General Information of Target

Target ID LDTP09803
Target Name Nuclear receptor subfamily 4 group A member 3 (NR4A3)
Gene Name NR4A3
Gene ID 8013
Synonyms
CHN; CSMF; MINOR; NOR1; TEC; Nuclear receptor subfamily 4 group A member 3; Mitogen-induced nuclear orphan receptor; Neuron-derived orphan receptor 1; Nuclear hormone receptor NOR-1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MYNTVWSMDRDDADWREVMMPYSTELIFYIEMDPPALPPKPPKPMTSAVPNGMKDSSVSL
QDAEWYWGDISREEVNDKLRDMPDGTFLVRDASTKMQGDYTLTLRKGGNNKLIKIYHRDG
KYGFSDPLTFNSVVELINHYHHESLAQYNPKLDVKLMYPVSRYQQDQLVKEDNIDAVGKK
LQEYHSQYQEKSKEYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCHTQEQHSKEY
IERFRREGNEKEIERIMMNYDKLKSRLGEIHDSKMRLEQDLKNQALDNREIDKKMNSIKP
DLIQLRKIRDQHLVWLNHKGVRQKRLNVWLGIKNEDADENYFINEEDENLPHYDEKTWFV
EDINRVQAEDLLYGKPDGAFLIRESSKKGCYACSVVADGEVKHCVIYSTARGYGFAEPYN
LYSSLKELVLHYQQTSLVQHNDSLNVRLAYPVHAQMPSLCR
Target Type
Literature-reported
Target Bioclass
Transcription factor
Family
Nuclear hormone receptor family, NR4 subfamily
Subcellular location
Nucleus
Function
Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes. Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site. Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A. Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development. Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription. Also plays a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site. In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation. Also plays a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle. Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface. Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis. Also participates in cardiac hypertrophy by activating PARP1.
TTD ID
T93949
Uniprot ID
Q92570
DrugMap ID
TTJQB49
Ensemble ID
ENST00000330847.1
HGNC ID
HGNC:7982
ChEMBL ID
CHEMBL1961792

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
FTC133 SNV: p.E158K .
HCT116 SNV: p.P197S .
HCT15 SNV: p.A535V; p.F626L .
HLF SNV: p.Q345H .
HT115 SNV: p.D519Y .
IGR1 SNV: p.S526N DBIA    Probe Info 
JURKAT SNV: p.C496Y .
LNCaP clone FGC SNV: p.Q321R .
OVK18 Deletion: p.A202RfsTer135
SNV: p.V76M
.

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C605(5.56); C339(1.59)  LDD3332  [1]
BTD
 Probe Info 
C559(0.70)  LDD2106  [2]
TFBX
 Probe Info 
C312(0.00); C347(0.00); C594(0.00)  LDD0148  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A2058 C605(1.72)  LDD2253  [1]
 LDCM0023  KB03 A2058 C605(2.27)  LDD2670  [1]
 LDCM0024  KB05 MKN45 C605(5.56); C339(1.59)  LDD3332  [1]
 LDCM0513  Nucleophilic fragment 19b MDA-MB-231 C559(0.70)  LDD2106  [2]
 LDCM0533  Nucleophilic fragment 29b MDA-MB-231 C559(1.00)  LDD2126  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
3 beta-hydroxysteroid dehydrogenase type 7 (HSD3B7) 3-beta-HSD family Q9H2F3
Alkaline phosphatase, placental type (ALPP) Alkaline phosphatase family P05187
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) . Q13526
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Macoilin (MACO1) Macoilin family Q8N5G2
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein SIX3 (SIX3) SIX/Sine oculis homeobox family O95343
Other
Click To Hide/Show 25 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cyclin-dependent kinase 4 inhibitor D (CDKN2D) CDKN2 cyclin-dependent kinase inhibitor family P55273
Chordin (CHRD) Chordin family Q9H2X0
Cysteine-rich tail protein 1 (CYSRT1) CYSRT1 family A8MQ03
EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) Fibulin family Q12805
Keratin-associated protein 10-5 (KRTAP10-5) KRTAP type 10 family P60370
Keratin-associated protein 10-8 (KRTAP10-8) KRTAP type 10 family P60410
Keratin-associated protein 12-3 (KRTAP12-3) KRTAP type 12 family P60328
Keratin-associated protein 12-4 (KRTAP12-4) KRTAP type 12 family P60329
Keratin-associated protein 4-11 (KRTAP4-11) KRTAP type 4 family Q9BYQ6
Keratin-associated protein 4-2 (KRTAP4-2) KRTAP type 4 family Q9BYR5
Keratin-associated protein 4-4 (KRTAP4-4) KRTAP type 4 family Q9BYR3
Keratin-associated protein 5-11 (KRTAP5-11) KRTAP type 5 family Q6L8G4
Keratin-associated protein 5-3 (KRTAP5-3) KRTAP type 5 family Q6L8H2
Keratin-associated protein 5-6 (KRTAP5-6) KRTAP type 5 family Q6L8G9
Keratin-associated protein 5-9 (KRTAP5-9) KRTAP type 5 family P26371
Keratin-associated protein 9-2 (KRTAP9-2) KRTAP type 9 family Q9BYQ4
Keratin-associated protein 9-3 (KRTAP9-3) KRTAP type 9 family Q9BYQ3
Keratin-associated protein 9-8 (KRTAP9-8) KRTAP type 9 family Q9BYQ0
Late cornified envelope protein 2B (LCE2B) LCE family O14633
Late cornified envelope protein 2D (LCE2D) LCE family Q5TA82
Zinc finger protein 330 (ZNF330) NOA36 family Q9Y3S2
Tetraspanin-4 (TSPAN4) Tetraspanin (TM4SF) family O14817
Keratinocyte proline-rich protein (KPRP) . Q5T749
Vasorin (VASN) . Q6EMK4
von Willebrand factor C domain-containing protein 2-like (VWC2L) . B2RUY7

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Dasatinib Small molecular drug DB01254

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 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
3 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255