Target Information

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Target General Information
Drugs and Modes of Action
Drug Binding Sites of Target
Different Human System Profiles of Target
Chemical Structure based Activity Landscape of Target
Drug Property Profile of Target
Co-Targets
Target Poor or Non Binders
Target Regulators
Target Profiles in Patients
Target Affiliated Biological Pathways
Target-Related Models and Studies
References
Drug Binding Sites of Target  Top
Ligand Name: Atorvastatin Ligand Info
Structure Description COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH ATORVASTATIN PDB:1HWK
Method X-ray diffraction Resolution 2.22 Å Mutation Yes [93]
PDB Sequence
PRPNEECLLS
463
DAEIIQLVNA
473
KHIPAYKLET
483
LIETHERGVS
493
IRRQLLSKKL
503

SEPSSLQYLP
513
YRDYNYSLVM
523
GACCENVIGY
533
MPIPVGVAGP
543
LCLDEKEFQV
553

PMATTEGCLV
563
ASTNRGCRAI
573
GLGGGASSRV
583
LADGMTRGPV
593
VRLPRACDSA
603

EVKAWLETSE
613
GFAVIKEAFD
623
STSRFARLQK
633
LHTSIAGRNL
643
YIRFQSRSGD
653

AMGMNMISKG
663
TEKALSKLHE
673
YFPEMQILAV
683
SGNYCTDKKP
693
AAINWIEGRG
703

KSVVCEAVIP
713
AKVVREVLKT
723
TTEAMIEVNI
733
NKNLVGSAMA
743
GSIGGYNAHA
753

ANIVTAIYIA
763
CGQDAAQNVG
773
SSNCITLMEA
783
SGPTNEDLYI
793
SCTMPSIEIG
803

TVGGGTNLLP
813
QQACLQMLGV
823
QGACKDNPGE
833
NARQLARIVC
843
GTVMAGELSL
853

MAALAAGH
Residue
Distance (Å)
ARG590
2.766
MET657
4.658
SER661
3.273
VAL683
3.286
SER684
2.654
ASN686
3.788
Residue
Distance (Å)
CYS688
4.203
ASP690
2.793
LYS691
2.843
LYS692
3.392
ASP767
4.968
Ligand Name: Fluvastatin Ligand Info
Structure Description COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH FLUVASTATIN PDB:1HWI
Method X-ray diffraction Resolution 2.30 Å Mutation Yes [93]
PDB Sequence
LSDAEIIQLV
471
NLETLIETHE
489
RGVSIRRQLL
499
SKKLSEPSSL
509
QYLPYRDYNY
519

SLVMGACCEN
529
VIGYMPIPVG
539
VAGPLCLDEK
549
EFQVPMATTE
559
GCLVASTNRG
569

CRAIGLGGGA
579
SSRVLADGMT
589
RGPVVRLPRA
599
CDSAEVKAWL
609
ETSEGFAVIK
619

EAFDSTSRFA
629
RLQKLHTSIA
639
GRNLYIRFQS
649
RSGDAMGMNM
659
ISKGTEKALS
669

KLHEYFPEMQ
679
ILAVSGNYCT
689
DKKPAAINWI
699
EGRGKSVVCE
709
AVIPAKVVRE
719

VLKTTTEAMI
729
EVNINKNLVG
739
SAMAGSIGGY
749
NAHAANIVTA
759
IYIACGQDAA
769

QNVGSSNCIT
779
LMEASGPTNE
789
DLYISCTMPS
799
IEIGTVGGGT
809
NLLPQQACLQ
819

MLGVQGACKD
829
NPGENARQLA
839
RIVCGTVMAG
849
ELSLMAALAA
859
GHL
Residue
Distance (Å)
ARG590
3.212
MET657
3.938
SER661
3.894
GLU665
4.743
VAL683
2.754
SER684
2.786
Residue
Distance (Å)
ASN686
3.641
CYS688
4.342
ASP690
2.827
LYS691
2.814
LYS692
3.000
ASP767
4.831
Click to View More Binding Site Information of This Target with Different Ligands
Different Human System Profiles of Target  Top
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).
Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
Biological Network Descriptors
Protein Name Pfam ID Percentage of Identity (%) E value
Patched domain-containing protein 4 (PTCHD4)
PF02460
20.732 (34/164) 1.00E-03
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.
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
KEGG Pathway Pathway ID Affiliated Target Pathway Map
Terpenoid backbone biosynthesis hsa00900 Affiliated Target
  Class: Metabolism => Metabolism of terpenoids and polyketides Pathway Hierarchy
AMPK signaling pathway hsa04152 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Bile secretion hsa04976 Affiliated Target
  Class: Organismal Systems => Digestive system Pathway Hierarchy
Degree 11 Degree centrality 1.18E-03 Betweenness centrality 1.62E-04
Closeness centrality 2.09E-01 Radiality 1.36E+01 Clustering coefficient 3.64E-01
Neighborhood connectivity 1.76E+01 Topological coefficient 1.68E-01 Eccentricity 11
Download Click to Download the Full PPI Network of This Target

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