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P63316 (TNNC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Troponin C, slow skeletal and cardiac muscles

Short name=TN-C
Gene names
Name:TNNC1
Synonyms:TNNC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length161 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Involvement in disease

Cardiomyopathy, dilated 1Z (CMD1Z) [MIM:611879]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Cardiomyopathy, familial hypertrophic 13 (CMH13) [MIM:613243]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.11 Ref.12 Ref.13

Miscellaneous

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

Sequence similarities

Belongs to the troponin C family.

Contains 4 EF-hand domains.

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   DiseaseCardiomyopathy
Disease mutation
   DomainRepeat
   LigandCalcium
Metal-binding
   Molecular functionMuscle protein
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle contraction

Inferred from mutant phenotype Ref.10. Source: BHF-UCL

diaphragm contraction

Inferred from electronic annotation. Source: Ensembl

muscle filament sliding

Traceable author statement. Source: Reactome

regulation of ATPase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of muscle contraction

Traceable author statement Ref.3. Source: UniProtKB

regulation of muscle filament sliding speed

Inferred from sequence or structural similarity. Source: BHF-UCL

response to metal ion

Inferred from electronic annotation. Source: Ensembl

ventricular cardiac muscle tissue morphogenesis

Inferred from mutant phenotype Ref.10. Source: BHF-UCL

   Cellular_componentactin cytoskeleton

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

troponin complex

Inferred from direct assay PubMed 10850966PubMed 12093807. Source: UniProtKB

   Molecular_functionactin filament binding

Inferred from sequence or structural similarity. Source: BHF-UCL

calcium ion binding

Inferred from direct assay PubMed 12840750PubMed 18092822. Source: BHF-UCL

calcium-dependent protein binding

Inferred from physical interaction PubMed 7957210. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 18092822. Source: BHF-UCL

troponin I binding

Inferred from physical interaction PubMed 11735257Ref.10PubMed 7957210. Source: UniProtKB

troponin T binding

Inferred from physical interaction Ref.10PubMed 8205619. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 161161Troponin C, slow skeletal and cardiac muscles
PRO_0000073697

Regions

Domain16 – 5136EF-hand 1
Domain52 – 8736EF-hand 2
Domain92 – 12736EF-hand 3
Domain128 – 16134EF-hand 4
Calcium binding65 – 76121
Calcium binding105 – 116122
Calcium binding141 – 152123

Amino acid modifications

Modified residue11N-acetylmethionine

Natural variations

Natural variant81A → V in CMH13; increases calcium sensitivity of the myofilaments. Ref.12 Ref.13
VAR_063070
Natural variant291L → Q in CMH13; impairs protein kinase A dependent signaling from cardiac troponin I to troponin C. Ref.9 Ref.11
VAR_019776
Natural variant841C → Y in CMH13; increases calcium sensitivity of the myofilaments. Ref.12 Ref.13
VAR_063071
Natural variant1341E → D in CMH13; no changes in calcium sensitivity of the myofilaments. Ref.12 Ref.13
VAR_063072
Natural variant1451D → E in CMH13; increases calcium sensitivity of the myofilaments. Ref.12 Ref.13
VAR_063073
Natural variant1591G → R in CMD1Z. Ref.10
VAR_043988

Experimental info

Sequence conflict961Missing in AAB91994. Ref.4
Sequence conflict1151D → E AA sequence Ref.1

Secondary structure

................................. 161
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P63316 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: 34DCCC46D503A312

FASTA16118,403
        10         20         30         40         50         60 
MDDIYKAAVE QLTEEQKNEF KAAFDIFVLG AEDGCISTKE LGKVMRMLGQ NPTPEELQEM 

        70         80         90        100        110        120 
IDEVDEDGSG TVDFDEFLVM MVRCMKDDSK GKSEEELSDL FRMFDKNADG YIDLDELKIM 

       130        140        150        160 
LQATGETITE DDIEELMKDG DKNNDGRIDY DEFLEFMKGV E 

« Hide

References

« Hide 'large scale' references
[1]"The amino acid sequence of human cardiac troponin-C."
Roher A., Lieska N., Spitz W.
Muscle Nerve 9:73-77(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE.
Tissue: Heart muscle.
[2]"Differential expression of slow and fast skeletal muscle troponin C. Slow skeletal muscle troponin C is expressed in human fibroblasts."
Gahlmann R., Wade R., Gunning R., Kedes L.
J. Mol. Biol. 201:379-391(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Slow skeletal muscle.
[3]"Cloning, structural analysis, and expression of the human slow twitch skeletal muscle/cardiac troponin C gene."
Schreier T., Kedes L., Gahlmann R.
J. Biol. Chem. 265:21247-21253(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Slow skeletal muscle.
[4]"H. sapiens mRNA for cardiac ventricular troponin C in idiopathic dilated cardiomyopathy."
Margossian S.S., Yang F., Umeda P.K., Sciaky D., Anderson P.A.W.
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Blood.
[6]"Calcium-induced structural transition in the regulatory domain of human cardiac troponin C."
Spyracopoulos L., Li M.X., Sia S.K., Gagne S.M., Chandra M., Solaro R.J., Sykes B.D.
Biochemistry 36:12138-12146(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-89.
Tissue: Heart muscle.
[7]"Structural and functional domains of the troponin complex revealed by limited digestion."
Takeda S., Kobayashi T., Taniguchi H., Hayashi H., Maeda Y.
Eur. J. Biochem. 246:611-617(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS).
[8]"Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I."
Lindhout D.A., Sykes B.D.
J. Biol. Chem. 278:27024-27034(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 89-161.
Tissue: Heart muscle.
[9]"First mutation in cardiac troponin C, L29Q, in a patient with hypertrophic cardiomyopathy."
Hoffmann B., Schmidt-Traub H., Perrot A., Osterziel K.J., Gessner R.
Hum. Mutat. 17:524-524(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMH13 GLN-29.
[10]"Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy."
Mogensen J., Murphy R.T., Shaw T., Bahl A., Redwood C., Watkins H., Burke M., Elliott P.M., McKenna W.J.
J. Am. Coll. Cardiol. 44:2033-2040(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMD1Z ARG-159.
[11]"Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the transduction of the protein kinase A dependent phosphorylation signal from cardiac troponin I to C."
Schmidtmann A., Lindow C., Villard S., Heuser A., Mugge A., Gessner R., Granier C., Jaquet K.
FEBS J. 272:6087-6097(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CMH13 GLN-29.
[12]"Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C."
Landstrom A.P., Parvatiyar M.S., Pinto J.R., Marquardt M.L., Bos J.M., Tester D.J., Ommen S.R., Potter J.D., Ackerman M.J.
J. Mol. Cell. Cardiol. 45:281-288(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH13 VAL-8; TYR-84; ASP-134 AND GLU-145, CHARACTERIZATION OF VARIANTS CMH13 VAL-8; TYR-84; ASP-134 AND GLU-145.
[13]"A functional and structural study of troponin C mutations related to hypertrophic cardiomyopathy."
Pinto J.R., Parvatiyar M.S., Jones M.A., Liang J., Ackerman M.J., Potter J.D.
J. Biol. Chem. 284:19090-19100(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS CMH13 VAL-8; TYR-84; ASP-134 AND GLU-145.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X07897 mRNA. Translation: CAA30736.1.
M37984 Genomic DNA. Translation: AAA36772.1.
AF020769 mRNA. Translation: AAB91994.1.
BC030244 mRNA. Translation: AAH30244.1.
RefSeqNP_003271.1. NM_003280.2.
UniGeneHs.118845.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
3RV5X-ray2.20A/B/C/D1-89[»]
3SD6X-ray1.37A1-89[»]
3SWBX-ray1.67A1-89[»]
4GJEX-ray1.60A1-89[»]
4GJFX-ray1.90A1-89[»]
4GJGX-ray2.00A3-89[»]
ProteinModelPortalP63316.
SMRP63316. Positions 1-161.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112988. 13 interactions.
IntActP63316. 6 interactions.
STRING9606.ENSP00000232975.

Chemistry

ChEMBLCHEMBL2095202.
DrugBankDB01244. Bepridil.
DB01375. Dihydroxyaluminium.
DB00922. Levosimendan.

PTM databases

PhosphoSiteP63316.

Polymorphism databases

DMDM54042075.

Proteomic databases

PaxDbP63316.
PRIDEP63316.

Protocols and materials databases

DNASU7134.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000232975; ENSP00000232975; ENSG00000114854.
GeneID7134.
KEGGhsa:7134.
UCSCuc003deb.3. human.

Organism-specific databases

CTD7134.
GeneCardsGC03M052485.
HGNCHGNC:11943. TNNC1.
HPACAB002450.
HPA044848.
MIM191040. gene.
611879. phenotype.
613243. phenotype.
neXtProtNX_P63316.
Orphanet154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA36632.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5126.
HOGENOMHOG000233018.
HOVERGENHBG012180.
InParanoidP63316.
KOK05865.
OMAMNDIYKA.
OrthoDBEOG76X61W.
PhylomeDBP63316.
TreeFamTF318191.

Enzyme and pathway databases

ReactomeREACT_17044. Muscle contraction.

Gene expression databases

ArrayExpressP63316.
BgeeP63316.
CleanExHS_TNNC1.
GenevestigatorP63316.

Family and domain databases

Gene3D1.10.238.10. 2 hits.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001125. Recoverin_like.
[Graphical view]
PfamPF13499. EF-hand_7. 1 hit.
[Graphical view]
PRINTSPR00450. RECOVERIN.
SMARTSM00054. EFh. 4 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNNC1. human.
EvolutionaryTraceP63316.
GeneWikiTroponin_C_type_1.
GenomeRNAi7134.
NextBio27913.
PROP63316.
SOURCESearch...

Entry information

Entry nameTNNC1_HUMAN
AccessionPrimary (citable) accession number: P63316
Secondary accession number(s): O14800, P02590, P04463
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: October 11, 2004
Last modified: April 16, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM