Retinoic acid receptor-α
Target not currently curated in GtoImmuPdb
Target id: 590
Nomenclature: Retinoic acid receptor-α
Systematic Nomenclature: NR1B1
Family: 1B. Retinoic acid receptors
Annotation status:
Annotated and expert reviewed. Please contact us if you can help with updates.
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Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Selected 3D Structures
- Natural/Endogenous Ligands
- Agonists
- Antagonists
- DNA Binding
- Co-binding Partners
- Main Co-regulators
- Main Target Genes
- Tissue Distribution
- Functional Assays
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- References
- How to cite this page
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 462 | 17q21.1 | RARA | retinoic acid receptor alpha | 49,55 |
| Mouse | 462 | 11D | Rara | retinoic acid receptor, alpha | 40-41,49,72 |
| Rat | 459 | 10 | Rara | retinoic acid receptor | 1,49 |
| Previous and Unofficial Names |
| RAR alpha 1 | RAR | RARα | retinoic acid receptor |
| Database Links |
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| Specialist databases | |
| NURSA Receptor | 10.1621/JN9YSZCSCU (Hs) |
| Other databases | |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL2055 (Hs), CHEMBL2792 (Mm) |
| DrugBank Target | P10276 (Hs) |
| Ensembl Gene | ENSG00000131759 (Hs), ENSMUSG00000037992 (Mm), ENSRNOG00000009972 (Rn) |
| Entrez Gene | 5914 (Hs), 19401 (Mm), 24705 (Rn) |
| Human Protein Atlas | ENSG00000131759 (Hs) |
| KEGG Gene | hsa:5914 (Hs), mmu:19401 (Mm), rno:24705 (Rn) |
| OMIM | 180240 (Hs) |
| Orphanet | ORPHA118227 (Hs) |
| RefSeq Nucleotide | NM_001145302 (Hs), NM_009024 (Mm), NM_001177302 (Mm), NM_001177303 (Mm), NM_001176528 (Mm), NM_031528 (Rn) |
| RefSeq Protein | NP_001138773 (Hs), NP_001019980 (Hs), NP_033050 (Mm), NP_113716 (Rn) |
| SynPHARM |
6273 (in complex with BMS614) 83084 (in complex with Ro 40-6055) 7547 (in complex with Ro 40-6055) 79003 (in complex with tretinoin) |
| UniProtKB | P10276 (Hs), P11416 (Mm) |
| Wikipedia | RARA (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| tretinoin |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| All-trans-retinoic acid is the most potent endogenous retinoid. The existence of 9-cis retinoic acid as a natural bioactive retinoid remains to be established. Synthetic compounds (reported above) are not metabolized by CYP26. No significant species variation has been reported. The possibility of establishing a hydrogen bond between an amino group present in the linker of the identified RARα-selective agonists and the RARα-specific Ser232 is predicted to favour RARα selectivity. Adapalene is selective for the β and γ RARs over the α isoform [10]. |
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| Antagonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonist Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No significant species variation has been reported. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DNA Binding |
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| DNA Binding Comments | |||||||
| The classical sequence is a 5-pb-spaced direct repeat (DR5). In DR5 and DR2 RXR occupies the 5' element, whereas RARa occupies the 3' one (5'-RXR-RARa-3'). In DR1 elements, the polarity of these elements is inverted (5'-RARa-RXR-3'). | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| cyclin H/cdk7/TFIIH | Physical, Functional | TFIIH phosphorylates RARa1 in its A/B region (ser 77) by cdk7 subunit. | 7,56-57 |
| AP-1 | Physical, Functional | RAR inhibits AP-1 driven transactivation and AP-1 represses RAR-mediated transcription | 13,36,52,62,73 |
| CRABPII | Physical, Functional | Indispensable to RARα-mediated transcription from the RARα2 | 21 |
| PARP-1 | Physical, Functional | Indispensable to RARα-mediated transcription from the RARα2 | 54 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NCOA1 | Co-activator | No | Yes | Yes | A member of the p160 family | 53,70 |
| NCOR1 | Co-repressor | No | No | No | Binding of an agonist to RARa causes NCoR dissociation | 30,50 |
| EP300 | Co-activator | No | Yes | Yes | A common cointegrator | 28 |
| CREBBP | Co-activator | No | Yes | Yes | A common cointegrator | 28 |
| MED1 | Co-activator | No | Yes | Yes | A member of the DRIP/TRAP/SMCC complex | 28,37,47 |
| NCOA3 | Co-activator | No | Yes | Yes | A member of the p160 family | 12 |
| NCOA2 | Co-activator | No | Yes | Yes | A member of the p160 family | 69 |
| NCOR2 | Co-repressor | No | No | No | Binding of an agonist to RARa causes SMRT dissociation | 13,61,71 |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| CYP26 | Human | Activated | Footprint, Transient transfection,ChIP,EMSA | CYP26 is also activated by RARa in mouse and rat. Note: promoter harbors a DR5 element. | 45 |
| RARB | Human | Activated | Footprint, Transient transfection,ChIP,EMSA | Activation is seen across all species including mouse and rat. Note: promoter harbors a DR5 element. | 14,16,18,26 |
| Crabp2 | Mouse | Activated | Transient transfection, EMSA | Promoter harbors a DR2 element. | 16,25 |
| Hoxa1 | Mouse | Activated | Promoter harbors a DR5 element. | 16,24,38 | |
| Rbp1 | Mouse | Activated | Transient transfection | Promoter harbors a DR2 element. | 16,63 |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Ubiquitous distribution pattern of the Rarα1 is also reported in both the mouse and rat. | ||||||||
| Functional Assays
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| Note that both the specific RARα1 null and RARα2 null mutants are apparently normal. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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References
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1B. Retinoic acid receptors: Retinoic acid receptor-α. Last modified on 28/03/2019. Accessed on 18/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=590.
