Telethonin - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot O15273 (TELT_HUMAN)

Last modified December 16, 2008. Version 72. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
Telethonin
Alternative name(s):
Titin cap protein

Gene names

Name:

TCAP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	167 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Muscle assembly regulating factor. Mediates the antiparallel assembly of titin (TTN) molecules at the sarcomeric Z-disk.
Subunit structure	Interacts with MYOZ1 and MYOZ3. Interacts directly with the N-terminal Ig-like domains of 2 titin (TTN) molecules. Ref.5 Ref.6 Ref.7
Subcellular location	Cytoplasm › myofibril › sarcomere. Ref.9
Tissue specificity	Heart and skeletal muscle.
Involvement in disease	Defects in TCAP are a cause of cardiomyopathy familial hypertrophic (CMH) [MIM:192600]; also designated FHC or HCM. Familial hypertrophic cardiomyopathy is 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. Ref.15 Defects in TCAP are a cause of limb-girdle muscular dystrophy type 2G (LGMD2G) [MIM:601954]. LGMD2G is an autosomal recessive degenerative myopathy characterized by proximal and distal muscle weakness and atrophy in the limbs, dystrophic changes on muscle biopsy, and absence of telethonin. Cardiac muscle is involved in a subset of patients. Ref.10 Defects in TCAP are the cause of cardiomyopathy dilated type 1N (CMD1N) [MIM:607487]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Ref.15 Ref.11 Ref.12
Miscellaneous	The C-terminal domain appears to be unstructured in solution. It may promote the assembly of higher order TTN complexes.

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Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation Limb-girdle muscular dystrophy
Technical term	3D-structure
Gene Ontology (GO)
Biological process	adult heart development Inferred from expression pattern. Source: UniProtKB cardiac muscle contraction Inferred from expression pattern. Source: UniProtKB cardiac muscle fiber development Inferred from mutant phenotype. Source: UniProtKB cardiac muscle morphogenesis Inferred from mutant phenotype. Source: UniProtKB detection of mechanical stimulus Traceable author statement. Source: UniProtKB muscle thick filament assembly Inferred from mutant phenotype. Source: UniProtKB muscle thin filament assembly Inferred from mutant phenotype. Source: UniProtKB response to stress Traceable author statement. Source: UniProtKB sarcomere organization Inferred from mutant phenotype. Source: UniProtKB skeletal muscle contraction Inferred from expression pattern. Source: UniProtKB
Cellular component	Z disc Inferred from direct assay. Source: UniProtKB
Molecular function	phosphate binding Inferred from direct assay. Source: UniProtKB protein N-terminus binding Inferred from physical interaction. Source: UniProtKB structural constituent of muscle Ref.1 Traceable author statement. Source: ProtInc titin Z domain binding Inferred from physical interaction. Source: UniProtKB titin binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
TTN	Q8WZ42	1	EBI-954089,EBI-681210

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 167

167

Telethonin

PRO_0000072483

Natural variations

Natural variant

Missing Rare polymorphism; could be asssociated with CMD1N. Ref.12 Ref.13 Ref.14

VAR_026649

Natural variant

R → W in CMD1N. Ref.12

VAR_026650

Natural variant

L → H: dbSNP rs17851031. Ref.4

VAR_029445

Natural variant

R → Q in CMD1N. Ref.11

VAR_015397

Natural variant

P → L in CMD1N. Ref.12

VAR_026651

Natural variant

106

R → C: dbSNP rs45578741.

VAR_051421

Natural variant

132

E → Q in CMD1N; impairs the interaction with MLP, TTN and MYOZ2. Ref.15

VAR_029446

Natural variant

137

T → I in CMH; augments the ability to imteract with TTN and MYOZ2. Ref.15

VAR_029447

Natural variant

153

R → H in CMH. Ref.15

VAR_029448

Secondary structure

167

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

O15273-1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: A3B0E27D8C84F6C5
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FASTA

167

19,052

        10         20         30         40         50         60 
MATSELSCEV SEENCERREA FWAEWKDLTL STRPEEGCSL HEEDTQRHET YHQQGQCQVL 

        70         80         90        100        110        120 
VQRSPWLMMR MGILGRGLQE YQLPYQRVLP LPIFTPAKMG ATKEEREDTP IQLQELLALE 

       130        140        150        160 
TALGGQCVDR QEVAEITKQL PPVVPVSKPG ALRRSLSRSM SQEAQRG

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Telethonin, a novel sarcomeric protein of heart and skeletal muscle." Valle G., Faulkner G., de Antoni A., Pacchioni B., Pallavicini A., Pandolfo D., Tiso N., Toppo S., Trevisan S., Lanfranchi G. FEBS Lett. 415:163-168(1997) [PubMed: 9350988] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[2]	"Human telethonin genomic sequence." Pallavicini A., Valle G., Lanfranchi G. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Structure of the human telethonin gene." Mues A., Gautel M. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-74. Tissue: Prostate.
[5]	"Two immunoglobulin-like domains of the Z-disc portion of titin interact in a conformation-dependent way with telethonin." Mues A., van der Ven P.F.M., Young P., Furst D.O., Gautel M. FEBS Lett. 428:111-114(1998) [PubMed: 9645487] [Abstract] Cited for: INTERACTION WITH TTN.
[6]	"FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle." Faulkner G., Pallavicini A., Comelli A., Salamon M., Bortoletto G., Ievolella C., Trevisan S., Kojic' S., Dalla Vecchia F., Laveder P., Valle G., Lanfranchi G. J. Biol. Chem. 275:41234-41242(2000) [PubMed: 10984498] [Abstract] Cited for: INTERACTION WITH MYOZ1.
[7]	"Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins." Frey N., Olson E.N. J. Biol. Chem. 277:13998-14004(2002) [PubMed: 11842093] [Abstract] Cited for: INTERACTION WITH MYOZ3.
[8]	"Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk." Zou P., Pinotsis N., Lange S., Song Y.-H., Popov A., Mavridis I., Mayans O.M., Gautel M., Wilmanns M. Nature 439:229-233(2006) [PubMed: 16407954] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 1-90 IN COMPLEX WITH TTN.
[9]	"Evidence for a dimeric assembly of two titin/telethonin complexes induced by the telethonin C-terminus." Pinotsis N., Petoukhov M., Lange S., Svergun D., Zou P., Gautel M., Wilmanns M. J. Struct. Biol. 155:239-250(2006) [PubMed: 16713295] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH TTN, SUBCELLULAR LOCATION.
[10]	"Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin." Moreira E.S., Wiltshire T.J., Faulkner G., Nilforoushan A., Vainzof M., Suzuki O.T., Valle G., Reeves R., Zatz M., Passos-Bueno M.R., Jenne D.E. Nat. Genet. 24:163-166(2000) [PubMed: 10655062] [Abstract] Cited for: INVOLVEMENT IN LGMD2G.
[11]	"The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy." Knoell R., Hoshijima M., Hoffman H.M., Person V., Lorenzen-Schmidt I., Bang M.-L., Hayashi T., Shiga N., Yasukawa H., Schaper W., McKenna W., Yokoyama M., Schork N.J., Omens J.H., McCulloch A.D., Kimura A., Gregorio C.C., Poller W. , Schaper J., Schultheiss H.P., Chien K.R. Cell 111:943-955(2002) [PubMed: 12507422] [Abstract] Cited for: VARIANT CMD1N GLN-87.
[12]	"Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin." Bos J.M., Poley R.N., Ny M., Tester D.J., Xu X., Vatta M., Towbin J.A., Gersh B.J., Ommen S.R., Ackerman M.J. Mol. Genet. Metab. 88:78-85(2006) [PubMed: 16352453] [Abstract] Cited for: VARIANTS CMD1N TRP-70 AND LEU-90, VARIANT GLU-13 DEL.
[13]	"Deletion of Glu at codon 13 in the TCAP gene encoding the Z-disc protein titin-cap/telethonin is a rare non-synonymous polymorphism." Perrot A., Posch M.G., Osterziel K.J. Mol. Genet. Metab. 88:199-200(2006) [PubMed: 16490376] [Abstract] Cited for: VARIANT GLU-13 DEL.
[14]	"Deletion of Glu at codon 13 of the TCAP gene encoding the titin-cap-telethonin is a rare polymorphism in a large Italian population." Marziliano N., Pilotto A., Grasso M., Pasotti M., Arbustini E. Mol. Genet. Metab. 89:286-287(2006) [PubMed: 16650785] [Abstract] Cited for: VARIANT GLU-13 DEL.
[15]	"Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy." Hayashi T., Arimura T., Itoh-Satoh M., Ueda K., Hohda S., Inagaki N., Takahashi M., Hori H., Yasunami M., Nishi H., Koga Y., Nakamura H., Matsuzaki M., Choi B.Y., Bae S.W., You C.W., Han K.H., Park J.E. , Knoell R., Hoshijima M., Chien K.R., Kimura A. J. Am. Coll. Cardiol. 44:2192-2201(2004) [PubMed: 15582318] [Abstract] Cited for: VARIANTS CMH ILE-137 AND HIS-153, VARIANT CMD1N GLN-132, CHARACTERIZATION OF VARIANTS CMH ILE-137 AND HIS-153, CHARACTERIZATION OF VARIANT CMD1N GLN-132.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

AJ000491 mRNA. Translation: CAA04129.1.
AJ010063 Genomic DNA. Translation: CAA08987.1.
AJ011098 Genomic DNA. Translation: CAA09479.1.
BC012628 mRNA. Translation: AAH12628.1.
BC013330 mRNA. Translation: AAH13330.1.

RefSeq

NP_003664.1.

UniGene

Hs.514146

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YA5	X-ray	2.44	T	1-90	[»]
2F8V	X-ray	2.75	T/Y	1-167	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O15273. 2 interactions.

PTM databases

PhosphoSite

O15273.

Proteomic databases

PRIDE

O15273.

Genome annotation databases

Ensembl

ENSG00000173991. Homo sapiens. [Contig view]

GeneID

8557.

KEGG

hsa:8557.

Organism-specific databases

GeneCards

GC17P035073.

H-InvDB

HIX0013781.

HGNC

HGNC:11610. TCAP.

HPA

CAB004591.

MIM

192600. phenotype.
601954. phenotype.
604488. gene.
607487. phenotype.

Orphanet

154. Cardiomyopathy, familial dilated.
155. Cardiomyopathy, hypertrophic, primary or idiopathic.
34514. Muscular dystrophy, limb girdle, autosomal recessive, type 2G.

PharmGKB

PA36370.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O15273.

HOVERGEN

O15273.

Gene expression databases

ArrayExpress

O15273.

CleanEx

HS_TCAP.

GermOnline

ENSG00000173991. Homo sapiens.

Family and domain databases

InterPro

IPR015667. Telethonin.
[Graphical view]

PANTHER

PTHR15143. Telethonin. 1 hit.

ProtoNet

Search...

Other Resources

LinkHub

O15273.

NextBio

32073.

SOURCE

Search...

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Entry information

Entry name

TELT_HUMAN

Accession

Primary (citable) accession number: O15273
Secondary accession number(s): Q96L27

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 1, 1998
Last modified:	December 16, 2008
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Natural variations

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents