Target Information

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Target General Information
Drug Binding Sites of Target
Different Human System Profiles of Target
Chemical Structure based Activity Landscape of Target
Target Poor or Non Binders
Target Regulators
References
Drug Binding Sites of Target  Top
Ligand Name: Glyoxalate, Glyoxylate Ligand Info
Structure Description Crystal structure of human menin in complex with MLL1 and LEDGF PDB:3U88
Method X-ray diffraction Resolution 3.00 Å Mutation No [2]
PDB Sequence
RWRFPARPGT
15
GRRGLGGAPR
32
QRVPALLRVG
109
PGFDAALQVS
119
AAIGTNLRRF
129

RAVFGE
Residue
Distance (Å)
TRP7
3.972
Residue
Distance (Å)
Ligand Name: 5'-{[(3S)-3-amino-3-carboxypropyl]({1-[(4-chlorophenyl)methyl]azetidin-3-yl}methyl)amino}-5'-deoxyadenosine Ligand Info
Structure Description MLL1 SET N3861I/Q3867L bound to inhibitor 14 (TC-5139) PDB:6U9N
Method X-ray diffraction Resolution 1.95 Å Mutation Yes [3]
PDB Sequence
LPMPMRFRHL
3823
KKTSKEAVGV
3833
YRSPIHGRGL
3843
FCKRNIDAGE
3853
MVIEYAGIVI
3863

RSILTDKREK
3873
YYDSKGIGCY
3883
MFRIDDSEVV
3893
DATMHGNAAR
3903
FINHSCEPNC
3913

YSRVINIDGQ
3923
KHIVIFAMRK
3933
IYRGEELTYD
3943
YKKLPCNCGA
3961
KKCRKFL
Residue
Distance (Å)
ILE3838
3.325
HIS3839
2.333
GLY3840
3.256
ARG3841
2.828
GLY3842
4.782
GLY3881
3.472
CYS3882
2.459
TYR3883
2.559
ARG3903
3.074
PHE3904
2.515
Residue
Distance (Å)
ILE3905
3.296
ASN3906
1.956
HIS3907
1.843
SER3908
3.685
TYR3944
2.452
PRO3956
2.847
CYS3957
2.684
ASN3958
2.836
CYS3959
2.911
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
E3 ubiquitin-protein ligase Jade-2 (JADE2)
PF10513 ; 
PF13831 ; 
PF13832
More >>
 27.273 (39/143) 7.62E-04
Bromodomain and PHD finger containing 1 (BRPF1)
PF00439 ; 
PF10513 ; 
PF13831 ; 
PF00855 ; 
PF13832
More >>
 29.787 (28/94) 2.00E-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      
KEGG Pathway Pathway ID Affiliated Target Pathway Map
Lysine degradation hsa00310 Affiliated Target
  Class: Metabolism => Amino acid metabolism Pathway Hierarchy
Degree 13 Degree centrality 1.40E-03 Betweenness centrality 9.47E-05
Closeness centrality 2.23E-01 Radiality 1.39E+01 Clustering coefficient 2.56E-01
Neighborhood connectivity 3.19E+01 Topological coefficient 1.20E-01 Eccentricity 11
Download Click to Download the Full PPI Network of This Target

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