Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T12966
(Former ID: TTDS00409)
|
|||||
| Target Name |
Troponin C (TN-C)
|
|||||
| Synonyms |
Troponin C, slow skeletal and cardiac muscles; TNNC
Click to Show/Hide
|
|||||
| Gene Name |
TNNC1
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Acquired cutaneous blood vessel malformation [ICD-11: EF20] | |||||
| 2 | Heart failure [ICD-11: BD10-BD1Z] | |||||
| Function |
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.
Click to Show/Hide
|
|||||
| UniProt ID | ||||||
| Sequence |
MDDIYKAAVEQLTEEQKNEFKAAFDIFVLGAEDGCISTKELGKVMRMLGQNPTPEELQEM
IDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIM LQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMKGVE Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Dihydroxyaluminium | Drug Info | Approved | Skin inflammation | [2] | |
| 2 | Levosimendan | Drug Info | Approved | Congestive heart failure | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Stimulator | [+] 2 Stimulator drugs | + | ||||
| 1 | Dihydroxyaluminium | Drug Info | [4], [5] | |||
| 2 | Levosimendan | Drug Info | [1], [6] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Trifluoperazine | Ligand Info | |||||
| Structure Description | Crystal structure of the N-terminal domain of human cardiac troponin C in complex with trifluoperazine (orthrombic crystal form) | PDB:1WRK | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | Yes | [7] |
| PDB Sequence |
IYKAAVEQLT
13 EEQKNEFKAA23 FDIFVLGAED33 GSISTKELGK43 VMRMLGQNPT53 PEELQEMIDE 63 VDEDGSGTVD73 FDEFLVMMVR83 SM
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: ATX-101 | Ligand Info | |||||
| Structure Description | Crystal structure of human cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid | PDB:3RV5 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [8] |
| PDB Sequence |
DIYKAAVEQL
12 TEEQKNEFKA22 AFDIFVLGAE32 DGCISTKELG42 KVRLGQNPTP54 EELQEIDEVD 65 EDGSGTVDFD75 EFLVVRC
|
|||||
|
|
||||||
| 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
|
|
|
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.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Calcium signaling pathway | hsa04020 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cardiac muscle contraction | hsa04260 | Affiliated Target |
|
| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Adrenergic signaling in cardiomyocytes | hsa04261 | Affiliated Target |
|
| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 2.94E-07 |
|---|---|---|---|---|---|
| Closeness centrality | 1.49E-01 | Radiality | 1.19E+01 | Clustering coefficient | 6.19E-01 |
| Neighborhood connectivity | 8.57E+00 | Topological coefficient | 3.90E-01 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | Cardiac muscle contraction | |||||
| 3 | Adrenergic signaling in cardiomyocytes | |||||
| 4 | Hypertrophic cardiomyopathy (HCM) | |||||
| 5 | Dilated cardiomyopathy | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Muscle/Heart Contraction | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Striated Muscle Contraction | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Striated Muscle Contraction | |||||
| 2 | Muscle contraction | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Timing of levosimendan in cardiac surgery. Anadolu Kardiyol Derg. 2009 Jun;9(3):223-30. | |||||
| REF 2 | Drug information of Dihydroxyaluminium, Health Canada, 2007. | |||||
| REF 3 | Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95. | |||||
| REF 4 | A retrospective analysis of changes in inflammatory markers in patients treated with bacterial viruses. Clin Exp Med. 2009 Dec;9(4):303-12. | |||||
| REF 5 | Effects of various aluminium compounds given orally to mice on Al tissue distribution and tissue concentrations of essential elements. Pharmacol Toxicol. 2000 Mar;86(3):135-9. | |||||
| REF 6 | Levosimendan does not improve survival time in a rat model of verapamil toxicity. J Med Toxicol. 2009 Mar;5(1):3-7. | |||||
| REF 7 | Crystal structure of the N-terminal domain of human cardiac troponin C in complex with trifluoperazine | |||||
| REF 8 | Crystal structure of cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid reveals novel conformation. J Mol Biol. 2011 Oct 28;413(3):699-711. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.