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FLASH GENE

Symbol

RARA

contributors: mct/ - updated : 13-06-2015

HGNC name	retinoic acid receptor, alpha
HGNC id	9864

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001145302 7 - 3122 NP_001138774 - 365 - 1992 1311253 NM_000964 9 splicing 3301 NP_000955 50 462 - 1992 1311253 NM_001024809 8 - 3494 NP_001019980 50 457 - 1992 1311253 NM_001145301 9 splicing 3413 NP_001138773 - 462 - 1992 1311253

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system breast mammary gland

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte

cell lineage
cell lines
fluid/secretion	blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal modulator domain, an activation function domain (AF-1)
	a central DNA-binding domain (DBD) followed by a short hinge/D region
	a central bipartite (class II) zinc finger DNA binding domain
	a C terminal ligand domain, a ligand-binding and ligand-dependent transactivation function domain (LBD/AF-2)

HOMOLOGY

Homologene

FAMILY	steroid/thyroid hormone receptor superfamily
	NR1 subfamily

CATEGORY

transcription factor , receptor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	negatively regulating growth plate chondrocyte proliferation and matrix synthesis
	role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production
	requirement of RARalpha-mediated retinoid signaling specifically in germ cells

CELLULAR PROCESS	cell life, differentiation
	nucleotide, transcription
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

text	adipocyte differentiation

PATHWAY

metabolism

signaling

signal transduction

a component	component with PML, RXRA,TIF1 of a transcription complex, retinoic acid dependent
	receptor RXRA : RARA (RXRalpha:RARalpha) are repressor of ABCC3 activation by transcription factor Sp1

INTERACTION

DNA

RNA

small molecule

protein	retinoic acid receptor binding
	interacting with BNIP1 (repressed by TNIP1)
	is a novel negative regulator of the IFN/STAT pathway, suggesting that this repression through RARA inhibition may prevent liver cancer
	PML/RARA binds to FAS and blocks FAS-mediated apoptosis in acute promyelocytic leukemia (APL) by forming an apoptotic inhibitory complex with CFLAR
	TRIM32 interacts with RARA and enhances its transcriptional activity in the presence of RA
	CACUL1 is a novel type of RARA coregulator that interacts with RARA and inhibits its transcriptional activity
	USP37 interacted with ZBTB16/RARA through the PLZF moiety and sustained ZBTB16/RARA steady state levels
	RARA-ZBTB16 acts as a modifier oncogene that subverts differentiation in the granulocytic lineage by associating with CEBPA and inhibiting its activity
	UCP1 expression is differently affected by RARA in mouse and human adipocytes (PMUID: 24059847)

cell & other

REGULATION

activated by

both all-trans (T-RA) and its 9-cis isomer (9-cis-RA) retinoic acids

Other

regulated by TADA3 which regulates retinoic acid receptor RARA-mediated transactivation

ASSOCIATED DISORDERS

corresponding disease(s)

RARA

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       PML-RARalpha fusion alone can confer properties of self-renewal to committed hematopoietic progenitors before the onset of acute promyelocytic leukemia tumoral fusion       STAT5B-RARA fusion transcript in acute promyelocytic leukemia with the normal chromosome 17 on G-banding tumoral fusion       fusion partner of BCOR in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia tumoral fusion       FIP1L1-RARA plays a pivotal role in its homodimerization and transcriptional repressor activity, contributingto the pathogenesis of distinct types of leukemia

Susceptibility

to obesity to meningomyelocele (MM)

Variant & Polymorphism SNP	rs12051734 conferred a protective effect for MM susceptibility (MID: 21254357)

Candidate gene	for isolated cleft lip/palate
Marker
Therapy target	PML-RARA degradation or therapy-triggered degradation of oncoproteins could be a general strategy to eradicate cancer stem cells

ANIMAL & CELL MODELS