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FLASH GENE

Symbol

TNNC1

contributors: npt/mct - updated : 27-12-2016

HGNC name	troponin C type 1 (slow)
HGNC id	11943

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CMH13 cardiomyopathy, familial, hypertrophic, 13 RCM5 restrictive cardiomyopathy 5
Location	3p21.1      Physical location : 52.485.107 - 52.488.057
Synonym name	cardiac troponin C
	troponin C, slow
	troponin C, slow skeletal and cardiac muscles
Synonym symbol(s)	TNC, TNNC, cTnc

DNA

TYPE	functioning gene
STRUCTURE	2.95 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003280 6 - 705 NP_003271 - 161 - 1997 9365790

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Homo sapiens Reproductive male system prostate       Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac   highly Homo sapiens Muscular striatum skeletal   highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	12-residue alpha-helix at the N terminus, EF-hand loop (NH2-DEDGSGTVDFDE-COOH) with six residues (bold) that coordinate Ca2+ binding and six residues that do not appear to influence Ca2+ binding directly
	the N helix, containing Ca++ binding site, that responds to Ca2+ to regulate muscle contraction, and N terminus plays an important role in the regulation of cardiac muscle contraction by moving the C-terminal region of TNNI3 from its actin-binding inhibitory location and enhancing the movement of tropomyosin away from its inhibitory position
	two globular EF-hand domains connected by a flexible linker
	a C-domain sites that are thought to be permanently occupied by Ca2+ and/or Mg2+, thus playing a structural role by anchoring TNNC1 into the thin filament (Swindle 2010), and Ca(2+)/Mg(2+) sites (III and IV) modulate crossbridge-mediated thin filament activation in cardiac myofibrils

secondary structure

a central helix and conserved acidic AAs within the exposed middle segment of the central helix are important for the proper regulatory function of the cTn complex

conjugated

Other

HOMOLOGY

interspecies

homolog to C.elegans T21H3.3

Homologene

FAMILY

troponin C family

CATEGORY

motor/contractile , regulatory , structural protein

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
	intracellular,nucleus,nucleoplasm

basic FUNCTION	preventing actin and myosin interaction in resting muscle tissue
	involved in regulation of striated muscle contraction
	its Ca(2+) binding properties modulate the rate of cardiac muscle contraction at submaximal levels of Ca(2+) activation
	is required both for the function and structural integrity of the contractile machinery in cardiomyocytes
	important regulatory molecule in cardiomyocytes
	may act as a hub, sensing physiological and pathological stimuli to modulate the Ca(2+)-binding properties of the thin filament and influence the contractile performance of the heart
	calcium-binding subunit of the troponin complex responsible for initiating striated muscle contraction in response to calcium influx
	Ca2+ sensor and key regulator of contraction
	role of TNNC1 mutations in the development of cardiomyopathy

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	muscle development

PATHWAY

metabolism

signaling

a component	constituent of the troponin complex forming the calcium-sensitive molecular switch that regulates striated muscle contraction in response to modifications in intracellular concentration, cardiac and slow twitch skeletal muscle
	calcium-binding subunit of troponin

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	interacting with both thin and thick filament proteins which influence the ability of TNNC1 to sense and respond to Ca(2+)
	interactions with the other contractile proteins play a crucial role in modulating the binding of calcium to TNNC1 in increasingly complex biochemical systems
	TNNI3 has a unique 31-AAs N-terminal region that binds cardiac troponin C (TNNC1) to increase the calcium sensitivity of the sarcomere

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CMH13 , RCM5

Susceptibility

to dilated cardiomyopathy (DCM) to Hypertrophic Cardiomyopathy

Variant & Polymorphism other	Y5H, M103I, G159D and Q50R, and I148V variants associated with DCM
	TNNC1-A8V mutant increases the Ca(2+)-binding affinity of the thin filament and elicits changes in Ca(2+) homeostasis and cellular remodeling, which leads to diastolic dysfunction, and to hypertrophic cardiomyopathy

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS