Target Information
| Target General Information | Top | |||||
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| Target ID |
T01597
(Former ID: TTDI02035)
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| Target Name |
Catalase (CAT)
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| Synonyms |
Human catalase
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| Gene Name |
CAT
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Skin sensation disturbance [ICD-11: ME65] | |||||
| Function |
Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells. Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide.
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| BioChemical Class |
Peroxide acceptor oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.11.1.6
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| Sequence |
MADSRDPASDQMQHWKEQRAAQKADVLTTGAGNPVGDKLNVITVGPRGPLLVQDVVFTDE
MAHFDRERIPERVVHAKGAGAFGYFEVTHDITKYSKAKVFEHIGKKTPIAVRFSTVAGES GSADTVRDPRGFAVKFYTEDGNWDLVGNNTPIFFIRDPILFPSFIHSQKRNPQTHLKDPD MVWDFWSLRPESLHQVSFLFSDRGIPDGHRHMNGYGSHTFKLVNANGEAVYCKFHYKTDQ GIKNLSVEDAARLSQEDPDYGIRDLFNAIATGKYPSWTFYIQVMTFNQAETFPFNPFDLT KVWPHKDYPLIPVGKLVLNRNPVNYFAEVEQIAFDPSNMPPGIEASPDKMLQGRLFAYPD THRHRLGPNYLHIPVNCPYRARVANYQRDGPMCMQDNQGGAPNYYPNSFGAPEQQPSALE HSIQYSGEVRRFNTANDDNVTQVRAFYVNVLNEEQRKRLCENIAGHLKDAQIFIQKKAVK NFTEVHPDYGSHIQALLDKYNAEKPKNAIHTFVQSGSHLAAREKANL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A03234 ; BADD_A04153 ; BADD_A04623 | |||||
| HIT2.0 ID | T16A2X | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | EUK-189 | Drug Info | Phase 1 | Skin burns | [1] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | EUK-189 | Drug Info | [1] | |||
| 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: NADPH | Ligand Info | |||||
| Structure Description | HUMAN ERYTHROCYTE CATALASE | PDB:1DGF | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [2] |
| PDB Sequence |
RDPASDQMQH
14 WKEQRAAQKA24 DVLTTGAGNP34 VGDKLNVITV44 GPRGPLLVQD54 VVFTDEMAHF 64 DRERIPERVV74 HAKGAGAFGY84 FEVTHDITKY94 SKAKVFEHIG104 KKTPIAVRFS 114 TVAGESGSAD124 TVRDPRGFAV134 KFYTEDGNWD144 LVGNNTPIFF154 IRDPILFPSF 164 IHSQKRNPQT174 HLKDPDMVWD184 FWSLRPESLH194 QVSFLFSDRG204 IPDGHRHMNG 214 YGSHTFKLVN224 ANGEAVYCKF234 HYKTDQGIKN244 LSVEDAARLS254 QEDPDYGIRD 264 LFNAIATGKY274 PSWTFYIQVM284 TFNQAETFPF294 NPFDLTKVWP304 HKDYPLIPVG 314 KLVLNRNPVN324 YFAEVEQIAF334 DPSNMPPGIE344 ASPDKMLQGR354 LFAYPDTHRH 364 RLGPNYLHIP374 VNCPYRARVA384 NYQRDGPMCM394 QDNQGGAPNY404 YPNSFGAPEQ 414 QPSALEHSIQ424 YSGEVRRFNT434 ANDDNVTQVR444 AFYVNVLNEE454 QRKRLCENIA 464 GHLKDAQIFI474 QKKAVKNFTE484 VHPDYGSHIQ494 ALLDKYN
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PRO151
3.570
HIS194
2.632
PHE198
3.370
SER201
3.067
ASP202
4.512
ARG203
2.829
ASN213
2.589
TYR215
4.270
HIS235
3.479
LYS237
2.721
ILE242
4.348
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: [Histidin-1-YL-4H-[1,2,4]triazol-5-YL]-amine | Ligand Info | |||||
| Structure Description | HUMAN ERYTHROCYTE CATALASE 3-AMINO-1,2,4-TRIAZOLE COMPLEX | PDB:1DGH | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
SRDPASDQMQ
13 HWKEQRAAQK23 ADVLTTGAGN33 PVGDKLNVIT43 VGPRGPLLVQ53 DVVFTDEMAH 63 FDRERIPERV73 VAKGAGAFGY84 FEVTHDITKY94 SKAKVFEHIG104 KKTPIAVRFS 114 TVAGESGSAD124 TVRDPRGFAV134 KFYTEDGNWD144 LVGNNTPIFF154 IRDPILFPSF 164 IHSQKRNPQT174 HLKDPDMVWD184 FWSLRPESLH194 QVSFLFSDRG204 IPDGHRHMNG 214 YGSHTFKLVN224 ANGEAVYCKF234 HYKTDQGIKN244 LSVEDAARLS254 QEDPDYGIRD 264 LFNAIATGKY274 PSWTFYIQVM284 TFNQAETFPF294 NPFDLTKVWP304 HKDYPLIPVG 314 KLVLNRNPVN324 YFAEVEQIAF334 DPSNMPPGIE344 ASPDKMLQGR354 LFAYPDTHRH 364 RLGPNYLHIP374 VNCPYRARVA384 NYQRDGPMCM394 QDNQGGAPNY404 YPNSFGAPEQ 414 QPSALEHSIQ424 YSGEVRRFNT434 ANDDNVTQVR444 AFYVNVLNEE454 QRKRLCENIA 464 GHLKDAQIFI474 QKKAVKNFTE484 VHPDYGSHIQ494 ALLDKYN
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| 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).
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
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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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Tryptophan metabolism | hsa00380 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Glyoxylate and dicarboxylate metabolism | hsa00630 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| FoxO signaling pathway | hsa04068 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Peroxisome | hsa04146 | Affiliated Target |
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| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| Longevity regulating pathway | hsa04211 | Affiliated Target |
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| Class: Organismal Systems => Aging | Pathway Hierarchy | ||
| Longevity regulating pathway - multiple species | hsa04213 | Affiliated Target |
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| Class: Organismal Systems => Aging | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 25 | Degree centrality | 2.69E-03 | Betweenness centrality | 9.03E-03 |
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| Closeness centrality | 2.37E-01 | Radiality | 1.42E+01 | Clustering coefficient | 2.23E-01 |
| Neighborhood connectivity | 2.62E+01 | Topological coefficient | 7.68E-02 | 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 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-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 2 BioCyc Pathways | + | ||||
| 1 | Reactive oxygen species degradation | |||||
| 2 | Ethanol degradation IV | |||||
| KEGG Pathway | [+] 6 KEGG Pathways | + | ||||
| 1 | Tryptophan metabolism | |||||
| 2 | Glyoxylate and dicarboxylate metabolism | |||||
| 3 | Biosynthesis of antibiotics | |||||
| 4 | FoxO signaling pathway | |||||
| 5 | Peroxisome | |||||
| 6 | Amyotrophic lateral sclerosis (ALS) | |||||
| Pathwhiz Pathway | [+] 3 Pathwhiz Pathways | + | ||||
| 1 | Degradation of Superoxides | |||||
| 2 | Ethanol Degradation | |||||
| 3 | Tryptophan Metabolism | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | FoxO family signaling | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Detoxification of Reactive Oxygen Species | |||||
| 2 | Purine catabolism | |||||
| WikiPathways | [+] 8 WikiPathways | + | ||||
| 1 | DNA Damage Response (only ATM dependent) | |||||
| 2 | Tryptophan metabolism | |||||
| 3 | Oxidative Stress | |||||
| 4 | Detoxification of Reactive Oxygen Species | |||||
| 5 | Amyotrophic lateral sclerosis (ALS) | |||||
| 6 | Metabolism of nucleotides | |||||
| 7 | Folate Metabolism | |||||
| 8 | Selenium Micronutrient Network | |||||
| References | Top | |||||
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| REF 1 | Evaluation of EUK-189, a synthetic superoxide dismutase/catalase mimetic as a radiation countermeasure. Immunopharmacol Immunotoxicol. 2008;30(2):271-90. | |||||
| REF 2 | Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. J Mol Biol. 2000 Feb 11;296(1):295-309. | |||||
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