General Information of Target

Target ID LDTP02489
Target Name Retinoic acid receptor alpha (RARA)
Gene Name RARA
Gene ID 5914
Synonyms
NR1B1; Retinoic acid receptor alpha; RAR-alpha; Nuclear receptor subfamily 1 group B member 1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT
IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM
VYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL
TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTV
EFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA
GFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK
VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGL
DTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
Target Type
Clinical trial
Target Bioclass
Transcription factor
Family
Nuclear hormone receptor family, NR1 subfamily
Subcellular location
Nucleus
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 deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression. Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2. 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. Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells. In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response.
TTD ID
T94085
Uniprot ID
P10276
DrugMap ID
TTW38KT
Ensemble ID
ENST00000254066.10
HGNC ID
HGNC:9864
ChEMBL ID
CHEMBL2055

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CAMA1 SNV: p.Q296E .
CHL1 SNV: p.P30S .
HG3 SNV: p.R294L .
JURKAT Deletion: p.P30LfsTer12 .
LU65 SNV: p.R339S .
MOLT4 SNV: p.D226N .
NALM6 SNV: p.Q45Ter .
REH SNV: p.R83H .
SUPT1 SNV: p.C140R .
TE10 SNV: p.D323N .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info 
C203(1.06)  LDD1702  [1]
BDBM50514113
 Probe Info 
2.24  LDD0041  [2]
DBIA
 Probe Info 
C174(0.84)  LDD1511  [3]
IA-alkyne
 Probe Info 
C148(0.00); C124(0.00)  LDD0165  [4]
NAIA_5
 Probe Info 
N.A.  LDD2223  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0259  AC14 HEK-293T C265(1.18)  LDD1512  [3]
 LDCM0281  AC21 HEK-293T C174(0.88)  LDD1520  [3]
 LDCM0282  AC22 HEK-293T C265(0.90)  LDD1521  [3]
 LDCM0289  AC29 HEK-293T C174(0.95)  LDD1528  [3]
 LDCM0291  AC30 HEK-293T C265(1.13)  LDD1530  [3]
 LDCM0298  AC37 HEK-293T C174(0.88)  LDD1537  [3]
 LDCM0299  AC38 HEK-293T C265(0.95)  LDD1538  [3]
 LDCM0307  AC45 HEK-293T C174(0.86)  LDD1546  [3]
 LDCM0308  AC46 HEK-293T C265(1.16)  LDD1547  [3]
 LDCM0312  AC5 HEK-293T C174(0.90)  LDD1551  [3]
 LDCM0316  AC53 HEK-293T C174(0.83)  LDD1555  [3]
 LDCM0317  AC54 HEK-293T C265(0.95)  LDD1556  [3]
 LDCM0323  AC6 HEK-293T C265(1.16)  LDD1562  [3]
 LDCM0325  AC61 HEK-293T C174(0.80)  LDD1564  [3]
 LDCM0326  AC62 HEK-293T C265(0.99)  LDD1565  [3]
 LDCM0248  AKOS034007472 HEK-293T C174(0.84)  LDD1511  [3]
 LDCM0632  CL-Sc Hep-G2 C203(0.88)  LDD2227  [5]
 LDCM0368  CL10 HEK-293T C265(1.10)  LDD1572  [3]
 LDCM0409  CL21 HEK-293T C174(0.90)  LDD1613  [3]
 LDCM0410  CL22 HEK-293T C265(1.45)  LDD1614  [3]
 LDCM0422  CL33 HEK-293T C174(0.99)  LDD1626  [3]
 LDCM0423  CL34 HEK-293T C265(1.26)  LDD1627  [3]
 LDCM0435  CL45 HEK-293T C174(0.91)  LDD1639  [3]
 LDCM0436  CL46 HEK-293T C265(1.09)  LDD1640  [3]
 LDCM0448  CL57 HEK-293T C174(0.99)  LDD1651  [3]
 LDCM0449  CL58 HEK-293T C265(1.27)  LDD1652  [3]
 LDCM0461  CL69 HEK-293T C174(0.97)  LDD1664  [3]
 LDCM0463  CL70 HEK-293T C265(1.36)  LDD1666  [3]
 LDCM0475  CL81 HEK-293T C174(0.84)  LDD1678  [3]
 LDCM0476  CL82 HEK-293T C265(1.25)  LDD1679  [3]
 LDCM0484  CL9 HEK-293T C174(0.91)  LDD1687  [3]
 LDCM0488  CL93 HEK-293T C174(0.96)  LDD1691  [3]
 LDCM0489  CL94 HEK-293T C265(1.40)  LDD1692  [3]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C203(1.06)  LDD1702  [1]
 LDCM0002  Ward_cp1 U2OS 2.24  LDD0041  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Histone-lysine N-methyltransferase EZH2 (EZH2) Histone-lysine methyltransferase family Q15910
Polyunsaturated fatty acid lipoxygenase ALOX15B (ALOX15B) Lipoxygenase family O15296
DNA-dependent protein kinase catalytic subunit (PRKDC) PI3/PI4-kinase family P78527
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) Sirtuin family Q96EB6
Nuclear receptor coactivator 1 (NCOA1) SRC/p160 nuclear receptor coactivator family Q15788
Nuclear receptor coactivator 3 (NCOA3) SRC/p160 nuclear receptor coactivator family Q9Y6Q9
Transporter and channel
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Bardet-Biedl syndrome 4 protein (BBS4) BBS4 family Q96RK4
Beclin-1 (BECN1) Beclin family Q14457
Optineurin (OPTN) . Q96CV9
Transcription factor
Click To Hide/Show 9 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Nuclear factor erythroid 2-related factor 2 (NFE2L2) BZIP family Q16236
Zinc finger protein 423 (ZNF423) Krueppel C2H2-type zinc-finger protein family Q2M1K9
Nuclear receptor corepressor 1 (NCOR1) N-CoR nuclear receptor corepressors family O75376
Nuclear receptor corepressor 2 (NCOR2) N-CoR nuclear receptor corepressors family Q9Y618
Peroxisome proliferator-activated receptor gamma (PPARG) Nuclear hormone receptor family P37231
Retinoic acid receptor RXR-alpha (RXRA) Nuclear hormone receptor family P19793
Retinoic acid receptor RXR-beta (RXRB) Nuclear hormone receptor family P28702
Retinoic acid receptor RXR-gamma (RXRG) Nuclear hormone receptor family P48443
ALX homeobox protein 1 (ALX1) Paired homeobox family Q15699
Other
Click To Hide/Show 11 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cyclin-D1-binding protein 1 (CCNDBP1) CCNDBP1 family O95273
Cyclin-H (CCNH) Cyclin family P51946
Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) G-alpha family P50148
Mediator of RNA polymerase II transcription subunit 1 (MED1) Mediator complex subunit 1 family Q15648
Mediator of RNA polymerase II transcription subunit 25 (MED25) Mediator complex subunit 25 family Q71SY5
Tektin-4 (TEKT4) Tektin family Q8WW24
Small ubiquitin-related modifier 1 (SUMO1) Ubiquitin family P63165
Integrin beta-1-binding protein 2 (ITGB1BP2) . Q9UKP3
Microspherule protein 1 (MCRS1) . Q96EZ8
Nuclear receptor-interacting protein 1 (NRIP1) . P48552
Pleckstrin homology domain-containing family F member 2 (PLEKHF2) . Q9H8W4

The Drug(s) Related To This Target

Approved
Click To Hide/Show 7 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Acitretin Small molecular drug DB00459
Adapalene Small molecular drug DB00210
Alitretinoin Small molecular drug DB00523
Isotretinoin Small molecular drug DB00982
Tazarotene Small molecular drug DB00799
Tretinoin Small molecular drug DB00755
Trifarotene Small molecular drug DB12808
Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Tamibarotene Small molecular drug D02GTY
Phase 1
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Irx-5183 . D0T3DO
Sy-1425 . D0HY3D
Investigative
Click To Hide/Show 9 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Agn193109 Small molecular drug D0Q0IR
Agn193836 Small molecular drug D02OAI
Bms614 Small molecular drug D03DEJ
Bms753 Small molecular drug D07YTL
Cd666 Small molecular drug D0F8CC
Ro 40-6055 Small molecular drug D0RD0R
Ro 41-5253 Small molecular drug D0JQ1D
Lgd-1550 . DB05785
Ro-40-0655 . D07TPL
Patented
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pmid27336223-compound-4 Small molecular drug D02FAA
Pmid27336223-compound-5 Small molecular drug D0AW3F
Discontinued
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Etretinate Small molecular drug DB00926
Lg100268 Small molecular drug D0YO4D

References

1 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
2 Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells. ACS Chem Biol. 2016 Dec 16;11(12):3268-3272. doi: 10.1021/acschembio.6b00766. Epub 2016 Oct 31.
3 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
4 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
5 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264