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Protein

Telethonin

Gene

TCAP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Muscle assembly regulating factor. Mediates the antiparallel assembly of titin (TTN) molecules at the sarcomeric Z-disk.

GO - Molecular functioni

  • BMP binding Source: BHF-UCL
  • FATZ binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • protein binding, bridging Source: BHF-UCL
  • structural constituent of muscle Source: BHF-UCL
  • titin binding Source: BHF-UCL
  • titin Z domain binding Source: BHF-UCL

GO - Biological processi

  • adult heart development Source: BHF-UCL
  • cardiac muscle contraction Source: BHF-UCL
  • cardiac muscle fiber development Source: BHF-UCL
  • cardiac muscle hypertrophy Source: BHF-UCL
  • cardiac muscle hypertrophy in response to stress Source: BHF-UCL
  • cardiac muscle tissue morphogenesis Source: BHF-UCL
  • cardiac myofibril assembly Source: BHF-UCL
  • detection of mechanical stimulus Source: BHF-UCL
  • detection of muscle stretch Source: BHF-UCL
  • muscle filament sliding Source: Reactome
  • otic vesicle formation Source: Ensembl
  • protein complex assembly Source: ProtInc
  • response to muscle stretch Source: BHF-UCL
  • sarcomere organization Source: BHF-UCL
  • sarcomerogenesis Source: BHF-UCL
  • skeletal muscle contraction Source: BHF-UCL
  • skeletal muscle myosin thick filament assembly Source: BHF-UCL
  • skeletal muscle thin filament assembly Source: BHF-UCL
  • somitogenesis Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_16969. Striated Muscle Contraction.

Names & Taxonomyi

Protein namesi
Recommended name:
Telethonin
Alternative name(s):
Titin cap protein
Gene namesi
Name:TCAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:11610. TCAP.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • I band Source: BHF-UCL
  • Z disc Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, familial hypertrophic (CMH)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:192600
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti137 – 1371T → I in CMH; augments the ability to imteract with TTN and MYOZ2. 1 Publication
VAR_029447
Natural varianti153 – 1531R → H in CMH. 1 Publication
VAR_029448
Limb-girdle muscular dystrophy 2G (LGMD2G)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn 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.

See also OMIM:601954
Cardiomyopathy, dilated 1N (CMD1N)3 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.

See also OMIM:607487
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131Missing Rare polymorphism; could be associated with CMD1N. 3 Publications
VAR_026649
Natural varianti70 – 701R → W in CMD1N. 1 Publication
VAR_026650
Natural varianti87 – 871R → Q in CMD1N. 1 Publication
VAR_015397
Natural varianti90 – 901P → L in CMD1N. 1 Publication
VAR_026651
Natural varianti132 – 1321E → Q in CMD1N; impairs the interaction with CSRP3, TTN and MYOZ2. 1 Publication
VAR_029446

Keywords - Diseasei

Cardiomyopathy, Disease mutation, Limb-girdle muscular dystrophy

Organism-specific databases

MIMi192600. phenotype.
601954. phenotype.
607487. phenotype.
Orphaneti34514. Autosomal recessive limb-girdle muscular dystrophy type 2G.
154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA36370.

Polymorphism and mutation databases

BioMutaiTCAP.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 167167TelethoninPRO_0000072483Add
BLAST

Proteomic databases

PaxDbiO15273.
PRIDEiO15273.

PTM databases

PhosphoSiteiO15273.

Expressioni

Tissue specificityi

Heart and skeletal muscle.

Gene expression databases

BgeeiO15273.
CleanExiHS_TCAP.
ExpressionAtlasiO15273. baseline and differential.
GenevisibleiO15273. HS.

Organism-specific databases

HPAiCAB004591.
HPA026477.

Interactioni

Subunit structurei

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.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CSRP3P504613EBI-954089,EBI-5658719
MYOZ2Q9NPC62EBI-954089,EBI-746712
TTNQ8WZ427EBI-954089,EBI-681210

Protein-protein interaction databases

BioGridi114127. 14 interactions.
DIPiDIP-35730N.
IntActiO15273. 25 interactions.
MINTiMINT-145661.
STRINGi9606.ENSP00000312624.

Structurei

Secondary structure

1
167
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 1411Combined sources
Turni15 – 184Combined sources
Beta strandi19 – 3315Combined sources
Helixi35 – 373Combined sources
Beta strandi38 – 447Combined sources
Turni45 – 484Combined sources
Beta strandi49 – 557Combined sources
Beta strandi57 – 626Combined sources
Beta strandi67 – 737Combined sources
Beta strandi78 – 847Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YA5X-ray2.44T1-90[»]
2F8VX-ray2.75T/Y1-167[»]
ProteinModelPortaliO15273.
SMRiO15273. Positions 1-89.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15273.

Family & Domainsi

Phylogenomic databases

eggNOGiNOG43340.
GeneTreeiENSGT00390000012014.
HOGENOMiHOG000237275.
HOVERGENiHBG004497.
InParanoidiO15273.
OMAiTYHRQGQ.
OrthoDBiEOG76MK9Q.
PhylomeDBiO15273.
TreeFamiTF333228.

Family and domain databases

Gene3Di2.20.160.10. 1 hit.
InterProiIPR015667. Telethonin.
IPR023111. Titin-like_domain.
[Graphical view]
PANTHERiPTHR15143. PTHR15143. 1 hit.
PfamiPF09470. Telethonin. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O15273-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATSELSCEV SEENCERREA FWAEWKDLTL STRPEEGCSL HEEDTQRHET
60 70 80 90 100
YHQQGQCQVL VQRSPWLMMR MGILGRGLQE YQLPYQRVLP LPIFTPAKMG
110 120 130 140 150
ATKEEREDTP IQLQELLALE TALGGQCVDR QEVAEITKQL PPVVPVSKPG
160
ALRRSLSRSM SQEAQRG
Length:167
Mass (Da):19,052
Last modified:January 1, 1998 - v1
Checksum:iA3B0E27D8C84F6C5
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131Missing Rare polymorphism; could be associated with CMD1N. 3 Publications
VAR_026649
Natural varianti70 – 701R → W in CMD1N. 1 Publication
VAR_026650
Natural varianti74 – 741L → H.1 Publication
Corresponds to variant rs17851031 [ dbSNP | Ensembl ].
VAR_029445
Natural varianti87 – 871R → Q in CMD1N. 1 Publication
VAR_015397
Natural varianti90 – 901P → L in CMD1N. 1 Publication
VAR_026651
Natural varianti106 – 1061R → C.
Corresponds to variant rs45578741 [ dbSNP | Ensembl ].
VAR_051421
Natural varianti132 – 1321E → Q in CMD1N; impairs the interaction with CSRP3, TTN and MYOZ2. 1 Publication
VAR_029446
Natural varianti137 – 1371T → I in CMH; augments the ability to imteract with TTN and MYOZ2. 1 Publication
VAR_029447
Natural varianti153 – 1531R → H in CMH. 1 Publication
VAR_029448

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11342.1.
RefSeqiNP_003664.1. NM_003673.3.
UniGeneiHs.77628.

Genome annotation databases

EnsembliENST00000309889; ENSP00000312624; ENSG00000173991.
GeneIDi8557.
KEGGihsa:8557.
UCSCiuc002hsh.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11342.1.
RefSeqiNP_003664.1. NM_003673.3.
UniGeneiHs.77628.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YA5X-ray2.44T1-90[»]
2F8VX-ray2.75T/Y1-167[»]
ProteinModelPortaliO15273.
SMRiO15273. Positions 1-89.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114127. 14 interactions.
DIPiDIP-35730N.
IntActiO15273. 25 interactions.
MINTiMINT-145661.
STRINGi9606.ENSP00000312624.

PTM databases

PhosphoSiteiO15273.

Polymorphism and mutation databases

BioMutaiTCAP.

Proteomic databases

PaxDbiO15273.
PRIDEiO15273.

Protocols and materials databases

DNASUi8557.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309889; ENSP00000312624; ENSG00000173991.
GeneIDi8557.
KEGGihsa:8557.
UCSCiuc002hsh.3. human.

Organism-specific databases

CTDi8557.
GeneCardsiGC17P037818.
GeneReviewsiTCAP.
HGNCiHGNC:11610. TCAP.
HPAiCAB004591.
HPA026477.
MIMi192600. phenotype.
601954. phenotype.
604488. gene.
607487. phenotype.
neXtProtiNX_O15273.
Orphaneti34514. Autosomal recessive limb-girdle muscular dystrophy type 2G.
154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA36370.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG43340.
GeneTreeiENSGT00390000012014.
HOGENOMiHOG000237275.
HOVERGENiHBG004497.
InParanoidiO15273.
OMAiTYHRQGQ.
OrthoDBiEOG76MK9Q.
PhylomeDBiO15273.
TreeFamiTF333228.

Enzyme and pathway databases

ReactomeiREACT_16969. Striated Muscle Contraction.

Miscellaneous databases

ChiTaRSiTCAP. human.
EvolutionaryTraceiO15273.
GeneWikiiTelethonin.
GenomeRNAii8557.
NextBioi32073.
PROiO15273.
SOURCEiSearch...

Gene expression databases

BgeeiO15273.
CleanExiHS_TCAP.
ExpressionAtlasiO15273. baseline and differential.
GenevisibleiO15273. HS.

Family and domain databases

Gene3Di2.20.160.10. 1 hit.
InterProiIPR015667. Telethonin.
IPR023111. Titin-like_domain.
[Graphical view]
PANTHERiPTHR15143. PTHR15143. 1 hit.
PfamiPF09470. Telethonin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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.
    , 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. 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.

Entry informationi

Entry nameiTELT_HUMAN
AccessioniPrimary (citable) accession number: O15273
Secondary accession number(s): Q96L27
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: July 22, 2015
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.