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O15273 (TELT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Telethonin
Alternative name(s):
Titin cap protein
Gene names
Name:TCAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length167 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

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, MYOZ2 and MYOZ3. Interacts with CSRP3. Interacts directly with the N-terminal Ig-like domains of 2 titin (TTN) molecules. Interacts with ANKRD2; the interaction is direct. Ref.5 Ref.6 Ref.7 Ref.8 Ref.16

Subcellular location

Cytoplasmmyofibrilsarcomere Ref.10.

Tissue specificity

Heart and skeletal muscle.

Involvement in disease

Cardiomyopathy, familial hypertrophic (CMH) [MIM:192600]: 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.16

Limb-girdle muscular dystrophy 2G (LGMD2G) [MIM:601954]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Cardiomyopathy, dilated 1N (CMD1N) [MIM:607487]: 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.12 Ref.13 Ref.16

Miscellaneous

The C-terminal domain appears to be unstructured in solution. It may promote the assembly of higher-order TTN complexes.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseCardiomyopathy
Disease mutation
Limb-girdle muscular dystrophy
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult heart development

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

cardiac muscle contraction

Inferred from mutant phenotype Ref.12Ref.16. Source: BHF-UCL

cardiac muscle fiber development

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

cardiac muscle hypertrophy

Inferred from mutant phenotype Ref.16. Source: BHF-UCL

cardiac muscle hypertrophy in response to stress

Inferred from mutant phenotype Ref.12. Source: BHF-UCL

cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

cardiac myofibril assembly

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

detection of mechanical stimulus

Traceable author statement PubMed 17921333. Source: BHF-UCL

detection of muscle stretch

Inferred from mutant phenotype Ref.12. Source: BHF-UCL

muscle filament sliding

Traceable author statement. Source: Reactome

otic vesicle formation

Inferred from electronic annotation. Source: Ensembl

protein complex assembly

Traceable author statement PubMed 9817758. Source: ProtInc

response to muscle stretch

Traceable author statement PubMed 17921333. Source: BHF-UCL

sarcomere organization

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

sarcomerogenesis

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

skeletal muscle contraction

Inferred from expression pattern PubMed 9817758. Source: BHF-UCL

skeletal muscle myosin thick filament assembly

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

skeletal muscle thin filament assembly

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

somitogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentI band

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

Z disc

Inferred from direct assay PubMed 17921333PubMed 9817758. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

   Molecular_functionFATZ binding

Inferred from physical interaction Ref.16. Source: BHF-UCL

ion channel binding

Inferred from physical interaction PubMed 11697903. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.6Ref.7. Source: UniProtKB

protein binding, bridging

Inferred from direct assay Ref.16. Source: BHF-UCL

structural constituent of muscle

Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL

titin Z domain binding

Inferred from physical interaction PubMed 11846417. Source: BHF-UCL

titin binding

Inferred from physical interaction PubMed 11846417Ref.16PubMed 9817758. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 167167Telethonin
PRO_0000072483

Natural variations

Natural variant131Missing Rare polymorphism; could be associated with CMD1N. Ref.13 Ref.14 Ref.15
VAR_026649
Natural variant701R → W in CMD1N. Ref.13
VAR_026650
Natural variant741L → H. Ref.4
Corresponds to variant rs17851031 [ dbSNP | Ensembl ].
VAR_029445
Natural variant871R → Q in CMD1N. Ref.12
VAR_015397
Natural variant901P → L in CMD1N. Ref.13
VAR_026651
Natural variant1061R → C.
Corresponds to variant rs45578741 [ dbSNP | Ensembl ].
VAR_051421
Natural variant1321E → Q in CMD1N; impairs the interaction with CSRP3, TTN and MYOZ2. Ref.16
VAR_029446
Natural variant1371T → I in CMH; augments the ability to imteract with TTN and MYOZ2. Ref.16
VAR_029447
Natural variant1531R → H in CMH. Ref.16
VAR_029448

Secondary structure

................ 167
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O15273 [UniParc].

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

FASTA16719,052
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOZ3.
[8]"The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle."
Kojic S., Medeot E., Guccione E., Krmac H., Zara I., Martinelli V., Valle G., Faulkner G.
J. Mol. Biol. 339:313-325(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ANKRD2.
[9]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 1-90 IN COMPLEX WITH TTN.
[10]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH TTN, SUBCELLULAR LOCATION.
[11]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN LGMD2G.
[12]"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. expand/collapse author list , Schaper J., Schultheiss H.P., Chien K.R.
Cell 111:943-955(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMD1N GLN-87.
[13]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CMD1N TRP-70 AND LEU-90, VARIANT GLU-13 DEL.
[14]"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] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-13 DEL.
[15]"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] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-13 DEL.
[16]"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. expand/collapse author list , Knoell R., Hoshijima M., Chien K.R., Kimura A.
J. Am. Coll. Cardiol. 44:2192-2201(2004) [PubMed] [Europe PMC] [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, INTERACTION WITH CSRP3; MYOZ2 AND TTN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11342.1.
RefSeqNP_003664.1. NM_003673.3.
UniGeneHs.77628.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YA5X-ray2.44T1-90[»]
2F8VX-ray2.75T/Y1-167[»]
ProteinModelPortalO15273.
SMRO15273. Positions 1-89.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114127. 12 interactions.
DIPDIP-35730N.
IntActO15273. 24 interactions.
MINTMINT-145661.
STRING9606.ENSP00000312624.

PTM databases

PhosphoSiteO15273.

Proteomic databases

PaxDbO15273.
PRIDEO15273.

Protocols and materials databases

DNASU8557.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309889; ENSP00000312624; ENSG00000173991.
GeneID8557.
KEGGhsa:8557.
UCSCuc002hsh.3. human.

Organism-specific databases

CTD8557.
GeneCardsGC17P037818.
GeneReviewsTCAP.
HGNCHGNC:11610. TCAP.
HPACAB004591.
HPA026477.
MIM192600. phenotype.
601954. phenotype.
604488. gene.
607487. phenotype.
neXtProtNX_O15273.
Orphanet34514. Autosomal recessive limb-girdle muscular dystrophy type 2G.
154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA36370.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43340.
HOGENOMHOG000237275.
HOVERGENHBG004497.
InParanoidO15273.
OMASTHEDCV.
OrthoDBEOG76MK9Q.
PhylomeDBO15273.
TreeFamTF333228.

Enzyme and pathway databases

ReactomeREACT_17044. Muscle contraction.

Gene expression databases

ArrayExpressO15273.
BgeeO15273.
CleanExHS_TCAP.
GenevestigatorO15273.

Family and domain databases

Gene3D2.20.160.10. 1 hit.
InterProIPR015667. Telethonin.
IPR023111. Titin-like_domain.
[Graphical view]
PANTHERPTHR15143. PTHR15143. 1 hit.
PfamPF09470. Telethonin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTCAP. human.
EvolutionaryTraceO15273.
GeneWikiTelethonin.
GenomeRNAi8557.
NextBio32073.
PROO15273.
SOURCESearch...

Entry information

Entry nameTELT_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 126 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

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 17

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