Protein / target
Retinoic acid receptor alpha
Protein at a glance
Biological role
MRNA regulatory element binding translation repressor activity
Primary system
Nervous system
Strongest disease association
neoplasm
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
7 approved · 4 in clinical development
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). 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:21152046, PubMed:28167758, PubMed:37478846). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, 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:19850744, PubMed:20215566, PubMed:37478846, PubMed:9267036). 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)
Subcellular location
Domains and Gene Ontology detail (74)Hide
Domains & features
Gene Ontology
- Cchromatin
- Ccytoplasm
- Ccytosol
- Cdendrite
- Cnucleolus
- Cnucleoplasm
- Cnucleus
- Cperinuclear region of cytoplasm
- Cplasma membrane
- Cprotein-containing complex
- CRNA polymerase II transcription regulator complex
- Falpha-actinin binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21…
- ·RNA polymerase II transcription regulator complex
- ·DNA-binding transcription factor activity
- ·DNA-binding transcription factor activity, RNA polymerase II-specific
Nuclear receptor signalling
- ·DNA-binding transcription factor activity
- ·DNA-binding transcription factor activity, RNA polymerase II-specific
- ·nuclear receptor activity
- ·Nuclear Receptor transcription pathway
Immune signalling
- ·Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21…
- ·positive regulation of interleukin-13 production
- ·positive regulation of interleukin-4 production
- ·positive regulation of interleukin-5 production
Kinase signalling
- ·protein kinase A binding
- ·protein kinase B binding
- ·protein phosphorylation
Apoptosis & cell death
- ·regulation of apoptotic process
View underlying pathways (6)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Retinoic acid receptor agonist
Appears in clinical studies involving acne, acne, glioma, renal cell carcinoma
Retinoic acid receptor agonist
Appears in clinical studies involving hyperpigmentation of the skin, acne, acute promyelocytic leukemia, freckles
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,955 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 11 total
hyperpigmentation of the skin · acne · acute promyelocytic leukemia
Kaposi's sarcoma · Eczematoid dermatitis · Kaposi's sarcoma
acute promyelocytic leukemia · plasma cell myeloma · lymphoma
myelodysplastic syndrome · Alzheimer disease · tropical spastic paraparesis
psoriasis · keratosis
acne · acne · glioma
acne · acne · molluscum contagiosum
psoriasis · psoriasis vulgaris · hand eczema
psoriasis vulgaris · acne · psoriasis
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: ISOTRETINOIN (ANDA213571)
- Label change
Label change: ISOTRETINOIN (NDA211913)
- Label change
Label change: ISOTRETINOIN (NDA021951)
- Regulatory approval
Approval: TRETINOIN (ANDA214590)
- Supplemental approval
Supplemental approval: ISOTRETINOIN (NDA211913)
- Supplemental approval
Supplemental approval: ISOTRETINOIN (ANDA213571)
- Supplemental approval
Supplemental approval: ISOTRETINOIN (NDA021951)
- New publicationDifferentiation of SH-SY5Y neuroblastoma cells using retinoic acid and BDNF: a model for neuronal and synaptic differentiation in neurodegeneration.
- Label change
Label change: ISOTRETINOIN (NDA021951)
- New publicationGuidelines of care for the management of acne vulgaris.
- New publicationRisk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis.
- New publicationEffect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.