Tclin RARA Retinoic acid receptor alpha

Protein Summary

Description

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). 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]

Uniprot Accession IDs

• P10276
• B8Y636
• P78456
• Q13440
• Q13441
• Q96S41
• Q9NQS0
• RAR-alpha

Gene Name

• RARA

Ensembl ID

• ENST00000254066
• ENSP00000254066
• ENSG00000131759
• ENST00000394081
• ENSP00000377643
• ENST00000394089
• ENSP00000377649
• ENST00000425707
• ENSP00000389993

Symbol

• NR1B1
• RAR
• NR1B1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
molecular function	1
transcription factor	0.91
biological term	0.89

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1256.63   (req: < 5)

Gene RIFs: 203   (req: <= 3)

Antibodies: 708   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1256.63   (req: >= 5)

Gene RIFs: 203   (req: > 3)

Antibodies: 708   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 85

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 87

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 8

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (8)

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1 – 8 of 8

tretinoin

RARATclin NR

AGONIST pEC50 : 6.7

bexarotene

RARATclin NR

pEC50 : 8.22

alitretinoin

RARATclin NR

AGONIST pEC50 : 6.52

adapalene

RARATclin NR

pKi : 5.96

tazarotene

RARATclin NR

AGONIST pEC50 : 7.2

trifarotene

RARATclin NR

pEC50 : 6.3

acitretin

RARATclin NR

AGONIST :

etretinate

RARATclin NR

AGONIST :

Active Ligands (87)

Explore Active Ligands

1 – 10 of 87

ALRT 1550

RARATclin NR

pKi : 7.2

CHEMBL111589

RARATclin NR

pEC50 : 7.4

LG100754

RARATclin NR

pEC50 : 8.4

CHEMBL109847

RARATclin NR

pEC50 : 7.85

CHEMBL284937

RARATclin NR

pIC50 : 7

CHEMBL89331

RARATclin NR

pEC50 : 7.23

TTNPB

RARATclin NR

pKd : 7.44

CHEMBL42314

RARATclin NR

pKi : 7.27

CHEMBL451835

RARATclin NR

pEC50 : 9.22

CD666

RARATclin NR

: 5.65

Protein-Protein Interactions (254)

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1 – 10 of 254

• See Interactions on String-DB

RARG

Tclin

Family:  NR

Novelty:  0.00667159

p_int:  1

Score:  0.985

Data Source:  BioPlex,STRINGDB

RARB

Tclin

Family:  NR

Novelty:  0.00257427

p_int:  0.999999931

p_wrong:  6.9e-8

Score:  0.992

Data Source:  BioPlex,STRINGDB

RXRB

Tclin

Family:  NR

Novelty:  0.01503977

p_int:  0.952632226

p_ni:  0.000109527

p_wrong:  0.047258247

Score:  0.998

Data Source:  BioPlex,STRINGDB

RXRA

Tclin

Family:  NR

Novelty:  0.00244343

Score:  0.998

Data Source:  Reactome,STRINGDB

NCOR1

Tchem

Family:  TF

Novelty:  0.0021926

Score:  0.998

Data Source:  STRINGDB

NCOA1

Tchem

Family:  Epigenetic

Novelty:  0.00344663

Score:  0.99

Data Source:  STRINGDB

NCOR2

Tchem

Family:  TF

Novelty:  0.00066449

Score:  0.989

Data Source:  STRINGDB

RXRG

Tclin

Family:  NR

Novelty:  0.01646377

Score:  0.985

Data Source:  STRINGDB

EP300

Tchem

Family:  Epigenetic

Novelty:  0.00055009

Score:  0.969

Data Source:  STRINGDB

MED1

Tbio

Family:  Enzyme

Novelty:  0.00852082

Score:  0.967

Data Source:  STRINGDB

Pathways (33)

Reactome (16)

KEGG (5)

PathwayCommons (5)

WikiPathways (7)

Activation of HOX genes during differentiation (R-HSA-5619507)

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5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of HOX genes during differentiation	90 targets	R-HSA-5619507
Reactome	Activation of anterior HOX genes in hindbrain development during early embryogenesis	90 targets	R-HSA-5617472
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436

Name	Explore in Pharos	Explore in Source
Activation of HOX genes during differentiation	90 targets	R-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesis	90 targets	R-HSA-5617472
Developmental Biology	1055 targets	R-HSA-1266738
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436

Gene Ontology Terms (95)

Functions (26)

Components (10)

Processes (59)

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10

1 – 10 of 26

GO Term	Evidence	Assigned by
chromatin DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription factor activity	Inferred from Direct Assay (IDA)	UniProtKB
protein heterodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase A binding	Inferred from Direct Assay (IDA)	UniProtKB
retinoic acid binding	Inferred from Direct Assay (IDA)	BHF-UCL
retinoic acid receptor activity	Inferred from Direct Assay (IDA)	BHF-UCL
retinoic acid-responsive element binding	Inferred from Direct Assay (IDA)	UniProtKB
signaling receptor binding	Inferred from Direct Assay (IDA)	UniProtKB
transcription coactivator activity	Inferred from Direct Assay (IDA)	UniProtKB
transcription corepressor activity	Inferred from Direct Assay (IDA)	UniProtKB

GWAS Traits (12)

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5

1 – 5 of 12

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted hip circumference	EFO_0008039	1	1	1		35
body height	EFO_0004339	1	1	1		35
neutrophil percentage of leukocytes	EFO_0007990	1	1	1		29
skin disease	EFO_0000701	1	1	0	4	28.1
colon carcinoma	EFO_1001950	1	1	0	4	28.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 12

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted hip circumference	EFO_0008039	1		35
body height	EFO_0004339	1		35
neutrophil percentage of leukocytes	EFO_0007990	1		29
skin disease	EFO_0000701	0	4	28.1
colon carcinoma	EFO_1001950	0	4	28.1

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Chromosomal rearrangement
Complete proteome
Cytoplasm
DNA-binding
Isopeptide bond
Metal-binding
Nucleus
Phosphoprotein

GWAS Trait Find Similar Targets

No Header	No Header
anthropometric measurement
BMI-adjusted hip circumference
body height
colon carcinoma
hair color
hip circumference
household income
IGF-1 measurement
neutrophil percentage of leukocytes
response to cetuximab

MGI Phenotype Find Similar Targets

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cellular phenotype
craniofacial phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
immune system phenotype
limbs/digits/tail phenotype
mortality/aging
reproductive system phenotype

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	retinoic acid receptor alpha	VGNC:9556	454647
Mouse	retinoic acid receptor, alpha	MGI:97856	19401
Rat	retinoic acid receptor, alpha	RGD:3534	24705
Dog	retinoic acid receptor alpha	VGNC:45351	480526
Horse	retinoic acid receptor alpha	VGNC:22184	100054274

Species	Name	OMA	EggNOG	Inparanoid
Chimp	retinoic acid receptor alpha
Mouse	retinoic acid receptor, alpha
Rat	retinoic acid receptor, alpha
Dog	retinoic acid receptor alpha
Horse	retinoic acid receptor alpha

Publication Statistics

PubMed Score 1256.63

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PubTator Score 1447.89

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