O15273 (TELT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Telethonin

Alternative name(s):
Titin cap protein

Gene names

Name:

TCAP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	167 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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	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.15 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.10 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.11 Ref.12 Ref.15
Miscellaneous	The C-terminal domain appears to be unstructured in solution. It may promote the assembly of higher-order TTN complexes.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation Limb-girdle muscular dystrophy
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult heart development Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL cardiac muscle contraction Inferred from mutant phenotype Ref.11Ref.15. Source: BHF-UCL cardiac muscle fiber development Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL cardiac muscle hypertrophy in response to stress Inferred from mutant phenotype Ref.11. 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 muscle stretch Inferred from mutant phenotype Ref.11. Source: BHF-UCL muscle filament sliding Traceable author statement. Source: Reactome otic vesicle formation Inferred from electronic annotation. Source: Compara 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: Compara
Cellular_component	Z disc Inferred from direct assay PubMed 17921333PubMed 9817758. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome
Molecular_function	protein binding, bridging Inferred from direct assay Ref.15. Source: BHF-UCL structural constituent of muscle Inferred from mutant phenotype PubMed 9817758. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TTN	Q8WZ42	4	EBI-954089,EBI-681210

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

13

1

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

VAR_026649

Natural variant

70

1

R → W in CMD1N. Ref.12

VAR_026650

Natural variant

74

1

L → H. Ref.4
Corresponds to variant rs17851031 [ dbSNP | Ensembl ].

VAR_029445

Natural variant

87

1

R → Q in CMD1N. Ref.11

VAR_015397

Natural variant

90

1

P → L in CMD1N. Ref.12

VAR_026651

Natural variant

106

1

R → C.
Corresponds to variant rs45578741 [ dbSNP | Ensembl ].

VAR_051421

Natural variant

132

1

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

VAR_029446

Natural variant

137

1

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

VAR_029447

Natural variant

153

1

R → H in CMH. Ref.15

VAR_029448

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

167

Helix Strand Turn

Details...

Beta strand

4 – 14

11

Turn

15 – 18

4

Beta strand

19 – 33

15

Helix

35 – 37

3

Beta strand

38 – 44

7

Turn

45 – 48

4

Beta strand

49 – 55

7

Beta strand

57 – 62

6

Beta strand

67 – 73

7

Beta strand

78 – 84

7

Sequences

	Sequence		Length	Mass (Da)
	O15273 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: A3B0E27D8C84F6C5	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

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] [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]	"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.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [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.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.

IPI

IPI00005755.

RefSeq

NP_003664.1. NM_003673.3.

UniGene

Hs.77628.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

O15273.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35730N.

IntAct

O15273. 18 interactions.

MINT

MINT-145661.

STRING

9606.ENSP00000312624.

PTM databases

PhosphoSite

O15273.

Proteomic databases

PaxDb

O15273.

PRIDE

O15273.

Protocols and materials databases

DNASU

8557.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309889; ENSP00000312624; ENSG00000173991.

GeneID

8557.

KEGG

hsa:8557.

UCSC

uc002hsh.3. human.

Organism-specific databases

CTD

8557.

GeneCards

GC17P037818.

HGNC

HGNC:11610. TCAP.

HPA

CAB004591.
HPA026477.

MIM

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

neXtProt

NX_O15273.

Orphanet

34514. Autosomal recessive limb-girdle muscular dystrophy type 2G.
154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.

PharmGKB

PA36370.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG43340.

HOGENOM

HOG000237275.

HOVERGEN

HBG004497.

InParanoid

O15273.

OMA

RSMSQEA.

OrthoDB

EOG4V6ZHW.

PhylomeDB

O15273.

Enzyme and pathway databases

Reactome

REACT_17044. Muscle contraction.

Gene expression databases

ArrayExpress

O15273.

Bgee

O15273.

CleanEx

HS_TCAP.

Genevestigator

O15273.

GermOnline

ENSG00000173991. Homo sapiens.

Family and domain databases

Gene3D

2.20.160.10. 1 hit.

InterPro

IPR015667. Telethonin.
IPR023111. Titin-like_domain.
[Graphical view]

PANTHER

PTHR15143. PTHR15143. 1 hit.

Pfam

PF09470. Telethonin. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TCAP. human.

EvolutionaryTrace

O15273.

GenomeRNAi

8557.

NextBio

32073.

SOURCE

Search...

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:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.