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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

RARA Gene

protein-coding GIFtS: 73
GCID: GC17P038465

retinoic acid receptor, alpha

Explore 121 diseases affiliated with
RARA via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Retinoic Acid Receptor, Alpha¹ ²		Nucleophosmin-Retinoic Acid Receptor Alpha Fusion Protein NPM-RAR Long Form²
NR1B1¹ ² ³		Retinoic Acid Nuclear Receptor Alpha Variant 1²
RAR¹ ²		Retinoic Acid Nuclear Receptor Alpha Variant 2²
Nuclear Receptor Subfamily 1 Group B Member 1² ³		Retinoic Acid Receptor Alpha²
RAR-Alpha¹		Retinoic Acid Receptor, Alpha Polypeptide²

External Ids:	HGNC: 9864¹	Entrez Gene: 5914²	Ensembl: ENSG00000131759⁷	OMIM: 180240⁵	UniProtKB: P10276³

Export aliases for RARA gene to outside databases

Previous GC identifers: GC17P037961 GC17P040640 GC17P038374 GC17P038838 GC17P038860 GC17P035718 GC17P034259

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for RARA:

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)

UniProtKB/Swiss-Prot: RARA_HUMAN, P10276

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 MLL5.

Mediates retinoic acid-induced granulopoiesis

summary for RARA:

Retinoic acid receptors (RARs) are nuclear hormone receptors of the NRB1 class, which function as

heterodimers with retinoid X receptors (RXRs). There are three distinct RAR subtypes; RARalpha, RARbeta and

RARgamma. RARalpha is present in most tissue types, whereas RARbeta and RARgamma expression is more

selective. RXR-RAR heterodimers act as ligand-dependent transcriptional regulators by binding to the

specific retinoic acid response element (RARE) found in the promoter regions of target genes. In the absence

of an RAR agonist, RXR-RAR recruits co-repressor proteins such as NCoR and associated factors such as

histone deacetylase to maintain a condensed chromatin structure. RAR agonist binding stimulates co-repressor

release and co-activator complexes, such as histone acetyltransferase, are recruited to activate

transcription. RARs transduce retinoid signals in vivo, which mediates proper embryogenesis, differentiation

and growth arrest. Specifically, RXRalpha-RARgamma heterodimers are necessary for growth arrest and viseral

and primitive endodermal differentiation, whereas RXRalpha-RARalpha is required for cAMP-dependent parietal

endodermal differentiation. In vitro it has been difficult to elucidate the roles of individual subtypes as

functional RAR knockouts generate artificial redundancies that are thought not to exist under normal

conditions.

Gene Wiki entry for RARA (Retinoic acid receptor alpha)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010783.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the RARA gene promoter:
STAT1 Sp1 p53 C/EBPalpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): RARA promoter sequence

Search SABiosciences Chromatin IP Primers for RARA

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat RARA

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q21 Ensembl cytogenetic band: 17q21.2 HGNC cytogenetic band: 17q21.1

RARA Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RARA gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17P038465: view genomic region (about GC identifiers)

Start:	38,465,423 bp from pter	End:	38,513,895 bp from pter
Size:	48,473 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: RARA_HUMAN, P10276 (See protein sequence)

Recommended Name: Retinoic acid receptor alpha

Size: 462 amino acids; 50771 Da

Subunit: Heterodimer; with RXRA. Binds DNA preferentially as a heterodimer. Interacts with CDK7 (By similarity).

Interacts with coactivators NCOA3 and NCOA6. Interacts with NCOA7; the interaction requires ligand-binding. Interacts

with MLL5. Interacts (via the ligand-binding domain) with PRAME; the interaction is ligand (retinoic acid)-dependent.

Interacts with AKT1; the interaction phosphorylates RARA and represses transactivation. Interacts with PRKAR1A; the

interaction negatively regulates RARA transcriptional activity. Interacts with NCOR1 and NCOR2. Interacts with PRMT2.

Interacts with LRIF1. Interacts with ASXL1 and NCOA1

Subcellular location: 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

Sequence caution: Sequence=AAB00112.1; Type=Erroneous initiation; Sequence=AAB00113.1; Type=Erroneous initiation;

Sequence=BAB62809.1; Type=Erroneous initiation;

6 PDB 3D structures from and Proteopedia for RARA:

1DKF (3D)

1DSZ (3D)

3A9E (3D)

3KMR (3D)

3KMZ (3D)

4DQM (3D)

Secondary accessions: B8Y636 P78456 Q13440 Q13441 Q96S41 Q9NQS0

Alternative splicing: 3 isoforms: P10276-1 P10276-2 P10276-3 (Does not bind nor transactivate RARE on its own but may do so as a heterodimer with Alpha-1)

Explore the universe of human proteins at neXtProt for RARA: NX_P10276

Post-translational modifications:

Phosphorylated on serine and threonine residues. Phosphorylation does not change during cell cycle. Phosphorylation on

Ser-77 is crucial for transcriptional activity (By similarity). Phosphorylation by AKT1 is required for the repressor

activity but has no effect on DNA binding, protein stability nor subcellular localization. Phosphorylated by PKA in

vitro. This phosphorylation on Ser-219 and Ser-369 is critical for ligand binding, nuclear localization and

transcriptional activity in response to FSH signaling¹

Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding. On all-trans retinoic acid (ATRA)

binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171.

Probably desumoylated by SENP6. Sumoylation levels determine nuclear localization and regulate ATRA-mediated

transcriptional activity¹

Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation¹

Ubiquitinated¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P10276

RARA Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (4 alternative transcripts):

NP_000955.1 NP_001019980.1 NP_001138773.1 NP_001138774.1

ENSEMBL proteins:

ENSP00000464287 ENSP00000254066 ENSP00000377649 ENSP00000389993 ENSP00000377648

ENSP00000377643 ENSP00000462514

Reactome Protein details: P10276
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate (see all 4): RARA OriGene Custom Protein Services for RARA
	GenScript Custom Purified and Recombinant Proteins Services for RARA
	Novus Biologicals RARA Proteins Novus Biologicals RARA Lysates
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for RARA
	Browse Proteins at Uscn

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000790	nuclear chromatin	IDA	17363140
GO:0005634	nucleus	IDA	18845237
GO:0005654	nucleoplasm	TAS	--
GO:0005737	cytoplasm	IDA	19850744
GO:0009986	cell surface	IC	2825025

RARA for ontologies About GeneDecksing

RARA Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of RARA
	R&D Systems Antibodies for RARA (RAR alpha/NR1B1)
	Cell Signaling Technology (CST) Antibodies for RARA
	OriGene Antibodies (see all 3): RARA OriGene Custom Antibody Services for RARA
	GenScript Custom Superior Antibodies Services for RARA
	Novus Biologicals RARA Antibodies
	Abcam antibodies for RARA
	Browse Antibodies at Uscn
	ThermoFisher Antibody for RARA

Assay Products for RARA:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for RARA
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

RARA for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR008946 Nucl_hormone_rcpt_ligand-bd

IPR001723 Str_hrmn_rcpt

IPR003078 Retinoic_acid_rcpt

IPR013088 Znf_NHR/GATA

IPR000536 Nucl_hrmn_rcpt_lig-bd_core

Graphical View of Domain Structure for InterPro Entry P10276

ProtoNet protein and cluster: P10276

2 Blocks protein families:

IPB001723 Steroid hormone receptor signature

IPB003078 Retinoic acid receptor (1B nuclear receptor) signature

UniProtKB/Swiss-Prot: RARA_HUMAN, P10276

Domain: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding

domain

Similarity: Belongs to the nuclear hormone receptor family. NR1 subfamily

Similarity: Contains 1 nuclear receptor DNA-binding domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: