RARA
entrez
5914
canonical
uniprot
P10276
canonical
ensembl
ENSG00000131759
resolver
ensp
ENSP00000254066
resolver
ensp
ENSP00000377643
resolver
ensp
ENSP00000377648
resolver
ensp
ENSP00000377649
resolver
ensp
ENSP00000389993
resolver
ensp
ENSP00000527144
resolver
ensp
ENSP00000527146
resolver
ensp
ENSP00000621776
resolver
enst
ENST00000394086
resolver
genesymbol
NR1B1
resolver
genesymbol
RARA
resolver
genesymbol_syn
NR1B1
resolver
genesymbol_syn
RARA
resolver
hgnc
HGNC:9864
resolver
uniprot
A8K840
resolver
uniprot
A8MUP8
resolver
uniprot
B8Y636
resolver
uniprot
F1D8N9
resolver
uniprot
P78456
resolver
uniprot
Q13440
resolver
uniprot
Q13441
resolver
uniprot
Q6I9R7
resolver
uniprot
Q96S41
resolver
uniprot
Q9NQS0
resolver
uniprot_entry
A8K840_HUMAN
resolver
uniprot_entry
A8MUP8_HUMAN
resolver
uniprot_entry
F1D8N9_HUMAN
resolver
uniprot_entry
Q6I9R7_HUMAN
resolver
uniprot_entry
RARA_HUMAN
resolver
uniprot_sec
B8Y636
resolver
uniprot_sec
P78456
resolver
uniprot_sec
Q13440
resolver
uniprot_sec
Q13441
resolver
uniprot_sec
Q96S41
resolver
uniprot_sec
Q9NQS0
resolver
amino_acid_sequence
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPATIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTLTPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
uniprot
proteins
disease_involvement
DISEASE: 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. {ECO:0000269|PubMed:12691149, ECO:0000269|PubMed:8302850, ECO:0000269|PubMed:8562957}.
uniprot
proteins
function
FUNCTION: Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). 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 (PubMed:21152046, PubMed:28167758, PubMed:37478846). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, PubMed:28167758). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:19850744, PubMed:20215566, PubMed:37478846, PubMed:9267036). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758). {ECO:0000250|UniProtKB:P11416, ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:19398580, ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:21152046, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9267036}.
uniprot
proteins
mass_dalton
50771
uniprot
proteins
mutagenesis
MUTAGEN 95; /note="S->A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation."; /evidence="ECO:0000269|PubMed:16417524"; MUTAGEN 96; /note="S->A: Abolishes PKB/AKT1-mediated phosphorylation. Repressed transactivation."; /evidence="ECO:0000269|PubMed:16417524"; MUTAGEN 147; /note="K->R: Abrogates sumoylation in the presence or absence of ATRA and primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-166; R-171 and R-399."; /evidence="ECO:0000269|PubMed:19850744"; MUTAGEN 154; /note="S->A: No effect on PKB/AKT1-mediated phosphorylation. No repression of transactivation."; /evidence="ECO:0000269|PubMed:16417524"; MUTAGEN 157; /note="S->A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation."; /evidence="ECO:0000269|PubMed:16417524"; MUTAGEN 166; /note="K->R: Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-171 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-171 and R-399."; /evidence="ECO:0000269|PubMed:19850744"; MUTAGEN 171; /note="K->R: Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-166 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-399."; /evidence="ECO:0000269|PubMed:19850744"; MUTAGEN 219; /note="S->A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-369."; /evidence="ECO:0000269|PubMed:20215566"; MUTAGEN 219; /note="S->E: No effect on heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, no increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-369."; /evidence="ECO:0000269|PubMed:20215566"; MUTAGEN 240; /note="V->A: Abolished ubiquitination and degradation by UBR5."; /evidence="ECO:0000269|PubMed:37478846"; MUTAGEN 254; /note="I->A: Reduced ubiquitination and degradation by UBR5."; /evidence="ECO:0000269|PubMed:37478846"; MUTAGEN 258; /note="I->A: Reduced ubiquitination and degradation by UBR5."; /evidence="ECO:0000269|PubMed:37478846"; MUTAGEN 369; /note="S->A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-219."; /evidence="ECO:0000269|PubMed:20215566"; MUTAGEN 369; /note="S->E: Some inhibition of heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-219."; /evidence="ECO:0000269|PubMed:20215566"; MUTAGEN 396; /note="I->E: Abrogates interaction with NCOR1 or NCOR2. Increased affinity for NCOR1 and NCOR2 in the presence of BMS493. Increased transcriptional activity in the presence of agonist and decreased activity in the presence of neutral antagonist."; /evidence="ECO:0000269|PubMed:20543827"; MUTAGEN 399; /note="K->R: In the absence of ATRA, abolishes sumoylation and is mainly nuclear. In the presence of ATRA, some sumoylation, cytoplasmic location, reduced transcriptional activity and no SENP6 binding. Low sumoylation levels in the presence of ATRA and nuclear location in the absence of ATRA; when associated with R-166 or with R-171. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-171."; /evidence="ECO:0000269|PubMed:19850744"; MUTAGEN 409..410; /note="LI->AA: Abolishes interaction with ASXL1 and NCOA1."; /evidence="ECO:0000269|PubMed:16606617"; MUTAGEN 412; /note="E->Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-415."; /evidence="ECO:0000269|PubMed:16606617"; MUTAGEN 413..414; /note="ML->AA: Abolishes interaction with ASXL1 and NCOA1."; /evidence="ECO:0000269|PubMed:16606617"; MUTAGEN 415; /note="E->Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-412."; /evidence="ECO:0000269|PubMed:16606617
uniprot
proteins
post_translational_modification
PTM: 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 signaling. {ECO:0000250, ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:20215566}.; PTM: Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding. On all-trans retinoic acid (ATRA) binding, a conformational 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 activity. {ECO:0000269|PubMed:15809060, ECO:0000269|PubMed:19850744}.; PTM: Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation.; PTM: Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound RARA when it is not associated with coactivators (NCOAs) (PubMed:37478846). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (PubMed:37478846). {ECO:0000269|PubMed:37478846}.; PTM: Acetylated; acetylation is increased upon pulsatile shear stress and decreased upon oscillatory shear stress. {ECO:0000269|PubMed:28167758}.
uniprot
proteins
protein_family
NR1 subfamily
uniprot
proteins
protein_family
Nuclear hormone receptor family
uniprot
proteins
pubmed
10337631
uniprot
proteins
pubmed
10567404
uniprot
proteins
pubmed
10698945
uniprot
proteins
pubmed
10882070
uniprot
proteins
pubmed
11812818
uniprot
proteins
pubmed
11971969
uniprot
proteins
pubmed
12039952
uniprot
proteins
pubmed
12691149
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15509776
uniprot
proteins
pubmed
15809060
uniprot
proteins
pubmed
16179254
uniprot
proteins
pubmed
16417524
uniprot
proteins
pubmed
16606617
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17455211
uniprot
proteins
pubmed
19377461
uniprot
proteins
pubmed
19398580
uniprot
proteins
pubmed
19850744
uniprot
proteins
pubmed
20078863
uniprot
proteins
pubmed
20215566
uniprot
proteins
pubmed
20543827
uniprot
proteins
pubmed
21152046
uniprot
proteins
pubmed
2175878
uniprot
proteins
pubmed
22351778
uniprot
proteins
pubmed
24336203
uniprot
proteins
pubmed
26463675
uniprot
proteins
pubmed
28167758
uniprot
proteins
pubmed
2825025
uniprot
proteins
pubmed
2825036
uniprot
proteins
pubmed
30468856
uniprot
proteins
pubmed
37478846
uniprot
proteins
pubmed
8302850
uniprot
proteins
pubmed
8562957
uniprot
proteins
pubmed
9267036
uniprot
proteins
sequence_length
462
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:28167758}. Cytoplasm {ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:28167758}. Note=Nuclear localization depends on ligand binding, phosphorylation and sumoylation (PubMed:19850744). Translocation to the nucleus in the absence of ligand is dependent on activation of PKC and the downstream MAPK phosphorylation (By similarity). Increased nuclear localization upon pulsatile shear stress (PubMed:28167758). {ECO:0000250|UniProtKB:P11416, ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:28167758}.
uniprot
proteins