Target Information
| Target General Information | Top | |||||
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| Target ID |
T13902
(Former ID: TTDI00024)
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| Target Name |
Liver receptor homolog-1 (NR5A2)
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| Synonyms |
LRH1; CYP7A promoterbinding factor; B1binding factor; Alpha1fetoprotein transcription factor
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| Gene Name |
NR5A2
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. 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. Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. Activates the transcription of CYP2C38. Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis.
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| BioChemical Class |
Nuclear hormone receptor
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| UniProt ID | ||||||
| Sequence |
MSSNSDTGDLQESLKHGLTPIGAGLPDRHGSPIPARGRLVMLPKVETEALGLARSHGEQG
QMPENMQVSQFKMVNYSYDEDLEELCPVCGDKVSGYHYGLLTCESCKGFFKRTVQNNKRY TCIENQNCQIDKTQRKRCPYCRFQKCLSVGMKLEAVRADRMRGGRNKFGPMYKRDRALKQ QKKALIRANGLKLEAMSQVIQAMPSDLTISSAIQNIHSASKGLPLNHAALPPTDYDRSPF VTSPISMTMPPHGSLQGYQTYGHFPSRAIKSEYPDPYTSSPESIMGYSYMDSYQTSSPAS IPHLILELLKCEPDEPQVQAKIMAYLQQEQANRSKHEKLSTFGLMCKMADQTLFSIVEWA RSSIFFRELKVDDQMKLLQNCWSELLILDHIYRQVVHGKEGSIFLVTGQQVDYSIIASQA GATLNNLMSHAQELVAKLRSLQFDQREFVCLKFLVLFSLDVKNLENFQLVEGVQEQVNAA LLDYTMCNYPQQTEKFGQLLLRLPEIRAISMQAEEYLYYKHLNGDVPYNNLLIEMLHAKR A Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Cysteine Sulfenic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of PIP3 bound human nuclear receptor LRH-1 (Liver Receptor Homolog 1, NR5A2) in complex with a co-regulator DAX-1 (NR0B1) peptide at 1.86 A resolution | PDB:4RWV | ||||
| Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | No | [2] |
| PDB Sequence |
SPASIPHLIL
306 ELLKEPDEPQ317 VQAKIMAYLQ327 QEQANRSKHE337 KLSTFGLMCK347 MADQTLFSIV 357 EWARSSIFFR367 ELKVDDQMKL377 LQNCWSELLI387 LDHIYRQVVH397 GKEGSIFLVT 407 GQQVDYSIIA417 SQAGATLNNL427 MSHAQELVAK437 LRSLQFDQRE447 FVCLKFLVLF 457 SLDVKNLENF467 QLVEGVQEQV477 NAALLDYTMC487 NYPQQTEKFG497 QLLLRLPEIR 507 AISMQAEEYL517 YYKHLNGDVP527 YNNLLIEMLH537 AK
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| Ligand Name: (3as,6ar)-5-[(4e)-Oct-4-En-4-Yl]-N,4-Diphenyl-2,3,6,6a-Tetrahydropentalen-3a(1h)-Amine | Ligand Info | |||||
| Structure Description | Human LRH1 LBD bound to GR470 | PDB:3PLZ | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [3] |
| PDB Sequence |
SIPHLILELL
309 KCEPDEPQVQ319 AKIMAYLQQE329 KLSTFGLMCK347 MADQTLFSIV357 EWARSSIFFR 367 ELKVDDQMKL377 LQNCWSELLI387 LDHIYRQVVH397 GKEGSIFLVT407 GQQVDYSIIA 417 SQAGATLNNL427 MSHAQELVAK437 LRSLQFDQRE447 FVCLKFLVLF457 SLDVKNLENF 467 QLVEGVQEQV477 NAALLDYTMC487 NYPQQTEKFG497 QLLLRLPEIR507 AISMQAEEYL 517 YYKHLNGDVP527 YNNLLIEMLH537 A
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PHE342
3.887
MET345
3.472
CYS346
4.027
MET348
4.203
ALA349
4.074
TRP382
3.799
SER383
3.716
LEU386
4.138
ILE387
3.773
HIS390
3.217
ARG393
4.391
ILE403
3.268
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 2.91E-05 |
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| Closeness centrality | 2.36E-01 | Radiality | 1.41E+01 | Clustering coefficient | 1.00E-01 |
| Neighborhood connectivity | 7.28E+01 | Topological coefficient | 2.22E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Liver receptor homolog-1 (LRH-1): a potential therapeutic target for cancer. Cancer Biol Ther. 2015;16(7):997-1004. | |||||
| REF 2 | Crystal structure of a Homo sapiens hepatocytic transcription factor hB1F-2 (B1F2) in complex with nuclear receptor subfamily 0 group B member 1 (NR0B1, residues 140-154) from human at 1.86 A resolution | |||||
| REF 3 | Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2). J Med Chem. 2011 Apr 14;54(7):2266-81. | |||||
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