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FLASH GENE

Symbol

TCAP

contributors: mct/pgu - updated : 28-03-2012

HGNC name	titin-cap (telethonin)
HGNC id	11610

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CMD1N cardiomyopathy, dilated 1N LGMD2G limb girdle muscular dystrophy 2G
Location	17q12      Physical location : 37.821.598 - 37.822.806
Synonym name	19 kDa sarcomeric protein
	titin-cap protein
	limb girdle muscular dystrophy 2G (autosomal recessive)
Synonym symbol(s)	TELE, TELETHONIN, TELT, T-cap, TELE, CMD1N, LGMD2G

DNA

TYPE	functioning gene
STRUCTURE	1.21 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	highly conserved 421 bp promoter proximal promoter fragment that contains two E boxes and multiple putative Mef2 binding sequences (

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D17S2005 - D17S1542 - D17S1867 - D17S1660 - D17S946 - D17S838 - [D17S1818 - D17S1814 ] - THRA - RARA RARA - D17S2038 - qter
Text	[TCAP ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003673 2 - 963 NP_003664 19 167 - 2002 12379311

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 Reproductive male system prostate     moderately Respiratory lung         Visual eye       moderately

tissue

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

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminus forming a unique structure linking two titin N-termini at the Z-disc
	C-terminus that may have a regulatory function

HOMOLOGY

interspecies

homolog to murine Tcap (90.4 pc)

Homologene

FAMILY

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
	intracellular,nucleus
text	localized to the Z-disc of skeletal and cardiac muscles
	co-localized with SCN5A
	co-localized in the nucleus with MDM2

basic FUNCTION	required for the structural integrity of sarcomere
	muscle assembly regulating factor, mediating the antiparallel assembly of titin (ttn) molecules at the sarcomeric z-disk
	in skeletal muscle, anchoring TTN in the Z-disk
	acting as a kinase
	may play a role in intestinal pseudo-obstruction
	one of the titin interacting Z-disc proteins involved in the regulation and development of normal sarcomeric structure
	is a stretch-sensitive Z-disc protein that binds to proteins in the t-tubule membrane
	is a critical, load-sensitive regulator of t-tubule structure and function
	plays an important role in the response to cardiac overload
	might be a load-dependent molecular regulator of the t-tubule membrane in the skeletal muscle
	involved in the regulation of t-tubule structure, especially after mechanical overload

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	protein constituent of sarcomere
	titin/TCAP/MLP complex serving as a mechanical stretch sensor
	complex between the muscle proteins titin and telethonin forms a highly directed molecular bond

INTERACTION

DNA

RNA

small molecule

protein	binding to N terminal Ig repeats Z1 and Z2 of titin
	binding to CSRP3 (Z disc MLP/TCAP complex, key component of the cardiomyocytes stretch sensor machinery)
	interacting with MYOZ1 and MYOZ3
	interacting with SCN5A
	binding to BMP10
	important role for MYOD1 in activating TCAP expression through the promoter proximal E box

cell & other

REGULATION

Other

downregulated at the protein level through the proteasomal pathway, by MDM2

ASSOCIATED DISORDERS

corresponding disease(s)

LGMD2G , CMD1N

related resource

Limb-Girdle Muscular Dystrophy pages

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   loss of telethonin mRNA and nuclear accumulation of this protein is associated with heart failure, an effect that may contribute to enhanced rates of apoptosis found in these hearts

Susceptibility

to hypertrophic cardiomyopathy (HCM) to dilated cardiomyopathy (DCM)

Variant & Polymorphism other	T137I and R153H, were found in patients with HCM (mutation augment the ability of TCAP to interact with titin and MYOZ2)
	E132Q, in a patient with DCM (mutation impair the interaction of TCAP with MLP, titin, and MYOZ2)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS