Target Information
| Target General Information | Top | |||||
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| Target ID |
T95446
(Former ID: TTDI01943)
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| Target Name |
Cytochrome P450 reductase (P450)
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| Synonyms |
P450R; NADPH--cytochrome P450 reductase; CYPOR; CPR
Click to Show/Hide
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| Gene Name |
POR
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| Target Type |
Discontinued target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Psoriasis [ICD-11: EA90] | |||||
| 2 | Eczema [ICD-11: EA80-EA89] | |||||
| 3 | Pruritus [ICD-11: EC90] | |||||
| Function |
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
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| BioChemical Class |
NADH/NADPH oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.6.2.4
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| Sequence |
MGDSHVDTSSTVSEAVAEEVSLFSMTDMILFSLIVGLLTYWFLFRKKKEEVPEFTKIQTL
TSSVRESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEYDLA DLSSLPEIDNALVVFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKFAVFGLGNKTYEH FNAMGKYVDKRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEHFGVEATGEES SIRQYELVVHTDIDAAKVYMGEMGRLKSYENQKPPFDAKNPFLAAVTTNRKLNQGTERHL MHLELDISDSKIRYESGDHVAVYPANDSALVNQLGKILGADLDVVMSLNNLDEESNKKHP FPCPTSYRTALTYYLDITNPPRTNVLYELAQYASEPSEQELLRKMASSSGEGKELYLSWV VEARRHILAILQDCPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVHICAVVVEYET KAGRINKGVATNWLRAKEPAGENGGRALVPMFVRKSQFRLPFKATTPVIMVGPGTGVAPF IGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELAQFHRDGALTQLNVAFSREQS HKVYVQHLLKQDREHLWKLIEGGAHIYVCGDARNMARDVQNTFYDIVAELGAMEHAQAVD YIKKLMTKGRYSLDVWS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A02233 | |||||
| HIT2.0 ID | T09AAD | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | DuP-630 | Drug Info | Terminated | Dermatitis | [3] | |
| 2 | DuP-983 | Drug Info | Terminated | Pruritus | [4] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | DuP-630 | Drug Info | [5] | |||
| 2 | DuP-983 | Drug Info | [5] | |||
| 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: flavin mononucleotide | Ligand Info | |||||
| Structure Description | Crystal Structure of Human NADPH-Cytochrome P450 Reductase | PDB:3QE2 | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [6] |
| PDB Sequence |
ESSFVEKMKK
78 TGRNIIVFYG88 SQTGTAEEFA98 NRLSKDAHRY108 GMRGMSADPE118 EYDLADLSSL 128 PEIDNALVVF138 CMATYGEGDP148 TDNAQDFYDW158 LQETDVDLSG168 VKFAVFGLGN 178 KTYEHFNAMG188 KYVDKRLEQL198 GAQRIFELGL208 GDDDGNLEED218 FITWREQFWL 228 AVCEHFGVEA238 TSSIRQYELV251 VHTDIDAAKV261 YMGEMGRLKS271 YENQKPPFDA 281 KNPFLAAVTT291 NRKLNQGTER301 HLMHLELDIS311 DSKIRYESGD321 HVAVYPANDS 331 ALVNQLGKIL341 GADLDVVMSL351 NNLDEESNKK361 HPFPCPTSYR371 TALTYYLDIT 381 NPPRTNVLYE391 LAQYASEPSE401 QELLRKMASS411 SGEGKELYLS421 WVVEARRHIL 431 AILQDCPSLR441 PPIDHLCELL451 PRLQARYYSI461 ASSSKVHPNS471 VHICAVVVEY 481 ETKAGRINKG491 VATNWLRAKE501 PVRALVPMFV516 RKSQFRLPFK526 ATTPVIMVGP 536 GTGVAPFIGF546 IQERAWLRQQ556 GKEVGETLLY566 YGCRRSDEDY576 LYREELAQFH 586 RDGALTQLNV596 AFSREQSHKV606 YVQHLLKQDR616 EHLWKLIEGG626 AHIYVCGDAR 636 NMARDVQNTF646 YDIVAELGAM656 EHAQAVDYIK666 KLMTKGRYSL676 DVWS |
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GLY88
4.304
SER89
2.521
GLN90
2.678
THR91
2.548
GLY92
3.514
THR93
2.671
ALA94
2.782
GLU95
4.647
ALA141
3.319
THR142
2.635
TYR143
2.673
GLY144
3.660
GLU145
4.127
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Flavin-Adenine Dinucleotide | Ligand Info | |||||
| Structure Description | Crystal Structure of NADPH-Cytochrome P450 Reductase (FAD/NADPH domain) | PDB:3QFS | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | No | [6] |
| PDB Sequence |
RQYELVVHTD
255 IDAAKVYMGE265 MGRLKSYENQ275 KPPFDAKNPF285 LAAVTTNRKL295 NQGTERHLMH 305 LELDISDSKI315 RYESGDHVAV325 YPANDSALVN335 QLGKILGADL345 DVVMSLNNLD 355 EESNKKHPFP365 CPTSYRTALT375 YYLDITNPPR385 TNVLYELAQY395 ASEPSEQELL 405 RKMASSSGEG415 KELYLSWVVE425 ARRHILAILQ435 DCPSLRPPID445 HLCELLPRLQ 455 ARYYSIASSS465 KVHPNSVHIC475 AVVVEYETKA485 GRINKGVATN495 WLRAKEPVGE 505 NGGRALVPMF515 VRKSQFRLPF525 KATTPVIMVG535 PGTGVAPFIG545 FIQERAWLRQ 555 QGKEVGETLL565 YYGCRRSDED575 YLYREELAQF585 HRDGALTQLN595 VAFSREQSHK 605 VYVQHLLKQD615 REHLWKLIEG625 GAHIYVCGDA635 RNMARDVQNT645 FYDIVAELGA 655 MEHAQAVDYI665 KKLMTKGRYS675 LDVWS
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HIS322
3.476
THR381
4.505
ASN382
4.568
ARG427
3.103
ARG457
2.774
TYR458
2.630
TYR459
2.757
SER460
3.075
CYS475
2.993
ALA476
3.125
VAL477
3.168
VAL479
3.663
TYR481
3.519
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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
Human Tissue Distribution
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 2.43E-04 |
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| Closeness centrality | 1.75E-01 | Radiality | 1.28E+01 | Clustering coefficient | 2.67E-01 |
| Neighborhood connectivity | 1.40E+01 | Topological coefficient | 1.92E-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 Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 5 BioCyc Pathways | + | ||||
| 1 | Superpathway of tryptophan utilization | |||||
| 2 | Superpathway of melatonin degradation | |||||
| 3 | Melatonin degradation I | |||||
| 4 | Vitamin D<sub>3</sub> biosynthesis | |||||
| 5 | Bile acid biosynthesis, neutral pathway | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Oxidation by Cytochrome P450 | |||||
| References | Top | |||||
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| REF 1 | Peritoneal cancer treatment with CYP2B1 transfected, microencapsulated cells and ifosfamide. Cancer Gene Ther. 2006 Jan 1;13(1):65-73. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022961) | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003777) | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003352) | |||||
| REF 5 | CN patent application no. 1096855, Composition produced by treatment and induction of nitrogen mono oxide synthase expressed matter, and use thereof. | |||||
| REF 6 | Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13486-91. | |||||
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