InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RARA

Summary

InnateDB Protein

IDBP-377720.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RARA

Protein Name

retinoic acid receptor, alpha

Synonyms

NR1B1; RAR;

Species

Homo sapiens

Ensembl Protein

ENSP00000389993

InnateDB Gene

IDBG-47411 (RARA)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:16417524, ECO:0000269PubMed:19377461, ECO:0000269PubMed:19850744, ECO:0000269PubMed:20215566}.

Subcellular Localization

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.

Disease Associations

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.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 188 experimentally validated interaction(s) in this database.
They are also associated with 62 interaction(s) predicted by orthology.

Experimentally validated
Total	188 [view]
Protein-Protein	179 [view]
Protein-DNA	7 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	62 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001972	retinoic acid binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003707	steroid hormone receptor activity
GO:0003708	retinoic acid receptor activity
GO:0003713	transcription coactivator activity
GO:0003714	transcription corepressor activity
GO:0005102	receptor binding
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008270	zinc ion binding
GO:0019899	enzyme binding
GO:0019904	protein domain specific binding
GO:0031490	chromatin DNA binding
GO:0043422	protein kinase B binding
GO:0043565	sequence-specific DNA binding
GO:0044323	retinoic acid-responsive element binding
GO:0046982	protein heterodimerization activity
GO:0051018	protein kinase A binding

Biological Process

GO:0006355	regulation of transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0008284	positive regulation of cell proliferation
GO:0010467	gene expression
GO:0030520	intracellular estrogen receptor signaling pathway
GO:0030853	negative regulation of granulocyte differentiation
GO:0032355	response to estradiol
GO:0032526	response to retinoic acid
GO:0032689	negative regulation of interferon-gamma production
GO:0032720	negative regulation of tumor necrosis factor production
GO:0032736	positive regulation of interleukin-13 production
GO:0032753	positive regulation of interleukin-4 production
GO:0032754	positive regulation of interleukin-5 production
GO:0043277	apoptotic cell clearance
GO:0043401	steroid hormone mediated signaling pathway
GO:0045630	positive regulation of T-helper 2 cell differentiation
GO:0045787	positive regulation of cell cycle
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048384	retinoic acid receptor signaling pathway
GO:0051099	positive regulation of binding
GO:0071300	cellular response to retinoic acid
GO:0071391	cellular response to estrogen stimulus

Cellular Component

GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0009986	cell surface

Protein Structure and Domains

PDB ID

InterPro

IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001723 Steroid hormone receptor
IPR003070 Orphan nuclear receptor
IPR003078 Retinoic acid receptor
IPR008946 Nuclear hormone receptor, ligand-binding

PFAM

PF00104

PRINTS

PR00398
PR01284
PR01292

PIRSF

SMART

SM00430

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt