RAR-related orphan receptor-α

Target id: 598

Nomenclature: RAR-related orphan receptor-α

Systematic Nomenclature: NR1F1

Family: 1F. Retinoic acid-related orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 523 15q21-q22 RORA RAR-related orphan receptor A 9
Mouse 523 9D Rora RAR-related orphan receptor alpha 17-18
Rat 309 8q24 Rora RAR-related orphan receptor A
Previous and Unofficial Names
ROR1
ROR2
ROR3
RORα
RZRα
nuclear receptor ROR-alpha
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
NURSA Receptor
OMIM
PharmGKB Gene
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human RORα ligand binding domain in complex with cholesterol sulfate
PDB Id:  1S0X
Ligand:  cholesterol sulphate
Resolution:  2.2Å
Species:  Human
References:  12
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
cholesterol sulphate Hs Agonist - - 3,13
[3,13]
7-hydroxycholesterol Hs Agonist - - 3
[3]
cholesterol Hs Agonist - - 13,23
[13,23]
Agonist Comments
A recent study identified cholesterol as the lipid bound to purified RORα LBD expressed in insect cells. The same study demonstated that RORα transcriptional activity is modulated by lovastatin, a cholesterol lowering drug, in an in vitro reporter assay, thereby suggesting a cholesterol sensor role for RORα.
DNA Binding
Structure:  Monomer, Homodimer
HRE core sequence:  T/A A/T T/A C A/T A/GGGTCA
Response element:  DR2, Half site
DNA Binding Comments
RORs bind to DNA as monomers on monomeric half-site elements with an 5’ A/T rich extension which is identical to the response elements of the Rev-erbs orphan receptors (T/A A/T T/A C A/T A/GGGTCA). RORα may also bind as a homodimer to Rev-DR2 sites (composed of one classical RevRE followed in 3’ by an AGGTCA motif; these two motifs are separated by two bases that are always a C and a T). It is now clear that these dimers are not energetically favoured and there is no evidence that homodimer binding is favoured over monomer binding in vitro.
Co-binding Partners
Name Interaction Effect Reference
Nm23-1 Physical 14
Nm23-2 Physical 14
MYOD1 Physical, Functional 19
Main Co-regulators
Name Activity Specific Ligand dependent AF-2 dependent Comments References
HR None No Yes Yes Mutagenesis of conserved amino acids in the ligand binding domain indicates that RORa activity is ligand-dependent, suggesting that corepressor activity is maintained in the presence of ligand. Despite similar recognition helices shared with coactivators, Hr does not compete for the same molecular determinants at the surface of the RORa ligand binding domain, indicating that Hr-mediated repression is not simply through displacement of coactivators. Remarkably, the specificity of Hr corepressor action can be transferred to a retinoic acid receptor by exchanging the activation function 2 (AF-2) helix. Repression of the chimeric receptor is observed in the presence of retinoic acid, demonstrating that in this context, Hr is indeed a ligand-oblivious nuclear receptor corepressor. These results suggest a novel molecular mechanism for corepressor action and demonstrate that the AF-2 helix can play a dynamic role in controlling corepressor as well as coactivator interactions. 11
NCOR1 Co-repressor No No No A repression domain was mapped in RORα and it was shown that this repression domain is more active in some cell types 2
NCOR2 Co-repressor No No No A repression domain was mapped in RORα and it was shown that this repression domain is more active in some cell types 2
EP300 Co-activator No No Yes 19
NCOA2 Co-activator No No Yes 3
MED1 Co-activator No No Yes 3
Main Target Genes
Name Species Effect Technique Comments References
NDRG1 Human Activated Transient transfection, EMSA, Other NDRG1 (N-Myc) is regulated by RORs (activation) and Rev Erbs (inhibition) via the same RORE present in its promoter 7
APOA5 Human Activated Transient transfection, EMSA, Other Consistent with role in liver metabolism, ROR alpha regulates ApoA5 expression. 8
LAMB1 Human Activated Transient transfection, EMSA, Other 16
FGB Human Activated ChIP, Transient transfection, EMSA 5
NR1D1 Human Activated EMSA, ChIP 6,24
Arntl Mouse Activated Transient transfection, EMSA, Other ROR alpha as well as ROR beta and gamma, is involved in the molecular mechanism supporting the circadian pacemaker. It have been shown that the bHLH PAS protein Bmal1 expression is directly regulated by RORs and Rev erbs which compete for the same response element. 22,25
Tissue Distribution
ubiquitous
Species:  None
Technique:  In situ hybridization, Northern blot, other
References:  1,4,9-10,19-20,26-27
Tissue Distribution Comments
RORα was found to be expressed as a series of mRNA transcripts. The predominant species is a ~15 kb mRNA present in many organs (lung, muscle, brain, heart, peripheral blood leucocytes, spleen, liver, ovary, etc.) but smaller bands are also visible at 2.3 kb with a narrower distribution (leucocytes, testis, lung and liver). Other bands at 7.5, 5.5 and 2.0 kb are also visible but with a weaker intensity. These may corresponds to the four different isoforms described. RORα was found to be expressed in murine lens. RORα is also expressed in rat intestinal epithelium. By detection of the β-gal activity in a heterozygous mice strain containing one allele in which part of RORα gene was replaced by the β-gal enzyme, an expression in various area of the brain including retinal ganglion cells, cerebellum, some nucleus in the thalamus and the suprachiasmatic nucleus, testis and skin was detected. RORβ is up-regulated during the differentiation of 3T3-L1 cells into adipocytes as well as during osteogenic differentiation. Recently, it was shown that RORα is expressed in cartilage. The same expression patterns are seen in human, mice and rats.
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0002152 abnormal brain morphology PMID: 13912552 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000857 abnormal cerebellar foliation PMID: 13912552 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0004098 abnormal cerebellar granule cell morphology PMID: 4673255 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0004098 abnormal cerebellar granule cell morphology PMID: 641237 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000886 abnormal cerebellar granule layer PMID: 13912552 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0000886 abnormal cerebellar granule layer PMID: 641237 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL
MGI:104661  MP:0000886 abnormal cerebellar granule layer PMID: 1511513 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009956 abnormal cerebellar layer morphology PMID: 4673255 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0009956 abnormal cerebellar layer morphology PMID: 641237 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL
MGI:104661  MP:0009956 abnormal cerebellar layer morphology PMID: 1511513 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000889 abnormal cerebellar molecular layer PMID: 13912552 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000875 abnormal cerebellar Purkinje cell layer PMID: 9520475 
Rorasg-3J Rorasg-3J/Rorasg-3J
C57BL/6J-Rora/J
MGI:104661  MP:0000875 abnormal cerebellar Purkinje cell layer
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0000875 abnormal cerebellar Purkinje cell layer PMID: 641237 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0009979 abnormal cerebellum deep nucleus morphology PMID: 7260600 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000849 abnormal cerebellum morphology PMID: 13912552  723931 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0000849 abnormal cerebellum morphology PMID: 6960362 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0000849 abnormal cerebellum morphology PMID: 368650 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL
MGI:104661  MP:0000849 abnormal cerebellum morphology PMID: 1511513 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0006333 abnormal cochlear nucleus morphology PMID: 2077109 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001927 abnormal estrous cycle PMID: 1590727 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0002910 abnormal excitatory postsynaptic currents PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0003126 abnormal external female genitalia morphology PMID: 1590727 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0003699 abnormal female reproductive system physiology PMID: 1590727 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0002161 abnormal fertility/fecundity PMID: 8352721 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0001406 abnormal gait PMID: 13912552 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0003953 abnormal hormone level PMID: 2123001 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0002722 abnormal immune system organ morphology PMID: 1565842 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001790 abnormal immune system physiology PMID: 1565842 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0003684 abnormal inferior olivary complex PMID: 2231177  7842506 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL
MGI:104661  MP:0003684 abnormal inferior olivary complex PMID: 1511513 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0004263 abnormal limb posture PMID: 13912552 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0002118 abnormal lipid homeostasis PMID: 9851961 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0002333 abnormal lung compliance PMID: 16973978 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0002451 abnormal macrophage physiology PMID: 2230805 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0003698 abnormal male reproductive system physiology PMID: 7667406  8352721 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001386 abnormal maternal nurturing PMID: 8346298 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0002066 abnormal motor capabilities/coordination/movement PMID: 13912552 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0002804 abnormal motor learning PMID: 9520475 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0002804 abnormal motor learning PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0003633 abnormal nervous system physiology PMID: 2901364 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0002204 abnormal neurotransmitter level PMID: 6127146 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0003964 abnormal noradrenaline level PMID: 6123371 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001984 abnormal olfaction PMID: 10696797  9035249 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009947 abnormal olfactory bulb external plexiform layer morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009948 abnormal olfactory bulb glomerular layer morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009949 abnormal olfactory bulb granule cell layer morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009942 abnormal olfactory bulb granule cell morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009950 abnormal olfactory bulb internal plexiform layer morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009946 abnormal olfactory bulb layer morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0009951 abnormal olfactory bulb mitral cell layer morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000819 abnormal olfactory bulb morphology PMID: 10321020 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0010057 abnormal olfactory bulb outer nerve layer morphology PMID: 10321020 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0008572 abnormal Purkinje cell dendrite morphology PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0008572 abnormal Purkinje cell dendrite morphology PMID: 641237 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0008579 abnormal Purkinje cell differentiation PMID: 641237 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000877 abnormal Purkinje cell morphology PMID: 2077109 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0000877 abnormal Purkinje cell morphology PMID: 466453  641237  7352029 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0002277 abnormal respiratory mucosa morphology PMID: 16973978 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001463 abnormal spatial learning PMID: 8577876 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL/6J
MGI:104661  MP:0001463 abnormal spatial learning PMID: 8848495 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0004494 abnormal synaptic glutamate release PMID: 6127146 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0000250 abnormal vasoconstriction PMID: 11964376 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001613 abnormal vasodilation PMID: 11964376 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0009958 absent cerebellar granule cells PMID: 9520475 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000408 absent duvet hair PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0001393 ataxia PMID: 13912552  8013566  9520475 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0001393 ataxia PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0005338 atherosclerotic lesions PMID: 9851961 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0001265 decreased body size PMID: 13912552 
Rorasg-3J Rorasg-3J/Rorasg-3J
C57BL/6J-Rora/J
MGI:104661  MP:0001265 decreased body size
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0008924 decreased cerebellar granule cell number PMID: 4673255 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL
MGI:104661  MP:0008924 decreased cerebellar granule cell number PMID: 1511513 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0005179 decreased circulating cholesterol level PMID: 9851961 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0000186 decreased circulating HDL cholesterol level PMID: 9851961 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0010053 decreased grip strength PMID: 9520475 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0010053 decreased grip strength PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0004876 decreased mean systemic arterial blood pressure PMID: 11964376 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000880 decreased Purkinje cell number PMID: 9520475 
Roratm1Vgi Roratm1Vgi/Roratm1Vgi
involves: 129S1/Sv * 129X1/SvJ * ICR
MGI:104661  MP:0000880 decreased Purkinje cell number PMID: 9510031 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL
MGI:104661  MP:0000880 decreased Purkinje cell number PMID: 1511513 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0000884 delaminated Purkinje cell layer PMID: 641237 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0009008 delayed estrous cycle PMID: 1590727 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000885 ectopic Purkinje cell PMID: 9520475 
Roratm1Vgi Roratm1Vgi/Roratm1Vgi
involves: 129S1/Sv * 129X1/SvJ * ICR
MGI:104661  MP:0000885 ectopic Purkinje cell PMID: 9510031 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0001402 hypoactivity PMID: 13912552 
Roratm1Vgi Roratm1Vgi/Roratm1Vgi
involves: 129S1/Sv * 129X1/SvJ * ICR
MGI:104661  MP:0001525 impaired balance PMID: 9510031 
Rorasg-3J Rorasg-3J/Rorasg-3J
C57BL/6J-Rora/J
MGI:104661  MP:0001525 impaired balance
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0001405 impaired coordination PMID: 13912552  9520475 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0001405 impaired coordination PMID: 9520475 
Rorasg-3J Rorasg-3J/Rorasg-3J
C57BL/6J-Rora/J
MGI:104661  MP:0001524 impaired limb coordination
Rorasg-3J Rorasg-3J/Rorasg-3J
C57BL/6J-Rora/J
MGI:104661  MP:0001523 impaired righting response
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0005601 increased angiogenesis PMID: 11739287 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0002497 increased IgE level PMID: 16973978 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0008651 increased interleukin-1 secretion PMID: 2230805 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0005339 increased susceptibility to atherosclerosis PMID: 9851961 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0008569 lethality at weaning PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0001513 limb grasping PMID: 9520475 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0001513 limb grasping PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001861 lung inflammation PMID: 16973978 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0002082 postnatal lethality PMID: 13912552 
Roratm1Vgi Roratm1Vgi/Roratm1Vgi
involves: 129S1/Sv * 129X1/SvJ * ICR
MGI:104661  MP:0002082 postnatal lethality PMID: 9510031 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0009017 prolonged estrus PMID: 1590727 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0009020 prolonged metestrus PMID: 1590727 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000876 Purkinje cell degeneration PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0001923 reduced female fertility PMID: 1590727 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000424 retarded hair growth PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000852 small cerebellum PMID: 13912552  4673255 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000852 small cerebellum PMID: 9520475 
Roratm1Vgi Roratm1Vgi/Roratm1Vgi
involves: 129S1/Sv * 129X1/SvJ * ICR
MGI:104661  MP:0000852 small cerebellum PMID: 9510031 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0000852 small cerebellum PMID: 6127146 
Rora+|Rorasg Rorasg/Rora+
involves: C57BL
MGI:104661  MP:0000852 small cerebellum PMID: 1511513 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0002741 small olfactory bulb PMID: 10321020 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0000416 sparse hair PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0003643 spleen atrophy PMID: 1565842 
Roratm1Mba Roratm1Mba/Roratm1Mba
involves: 129P2/OlaHsd * C57BL/6
MGI:104661  MP:0006099 thin cerebellar granule layer PMID: 9520475 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0006099 thin cerebellar granule layer PMID: 641237 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000890 thin cerebellar molecular layer PMID: 13912552 
Rorasg Rorasg/Rorasg
involves: C57BL
MGI:104661  MP:0000890 thin cerebellar molecular layer PMID: 641237 
Rorasg Rorasg/Rorasg
involves: C57BL/6
MGI:104661  MP:0003644 thymus atrophy PMID: 1565842 
Rorasg Rorasg/Rorasg
involves: obese stock
MGI:104661  MP:0000745 tremors PMID: 13912552 
Roratm1Vgi Roratm1Vgi/Roratm1Vgi
involves: 129S1/Sv * 129X1/SvJ * ICR
MGI:104661  MP:0000745 tremors PMID: 9510031 
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  nuclear receptor ROR-alpha isoform b- RORa2
Amino acids:  556
Protein accession: 
References:  15
Type:  Splice variant
Species:  Human
Description:  nuclear receptor ROR-alpha isoform a - RORa1
Amino acids:  523
Protein accession: 
References:  9,21
Type:  Splice variant
Species:  Human
Description:  nuclear receptor ROR-alpha isoform c-
Amino acids:  548
Protein accession: 
References:  15
Type:  Splice variant
Species:  Human
Description:  nuclear receptor ROR-alpha isoform d- RORa4
Amino acids:  468
Protein accession: 
References:  9,15,21
Biologically Significant Variant Comments
The four RORα isoforms differ in their N-Terminal domains and exhibit differential DNA binding preferences.

References

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5. Chauvet C, Bois-Joyeux B, Fontaine C, Gervois P, Bernard MA, Staels B, Danan JL. (2005) The gene encoding fibrinogen-beta is a target for retinoic acid receptor-related orphan receptor alpha. Mol. Endocrinol.19 (10): 2517-26. [PMID:15941850]

6. Delerive P, Chin WW, Suen CS. (2002) Identification of Reverb(alpha) as a novel ROR(alpha) target gene. J. Biol. Chem.277 (38): 35013-8. [PMID:12114512]

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8. Genoux A, Dehondt H, Helleboid-Chapman A, Duhem C, Hum DW, Martin G, Pennacchio LA, Staels B, Fruchart-Najib J, Fruchart JC. (2005) Transcriptional regulation of apolipoprotein A5 gene expression by the nuclear receptor RORalpha. Arterioscler. Thromb. Vasc. Biol.25 (6): 1186-92. [PMID:15790933]

9. Giguère V, Tini M, Flock G, Ong E, Evans RM, Otulakowski G. (1994) Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes Dev.8 (5): 538-53. [PMID:7926749]

10. Hamilton BA, Frankel WN, Kerrebrock AW, Hawkins TL, FitzHugh W, Kusumi K, Russell LB, Mueller KL, van Berkel V, Birren BW, Kruglyak L, Lander ES. (1996) Disruption of the nuclear hormone receptor RORalpha in staggerer mice. Nature379 (6567): 736-9. [PMID:8602221]

11. Harding HP, Atkins GB, Jaffe AB, Seo WJ, Lazar MA. (1997) Transcriptional activation and repression by RORalpha, an orphan nuclear receptor required for cerebellar development. Mol. Endocrinol.11 (11): 1737-46. [PMID:9328355]

12. Kallen J, Schlaeppi JM, Bitsch F, Delhon I, Fournier B. (2004) Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A. J. Biol. Chem.279 (14): 14033-8. [PMID:14722075]

13. Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, Fournier B. (2002) X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. Structure10 (12): 1697-707. [PMID:12467577]

14. Lau P, Bailey P, Dowhan DH, Muscat GE. (1999) Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD. Nucleic Acids Res.27 (2): 411-20. [PMID:9862959]

15. Lee JM, Kim IS, Kim H, Lee JS, Kim K, Yim HY, Jeong J, Kim JH, Kim JY, Lee H, Seo SB, Kim H, Rosenfeld MG, Kim KI, Baek SH. (2010) RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer. Mol. Cell37 (2): 183-95. [PMID:20122401]

16. Matsui T. (1996) Differential activation of the murine laminin B1 gene promoter by RAR alpha, ROR alpha, and AP-1. Biochem. Biophys. Res. Commun.220 (2): 405-10. [PMID:8645318]

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18. McBroom LD, Flock G, Giguère V. (1995) The nonconserved hinge region and distinct amino-terminal domains of the ROR alpha orphan nuclear receptor isoforms are required for proper DNA bending and ROR alpha-DNA interactions. Mol. Cell. Biol.15 (2): 796-808. [PMID:7823947]

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24. Raspè E, Mautino G, Duval C, Fontaine C, Duez H, Barbier O, Monte D, Fruchart J, Fruchart JC, Staels B. (2002) Transcriptional regulation of human Rev-erbalpha gene expression by the orphan nuclear receptor retinoic acid-related orphan receptor alpha. J. Biol. Chem.277 (51): 49275-81. [PMID:12377782]

25. Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA, FitzGerald GA, Kay SA, Hogenesch JB. (2004) A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron43 (4): 527-37. [PMID:15312651]

26. Steinmayr M, André E, Conquet F, Rondi-Reig L, Delhaye-Bouchaud N, Auclair N, Daniel H, Crépel F, Mariani J, Sotelo C, Becker-André M. (1998) staggerer phenotype in retinoid-related orphan receptor alpha-deficient mice. Proc. Natl. Acad. Sci. U.S.A.95 (7): 3960-5. [PMID:9520475]

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How to cite this page

1F. Retinoic acid-related orphans: RAR-related orphan receptor-α. Last modified on 23/10/2014. Accessed on 19/12/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=598.