ID TELT_HUMAN Reviewed; 167 AA. AC O15273; Q96L27; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 11-NOV-2015, entry version 140. DE RecName: Full=Telethonin; DE AltName: Full=Titin cap protein; GN Name=TCAP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Skeletal muscle; RX PubMed=9350988; DOI=10.1016/S0014-5793(97)01108-3; RA Valle G., Faulkner G., de Antoni A., Pacchioni B., Pallavicini A., RA Pandolfo D., Tiso N., Toppo S., Trevisan S., Lanfranchi G.; RT "Telethonin, a novel sarcomeric protein of heart and skeletal RT muscle."; RL FEBS Lett. 415:163-168(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Pallavicini A., Valle G., Lanfranchi G.; RT "Human telethonin genomic sequence."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Mues A., Gautel M.; RT "Structure of the human telethonin gene."; RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-74. RC TISSUE=Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP INTERACTION WITH TTN. RX PubMed=9645487; DOI=10.1016/S0014-5793(98)00501-8; RA Mues A., van der Ven P.F.M., Young P., Furst D.O., Gautel M.; RT "Two immunoglobulin-like domains of the Z-disc portion of titin RT interact in a conformation-dependent way with telethonin."; RL FEBS Lett. 428:111-114(1998). RN [6] RP INTERACTION WITH MYOZ1. RX PubMed=10984498; DOI=10.1074/jbc.M007493200; RA Faulkner G., Pallavicini A., Comelli A., Salamon M., Bortoletto G., RA Ievolella C., Trevisan S., Kojic' S., Dalla Vecchia F., Laveder P., RA Valle G., Lanfranchi G.; RT "FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z- RT disc of skeletal muscle."; RL J. Biol. Chem. 275:41234-41242(2000). RN [7] RP INTERACTION WITH MYOZ3. RX PubMed=11842093; DOI=10.1074/jbc.M200712200; RA Frey N., Olson E.N.; RT "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin RT family, interacts with multiple Z-disc proteins."; RL J. Biol. Chem. 277:13998-14004(2002). RN [8] RP INTERACTION WITH ANKRD2. RX PubMed=15136035; DOI=10.1016/j.jmb.2004.03.071; RA Kojic S., Medeot E., Guccione E., Krmac H., Zara I., Martinelli V., RA Valle G., Faulkner G.; RT "The Ankrd2 protein, a link between the sarcomere and the nucleus in RT skeletal muscle."; RL J. Mol. Biol. 339:313-325(2004). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 1-90 IN COMPLEX WITH TTN. RX PubMed=16407954; DOI=10.1038/nature04343; RA Zou P., Pinotsis N., Lange S., Song Y.-H., Popov A., Mavridis I., RA Mayans O.M., Gautel M., Wilmanns M.; RT "Palindromic assembly of the giant muscle protein titin in the RT sarcomeric Z-disk."; RL Nature 439:229-233(2006). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH TTN, AND RP SUBCELLULAR LOCATION. RX PubMed=16713295; DOI=10.1016/j.jsb.2006.03.028; RA Pinotsis N., Petoukhov M., Lange S., Svergun D., Zou P., Gautel M., RA Wilmanns M.; RT "Evidence for a dimeric assembly of two titin/telethonin complexes RT induced by the telethonin C-terminus."; RL J. Struct. Biol. 155:239-250(2006). RN [11] RP INVOLVEMENT IN LGMD2G. RX PubMed=10655062; DOI=10.1038/72822; RA Moreira E.S., Wiltshire T.J., Faulkner G., Nilforoushan A., RA Vainzof M., Suzuki O.T., Valle G., Reeves R., Zatz M., RA Passos-Bueno M.R., Jenne D.E.; RT "Limb-girdle muscular dystrophy type 2G is caused by mutations in the RT gene encoding the sarcomeric protein telethonin."; RL Nat. Genet. 24:163-166(2000). RN [12] RP VARIANT GLN-87. RX PubMed=12507422; DOI=10.1016/S0092-8674(02)01226-6; RA Knoell R., Hoshijima M., Hoffman H.M., Person V., Lorenzen-Schmidt I., RA Bang M.-L., Hayashi T., Shiga N., Yasukawa H., Schaper W., McKenna W., RA Yokoyama M., Schork N.J., Omens J.H., McCulloch A.D., Kimura A., RA Gregorio C.C., Poller W., Schaper J., Schultheiss H.P., Chien K.R.; RT "The cardiac mechanical stretch sensor machinery involves a Z disc RT complex that is defective in a subset of human dilated RT cardiomyopathy."; RL Cell 111:943-955(2002). RN [13] RP VARIANTS CMH25 TRP-70 AND LEU-90, AND VARIANT GLU-13 DEL. RX PubMed=16352453; DOI=10.1016/j.ymgme.2005.10.008; RA Bos J.M., Poley R.N., Ny M., Tester D.J., Xu X., Vatta M., RA Towbin J.A., Gersh B.J., Ommen S.R., Ackerman M.J.; RT "Genotype-phenotype relationships involving hypertrophic RT cardiomyopathy-associated mutations in titin, muscle LIM protein, and RT telethonin."; RL Mol. Genet. Metab. 88:78-85(2006). RN [14] RP VARIANT GLU-13 DEL. RX PubMed=16490376; DOI=10.1016/j.ymgme.2006.01.004; RA Perrot A., Posch M.G., Osterziel K.J.; RT "Deletion of Glu at codon 13 in the TCAP gene encoding the Z-disc RT protein titin-cap/telethonin is a rare non-synonymous polymorphism."; RL Mol. Genet. Metab. 88:199-200(2006). RN [15] RP VARIANT GLU-13 DEL. RX PubMed=16650785; DOI=10.1016/j.ymgme.2006.03.012; RA Marziliano N., Pilotto A., Grasso M., Pasotti M., Arbustini E.; RT "Deletion of Glu at codon 13 of the TCAP gene encoding the titin-cap- RT telethonin is a rare polymorphism in a large Italian population."; RL Mol. Genet. Metab. 89:286-287(2006). RN [16] RP VARIANTS CMH25 ILE-137 AND HIS-153, VARIANT GLN-132, CHARACTERIZATION RP OF VARIANTS CMH25 ILE-137 AND HIS-153, CHARACTERIZATION OF VARIANT RP GLN-132, AND INTERACTION WITH CSRP3; MYOZ2 AND TTN. RX PubMed=15582318; DOI=10.1016/j.jacc.2004.08.058; RA Hayashi T., Arimura T., Itoh-Satoh M., Ueda K., Hohda S., Inagaki N., RA Takahashi M., Hori H., Yasunami M., Nishi H., Koga Y., Nakamura H., RA Matsuzaki M., Choi B.Y., Bae S.W., You C.W., Han K.H., Park J.E., RA Knoell R., Hoshijima M., Chien K.R., Kimura A.; RT "Tcap gene mutations in hypertrophic cardiomyopathy and dilated RT cardiomyopathy."; RL J. Am. Coll. Cardiol. 44:2192-2201(2004). CC -!- FUNCTION: Muscle assembly regulating factor. Mediates the CC antiparallel assembly of titin (TTN) molecules at the sarcomeric CC Z-disk. CC -!- SUBUNIT: Interacts with MYOZ1, MYOZ2 and MYOZ3. Interacts with CC CSRP3. Interacts directly with the N-terminal Ig-like domains of 2 CC titin (TTN) molecules. Interacts with ANKRD2; the interaction is CC direct. {ECO:0000269|PubMed:10984498, ECO:0000269|PubMed:11842093, CC ECO:0000269|PubMed:15136035, ECO:0000269|PubMed:15582318, CC ECO:0000269|PubMed:16407954, ECO:0000269|PubMed:16713295, CC ECO:0000269|PubMed:9645487}. CC -!- INTERACTION: CC P50461:CSRP3; NbExp=3; IntAct=EBI-954089, EBI-5658719; CC Q9NPC6:MYOZ2; NbExp=2; IntAct=EBI-954089, EBI-746712; CC Q8WZ42:TTN; NbExp=7; IntAct=EBI-954089, EBI-681210; CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere CC {ECO:0000269|PubMed:16713295}. CC -!- TISSUE SPECIFICITY: Heart and skeletal muscle. CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 25 (CMH25) CC [MIM:607487]: A hereditary heart disorder characterized by CC ventricular hypertrophy, which is usually asymmetric and often CC involves the interventricular septum. The symptoms include CC dyspnea, syncope, collapse, palpitations, and chest pain. They can CC be readily provoked by exercise. The disorder has inter- and CC intrafamilial variability ranging from benign to malignant forms CC with high risk of cardiac failure and sudden cardiac death. CC {ECO:0000269|PubMed:15582318, ECO:0000269|PubMed:16352453}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Limb-girdle muscular dystrophy 2G (LGMD2G) [MIM:601954]: CC An autosomal recessive degenerative myopathy characterized by CC proximal and distal muscle weakness and atrophy in the limbs, CC dystrophic changes on muscle biopsy, and absence of telethonin. CC Cardiac muscle is involved in a subset of patients. CC {ECO:0000269|PubMed:10655062}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The C-terminal domain appears to be unstructured in CC solution. It may promote the assembly of higher-order TTN CC complexes. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ000491; CAA04129.1; -; mRNA. DR EMBL; AJ010063; CAA08987.1; -; Genomic_DNA. DR EMBL; AJ011098; CAA09479.1; -; Genomic_DNA. DR EMBL; BC012628; AAH12628.1; -; mRNA. DR EMBL; BC013330; AAH13330.1; -; mRNA. DR CCDS; CCDS11342.1; -. DR RefSeq; NP_003664.1; NM_003673.3. DR UniGene; Hs.77628; -. DR PDB; 1YA5; X-ray; 2.44 A; T=1-90. DR PDB; 2F8V; X-ray; 2.75 A; T/Y=1-167. DR PDBsum; 1YA5; -. DR PDBsum; 2F8V; -. DR ProteinModelPortal; O15273; -. DR SMR; O15273; 1-89. DR BioGrid; 114127; 19. DR DIP; DIP-35730N; -. DR IntAct; O15273; 25. DR MINT; MINT-145661; -. DR STRING; 9606.ENSP00000312624; -. DR PhosphoSite; O15273; -. DR BioMuta; TCAP; -. DR PaxDb; O15273; -. DR PRIDE; O15273; -. DR DNASU; 8557; -. DR Ensembl; ENST00000309889; ENSP00000312624; ENSG00000173991. DR GeneID; 8557; -. DR KEGG; hsa:8557; -. DR UCSC; uc002hsh.3; human. DR CTD; 8557; -. DR GeneCards; TCAP; -. DR GeneReviews; TCAP; -. DR HGNC; HGNC:11610; TCAP. DR HPA; CAB004591; -. DR HPA; HPA026477; -. DR MIM; 601954; phenotype. DR MIM; 604488; gene. DR MIM; 607487; phenotype. DR neXtProt; NX_O15273; -. DR Orphanet; 34514; Autosomal recessive limb-girdle muscular dystrophy type 2G. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR Orphanet; 155; Familial isolated hypertrophic cardiomyopathy. DR PharmGKB; PA36370; -. DR eggNOG; ENOG410IIUD; Eukaryota. DR eggNOG; ENOG4111SDJ; LUCA. DR GeneTree; ENSGT00390000012014; -. DR HOGENOM; HOG000237275; -. DR HOVERGEN; HBG004497; -. DR InParanoid; O15273; -. DR OMA; TYHRQGQ; -. DR OrthoDB; EOG76MK9Q; -. DR PhylomeDB; O15273; -. DR TreeFam; TF333228; -. DR Reactome; R-HSA-390522; Striated Muscle Contraction. DR ChiTaRS; TCAP; human. DR EvolutionaryTrace; O15273; -. DR GeneWiki; Telethonin; -. DR GenomeRNAi; 8557; -. DR NextBio; 32073; -. DR PRO; PR:O15273; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; O15273; -. DR CleanEx; HS_TCAP; -. DR ExpressionAtlas; O15273; baseline and differential. DR Genevisible; O15273; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0031674; C:I band; ISS:BHF-UCL. DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL. DR GO; GO:0036122; F:BMP binding; IPI:BHF-UCL. DR GO; GO:0051373; F:FATZ binding; IPI:BHF-UCL. DR GO; GO:0044325; F:ion channel binding; IPI:BHF-UCL. DR GO; GO:0030674; F:protein binding, bridging; IDA:BHF-UCL. DR GO; GO:0008307; F:structural constituent of muscle; IMP:BHF-UCL. DR GO; GO:0031432; F:titin binding; IPI:BHF-UCL. DR GO; GO:0070080; F:titin Z domain binding; IPI:BHF-UCL. DR GO; GO:0007512; P:adult heart development; IMP:BHF-UCL. DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL. DR GO; GO:0048739; P:cardiac muscle fiber development; IMP:BHF-UCL. DR GO; GO:0003300; P:cardiac muscle hypertrophy; IMP:BHF-UCL. DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IMP:BHF-UCL. DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:BHF-UCL. DR GO; GO:0055003; P:cardiac myofibril assembly; IMP:BHF-UCL. DR GO; GO:0050982; P:detection of mechanical stimulus; TAS:BHF-UCL. DR GO; GO:0035995; P:detection of muscle stretch; IMP:BHF-UCL. DR GO; GO:0030049; P:muscle filament sliding; TAS:Reactome. DR GO; GO:0030916; P:otic vesicle formation; IEA:Ensembl. DR GO; GO:0006461; P:protein complex assembly; TAS:ProtInc. DR GO; GO:0035994; P:response to muscle stretch; TAS:BHF-UCL. DR GO; GO:0045214; P:sarcomere organization; IMP:BHF-UCL. DR GO; GO:0048769; P:sarcomerogenesis; IMP:BHF-UCL. DR GO; GO:0003009; P:skeletal muscle contraction; IEP:BHF-UCL. DR GO; GO:0030241; P:skeletal muscle myosin thick filament assembly; IMP:BHF-UCL. DR GO; GO:0030240; P:skeletal muscle thin filament assembly; IMP:BHF-UCL. DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl. DR Gene3D; 2.20.160.10; -; 1. DR InterPro; IPR015667; Telethonin. DR InterPro; IPR023111; Titin-like_domain. DR PANTHER; PTHR15143; PTHR15143; 1. DR Pfam; PF09470; Telethonin; 1. PE 1: Evidence at protein level; KW 3D-structure; Cardiomyopathy; Complete proteome; Cytoplasm; KW Disease mutation; Limb-girdle muscular dystrophy; Phosphoprotein; KW Polymorphism; Reference proteome. FT CHAIN 1 167 Telethonin. FT /FTId=PRO_0000072483. FT MOD_RES 39 39 Phosphoserine. FT {ECO:0000250|UniProtKB:O70548}. FT VARIANT 13 13 Missing (rare polymorphism). FT {ECO:0000269|PubMed:16352453, FT ECO:0000269|PubMed:16490376, FT ECO:0000269|PubMed:16650785}. FT /FTId=VAR_026649. FT VARIANT 70 70 R -> W (in CMH25). FT {ECO:0000269|PubMed:16352453}. FT /FTId=VAR_026650. FT VARIANT 74 74 L -> H (in dbSNP:rs17851031). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_029445. FT VARIANT 87 87 R -> Q (found in a patient with dilated FT cardiomyopathy; unknown pathological FT significance). FT {ECO:0000269|PubMed:12507422}. FT /FTId=VAR_015397. FT VARIANT 90 90 P -> L (in CMH25; unknown pathological FT significance). FT {ECO:0000269|PubMed:16352453}. FT /FTId=VAR_026651. FT VARIANT 106 106 R -> C (in dbSNP:rs45578741). FT /FTId=VAR_051421. FT VARIANT 132 132 E -> Q (probable disease-associated FT mutation found in a patient with dilated FT cardiomyopathy; impairs the interaction FT with CSRP3, TTN and MYOZ2). FT {ECO:0000269|PubMed:15582318}. FT /FTId=VAR_029446. FT VARIANT 137 137 T -> I (in CMH25; increased interaction FT with TTN and MYOZ2). FT {ECO:0000269|PubMed:15582318}. FT /FTId=VAR_029447. FT VARIANT 153 153 R -> H (in CMH25). FT {ECO:0000269|PubMed:15582318}. FT /FTId=VAR_029448. FT STRAND 4 14 {ECO:0000244|PDB:1YA5}. FT TURN 15 18 {ECO:0000244|PDB:1YA5}. FT STRAND 19 33 {ECO:0000244|PDB:1YA5}. FT HELIX 35 37 {ECO:0000244|PDB:1YA5}. FT STRAND 38 44 {ECO:0000244|PDB:1YA5}. FT TURN 45 48 {ECO:0000244|PDB:1YA5}. FT STRAND 49 55 {ECO:0000244|PDB:1YA5}. FT STRAND 57 62 {ECO:0000244|PDB:1YA5}. FT STRAND 67 73 {ECO:0000244|PDB:1YA5}. FT STRAND 78 84 {ECO:0000244|PDB:1YA5}. SQ SEQUENCE 167 AA; 19052 MW; A3B0E27D8C84F6C5 CRC64; MATSELSCEV SEENCERREA FWAEWKDLTL STRPEEGCSL HEEDTQRHET YHQQGQCQVL VQRSPWLMMR MGILGRGLQE YQLPYQRVLP LPIFTPAKMG ATKEEREDTP IQLQELLALE TALGGQCVDR QEVAEITKQL PPVVPVSKPG ALRRSLSRSM SQEAQRG //