Target Information
| Target General Information | Top | |||||
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| Target ID |
T31543
(Former ID: TTDR00644)
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| Target Name |
Suppressor of tumorigenicity 14 protein (ST14)
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| Synonyms |
Tumor-associated differentially-expressed gene 15 protein; Tumor associated differentially-expressed gene-15 protein; TADG15; Serine protease TADG-15; Serine protease 14; SNC19; Prostamin; PRSS14; Membrane-type serine protease 1; Membrane type serine protease 1; Matriptase; MT-SP1
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| Gene Name |
ST14
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| Target Type |
Patented-recorded target
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| Function |
Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing. Degrades extracellular matrix.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.21.109
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| Sequence |
MGSDRARKGGGGPKDFGAGLKYNSRHEKVNGLEEGVEFLPVNNVKKVEKHGPGRWVVLAA
VLIGLLLVLLGIGFLVWHLQYRDVRVQKVFNGYMRITNENFVDAYENSNSTEFVSLASKV KDALKLLYSGVPFLGPYHKESAVTAFSEGSVIAYYWSEFSIPQHLVEEAERVMAEERVVM LPPRARSLKSFVVTSVVAFPTDSKTVQRTQDNSCSFGLHARGVELMRFTTPGFPDSPYPA HARCQWALRGDADSVLSLTFRSFDLASCDERGSDLVTVYNTLSPMEPHALVQLCGTYPPS YNLTFHSSQNVLLITLITNTERRHPGFEATFFQLPRMSSCGGRLRKAQGTFNSPYYPGHY PPNIDCTWNIEVPNNQHVKVRFKFFYLLEPGVPAGTCPKDYVEINGEKYCGERSQFVVTS NSNKITVRFHSDQSYTDTGFLAEYLSYDSSDPCPGQFTCRTGRCIRKELRCDGWADCTDH SDELNCSCDAGHQFTCKNKFCKPLFWVCDSVNDCGDNSDEQGCSCPAQTFRCSNGKCLSK SQQCNGKDDCGDGSDEASCPKVNVVTCTKHTYRCLNGLCLSKGNPECDGKEDCSDGSDEK DCDCGLRSFTRQARVVGGTDADEGEWPWQVSLHALGQGHICGASLISPNWLVSAAHCYID DRGFRYSDPTQWTAFLGLHDQSQRSAPGVQERRLKRIISHPFFNDFTFDYDIALLELEKP AEYSSMVRPICLPDASHVFPAGKAIWVTGWGHTQYGGTGALILQKGEIRVINQTTCENLL PQQITPRMMCVGFLSGGVDSCQGDSGGPLSSVEADGRIFQAGVVSWGDGCAQRNKPGVYT RLPLFRDWIKENTGV 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: Glutathione | Ligand Info | |||||
| Structure Description | Crystal Structure of MT-SP1 in complex with benzamidine | PDB:3P8G | ||||
| Method | X-ray diffraction | Resolution | 1.20 Å | Mutation | Yes | [7] |
| PDB Sequence |
VVGGTDADEG
25 EWPWQVSLHA35 LGQGHICGAS45 LISPNWLVSA55 AHCYIDDRGF60E RYSDPTQWTA 66 FLGLHDQSQR76 SAPGVQERRL85 KRIISHPFFN95 DFTFDYDIAL105 LELEKPAEYS 115 SMVRPICLPD125 ASHVFPAGKA135 IWVTGWGHTQ145 YGGTGALILQ156 KGEIRVIQQT 166 TCENLLPQQI176 TPRMMCVGFL185 SGGVDSCQGD194 SGGPLSSVEA204 DGRIFQAGVV 213 SWGDGCAQRN223 KPGVYTRLPL233 FRDWIKENTG243 V
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Benzamidine | Ligand Info | |||||
| Structure Description | Crystal Structure of MT-SP1 in complex with benzamidine | PDB:3P8G | ||||
| Method | X-ray diffraction | Resolution | 1.20 Å | Mutation | Yes | [7] |
| PDB Sequence |
VVGGTDADEG
25 EWPWQVSLHA35 LGQGHICGAS45 LISPNWLVSA55 AHCYIDDRGF60E RYSDPTQWTA 66 FLGLHDQSQR76 SAPGVQERRL85 KRIISHPFFN95 DFTFDYDIAL105 LELEKPAEYS 115 SMVRPICLPD125 ASHVFPAGKA135 IWVTGWGHTQ145 YGGTGALILQ156 KGEIRVIQQT 166 TCENLLPQQI176 TPRMMCVGFL185 SGGVDSCQGD194 SGGPLSSVEA204 DGRIFQAGVV 213 SWGDGCAQRN223 KPGVYTRLPL233 FRDWIKENTG243 V
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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 | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 1.62E-03 |
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| Closeness centrality | 1.63E-01 | Radiality | 1.25E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 3.00E+00 | Topological coefficient | 5.00E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| 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 Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | MicroRNAs in cancer | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2418). | |||||
| REF 2 | Meta-substituted phenyl sulfonyl amides of secondary amino acid amides, the production thereof, and use thereof as matriptase inhibitors. US8569313. | |||||
| REF 3 | Secondary amides of sulfonylated 3-amidinophenylalanine. New potent and selective inhibitors of matriptase. J Med Chem. 2006 Jul 13;49(14):4116-26. | |||||
| REF 4 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 5 | 1,2,4-Triazole derivatives as transient inactivators of kallikreins involved in skin diseases. Bioorg Med Chem Lett. 2013 Aug 15;23(16):4547-51. | |||||
| REF 6 | Toward the first class of suicide inhibitors of kallikreins involved in skin diseases. J Med Chem. 2015 Jan 22;58(2):598-612. | |||||
| REF 7 | Structure of catalytic domain of Matriptase in complex with Sunflower trypsin inhibitor-1. BMC Struct Biol. 2011 Jun 22;11:30. | |||||
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