Details of the Target

General Information of Target

Target ID LDTP04659
Target Name Oxysterols receptor LXR-beta (NR1H2)
Gene Name NR1H2
Gene ID 7376
Synonyms
LXRB; NER; UNR; Oxysterols receptor LXR-beta; Liver X receptor beta; Nuclear receptor NER; Nuclear receptor subfamily 1 group H member 2; Ubiquitously-expressed nuclear receptor
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSSPTTSSLDTPLPGNGPPQPGAPSSSPTVKEEGPEPWPGGPDPDVPGTDEASSACSTDW
VIPDPEEEPERKRKKGPAPKMLGHELCRVCGDKASGFHYNVLSCEGCKGFFRRSVVRGGA
RRYACRGGGTCQMDAFMRRKCQQCRLRKCKEAGMREQCVLSEEQIRKKKIRKQQQESQSQ
SQSPVGPQGSSSSASGPGASPGGSEAGSQGSGEGEGVQLTAAQELMIQQLVAAQLQCNKR
SFSDQPKVTPWPLGADPQSRDARQQRFAHFTELAIISVQEIVDFAKQVPGFLQLGREDQI
ALLKASTIEIMLLETARRYNHETECITFLKDFTYSKDDFHRAGLQVEFINPIFEFSRAMR
RLGLDDAEYALLIAINIFSADRPNVQEPGRVEALQQPYVEALLSYTRIKRPQDQLRFPRM
LMKLVSLRTLSSVHSEQVFALRLQDKKLPPLLSEIWDVHE
Target Type
Clinical trial
Target Bioclass
Transcription factor
Family
Nuclear hormone receptor family, NR1 subfamily
Subcellular location
Nucleus
Function
Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism. Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis. Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles. Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators. Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex.
TTD ID
T13714
Uniprot ID
P55055
DrugMap ID
TTXA6PH
Ensemble ID
ENST00000253727.10
HGNC ID
HGNC:7965
ChEMBL ID
CHEMBL4093

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HEC1 SNV: p.L225P; p.R266H DBIA    Probe Info 
HEC1B SNV: p.R266H .
JURKAT SNV: p.R428H .
MEC1 SNV: p.R416C DBIA    Probe Info 
MFE319 Insertion: p.Q174dup DBIA    Probe Info 
OVK18 SNV: p.L443P .
REH SNV: p.E322D .

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  		C87(1.24)  LDD3310  [1]
IPM
 Probe Info  		C87(1.69)  LDD1701  [2]
Photoprobe 2
 Probe Info  		S278(17.84)  LDD0307  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0226  AC11 HEK-293T C87(0.81)  LDD1509  [4]
 LDCM0237  AC12 HEK-293T C87(1.03)  LDD1510  [4]
 LDCM0278  AC19 HEK-293T C87(1.20)  LDD1517  [4]
 LDCM0280  AC20 HEK-293T C87(1.00)  LDD1519  [4]
 LDCM0287  AC27 HEK-293T C87(0.92)  LDD1526  [4]
 LDCM0288  AC28 HEK-293T C87(1.07)  LDD1527  [4]
 LDCM0290  AC3 HEK-293T C87(0.88)  LDD1529  [4]
 LDCM0296  AC35 HEK-293T C87(1.14)  LDD1535  [4]
 LDCM0297  AC36 HEK-293T C87(1.10)  LDD1536  [4]
 LDCM0301  AC4 HEK-293T C87(0.82)  LDD1540  [4]
 LDCM0305  AC43 HEK-293T C87(0.95)  LDD1544  [4]
 LDCM0306  AC44 HEK-293T C87(0.94)  LDD1545  [4]
 LDCM0314  AC51 HEK-293T C87(0.77)  LDD1553  [4]
 LDCM0315  AC52 HEK-293T C87(0.92)  LDD1554  [4]
 LDCM0322  AC59 HEK-293T C87(0.81)  LDD1561  [4]
 LDCM0324  AC60 HEK-293T C87(1.19)  LDD1563  [4]
 LDCM0406  CL19 HEK-293T C87(1.07)  LDD1610  [4]
 LDCM0408  CL20 HEK-293T C87(1.08)  LDD1612  [4]
 LDCM0420  CL31 HEK-293T C87(1.05)  LDD1624  [4]
 LDCM0421  CL32 HEK-293T C87(1.03)  LDD1625  [4]
 LDCM0433  CL43 HEK-293T C87(0.93)  LDD1637  [4]
 LDCM0434  CL44 HEK-293T C87(1.09)  LDD1638  [4]
 LDCM0446  CL55 HEK-293T C87(1.07)  LDD1649  [4]
 LDCM0447  CL56 HEK-293T C87(0.97)  LDD1650  [4]
 LDCM0459  CL67 HEK-293T C87(0.88)  LDD1662  [4]
 LDCM0460  CL68 HEK-293T C87(1.16)  LDD1663  [4]
 LDCM0462  CL7 HEK-293T C87(1.11)  LDD1665  [4]
 LDCM0472  CL79 HEK-293T C87(0.97)  LDD1675  [4]
 LDCM0473  CL8 HEK-293T C87(0.93)  LDD1676  [4]
 LDCM0474  CL80 HEK-293T C87(1.04)  LDD1677  [4]
 LDCM0486  CL91 HEK-293T C87(1.00)  LDD1689  [4]
 LDCM0487  CL92 HEK-293T C87(0.95)  LDD1690  [4]
 LDCM0022  KB02 22RV1 C87(1.30)  LDD2243  [1]
 LDCM0023  KB03 MDA-MB-231 C87(1.69)  LDD1701  [2]
 LDCM0024  KB05 COLO792 C87(1.24)  LDD3310  [1]
 LDCM0002  Ward_cp1 CCF-STTG1 S278(17.84)  LDD0307  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
MyoD family inhibitor (MDFI) MDFI family Q99750
Transcription factor
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Nuclear receptor corepressor 1 (NCOR1) N-CoR nuclear receptor corepressors family O75376
Peroxisome proliferator-activated receptor delta (PPARD) Nuclear hormone receptor family Q03181
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-gamma (RXRG) Nuclear hormone receptor family P48443
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Coronin-2A (CORO2A) WD repeat coronin family Q92828

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
Diacerein Small molecular drug DB11994
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Vtb-38543 . D01XMC
Investigative
Click To Hide/Show 29 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
12,17-dehydroxyriccardin C Small molecular drug D09UND
12-dehydroxyriccardin C Small molecular drug D0HA0U
17-dehydroxyriccardin C Small molecular drug D0Z8LE
2-benzyl-3-phenyl-7-(Trifluoromethyl)-2h-indazole Small molecular drug D0Z8RH
2-benzyl-4,5,6,7-tetrachloroisoindoline-1,3-dione Small molecular drug D01HDD
2-propanol, Isopropanol Small molecular drug D0W7LK
22r-hydroxycholesterol Small molecular drug D0K4GK
24(S), 25-epoxycholesterol Small molecular drug D0Q2RP
24(S)-hydroxycholesterol Small molecular drug D08URT
27-hydroxycholesterol Small molecular drug D0H2YM
4,17-dehydroxyriccardin C Small molecular drug D06VRA
4-dehydroxyriccardin C Small molecular drug D0IZ9O
Acetyl-podocarpic Dimer Small molecular drug D0C6QI
Az12260493 Small molecular drug D03YUL
Benzenesulfonyl Small molecular drug D08LFT
Desmosterol Small molecular drug D01RNA
Gsk-9772 Small molecular drug D00DLU
Gsk2033 Small molecular drug D0Z3TJ
Gw-3965 Small molecular drug D0PL4F
L-783483 Small molecular drug D08QXD
N-{4-[2-(3-methoxyphenyl)Ethyl]Phenyl}Phthalimide Small molecular drug D0R8LN
Rhein Small molecular drug DB13174
Riccardin C Small molecular drug D00HVP
Sr9238 Small molecular drug D0A1WR
To-901317 Small molecular drug DB07080
Way-214950 Small molecular drug D0V4RZ
111333-hexafluoro-2-{4-[(222-trifluoroethyl)Amino]Phenyl}Propan-2-ol . DB07082
Benzenesulfinic Acid . DB03848
Way-254011 . D0C2CY

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 Photoaffinity Labeling and Quantitative Chemical Proteomics Identify LXR as the Functional Target of Enhancers of Astrocytic apoE. Cell Chem Biol. 2021 Feb 18;28(2):148-157.e7. doi: 10.1016/j.chembiol.2020.09.002. Epub 2020 Sep 29.
4 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