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Protein

Troponin C, slow skeletal and cardiac muscles

Gene

TNNC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi65 – 761Add BLAST12
Calcium bindingi105 – 1162Add BLAST12
Calcium bindingi141 – 1523Add BLAST12

GO - Molecular functioni

  • actin filament binding Source: BHF-UCL
  • calcium-dependent protein binding Source: UniProtKB
  • calcium ion binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • troponin I binding Source: UniProtKB
  • troponin T binding Source: UniProtKB

GO - Biological processi

  • cardiac muscle contraction Source: BHF-UCL
  • diaphragm contraction Source: Ensembl
  • muscle filament sliding Source: Reactome
  • regulation of ATPase activity Source: BHF-UCL
  • regulation of muscle contraction Source: UniProtKB
  • regulation of muscle filament sliding speed Source: BHF-UCL
  • response to metal ion Source: Ensembl
  • skeletal muscle contraction Source: GO_Central
  • transition between fast and slow fiber Source: Ensembl
  • ventricular cardiac muscle tissue morphogenesis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Muscle protein

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000114854-MONOMER.
ReactomeiR-HSA-390522. Striated Muscle Contraction.

Names & Taxonomyi

Protein namesi
Recommended name:
Troponin C, slow skeletal and cardiac muscles
Short name:
TN-C
Gene namesi
Name:TNNC1
Synonyms:TNNC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:11943. TNNC1.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: HPA
  • cytosol Source: Reactome
  • mitochondrion Source: HPA
  • nucleoplasm Source: HPA
  • troponin complex Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, dilated 1Z (CMD1Z)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:611879
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043988159G → R in CMD1Z. 1 Publication1
Cardiomyopathy, familial hypertrophic 13 (CMH13)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
See also OMIM:613243
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0630708A → V in CMH13; increases calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs267607125dbSNPEnsembl.1
Natural variantiVAR_01977629L → Q in CMH13; impairs protein kinase A dependent signaling from cardiac troponin I to troponin C. 2 PublicationsCorresponds to variant rs267607123dbSNPEnsembl.1
Natural variantiVAR_06307184C → Y in CMH13; increases calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs267607126dbSNPEnsembl.1
Natural variantiVAR_063072134E → D in CMH13; no changes in calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs397516847dbSNPEnsembl.1
Natural variantiVAR_063073145D → E in CMH13; increases calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs267607124dbSNPEnsembl.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi7134.
MalaCardsiTNNC1.
MIMi611879. phenotype.
613243. phenotype.
OpenTargetsiENSG00000114854.
Orphaneti154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA36632.

Chemistry databases

ChEMBLiCHEMBL2095202.
DrugBankiDB01244. Bepridil.
DB01375. Dihydroxyaluminium.
DB01023. Felodipine.
DB00922. Levosimendan.
DB00831. Trifluoperazine.

Polymorphism and mutation databases

BioMutaiTNNC1.
DMDMi54042075.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000736971 – 161Troponin C, slow skeletal and cardiac musclesAdd BLAST161

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine1 Publication1
Modified residuei98PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP63316.
PaxDbiP63316.
PeptideAtlasiP63316.
PRIDEiP63316.

PTM databases

iPTMnetiP63316.
PhosphoSitePlusiP63316.

Expressioni

Gene expression databases

BgeeiENSG00000114854.
CleanExiHS_TNNC1.
ExpressionAtlasiP63316. baseline and differential.
GenevisibleiP63316. HS.

Organism-specific databases

HPAiCAB002450.
HPA044848.
HPA056897.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TNNI1P192373EBI-3906339,EBI-746692

GO - Molecular functioni

  • actin filament binding Source: BHF-UCL
  • calcium-dependent protein binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL
  • troponin I binding Source: UniProtKB
  • troponin T binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112988. 13 interactors.
IntActiP63316. 8 interactors.
STRINGi9606.ENSP00000232975.

Structurei

Secondary structure

1161
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 9Combined sources7
Helixi14 – 25Combined sources12
Turni30 – 32Combined sources3
Beta strandi35 – 37Combined sources3
Helixi38 – 47Combined sources10
Beta strandi51 – 53Combined sources3
Helixi54 – 64Combined sources11
Beta strandi66 – 68Combined sources3
Beta strandi71 – 73Combined sources3
Helixi74 – 85Combined sources12
Helixi86 – 89Combined sources4
Beta strandi90 – 92Combined sources3
Helixi94 – 104Combined sources11
Beta strandi106 – 108Combined sources3
Beta strandi109 – 112Combined sources4
Helixi114 – 123Combined sources10
Beta strandi124 – 126Combined sources3
Helixi130 – 140Combined sources11
Beta strandi144 – 149Combined sources6
Helixi150 – 157Combined sources8
Turni158 – 160Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AP4NMR-A1-89[»]
1IH0NMR-A91-161[»]
1J1DX-ray2.61A/D1-161[»]
1J1EX-ray3.30A/D1-161[»]
1LXFNMR-C1-89[»]
1MXLNMR-C1-89[»]
1OZSNMR-A90-161[»]
1SPYNMR-A1-89[»]
1WRKX-ray2.15A/B1-88[»]
1WRLX-ray2.60A/B/C/D/E/F1-88[»]
2JT0NMR-A1-161[»]
2JT3NMR-A1-161[»]
2JT8NMR-A1-161[»]
2JTZNMR-A1-161[»]
2JXLNMR-A1-89[»]
2KDHNMR-A91-161[»]
2KFXNMR-T1-89[»]
2KGBNMR-C1-89[»]
2KRDNMR-C1-89[»]
2L1RNMR-A1-89[»]
2L98NMR-A91-161[»]
2MKPNMR-C1-89[»]
2MLENMR-C91-161[»]
2MLFNMR-C91-161[»]
2MZPNMR-C1-89[»]
2N79NMR-C1-89[»]
2N7LNMR-C1-89[»]
3RV5X-ray2.20A/B/C/D1-89[»]
3SD6X-ray1.37A1-89[»]
3SWBX-ray1.67A1-89[»]
4GJEX-ray1.60A1-89[»]
4GJFX-ray1.90A1-89[»]
4GJGX-ray2.00A1-89[»]
4Y99X-ray2.00A1-161[»]
ProteinModelPortaliP63316.
SMRiP63316.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63316.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 51EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini52 – 87EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini92 – 127EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini128 – 161EF-hand 4PROSITE-ProRule annotationAdd BLAST34

Sequence similaritiesi

Belongs to the troponin C family.Curated
Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0027. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118901.
HOGENOMiHOG000233018.
HOVERGENiHBG012180.
InParanoidiP63316.
KOiK05865.
OMAiMNDIYKA.
OrthoDBiEOG091G0QHM.
PhylomeDBiP63316.
TreeFamiTF318191.

Family and domain databases

CDDicd00051. EFh. 2 hits.
Gene3Di1.10.238.10. 2 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
PF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 4 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P63316-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDDIYKAAVE QLTEEQKNEF KAAFDIFVLG AEDGCISTKE LGKVMRMLGQ
60 70 80 90 100
NPTPEELQEM IDEVDEDGSG TVDFDEFLVM MVRCMKDDSK GKSEEELSDL
110 120 130 140 150
FRMFDKNADG YIDLDELKIM LQATGETITE DDIEELMKDG DKNNDGRIDY
160
DEFLEFMKGV E
Length:161
Mass (Da):18,403
Last modified:October 11, 2004 - v1
Checksum:i34DCCC46D503A312
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96Missing in AAB91994 (Ref. 4) Curated1
Sequence conflicti115D → E AA sequence (PubMed:3951483).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0630708A → V in CMH13; increases calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs267607125dbSNPEnsembl.1
Natural variantiVAR_01977629L → Q in CMH13; impairs protein kinase A dependent signaling from cardiac troponin I to troponin C. 2 PublicationsCorresponds to variant rs267607123dbSNPEnsembl.1
Natural variantiVAR_06307184C → Y in CMH13; increases calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs267607126dbSNPEnsembl.1
Natural variantiVAR_063072134E → D in CMH13; no changes in calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs397516847dbSNPEnsembl.1
Natural variantiVAR_063073145D → E in CMH13; increases calcium sensitivity of the myofilaments. 2 PublicationsCorresponds to variant rs267607124dbSNPEnsembl.1
Natural variantiVAR_043988159G → R in CMD1Z. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X07897 mRNA. Translation: CAA30736.1.
M37984 Genomic DNA. Translation: AAA36772.1.
AF020769 mRNA. Translation: AAB91994.1.
BC030244 mRNA. Translation: AAH30244.1.
CCDSiCCDS2857.1.
RefSeqiNP_003271.1. NM_003280.2.
UniGeneiHs.118845.

Genome annotation databases

EnsembliENST00000232975; ENSP00000232975; ENSG00000114854.
GeneIDi7134.
KEGGihsa:7134.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X07897 mRNA. Translation: CAA30736.1.
M37984 Genomic DNA. Translation: AAA36772.1.
AF020769 mRNA. Translation: AAB91994.1.
BC030244 mRNA. Translation: AAH30244.1.
CCDSiCCDS2857.1.
RefSeqiNP_003271.1. NM_003280.2.
UniGeneiHs.118845.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AP4NMR-A1-89[»]
1IH0NMR-A91-161[»]
1J1DX-ray2.61A/D1-161[»]
1J1EX-ray3.30A/D1-161[»]
1LXFNMR-C1-89[»]
1MXLNMR-C1-89[»]
1OZSNMR-A90-161[»]
1SPYNMR-A1-89[»]
1WRKX-ray2.15A/B1-88[»]
1WRLX-ray2.60A/B/C/D/E/F1-88[»]
2JT0NMR-A1-161[»]
2JT3NMR-A1-161[»]
2JT8NMR-A1-161[»]
2JTZNMR-A1-161[»]
2JXLNMR-A1-89[»]
2KDHNMR-A91-161[»]
2KFXNMR-T1-89[»]
2KGBNMR-C1-89[»]
2KRDNMR-C1-89[»]
2L1RNMR-A1-89[»]
2L98NMR-A91-161[»]
2MKPNMR-C1-89[»]
2MLENMR-C91-161[»]
2MLFNMR-C91-161[»]
2MZPNMR-C1-89[»]
2N79NMR-C1-89[»]
2N7LNMR-C1-89[»]
3RV5X-ray2.20A/B/C/D1-89[»]
3SD6X-ray1.37A1-89[»]
3SWBX-ray1.67A1-89[»]
4GJEX-ray1.60A1-89[»]
4GJFX-ray1.90A1-89[»]
4GJGX-ray2.00A1-89[»]
4Y99X-ray2.00A1-161[»]
ProteinModelPortaliP63316.
SMRiP63316.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112988. 13 interactors.
IntActiP63316. 8 interactors.
STRINGi9606.ENSP00000232975.

Chemistry databases

ChEMBLiCHEMBL2095202.
DrugBankiDB01244. Bepridil.
DB01375. Dihydroxyaluminium.
DB01023. Felodipine.
DB00922. Levosimendan.
DB00831. Trifluoperazine.

PTM databases

iPTMnetiP63316.
PhosphoSitePlusiP63316.

Polymorphism and mutation databases

BioMutaiTNNC1.
DMDMi54042075.

Proteomic databases

EPDiP63316.
PaxDbiP63316.
PeptideAtlasiP63316.
PRIDEiP63316.

Protocols and materials databases

DNASUi7134.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000232975; ENSP00000232975; ENSG00000114854.
GeneIDi7134.
KEGGihsa:7134.

Organism-specific databases

CTDi7134.
DisGeNETi7134.
GeneCardsiTNNC1.
GeneReviewsiTNNC1.
HGNCiHGNC:11943. TNNC1.
HPAiCAB002450.
HPA044848.
HPA056897.
MalaCardsiTNNC1.
MIMi191040. gene.
611879. phenotype.
613243. phenotype.
neXtProtiNX_P63316.
OpenTargetsiENSG00000114854.
Orphaneti154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA36632.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0027. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118901.
HOGENOMiHOG000233018.
HOVERGENiHBG012180.
InParanoidiP63316.
KOiK05865.
OMAiMNDIYKA.
OrthoDBiEOG091G0QHM.
PhylomeDBiP63316.
TreeFamiTF318191.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000114854-MONOMER.
ReactomeiR-HSA-390522. Striated Muscle Contraction.

Miscellaneous databases

ChiTaRSiTNNC1. human.
EvolutionaryTraceiP63316.
GeneWikiiTroponin_C_type_1.
GenomeRNAii7134.
PROiP63316.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114854.
CleanExiHS_TNNC1.
ExpressionAtlasiP63316. baseline and differential.
GenevisibleiP63316. HS.

Family and domain databases

CDDicd00051. EFh. 2 hits.
Gene3Di1.10.238.10. 2 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
PF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 4 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNNC1_HUMAN
AccessioniPrimary (citable) accession number: P63316
Secondary accession number(s): O14800, P02590, P04463
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: October 11, 2004
Last modified: November 30, 2016
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Cardiac muscle Tn-C can bind 3 calcium ions per molecule. Domain I does not bind calcium.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.