Target Information
Target General Information | Top | |||||
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Target ID |
T79027
(Former ID: TTDI02040)
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Target Name |
Cytidine deaminase (CDA)
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Synonyms |
Cytidine aminohydrolase; CDA
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Gene Name |
CDA
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
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BioChemical Class |
Carbon-nitrogen hydrolase
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UniProt ID | ||||||
EC Number |
EC 3.5.4.5
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Sequence |
MAQKRPACTLKPECVQQLLVCSQEAKKSAYCPYSHFPVGAALLTQEGRIFKGCNIENACY
PLGICAERTAIQKAVSEGYKDFRAIAIASDMQDDFISPCGACRQVMREFGTNWPVYMTKP DGTYIVMTVQELLPSSFGPEDLQKTQ Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T53OZE |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | Tetrahydrouridine | Drug Info | Phase 2 | Solid tumour/cancer | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Tetrahydrouridine | Drug Info | [1], [2] |
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: 1-beta-Ribofuranosyl-1,3-diazepinone | Ligand Info | |||||
Structure Description | Crystal Structure of Human Cytidine Deaminase | PDB:1MQ0 | ||||
Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [3] |
PDB Sequence |
ECVQQLLVCS
22 QEAKQSAYCP32 YSHFPVGAAL42 LTQEGRIFKG52 CNIENACYPL62 GICAERTAIQ 72 KAVSEGYKDF82 RAIAIASDMQ92 DDFISPCGAC102 RQVMREFGTN112 WPVYMTKPDG 122 TYIVMTVQEL132 LPSSFGPEDL142
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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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Pyrimidine metabolism | hsa00240 | Affiliated Target |
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Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
Drug metabolism - other enzymes | hsa00983 | Affiliated Target |
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Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy |
Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 4.78E-04 |
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Closeness centrality | 1.71E-01 | Radiality | 1.27E+01 | Clustering coefficient | 2.86E-01 |
Neighborhood connectivity | 8.29E+00 | Topological coefficient | 2.59E-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 |
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 6 BioCyc Pathways | + | ||||
1 | Pyrimidine ribonucleosides degradation | |||||
2 | Pyrimidine ribonucleosides degradation | |||||
3 | Pyrimidine deoxyribonucleosides degradation | |||||
4 | Superpathway of pyrimidine deoxyribonucleoside salvage | |||||
5 | Pyrimidine ribonucleosides salvage I | |||||
6 | Pyrimidine deoxyribonucleosides salvage | |||||
KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | Pyrimidine metabolism | |||||
2 | Drug metabolism - other enzymes | |||||
3 | Metabolic pathways | |||||
Panther Pathway | [+] 3 Panther Pathways | + | ||||
1 | Pyrimidine Metabolism | |||||
2 | Salvage pyrimidine deoxyribonucleotides | |||||
3 | Salvage pyrimidine ribonucleotides | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Pyrimidine Metabolism | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Metabolism of nucleotides | |||||
2 | Fluoropyrimidine Activity |
References | Top | |||||
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REF 1 | Tetrahydrouridine inhibits cell proliferation through cell cycle regulation regardless of cytidine deaminase expression levels. PLoS One. 2012;7(5):e37424. | |||||
REF 2 | Quantitative determination of the cytidine deaminase inhibitor tetrahydrouridine (THU) in mouse plasma by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007;21(13):1991-7. | |||||
REF 3 | Structure of human cytidine deaminase bound to a potent inhibitor. J Med Chem. 2005 Feb 10;48(3):658-60. |
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