARA (NM_001024809)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat RARA
    Addgene plasmids for RARA 
    Primer
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      QuantiTect SYBR Green Assays in human, mouse, rat RARA
      QuantiFast Probe-based Assays in human, mouse, rat RARA

    Additional mRNA sequence: 

    AJ417079.1 AK098172.1 AK123052.1 AK130192.1 AK292205.1 AK303868.1 AK312564.1 AL834159.1 
    BC008727.2 BC071733.1 CR457438.1 EF535849.1 FJ487576.1 HQ692826.1 HQ692827.1 S50916.1 
    X06538.1 X06614.1 

    18 DOTS entries:

    DT.91783369  DT.92050958  DT.99941648  DT.95370577  DT.100765128  DT.101971683  DT.410549  DT.95370607 
    DT.100045856  DT.100830912  DT.95240375  DT.100722877  DT.100771550  DT.120902307  DT.95370753  DT.120902317 
    DT.91814374  DT.95370560 

    Selected AceView cDNA sequences (see all 179):

    AW298630 CD673268 BQ958419 BQ044936 BU543219 BM023375 BM722189 BI522425 
    BC008727 AK130192 X06614 BM817785 BE313602 BQ425845 BM679122 NM_000964 
    BI827961 AK098172 BE312686 AI589149 BF433022 BQ706025 BM675691 T83788 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for RARA (see all 8)    About this scheme

    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:                                                  -     -     -     -                                                         


    ECgene alternative splicing isoforms for RARA

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    RARA expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TGACCCCGCA
    RARA Expression
    About this image


    RARA expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 7) fully expand
     
     Tooth (Integumentary System)    fully expand to see all 8 entries
             Odontoblasts Dentin
             Dentin
     
     Epithelial Cells
             Dental Placode Cells Dental Placode
     
     Kidney (Urinary System)
             Interstitial Stroma Cells Interstitial Stroma
     
     Bone (Muscoskeletal System)    fully expand to see all 2 entries
             Bone marrow-derived mesenchymal stem cells
     
     Mesenchymal Stem Cells
             Bone marrow-derived mesenchymal stem cells
    RARA Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    RARA Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.654583
        Pathway & Disease-focused RT2 Profiler PCR Arrays including RARA: 
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Estrogen Receptor Signaling in human mouse rat
              TGFB Signaling Targets in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Cancer Drug Resistance in human mouse rat

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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RARA

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for RARA gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Rara1 , 5 retinoic acid receptor, alpha1, 5 91.56(n)1
    98.27(a)1
      11 (62.76 cM)5
    194011  NM_001177302.11  NP_001170773.11 
     989278185 
    chicken
    (Gallus gallus)
    Aves RARA1 retinoic acid receptor, alpha 87(n)
    95.27(a)
      395213  NM_204536.1  NP_989867.1 
    lizard
    (Anolis carolinensis)
    Reptilia RARA6
    retinoic acid receptor, alpha
    93(a)
    1 ↔ 1
    6(69727311-69962541)
    African clawed frog
    (Xenopus laevis)
    Amphibia rara2a2 retinoic acid receptor alpha 80.34(n)    X87365.1 
    zebrafish
    (Danio rerio)
    Actinopterygii rara2a2 retinoic acid receptor, alpha 2a 80.27(n)   30680  S74155.1 


    ENSEMBL Gene Tree for RARA (if available)
    TreeFam Gene Tree for RARA (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for RARA gene
    VDR2  PPARD2  RARG2  NR1I22  PPARA2  THRB2  NR1H42  NR1D22  
    RARB2  RORA2  RORB2  RORC2  NR1D12  NR1I32  PPARG2  NR1H22  
    THRA2  NR1H32  
    Selected SIMAP similar genes for RARA using alignment to 6 protein entries:     RARA_HUMAN (see all proteins) (see all similar genes):
    BCOR-RARA    PML-RAR    NR1B1    NR1B2    RARB    HNF4alpha
    RARG    RORA    NR1B3    PRKAR1A/RARA fusion    DKFZp761C0417    HNF4G
    NR5A1    NR3C2    VDR    ESR1    NR1A1    THRA

    Find genes that share paralogs with RARA           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for RARA (see all 767)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1136294551,2
    C,F--38492742(+) AGGTTC/TAAGCC 3 -- int11Minor allele frequency- T:0.50WA 2
    rs1870537591,2
    --39250595(+) ACCCCC/GACACT 1 -- us2k10--------
    rs1903424491,2
    C--39250765(+) CAGTGG/TGGGGT 1 -- us2k10--------
    rs1492475001,2
    --39250959(+) AGAGTA/GTCTGT 1 -- us2k10--------
    rs1151191291,2
    C,F--39251133(+) ACTGAG/AGCACA 1 -- us2k11Minor allele frequency- A:0.03WA 118
    rs1444250021,2
    --39251295(+) CTCCCC/GTCAAG 1 -- us2k10--------
    rs1168655191,2
    F--39251440(+) TCTAGC/TCCACC 1 -- us2k11Minor allele frequency- T:0.02NA 120
    rs1828657381,2
    --39251511(+) ACCTTC/GAAGTT 1 -- us2k10--------
    rs1480665751,2
    --39251528(+) TTGTAC/TTGAGG 1 -- us2k10--------
    rs1884145801,2
    --39251547(+) CCCCTA/CTATTT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for RARA (38465423 - 38513895 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for RARA:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2671593CNV Deletion23128226
    nsv908222CNV Loss21882294
    nsv833445CNV Loss17160897

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing RARA
    DNA2.0 Custom Variant and Variant Library Synthesis for RARA

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 180240   
    OMIM disorders: 612376  
    UniProtKB/Swiss-Prot: RARA_HUMAN, P10276
  • Note=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

  • 8 diseases for RARA:    
    About MalaCards
    acute promyelocytic leukemia    aleukemic leukemia cutis    epidermolytic acanthoma    caudal regression syndrome
    cutaneous mastocytosis    acanthoma    juvenile myelomonocytic leukemia    neuroblastoma

    5 diseases from the University of Copenhagen DISEASES database for RARA:
    Leukemia     Proteinuria     Nephritis     Nephrosis
    Cleft lip

    Find genes that share disorders with RARA           About GenesLikeMe

    Selected Novoseek inferred disease relationships for RARA gene (see all 89)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    leukemia promyelocytic acute 95.9 359 1668609 (2), 7987829 (2), 1652369 (2), 1317727 (2) (see all 99)
    promyelocytic leukemia 87.9 157 8387545 (3), 8238249 (2), 11454693 (2), 12794076 (2) (see all 87)
    leukemogenesis 76.1 19 7529139 (1), 11066449 (1), 2173802 (1), 8580793 (1) (see all 14)
    leukemia 69 134 10441338 (4), 1911341 (2), 8819070 (2), 12935958 (2) (see all 74)
    carcinoma embryonal 68.5 12 1661245 (1), 1320576 (1), 2162058 (1), 8604312 (1) (see all 10)
    myeloid leukemia 60.2 15 15339853 (2), 1970118 (1), 9952315 (1), 11607822 (1) (see all 13)
    teratocarcinoma 58.6 6 2152965 (2), 8218362 (1), 8353043 (1), 19917671 (1) (see all 5)
    minimal residual disease 56.1 3 1375840 (1), 7723389 (1), 7672716 (1)
    breast cancer 50.9 131 9205071 (6), 9387294 (5), 15870697 (4), 20080953 (4) (see all 57)
    cancer 46 64 12188922 (3), 19917671 (3), 9368510 (3), 10389997 (3) (see all 44)

    Genatlas disease: RARA
    acute promyelocytic leukemia or myeloid leukemia (APL),common breakpoints in translocation t (15;17) clustered in
    RARA second intron (see PML),in translocation t(11;17) (see ZNF145),in translocation t(5;17),and others

    Genetic Association Database (GAD): RARA
    Human Genome Epidemiology (HuGE) Navigator: RARA (25 documents)
    Tumor Gene Database (TGDB): RARA

    Export disorders for RARA gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for RARA gene, integrated from 10 sources (see all 1352):
    (articles sorted by number of sources associating them with RARA)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification of a receptor for the morphogen retinoic acid. (PubMed id 2825036)1, 2, 3 Giguere V.... Evans R.M. (Nature 1987)
    2. The retinoic acid receptor alpha (RARA) gene is not associated with myopia, hypermetropia, and ocular biometric measures. (PubMed id 19626135)1, 4, 9 Veerappan S....Baird P.N. (Mol. Vis. 2009)
    3. Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha. (PubMed id 16417524)1, 2, 9 Srinivas H.... Kurie J.M. (Biochem. J. 2006)
    4. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. (PubMed id 16179254)1, 2, 9 Epping M.T.... Bernards R. (Cell 2005)
    5. The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. (PubMed id 8562957)1, 2, 9 Redner R.L.... Corey S.J. (Blood 1996)
    6. Retinoic acid receptor alpha gene variants, multivitamin use, and liver intake as risk factors for oral clefts: a population-based case-control study in Denmark, 1991-1994. (PubMed id 12835288)1, 4, 9 Mitchell L.E....Christensen K. (Am. J. Epidemiol. 2003)
    7. Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes. (PubMed id 19902255)1, 4, 9 Ovsyannikova I.G....Poland G.A. (Hum. Genet. 2010)
    8. [Association between retinoic acid receptor alpha gene polymorphisms and nonsyndromic cleft lip with or without cleft palate susceptibility]. (PubMed id 17456381)1, 4, 9 Fan G.Z....Wu P.A. (Zhonghua Yi Xue Za Zhi 2007)
    9. RARalpha is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells. (PubMed id 17611697)1, 7, 9 Jimi S....Tamura K. (Int. J. Oncol. 2007)
    10. RIF-1, a novel nuclear receptor corepressor that associates with the nuclear matrix. (PubMed id 17455211)1, 2, 9 Li H.J.... Mendelsohn M. (J. Cell. Biochem. 2007)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 5914 HGNC: 9864 AceView: RARA Ensembl:ENSG00000131759 euGenes: HUgn5914
    ECgene: RARA Kegg: 5914 H-InvDB: RARA

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for RARA Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for RARA Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Retinoic_acid_receptor

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RARA gene:
    Search GeneIP for patents involving RARA

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014 , 7 Oct 2014

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