General Information of Target

Target ID LDTP06249
Target Name Nuclear receptor subfamily 1 group D member 2 (NR1D2)
Gene Name NR1D2
Gene ID 9975
Synonyms
Nuclear receptor subfamily 1 group D member 2; Orphan nuclear hormone receptor BD73; Rev-erb alpha-related receptor; RVR; Rev-erb-beta; V-erbA-related protein 1-related; EAR-1R
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEVNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNSDTNGNPKNGDL
ANIEGILKNDRIDCSMKTSKSSAPGMTKSHSGVTKFSGMVLLCKVCGDVASGFHYGVHAC
EGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSVGMSRDAVRFGRIP
KREKQRMLIEMQSAMKTMMNSQFSGHLQNDTLVEHHEQTALPAQEQLRPKPQLEQENIKS
SSPPSSDFAKEEVIGMVTRAHKDTFMYNQEQQENSAESMQPQRGERIPKNMEQYNLNHDH
CGNGLSSHFPCSESQQHLNGQFKGRNIMHYPNGHAICIANGHCMNFSNAYTQRVCDRVPI
DGFSQNENKNSYLCNTGGRMHLVCPMSKSPYVDPHKSGHEIWEEFSMSFTPAVKEVVEFA
KRIPGFRDLSQHDQVNLLKAGTFEVLMVRFASLFDAKERTVTFLSGKKYSVDDLHSMGAG
DLLNSMFEFSEKLNALQLSDEEMSLFTAVVLVSADRSGIENVNSVEALQETLIRALRTLI
MKNHPNEASIFTKLLLKLPDLRSLNNMHSEELLAFKVHP
Target Bioclass
Transcription factor
Family
Nuclear hormone receptor family, NR1 subfamily
Subcellular location
Nucleus
Function
Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle. Plays a role in the regulation of circadian sleep/wake cycle; essential for maintaining wakefulness during the dark phase or active period. Key regulator of skeletal muscle mitochondrial function; negatively regulates the skeletal muscle expression of core clock genes and genes involved in mitochondrial biogenesis, fatty acid beta-oxidation and lipid metabolism. May play a role in the circadian control of neutrophilic inflammation in the lung.
Uniprot ID
Q14995
Ensemble ID
ENST00000312521.9
HGNC ID
HGNC:7963
ChEMBL ID
CHEMBL1961784

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C374(1.00)  LDD0580  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0263  AC143 HCT 116 C374(1.00)  LDD0580  [1]
 LDCM0264  AC144 HCT 116 C374(0.88)  LDD0581  [1]
 LDCM0265  AC145 HCT 116 C374(1.02)  LDD0582  [1]
 LDCM0266  AC146 HCT 116 C374(1.02)  LDD0583  [1]
 LDCM0267  AC147 HCT 116 C374(1.03)  LDD0584  [1]
 LDCM0268  AC148 HCT 116 C374(1.11)  LDD0585  [1]
 LDCM0269  AC149 HCT 116 C374(1.20)  LDD0586  [1]
 LDCM0271  AC150 HCT 116 C374(1.32)  LDD0588  [1]
 LDCM0272  AC151 HCT 116 C374(1.25)  LDD0589  [1]
 LDCM0273  AC152 HCT 116 C374(0.99)  LDD0590  [1]
 LDCM0274  AC153 HCT 116 C374(1.18)  LDD0591  [1]
 LDCM0621  AC154 HCT 116 C374(1.09)  LDD2158  [1]
 LDCM0622  AC155 HCT 116 C374(1.10)  LDD2159  [1]
 LDCM0623  AC156 HCT 116 C374(1.02)  LDD2160  [1]
 LDCM0624  AC157 HCT 116 C374(1.00)  LDD2161  [1]
 LDCM0276  AC17 HCT 116 C374(0.96)  LDD0593  [1]
 LDCM0277  AC18 HCT 116 C374(0.74)  LDD0594  [1]
 LDCM0278  AC19 HCT 116 C374(1.06)  LDD0595  [1]
 LDCM0280  AC20 HCT 116 C374(0.88)  LDD0597  [1]
 LDCM0281  AC21 HCT 116 C374(0.74)  LDD0598  [1]
 LDCM0282  AC22 HCT 116 C374(0.82)  LDD0599  [1]
 LDCM0283  AC23 HCT 116 C374(0.90)  LDD0600  [1]
 LDCM0284  AC24 HCT 116 C374(0.90)  LDD0601  [1]
 LDCM0320  AC57 HCT 116 C374(1.57)  LDD0637  [1]
 LDCM0321  AC58 HCT 116 C374(1.98)  LDD0638  [1]
 LDCM0322  AC59 HCT 116 C374(2.27)  LDD0639  [1]
 LDCM0324  AC60 HCT 116 C374(2.60)  LDD0641  [1]
 LDCM0325  AC61 HCT 116 C374(2.17)  LDD0642  [1]
 LDCM0326  AC62 HCT 116 C374(1.92)  LDD0643  [1]
 LDCM0327  AC63 HCT 116 C374(1.45)  LDD0644  [1]
 LDCM0328  AC64 HCT 116 C374(2.09)  LDD0645  [1]
 LDCM0329  AC65 HCT 116 C374(1.95)  LDD0646  [1]
 LDCM0330  AC66 HCT 116 C374(1.62)  LDD0647  [1]
 LDCM0331  AC67 HCT 116 C374(1.75)  LDD0648  [1]
 LDCM0332  AC68 HCT 116 C374(0.36)  LDD0649  [1]
 LDCM0333  AC69 HCT 116 C374(0.49)  LDD0650  [1]
 LDCM0335  AC70 HCT 116 C374(0.71)  LDD0652  [1]
 LDCM0336  AC71 HCT 116 C374(0.63)  LDD0653  [1]
 LDCM0337  AC72 HCT 116 C374(1.41)  LDD0654  [1]
 LDCM0338  AC73 HCT 116 C374(0.54)  LDD0655  [1]
 LDCM0339  AC74 HCT 116 C374(0.57)  LDD0656  [1]
 LDCM0340  AC75 HCT 116 C374(1.37)  LDD0657  [1]
 LDCM0341  AC76 HCT 116 C374(0.77)  LDD0658  [1]
 LDCM0342  AC77 HCT 116 C374(0.63)  LDD0659  [1]
 LDCM0343  AC78 HCT 116 C374(0.43)  LDD0660  [1]
 LDCM0344  AC79 HCT 116 C374(0.47)  LDD0661  [1]
 LDCM0346  AC80 HCT 116 C374(0.51)  LDD0663  [1]
 LDCM0347  AC81 HCT 116 C374(0.35)  LDD0664  [1]
 LDCM0348  AC82 HCT 116 C374(0.48)  LDD0665  [1]
 LDCM0367  CL1 HCT 116 C374(1.19)  LDD0684  [1]
 LDCM0368  CL10 HCT 116 C374(1.28)  LDD0685  [1]
 LDCM0374  CL105 HCT 116 C374(0.80)  LDD0691  [1]
 LDCM0375  CL106 HCT 116 C374(0.75)  LDD0692  [1]
 LDCM0376  CL107 HCT 116 C374(0.67)  LDD0693  [1]
 LDCM0377  CL108 HCT 116 C374(0.77)  LDD0694  [1]
 LDCM0378  CL109 HCT 116 C374(0.91)  LDD0695  [1]
 LDCM0379  CL11 HCT 116 C374(1.20)  LDD0696  [1]
 LDCM0380  CL110 HCT 116 C374(0.91)  LDD0697  [1]
 LDCM0381  CL111 HCT 116 C374(0.83)  LDD0698  [1]
 LDCM0390  CL12 HCT 116 C374(1.91)  LDD0707  [1]
 LDCM0396  CL125 HCT 116 C374(1.77)  LDD0713  [1]
 LDCM0397  CL126 HCT 116 C374(1.08)  LDD0714  [1]
 LDCM0398  CL127 HCT 116 C374(1.96)  LDD0715  [1]
 LDCM0399  CL128 HCT 116 C374(2.10)  LDD0716  [1]
 LDCM0400  CL13 HCT 116 C374(1.27)  LDD0717  [1]
 LDCM0401  CL14 HCT 116 C374(1.46)  LDD0718  [1]
 LDCM0402  CL15 HCT 116 C374(1.38)  LDD0719  [1]
 LDCM0403  CL16 HCT 116 C374(0.86)  LDD0720  [1]
 LDCM0404  CL17 HCT 116 C374(0.92)  LDD0721  [1]
 LDCM0405  CL18 HCT 116 C374(1.31)  LDD0722  [1]
 LDCM0406  CL19 HCT 116 C374(1.29)  LDD0723  [1]
 LDCM0407  CL2 HCT 116 C374(1.15)  LDD0724  [1]
 LDCM0408  CL20 HCT 116 C374(1.50)  LDD0725  [1]
 LDCM0409  CL21 HCT 116 C374(2.00)  LDD0726  [1]
 LDCM0410  CL22 HCT 116 C374(1.66)  LDD0727  [1]
 LDCM0411  CL23 HCT 116 C374(1.07)  LDD0728  [1]
 LDCM0412  CL24 HCT 116 C374(1.65)  LDD0729  [1]
 LDCM0413  CL25 HCT 116 C374(1.46)  LDD0730  [1]
 LDCM0414  CL26 HCT 116 C374(0.99)  LDD0731  [1]
 LDCM0415  CL27 HCT 116 C374(1.24)  LDD0732  [1]
 LDCM0416  CL28 HCT 116 C374(1.16)  LDD0733  [1]
 LDCM0417  CL29 HCT 116 C374(1.45)  LDD0734  [1]
 LDCM0418  CL3 HCT 116 C374(1.08)  LDD0735  [1]
 LDCM0419  CL30 HCT 116 C374(1.15)  LDD0736  [1]
 LDCM0420  CL31 HEK-293T C374(0.93)  LDD1018  [1]
 LDCM0421  CL32 HEK-293T C374(0.90)  LDD1019  [1]
 LDCM0422  CL33 HEK-293T C374(0.75)  LDD1020  [1]
 LDCM0423  CL34 HEK-293T C374(0.91)  LDD1021  [1]
 LDCM0424  CL35 HEK-293T C374(0.97)  LDD1022  [1]
 LDCM0425  CL36 HEK-293T C374(0.93)  LDD1023  [1]
 LDCM0426  CL37 HEK-293T C374(1.04)  LDD1024  [1]
 LDCM0428  CL39 HEK-293T C374(0.85)  LDD1026  [1]
 LDCM0429  CL4 HCT 116 C374(1.08)  LDD0746  [1]
 LDCM0430  CL40 HEK-293T C374(0.91)  LDD1028  [1]
 LDCM0431  CL41 HEK-293T C374(0.92)  LDD1029  [1]
 LDCM0432  CL42 HEK-293T C374(0.94)  LDD1030  [1]
 LDCM0433  CL43 HEK-293T C374(0.96)  LDD1031  [1]
 LDCM0434  CL44 HEK-293T C374(1.01)  LDD1032  [1]
 LDCM0435  CL45 HEK-293T C374(0.85)  LDD1033  [1]
 LDCM0440  CL5 HCT 116 C374(1.54)  LDD0757  [1]
 LDCM0451  CL6 HCT 116 C374(1.50)  LDD0768  [1]
 LDCM0453  CL61 HEK-293T C374(0.92)  LDD1051  [1]
 LDCM0454  CL62 HEK-293T C374(0.95)  LDD1052  [1]
 LDCM0455  CL63 HEK-293T C374(0.91)  LDD1053  [1]
 LDCM0456  CL64 HEK-293T C374(0.98)  LDD1054  [1]
 LDCM0457  CL65 HEK-293T C374(0.96)  LDD1055  [1]
 LDCM0458  CL66 HEK-293T C374(0.88)  LDD1056  [1]
 LDCM0459  CL67 HEK-293T C374(0.88)  LDD1057  [1]
 LDCM0460  CL68 HEK-293T C374(1.00)  LDD1058  [1]
 LDCM0461  CL69 HEK-293T C374(0.91)  LDD1059  [1]
 LDCM0462  CL7 HCT 116 C374(1.80)  LDD0779  [1]
 LDCM0463  CL70 HEK-293T C374(1.19)  LDD1061  [1]
 LDCM0464  CL71 HEK-293T C374(0.87)  LDD1062  [1]
 LDCM0465  CL72 HEK-293T C374(0.87)  LDD1063  [1]
 LDCM0466  CL73 HEK-293T C374(0.83)  LDD1064  [1]
 LDCM0467  CL74 HEK-293T C374(0.87)  LDD1065  [1]
 LDCM0473  CL8 HCT 116 C374(1.19)  LDD0790  [1]
 LDCM0484  CL9 HCT 116 C374(1.04)  LDD0801  [1]
 LDCM0468  Fragment33 HEK-293T C374(1.13)  LDD1066  [1]
 LDCM0427  Fragment51 HEK-293T C374(1.43)  LDD1025  [1]
 LDCM0022  KB02 CAL-78 C193(1.68)  LDD2291  [2]
 LDCM0023  KB03 CAL-78 C193(2.50)  LDD2708  [2]
 LDCM0024  KB05 NCI-H1155 C193(2.17)  LDD3342  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein arginine N-methyltransferase 6 (PRMT6) Protein arginine N-methyltransferase family Q96LA8
Fibroblast growth factor receptor 3 (FGFR3) Tyr protein kinase family P22607
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Wolframin (WFS1) . O76024
GPCR
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Prosaposin receptor GPR37 (GPR37) G-protein coupled receptor 1 family O15354
Other
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Progranulin (GRN) Granulin family P28799
Heat shock protein beta-1 (HSPB1) Small heat shock protein (HSP20) family P04792
Gelsolin (GSN) Villin/gelsolin family P06396
RING finger protein 11 (RNF11) . Q9Y3C5
Sprouty-related, EVH1 domain-containing protein 1 (SPRED1) . Q7Z699
Ubiquilin-1 (UBQLN1) . Q9UMX0

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Sr-9009 . DB14013
Sr-9011 . DB14014

References

1 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
2 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