Target Information
| Target General Information | Top | |||||
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| Target ID |
T20186
(Former ID: TTDR00670)
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| Target Name |
Cardiac troponin I (TNNI3)
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| Synonyms |
TNNI3
Click to Show/Hide
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| Gene Name |
TNNI3
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
Click to Show/Hide
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| BioChemical Class |
Troponin
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| UniProt ID | ||||||
| Sequence |
MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQE
LEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTK NITEIADLTQKIFDLRGKFKRPTLRRVRISADAMMQALLGARAKESLDLRAHLKQVKKED TEKENREVGDWRKNIDALSGMEGRKKKFES Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T21UJU | |||||
| 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: 4-(3-cyano-3-methylazetidine-1-carbonyl)-N-[(3R,4S)-7-fluoro-4-hydroxy-6-methyl-3,4-dihydro-2H-1-benzopyran-3-yl]-5-methyl-1H-pyrrole-2-sulfonamide | Ligand Info | |||||
| Structure Description | NMR structure of cTnC-TnI chimera bound to calcium and A2 | PDB:7SVC | ||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [2] |
| PDB Sequence |
GDDIYKAAVE
10 QLTEEQKNEF20 KAAFDIFVLG30 AEDGCISTKE40 LGKVMRMLGQ50 NPTPEELQEM 60 IDEVDEDGSG70 TVDFDEFLVM80 MVRCMKDDSK90 GAGAGVRISA100 DAMMQALLGA 110 RAKESLDLRA120 HLKQVKKED
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PHE27
2.670
ILE36
2.638
LEU41
2.273
MET45
1.994
GLN50
2.300
ASN51
3.726
PRO52
2.201
THR53
4.348
GLU56
3.789
LEU57
3.784
GLU59
3.224
MET60
2.082
ILE61
2.534
GLU63
4.333
VAL64
2.381
VAL72
2.951
PHE77
2.587
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 4-(3-cyano-3-methylazetidine-1-carbonyl)-N-[(3S)-7-fluoro-6-methyl-3,4-dihydro-2H-1-benzopyran-3-yl]-5-methyl-1H-pyrrole-2-sulfonamide | Ligand Info | |||||
| Structure Description | NMR structure of cTnC-TnI chimera bound to calcium and A1 | PDB:7SUP | ||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [2] |
| PDB Sequence |
GDDIYKAAVE
10 QLTEEQKNEF20 KAAFDIFVLG30 AEDGCISTKE40 LGKVMRMLGQ50 NPTPEELQEM 60 IDEVDEDGSG70 TVDFDEFLVM80 MVRCMKDDSK90 GAGAGVRISA100 DAMMQALLGA 110 RAKESLDLRA120 HLKQVKKED
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PHE27
2.855
ILE36
2.986
LEU41
2.265
MET45
2.517
GLN50
2.463
ASN51
3.732
PRO52
2.513
THR53
4.337
GLU56
2.525
LEU57
4.629
GLU59
2.926
MET60
1.980
ILE61
2.535
GLU63
3.521
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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).
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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| cAMP signaling pathway | hsa04024 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cardiac muscle contraction | hsa04260 | Affiliated Target |
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| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Adrenergic signaling in cardiomyocytes | hsa04261 | Affiliated Target |
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| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 2.34E-04 |
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| Closeness centrality | 1.69E-01 | Radiality | 1.27E+01 | Clustering coefficient | 3.89E-01 |
| Neighborhood connectivity | 8.11E+00 | Topological coefficient | 3.08E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Circulating, imaging, and genetic biomarkers in cardiovascular risk prediction. Trends Cardiovasc Med. 2011 May;21(4):105-12. | |||||
| REF 2 | Structural and Thermodynamic Model for the Activation of Cardiac Troponin. Biochemistry. 2022 Apr 19;61(8):741-748. | |||||
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