Gene/Proteome Database (LMPD)

LMPD ID
LMP000216
Gene ID
5914
Species
Homo sapiens (Human)
Gene Name
retinoic acid receptor, alpha
Gene Symbol
RARA
Synonyms
NR1B1; RAR
Chromosome
17
Map Location
17q21
Summary
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]
Orthologs
View orthologs and multiple alignments for RARA

Proteins

retinoic acid receptor alpha isoform 1
Refseq ID NP_001138773
Protein GI 223718064
UniProt ID Q6I9R7
mRNA ID NM_001145301
Length 462
RefSeq Status REVIEWED
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPATIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTLTPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
retinoic acid receptor alpha isoform 1
Refseq ID NP_000955
Protein GI 4506419
UniProt ID Q6I9R7
mRNA ID NM_000964
Length 462
RefSeq Status REVIEWED
Protein sequence is identical to GI:223718064 (mRNA isoform)
retinoic acid receptor alpha isoform 2
Refseq ID NP_001019980
Protein GI 67459914
UniProt ID P10276
mRNA ID NM_001024809
Length 457
RefSeq Status REVIEWED
MYESVEVGGPTPNPFLVVDFYNQNRACLLPEKGLPAPGPYSTPLRTPLWNGSNHSIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTLTPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
retinoic acid receptor alpha isoform 4
Refseq ID NP_001138774
Protein GI 223718070
UniProt ID P10276
mRNA ID NM_001145302
Length 365
RefSeq Status REVIEWED
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPATVRNDRNKKKKEVPKPECSESYTLTPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP

Gene Information

Entrez Gene ID
5914
Gene Name
retinoic acid receptor, alpha
Gene Symbol
RARA
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0009986 IC:BHF-UCL C cell surface
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0030425 IEA:Ensembl C dendrite
GO:0043025 IEA:Ensembl C neuronal cell body
GO:0000790 IDA:BHF-UCL C nuclear chromatin
GO:0005654 TAS:Reactome C nucleoplasm
GO:0005634 IDA:UniProtKB C nucleus
GO:0048471 IEA:Ensembl C perinuclear region of cytoplasm
GO:0000977 IEA:Ensembl F RNA polymerase II regulatory region sequence-specific DNA binding
GO:0031490 IDA:UniProtKB F chromatin DNA binding
GO:0008144 IEA:Ensembl F drug binding
GO:0019899 IPI:UniProtKB F enzyme binding
GO:0048027 IEA:Ensembl F mRNA 5'-UTR binding
GO:0035014 IEA:Ensembl F phosphatidylinositol 3-kinase regulator activity
GO:0019904 IPI:UniProtKB F protein domain specific binding
GO:0046982 IDA:UniProtKB F protein heterodimerization activity
GO:0051018 IDA:UniProtKB F protein kinase A binding
GO:0043422 IPI:UniProtKB F protein kinase B binding
GO:0005102 IDA:UniProtKB F receptor binding
GO:0001972 IDA:BHF-UCL F retinoic acid binding
GO:0003708 IDA:BHF-UCL F retinoic acid receptor activity
GO:0044323 IDA:UniProtKB F retinoic acid-responsive element binding
GO:0003700 IDA:UniProtKB F sequence-specific DNA binding transcription factor activity
GO:0003707 IEA:InterPro F steroid hormone receptor activity
GO:0003713 IDA:UniProtKB F transcription coactivator activity
GO:0003714 IDA:UniProtKB F transcription corepressor activity
GO:0008134 IPI:UniProtKB F transcription factor binding
GO:0000900 IEA:Ensembl F translation repressor activity, nucleic acid binding
GO:0008270 IEA:InterPro F zinc ion binding
GO:0060010 IEA:Ensembl P Sertoli cell fate commitment
GO:0043277 IMP:UniProtKB P apoptotic cell clearance
GO:0071391 IDA:UniProtKB P cellular response to estrogen stimulus
GO:0071222 IEA:Ensembl P cellular response to lipopolysaccharide
GO:0071300 IDA:UniProtKB P cellular response to retinoic acid
GO:0060591 IEA:Ensembl P chondroblast differentiation
GO:0031076 IEA:Ensembl P embryonic camera-type eye development
GO:0060324 IEA:Ensembl P face development
GO:0007565 IEA:Ensembl P female pregnancy
GO:0010467 TAS:Reactome P gene expression
GO:0007281 IEA:Ensembl P germ cell development
GO:0002068 IEA:Ensembl P glandular epithelial cell development
GO:0003417 IEA:Ensembl P growth plate cartilage development
GO:0030520 IDA:BHF-UCL P intracellular estrogen receptor signaling pathway
GO:0060173 IEA:Ensembl P limb development
GO:0001889 IEA:Ensembl P liver development
GO:0035264 IEA:Ensembl P multicellular organism growth
GO:0043066 IEA:Ensembl P negative regulation of apoptotic process
GO:0061037 IEA:Ensembl P negative regulation of cartilage development
GO:0008285 IEA:Ensembl P negative regulation of cell proliferation
GO:0030853 IDA:UniProtKB P negative regulation of granulocyte differentiation
GO:0032689 IDA:BHF-UCL P negative regulation of interferon-gamma production
GO:0000122 IEA:Ensembl P negative regulation of transcription from RNA polymerase II promoter
GO:0045892 IDA:UniProtKB P negative regulation of transcription, DNA-templated
GO:0045947 IEA:Ensembl P negative regulation of translational initiation
GO:0032720 IDA:BHF-UCL P negative regulation of tumor necrosis factor production
GO:0001843 IEA:Ensembl P neural tube closure
GO:0003148 IEA:Ensembl P outflow tract septum morphogenesis
GO:0070374 IEA:Ensembl P positive regulation of ERK1 and ERK2 cascade
GO:0045630 IDA:BHF-UCL P positive regulation of T-helper 2 cell differentiation
GO:0051099 IMP:UniProtKB P positive regulation of binding
GO:0045787 IMP:UniProtKB P positive regulation of cell cycle
GO:0008284 IMP:UniProtKB P positive regulation of cell proliferation
GO:0032736 IDA:BHF-UCL P positive regulation of interleukin-13 production
GO:0032753 IDA:BHF-UCL P positive regulation of interleukin-4 production
GO:0032754 IDA:BHF-UCL P positive regulation of interleukin-5 production
GO:0045666 IEA:Ensembl P positive regulation of neuron differentiation
GO:0014068 IEA:Ensembl P positive regulation of phosphatidylinositol 3-kinase signaling
GO:0051897 IEA:Ensembl P positive regulation of protein kinase B signaling
GO:0045944 IDA:UniProtKB P positive regulation of transcription from RNA polymerase II promoter
GO:0045893 IDA:UniProtKB P positive regulation of transcription, DNA-templated
GO:0030850 IEA:Ensembl P prostate gland development
GO:0006468 IMP:UniProtKB P protein phosphorylation
GO:0031641 IEA:Ensembl P regulation of myelination
GO:0048167 IEA:Ensembl P regulation of synaptic plasticity
GO:0034097 IEA:Ensembl P response to cytokine
GO:0032355 IDA:BHF-UCL P response to estradiol
GO:0045471 IEA:Ensembl P response to ethanol
GO:0032526 IMP:BHF-UCL P response to retinoic acid
GO:0033189 IEA:Ensembl P response to vitamin A
GO:0048384 IMP:BHF-UCL P retinoic acid receptor signaling pathway
GO:0007165 IDA:BHF-UCL P signal transduction
GO:0007283 IEA:Ensembl P spermatogenesis
GO:0060534 IEA:Ensembl P trachea cartilage development
GO:0006367 TAS:Reactome P transcription initiation from RNA polymerase II promoter
GO:0001657 IEA:Ensembl P ureteric bud development
GO:0055012 IEA:Ensembl P ventricular cardiac muscle cell differentiation

Domain Information

InterPro Annotations

Accession Description
IPR008946 Nuclear hormone receptor, ligand-binding
IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR003078 Retinoic acid receptor
IPR001723 Steroid hormone receptor
IPR013088 Zinc finger, NHR/GATA-type
IPR001628 Zinc finger, nuclear hormone receptor-type

UniProt Annotations

Entry Information

Gene Name
retinoic acid receptor, alpha
Protein Entry
RARA_HUMAN
UniProt ID
Q6I9R7
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=3; Name=Alpha-1; IsoId=P10276-1; Sequence=Displayed; Name=Alpha-2; IsoId=P10276-2; Sequence=VSP_003629; Name=Alpha-1-deltaBC; IsoId=P10276-3; Sequence=VSP_043143; Note=Does not bind nor transactivate RARE on its own but may do so as a heterodimer with Alpha-1.;
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.
Domain Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
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 KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis. {ECO
Interaction P59598:Asxl1 (xeno); NbExp=4; IntAct=EBI-413374, EBI-5743705; Q15910:EZH2; NbExp=2; IntAct=EBI-413374, EBI-530054; P50148:GNAQ; NbExp=4; IntAct=EBI-413374, EBI-3909604; Q9UKP3:ITGB1BP2; NbExp=2; IntAct=EBI-413374, EBI-5659717; Q15648:MED1; NbExp=2; IntAct=EBI-413374, EBI-394459; Q71SY5:MED25; NbExp=10; IntAct=EBI-413374, EBI-394558; Q15788:NCOA1; NbExp=3; IntAct=EBI-413374, EBI-455189; Q9UPP1-2:PHF8; NbExp=2; IntAct=EBI-413374, EBI-6601215; P19793:RXRA; NbExp=4; IntAct=EBI-413374, EBI-78598; P48443:RXRG; NbExp=3; IntAct=EBI-413374, EBI-712405; Q96EB6:SIRT1; NbExp=3; IntAct=EBI-413374, EBI-1802965; P63165:SUMO1; NbExp=5; IntAct=EBI-413374, EBI-80140; Q2M1K9:ZNF423; NbExp=2; IntAct=EBI-413374, EBI-950016;
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
Ptm 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 activity.
Ptm Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation.
Ptm Ubiquitinated.
Sequence Caution Sequence=AAB00112.1; Type=Erroneous initiation; Evidence= ; Sequence=AAB00113.1; Type=Erroneous initiation; Evidence= ; Sequence=BAB62809.1; Type=Erroneous initiation; Evidence= ;
Similarity Belongs to the nuclear hormone receptor family. NR1 subfamily.
Similarity Contains 1 nuclear receptor DNA-binding domain.
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.
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 KMT2E/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. {ECO
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RARAID46.html";
Web Resource Name=Wikipedia; Note=Retinoic acid receptor entry; URL="http://en.wikipedia.org/wiki/Retinoic_acid_receptor";

Identical and Related Proteins

Unique RefSeq proteins for LMP000216 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
223718064 RefSeq NP_001138773 462 retinoic acid receptor alpha isoform 1
67459914 RefSeq NP_001019980 457 retinoic acid receptor alpha isoform 2
223718070 RefSeq NP_001138774 365 retinoic acid receptor alpha isoform 4

Identical Sequences to LMP000216 proteins

Reference Database Accession Length Protein Name
GI:223718070 GenBank ACK86665.1 365 retinoic acid receptor alpha isoform 1 deltaBC [Homo sapiens]
GI:67459914 GenBank AIC63142.1 457 RARA, partial [synthetic construct]
GI:67459914 RefSeq XP_003831469.1 457 PREDICTED: retinoic acid receptor alpha isoform X2 [Pan paniscus]
GI:67459914 RefSeq XP_003913018.1 457 PREDICTED: retinoic acid receptor alpha isoform X2 [Papio anubis]
GI:67459914 RefSeq XP_005584150.1 457 PREDICTED: retinoic acid receptor alpha isoform X3 [Macaca fascicularis]
GI:223718070 RefSeq XP_005584151.1 365 PREDICTED: retinoic acid receptor alpha isoform X4 [Macaca fascicularis]
GI:67459914 RefSeq XP_008010984.1 457 PREDICTED: retinoic acid receptor alpha isoform X2 [Chlorocebus sabaeus]
GI:223718064 RefSeq XP_009188818.1 462 PREDICTED: retinoic acid receptor alpha isoform X1 [Papio anubis]
GI:223718064 RefSeq XP_009188819.1 462 PREDICTED: retinoic acid receptor alpha isoform X1 [Papio anubis]
GI:223718064 RefSeq XP_009188820.1 462 PREDICTED: retinoic acid receptor alpha isoform X1 [Papio anubis]
GI:223718064 RefSeq XP_009188821.1 462 PREDICTED: retinoic acid receptor alpha isoform X1 [Papio anubis]
GI:223718064 RefSeq XP_010352784.1 462 PREDICTED: retinoic acid receptor alpha isoform X1 [Rhinopithecus roxellana]
GI:223718064 RefSeq XP_010352785.1 462 PREDICTED: retinoic acid receptor alpha isoform X1 [Rhinopithecus roxellana]
GI:67459914 RefSeq XP_010352786.1 457 PREDICTED: retinoic acid receptor alpha isoform X2 [Rhinopithecus roxellana]

Related Sequences to LMP000216 proteins

Reference Database Accession Length Protein Name
GI:223718064 DBBJ BAF84894.1 462 unnamed protein product [Homo sapiens]
GI:223718064 GenBank AAD05222.1 462 retinoic acid receptor alpha [Homo sapiens]
GI:67459914 GenBank AAV21453.1 457 Sequence 2 from patent US 6756213
GI:223718064 GenBank AAX29171.1 463 retinoic acid receptor alpha, partial [synthetic construct]
GI:67459914 GenBank ABH86776.1 457 Sequence 2 from patent US 7053045
GI:67459914 RefSeq XP_002808174.1 457 PREDICTED: LOW QUALITY PROTEIN: retinoic acid receptor alpha-like [Macaca mulatta]
GI:67459914 RefSeq XP_003942870.1 457 PREDICTED: retinoic acid receptor alpha isoform X2 [Saimiri boliviensis boliviensis]
GI:67459914 RefSeq XP_004041815.1 457 PREDICTED: retinoic acid receptor alpha isoform 1 [Gorilla gorilla gorilla]
GI:223718070 RefSeq XP_004311983.1 365 PREDICTED: retinoic acid receptor alpha isoform 4 [Tursiops truncatus]
GI:223718070 RefSeq XP_004395074.1 365 PREDICTED: retinoic acid receptor alpha isoform 5 [Odobenus rosmarus divergens]
GI:223718070 RefSeq XP_004434591.1 365 PREDICTED: retinoic acid receptor alpha isoform 4 [Ceratotherium simum simum]
GI:223718064 RefSeq XP_004764652.1 462 PREDICTED: retinoic acid receptor alpha isoform X2 [Mustela putorius furo]
GI:223718064 RefSeq XP_004764653.1 462 PREDICTED: retinoic acid receptor alpha isoform X3 [Mustela putorius furo]
GI:223718064 RefSeq XP_004799138.1 462 PREDICTED: retinoic acid receptor alpha isoform X2 [Mustela putorius furo]
GI:223718070 RefSeq XP_006188941.1 365 PREDICTED: retinoic acid receptor alpha [Camelus ferus]
GI:223718070 RefSeq XP_006214339.1 365 PREDICTED: retinoic acid receptor alpha isoform X3 [Vicugna pacos]
GI:223718070 RefSeq XP_006746244.1 365 PREDICTED: retinoic acid receptor alpha isoform X4 [Leptonychotes weddellii]
GI:67459914 RefSeq XP_009430501.1 482 PREDICTED: retinoic acid receptor alpha isoform X1 [Pan troglodytes]