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  6. Troponin C, slow skeletal and cardiac muscles

Tclin Troponin C, slow skeletal and cardiac muscles

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.

Troponin is a central regulatory protein of striated muscle contraction, and together with tropomyosin, is located on the actin filament. Troponin consists of 3 subunits: TnI, which is the inhibitor of actomyosin ATPase; TnT, which contains the binding site for tropomyosin; and TnC, the protein encoded by this gene. The binding of calcium to TnC abolishes the inhibitory action of TnI, thus allowing the interaction of actin with myosin, the hydrolysis of ATP, and the generation of tension. Mutations in this gene are associated with cardiomyopathy dilated type 1Z. [provided by RefSeq, Oct 2008]

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Property Summary

NCBI Gene PubMed Count 88
Grant Count 1
Funding $150,388.67
PubMed Score 10.79
PubTator Score 164.18

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Relevance (17)

Disease Z-score Confidence
Cardiomyopathy 110 4.0
Cardiomyopathy, Dilated 47
Cardiomyopathy, Dilated, 1z 1
Cardiomyopathy, Familial Hypertrophic, 1... 10 
Cardiomyopathy, Familial Hypertrophic, 1... 1 
Congestive heart failure 30
Dilated cardiomyopathy 50 5.0
Endometriosis 535
colon cancer 1,475
interstitial cystitis 2,299
lung adenocarcinoma 2,713
lung cancer 4,466
lung carcinoma 2,844
malignant mesothelioma 3,162
non-small cell lung cancer 2,798
pituitary cancer 1,972
psoriasis 6,685

Expression

  Differential Expression (10)

Disease log2 FC p
malignant mesothelioma 3.800 0.000
psoriasis -3.000 0.000
non-small cell lung cancer -4.464 0.000
colon cancer 1.100 0.017
lung cancer -2.100 0.000
interstitial cystitis -1.100 0.001
lung adenocarcinoma -3.200 0.000
Endometriosis -1.358 0.028
lung carcinoma -1.900 0.000
pituitary cancer -2.400 0.000

Synonym

Accession P63316 O14800 P02590 P04463 TN-C
Symbols TNC
TN-C
TNNC
CMD1Z
CMH13

Gene

TNNC1

PANTHER Protein Class (3)

 Grant Application (1)

PDB

1AP4   1IH0   1J1D   1J1E   1LXF   1MXL   1OZS   1SPY   1WRK   1WRL   2JT0   2JT3   2JT8   2JTZ   2JXL   2KDH   2KFX   2KGB   2KRD   2L1R   2L98   2MKP   2MLE   2MLF   2MZP   2N79   2N7L   3RV5   3SD6   3SWB   4GJE   4GJF   4GJG   4Y99  

 GO Function (6)

 GO Component (5)

 GO Process (10)

 Compartment GO Term (36)

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 OMIM Term (2)

Pathway (59)

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 UniProt Keyword (13)

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Drug (1)

Structure of levosimendan

levosimendan
pKd 3.15

MLP Assay (12)

AID Type Active / Inconclusive / Inactive Description
493008 screening 801 / 0 / 334660 Fluorescence-based biochemical primary high throughput screening assay to identify activators of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
493018 summary 0 / 0 / 0 Summary of the probe development efforts to identify activators of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
493244 screening 390 / 0 / 335070 Fluorescence-based biochemical primary high throughput screening assay to identify inhibitors of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
504337 summary 0 / 0 / 0 Summary of the probe development efforts to identify inhibitors of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
504383 screening 1166 / 0 / 1301 Fluorescence-based biochemical high throughput confirmation assay for activators of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
504635 screening 30 / 0 / 328 Fluorescence-based biochemical high throughput confirmation assay for inhibitors of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
504698 confirmatory 76 / 0 / 168 Fluorescence-based biochemical high throughput dose response assay for activators of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
504742 confirmatory 14 / 0 / 18 Fluorescence-based biochemical high throughput dose response assay for inhibitors of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF)
602231 other 0 / 0 / 4 Assay provider mechanism-of-action assay for activators of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF): biochemical assay to identify activators of the Ca2+-sensitivity of cardiac muscle contraction/tension
602232 other 2 / 0 / 14 Assay provider mechanism-of-action assay for activators of the calcium sensitivity of cardiac Regulated Thin Filaments (RTF): absorbance-based biochemical assay to identify sensitizers of the Ca2+ sensitivity of cardiac myofibrillar ATPase
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Gene RIF (56)

PMID Text
26341255 We used nuclear magnetic resonance and circular dichroism to solve the structure and characterize the backbone dynamics and stability of the regulatory domain of cTnC with the L29Q mutation.
26304555 conclusive evidence that TNNC1 is an uncommon but definitive HCM-susceptibility gene
26232335 Mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy.[review]
26111167 Troponin C (TnC) and the N-terminal helix of Troponin I (TnI N-helix), which occurs in vivo during muscle contraction.
25996354 Data suggest that mutation A162H in switch region of troponin I induces transitory curved conformation and promotes contraction of troponin I bound to regulatory domain of troponin C; this is countered by residue E164 to ensure proper relaxation.
25277212 FAK/CREB/TNNC1 has a role in mediating the effect of stromal MFAP5 on ovarian cancer metastatic potential
25246568 Data indicate that domain positioning impacts the effective concentration of cardiac isoform of troponin I (cTnI) presented to cardiac troponin C (cTnC).
25101951 The conformational dynamics of N-terminal lobe of TnC plays an important role in the regulation of cardiac muscle contraction.
24744096 in vitro characterisation of six cardiac Troponin C mutations causing hypertrophic and dilated cardiomyopathies (Review)
24650606 Central helix point mutations decreased affinity of Ca2+ saturated cardiac TNC for TnI128-180.
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AA Sequence 

MDDIYKAAVEQLTEEQKNEFKAAFDIFVLGAEDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSG      1 - 70
TVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDG     71 - 140
DKNNDGRIDYDEFLEFMKGVE                                                     141 - 161
//

Text Mined References (86)

PMID Year Title
26341255 2015 The structural and functional effects of the familial hypertrophic cardiomyopathy-linked cardiac troponin C mutation, L29Q.
26304555 2015 In Vivo Analysis of Troponin C Knock-In (A8V) Mice: Evidence that TNNC1 Is a Hypertrophic Cardiomyopathy Susceptibility Gene.
26232335 2015 Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs.
26111167 2015 Coarse-Grained Modeling of Peptide Docking Associated with Large Conformation Transitions of the Binding Protein: Troponin I Fragment-Troponin C System.
25996354 2015 Structure and Dynamics of the Acidosis-Resistant A162H Mutant of the Switch Region of Troponin I Bound to the Regulatory Domain of Troponin C.
25277212 2014 Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential.
25246568 2014 The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C.
25101951 2014 Regulatory domain of troponin moves dynamically during activation of cardiac muscle.
24744096 2014 Biochemical characterisation of Troponin C mutations causing hypertrophic and dilated cardiomyopathies.
24650606 2014 Molecular and functional consequences of mutations in the central helix of cardiac troponin C.
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