P63316 (TNNC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Troponin C, slow skeletal and cardiac muscles
Short name=TN-C

Gene names

Name:	TNNC1
Synonyms:	TNNC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	161 AA.
Sequence status	Complete.
Protein existence	Evidence 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 diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Muscle protein
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle contraction Inferred from mutant phenotype Ref.10. Source: BHF-UCL muscle filament sliding Traceable author statement. Source: Reactome regulation of ATPase activity Inferred from sequence or structural similarity. Source: BHF-UCL regulation of muscle filament sliding speed Inferred from sequence or structural similarity. Source: BHF-UCL ventricular cardiac muscle tissue morphogenesis Inferred from mutant phenotype Ref.10. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome troponin complex Inferred from direct assay PubMed 10850966PubMed 12093807. Source: UniProtKB
Molecular_function	actin filament binding Inferred from sequence or structural similarity. Source: BHF-UCL calcium ion binding Inferred from direct assay PubMed 12840750PubMed 18092822. Source: BHF-UCL protein homodimerization activity Inferred from direct assay PubMed 18092822. Source: BHF-UCL troponin I binding Inferred from direct assay PubMed 18092822. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 161

161

Troponin C, slow skeletal and cardiac muscles

PRO_0000073697

Regions

Domain

16 – 51

36

EF-hand 1

Domain

52 – 87

36

EF-hand 2

Domain

92 – 127

36

EF-hand 3

Domain

128 – 161

34

EF-hand 4

Calcium binding

65 – 76

12

1

Calcium binding

105 – 116

12

2

Calcium binding

141 – 152

12

3

Amino acid modifications

Modified residue

1

1

N-acetylmethionine

Natural variations

Natural variant

8

1

A → V in CMH13; increases calcium sensitivity of the myofilaments. Ref.12 Ref.13

VAR_063070

Natural variant

29

1

L → Q in CMH13; impairs protein kinase A dependent signaling from cardiac troponin I to troponin C. Ref.9 Ref.11

VAR_019776

Natural variant

84

1

C → Y in CMH13; increases calcium sensitivity of the myofilaments. Ref.12 Ref.13

VAR_063071

Natural variant

134

1

E → D in CMH13; no changes in calcium sensitivity of the myofilaments. Ref.12 Ref.13

VAR_063072

Natural variant

145

1

D → E in CMH13; increases calcium sensitivity of the myofilaments. Ref.12 Ref.13

VAR_063073

Natural variant

159

1

G → R in CMD1Z. Ref.10

VAR_043988

Experimental info

Sequence conflict

96

1

Missing in AAB91994. Ref.4

Sequence conflict

115

1

D → E AA sequence Ref.1

Secondary structure

1

.

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161

Helix Strand Turn

Details...

Helix

3 – 9

7

Helix

14 – 25

12

Turn

30 – 32

3

Beta strand

35 – 37

3

Helix

38 – 47

10

Beta strand

51 – 53

3

Helix

54 – 64

11

Beta strand

66 – 68

3

Beta strand

71 – 73

3

Helix

74 – 85

12

Beta strand

90 – 92

3

Helix

94 – 104

11

Beta strand

109 – 113

5

Helix

114 – 123

10

Beta strand

124 – 126

3

Helix

130 – 140

11

Beta strand

145 – 148

4

Helix

150 – 157

8

Turn

158 – 160

3

Sequences

	Sequence		Length	Mass (Da)
	P63316 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: 34DCCC46D503A312	FASTA	161	18,403
	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

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00470359.

RefSeq

NP_003271.1. NM_003280.2.

UniGene

Hs.118845.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AP4	NMR	-	A	1-89	[»]
1IH0	NMR	-	A	91-161	[»]
1J1D	X-ray	2.61	A/D	1-161	[»]
1J1E	X-ray	3.30	A/D	1-161	[»]
1LXF	NMR	-	C	1-89	[»]
1MXL	NMR	-	C	1-89	[»]
1OZS	NMR	-	A	90-161	[»]
1SPY	NMR	-	A	1-89	[»]
1WRK	X-ray	2.15	A/B	1-88	[»]
1WRL	X-ray	2.60	A/B/C/D/E/F	1-88	[»]
2JT0	NMR	-	A	1-161	[»]
2JT3	NMR	-	A	1-161	[»]
2JT8	NMR	-	A	1-161	[»]
2JTZ	NMR	-	A	1-161	[»]
2JXL	NMR	-	A	1-89	[»]
2KDH	NMR	-	A	91-161	[»]
2KFX	NMR	-	T	1-89	[»]
2KGB	NMR	-	C	1-89	[»]
2KRD	NMR	-	C	1-89	[»]
2L1R	NMR	-	A	1-89	[»]
2L98	NMR	-	A	91-161	[»]
3RV5	X-ray	2.20	A/B/C/D	1-89	[»]
3SD6	X-ray	1.37	A	1-89	[»]
3SWB	X-ray	1.67	A	1-89	[»]
4GJE	X-ray	1.60	A	1-89	[»]
4GJF	X-ray	1.90	A	1-89	[»]
4GJG	X-ray	2.00	A	3-89	[»]

ProteinModelPortal

P63316.

ModBase

Search...

Protein-protein interaction databases

IntAct

P63316. 6 interactions.

STRING

9606.ENSP00000232975.

PTM databases

PhosphoSite

P63316.

Polymorphism databases

DMDM

54042075.

Proteomic databases

PaxDb

P63316.

PRIDE

P63316.

Protocols and materials databases

DNASU

7134.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000232975; ENSP00000232975; ENSG00000114854.

GeneID

7134.

KEGG

hsa:7134.

UCSC

uc003deb.3. human.

Organism-specific databases

CTD

7134.

GeneCards

GC03M052485.

HGNC

HGNC:11943. TNNC1.

HPA

CAB002450.

MIM

191040. gene.
611879. phenotype.
613243. phenotype.

neXtProt

NX_P63316.

Orphanet

154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.

PharmGKB

PA36632.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5126.

HOGENOM

HOG000233018.

HOVERGEN

HBG012180.

InParanoid

P63316.

KO

K05865.

OMA

MNDIYKA.

OrthoDB

EOG46WZ9P.

PhylomeDB

P63316.

Enzyme and pathway databases

Reactome

REACT_17044. Muscle contraction.

Gene expression databases

ArrayExpress

P63316.

Bgee

P63316.

CleanEx

HS_TNNC1.

Genevestigator

P63316.

GermOnline

ENSG00000114854. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 2 hits.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001125. Recoverin.
[Graphical view]

Pfam

PF13499. EF_hand_5. 1 hit.
[Graphical view]

PRINTS

PR00450. RECOVERIN.

SMART

SM00054. EFh. 4 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2066.

ChiTaRS

TNNC1. human.

DrugBank

DB01244. Bepridil.
DB01375. Dihydroxyaluminium.
DB00922. Levosimendan.

EvolutionaryTrace

P63316.

GenomeRNAi

7134.

NextBio

27913.

SOURCE

Search...

Entry information

Entry name

TNNC1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.