Target Information
Target General Information | Top | |||||
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Target ID |
T79400
(Former ID: TTDI00054)
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Target Name |
Kallikrein-4 (KLK4)
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Synonyms |
Serine protease 17; Prostase; PSTS; PRSS17; Kallikreinlike protein 1; Kallikrein4; Kallikrein-like protein 1; KLKL1; KLK-L1; Enamel matrix serine proteinase 1; EMSP1
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Gene Name |
KLK4
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Target Type |
Patented-recorded target
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[1] | ||||
Function |
Required during the maturation stage of tooth development for clearance of enamel proteins and normal structural patterning of the crystalline matrix. Has a major role in enamel formation.
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BioChemical Class |
Peptidase
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UniProt ID | ||||||
EC Number |
EC 3.4.21.-
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Sequence |
MATAGNPWGWFLGYLILGVAGSLVSGSCSQIINGEDCSPHSQPWQAALVMENELFCSGVL
VHPQWVLSAAHCFQNSYTIGLGLHSLEADQEPGSQMVEASLSVRHPEYNRPLLANDLMLI KLDESVSESDTIRSISIASQCPTAGNSCLVSGWGLLANGRMPTVLQCVNVSVVSEEVCSK LYDPLYHPSMFCAGGGHDQKDSCNGDSGGPLICNGYLQGLVSFGKAPCGQVGVPGVYTNL CKFTEWIEKTVQAS Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T33KEM |
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: Urea | Ligand Info | |||||
Structure Description | Crystal structure of BbKI complexed with Human Kallikrein 4 | PDB:7JOW | ||||
Method | X-ray diffraction | Resolution | 1.91 Å | Mutation | No | [2] |
PDB Sequence |
IINGEDCSPH
25 SQPWQAALVM35 ENELFCSGVL46 VHPQWVLSAA56 HCFQNSYTIG66 LGLHSLEADQ 76 EPGSQMVEAS86 LSVRHPEYNR96 PLLANDLMLI106 KLDESVSESD116 TIRSISIASQ 127 CPTAGNSCLV138 SGWGLLANGR150 MPTVLQCVNV160 SVVSEEVCSK170 LYDPLYHPSM 180 FCAGGGQDQK188 DSCNGDSGGP198 LICNGYLQGL212 VSFGKAPCGQ221 VGVPGVYTNL 231 CKFTEWIEKT241 VQA
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Ligand Name: P-Amino benzamidine | Ligand Info | |||||
Structure Description | Human Kallikrein 4 complex with nickel and p-aminobenzamidine | PDB:2BDG | ||||
Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [3] |
PDB Sequence |
IINGEDCSPH
25 SQPWQAALVM35 ENELFCSGVL46 VHPQWVLSAA56 HCFQNSYTIG66 LGLHSLEADQ 76 EPGSQMVEAS86 LSVRHPEYNR96 PLLANDLMLI106 KLDESVSESD116 TIRSISIASQ 127 CPTAGNSCLV138 SGWGLLANGR150 MPTVLQCVNV160 SVVSEEVCSK170 LYDPLYHPSM 180 FCAGGGQDQK188 DSCNGDSGGP198 LICNGYLQGL212 VSFGKAPCGQ221 VGVPGVYTNL 231 CKFTEWIEKT241 VQA
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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).
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 | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 7.30E-05 |
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Closeness centrality | 1.80E-01 | Radiality | 1.30E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 8.25E+00 | Topological coefficient | 2.90E-01 | Eccentricity | 12 |
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 |
References | Top | |||||
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REF 1 | Serine protease inhibitors to treat inflammation: a patent review (2011-2016).Expert Opin Ther Pat. 2018 Feb;28(2):93-110. | |||||
REF 2 | Structural studies of complexes of kallikrein 4 with wild-type and mutated forms of the Kunitz-type inhibitor BbKI. doi:10.1107/S2059798321006483. | |||||
REF 3 | Crystal structures of human tissue kallikrein 4: activity modulation by a specific zinc binding site. J Mol Biol. 2006 Oct 6;362(5):1094-107. |
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