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Gene Review

TCAP  -  titin-cap

Homo sapiens

Synonyms: CMD1N, LGMD2G, T-cap, TELE, Telethonin, ...
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Disease relevance of TCAP


Psychiatry related information on TCAP

  • The correlation between the TELE and the sum of the boxes of the Clinical Dementia Rating scale (CDR-SB) was -0.71 (p < 0.0001) and -0.75 between the TICS and the CDR-SB (p < 0.0001) [6].
  • We studied 56 subjects, 30 patients with a clinical diagnosis of Alzheimer's disease (AD) and 26 healthy controls, using two telephone screens for cognitive impairment, a self-report interview referred to as the TELE and the Telephone Interview for Cognitive Status (TICS) [6].
  • Tele-education in child mental health for rural allied health workers [7].
  • The reliability of the center, which provides telemedicine, tele-education, and telecounseling services, was tested by comparing assessment via our system with in-person assessment, and the clinical outcome was assessed by rating the changes of behavioral symptoms [8].
  • This paper describes a tele-audiometric system developed for the application of realtime diagnostic audiometry via the Internet. A pilot study evaluated 31 adult participants in a double-blind study of two different systems (i.e., conventional versus Internet-based) for assessing auditory thresholds [9].

High impact information on TCAP

  • Titin kinase phosphorylates the muscle protein telethonin in early differentiating myocytes, indicating that this kinase may act in myofibrillogenesis [10].
  • The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity [11].
  • FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle [12].
  • Furthermore, by using a glutathione S-transferase overlay assay we find that FATZ also binds telethonin [12].
  • The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor [13].

Chemical compound and disease context of TCAP


Biological context of TCAP

  • Notably, MDM2 downregulated the protein level of TCAP through the proteasomal pathway, and this downregulation was inhibited by p14(ARF) [3].
  • We describe here that the N-terminal titin immunoglobulin domains Z1 and Z2 interact specifically with telethonin in yeast two-hybrid analysis and protein binding assays [15].
  • The interaction of telethonin with titin is therefore conformation-dependent, reflecting a possible phosphorylation regulation during myofibrillogenesis [15].
  • Heart size, judged as heart volume from tele-chest X-ray in supine position, showed a reduction in 36/61, no change in 15/61 and increase in 10/61 [16].
  • Telemedicine including tele-home care in the 21st century will use the Internet and digital HDTV (high-definition TV) technology for information and data management interchangeably both at domestic and global levels in the medical environment [17].

Anatomical context of TCAP

  • Telethonin is a 19-kDa sarcomeric protein, localized to the Z-disc of skeletal and cardiac muscles [2].
  • Immunofluorescence with antibodies against the N-terminal region of titin and telethonin detects both proteins at the Z-disc of human myotubes [15].
  • We then calculated the density of functional capillaries (Dcap) and the mean time of transit of blood through the capillaries (tcap) from hemodynamic variables obtained in vivo by positron tomography of five patients afflicted by cerebral ischemic stroke [18].
  • The validity of the ictal clinical data used was confirmed on the basis of 99 frontal lobe seizures recorded by tele-electroencephalogram or tele-stereo-electroencephalogram [19].
  • Continuous hemofiltration with polyethersulfone membranes evaluated by tele-monitoring [20].

Associations of TCAP with chemical compounds

  • CONCLUSIONS: A tele-affiliation education environment has been developed and tested between Yale University School of Medicine and Greece resulting in an improved infrastructure for health education and management [21].
  • Tele-tongs, shielded (PMMA: polymethylmethacrylate) syringes/vials and an automatic dose fractionating system were used [22].
  • In the field of cardio-vascular physiology and fluid regulation, the experiments: ORTHOSTATISME, DIURESE have been renewed and complemented by the TISSU experiment (proposed by a german scientist) and a real-time tele-assistance program using US echography technic and ground support from the french CADMOS support control center located in Toulouse [23].
  • The EPU can be tele-operated directly from ground and consists of three major subsystems to guarantee its functionality: Functional Platform, Base and Control Panel [24].

Physical interactions of TCAP

  • Tcap interacts with the calsarcin, which tethers the calcineurin to the Z-disc [13].
  • We show that titin ZIg1/2 could form a three-way complex with sAnk1 and T-cap [25].
  • In this study, we identified a novel specific MDM2-binding protein TCAP by the yeast two-hybrid screen [3].

Regulatory relationships of TCAP

  • Hence, not only the telethonin transcript is rapidly downregulated in denervated muscle but the protein itself undergoes dynamic changes while its known sarcomeric binding partner titin remains unaltered [26].

Other interactions of TCAP

  • Patients with MLP/TCAP-associated HCM clinically mimicked myofilament-HCM [27].
  • Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy [13].
  • These results suggest a possible role of telethonin in linking titin filaments at the Z-disk periphery [28].
  • Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system [29].

Analytical, diagnostic and therapeutic context of TCAP

  • Analytical ultracentrifugation and synchrotron radiation x-ray scattering were employed to study the solution structures of Z1Z2 and its complexes with telethonin, and low resolution models were constructed ab initio from the scattering data [28].
  • Antibodies against a recombinant telethonin fragment were used for Western blot analysis, confirming the presence of this 19 kDa protein in heart and skeletal muscle and revealing an immunofluorescence pattern typical of sarcomeric proteins, overlapping myosin [30].
  • Indirect immunofluorescence analysis of a wide variety of neuromuscular disorders including dystrophinopathies, metabolic myopathies, denervation disorders, congenital and inflammatory myopathies revealed that the characteristic Z-band staining of telethonin was preserved in all disease entities included in our study [26].
  • In order to assess the expression of telethonin in more frequently encountered myopathological conditions we generated and characterized a rabbit antiserum raised against the C-terminal end of telethonin by immunoblotting and immunogold EM [26].
  • New and exciting applications for VR have emerged in research, training, rehabilitation, teleoperation, virtual archeology and tele-immersion [31].


  1. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Knöll, 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 (2002) [Pubmed]
  2. Telethonin protein expression in neuromuscular disorders. Vainzof, M., Moreira, E.S., Suzuki, O.T., Faulkner, G., Valle, G., Beggs, A.H., Carpen, O., Ribeiro, A.F., Zanoteli, E., Gurgel-Gianneti, J., Tsanaclis, A.M., Silva, H.C., Passos-Bueno, M.R., Zatz, M. Biochim. Biophys. Acta (2002) [Pubmed]
  3. MDM2 interacts with and downregulates a sarcomeric protein, TCAP. Tian, L.F., Li, H.Y., Jin, B.F., Pan, X., Man, J.H., Zhang, P.J., Li, W.H., Liang, B., Liu, H., Zhao, J., Gong, W.L., Zhou, T., Zhang, X.M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  4. The seventh form of autosomal recessive limb-girdle muscular dystrophy is mapped to 17q11-12. Moreira, E.S., Vainzof, M., Marie, S.K., Sertié, A.L., Zatz, M., Passos-Bueno, M.R. Am. J. Hum. Genet. (1997) [Pubmed]
  5. A mutation in telethonin alters Nav1.5 function. Mazzone, A., Strege, P.R., Tester, D.J., Bernard, C.E., Faulkner, G., De Giorgio, R., Makielski, J.C., Stanghellini, V., Gibbons, S.J., Ackerman, M.J., Farrugia, G. J. Biol. Chem. (2008) [Pubmed]
  6. Characteristics of two telephone screens for cognitive impairment. Järvenpää, T., Rinne, J.O., Räihä, I., Koskenvuo, M., Löppönen, M., Hinkka, S., Kaprio, J. Dementia and geriatric cognitive disorders. (2002) [Pubmed]
  7. Tele-education in child mental health for rural allied health workers. Fahey, A., Day, N.A., Gelber, H. Journal of telemedicine and telecare. (2003) [Pubmed]
  8. A telemedicine system as a care modality for dementia patients in Korea. Lee, J.H., Kim, J.H., Jhoo, J.H., Lee, K.U., Kim, K.W., Lee, D.Y., Woo, J.I. Alzheimer disease and associated disorders. (2000) [Pubmed]
  9. Internet-based tele-audiometry system for the assessment of hearing: a pilot study. Givens, G.D., Blanarovich, A., Murphy, T., Simmons, S., Blach, D., Elangovan, S. Telemedicine journal and e-health : the official journal of the American Telemedicine Association. (2003) [Pubmed]
  10. Structural basis for activation of the titin kinase domain during myofibrillogenesis. Mayans, O., van der Ven, P.F., Wilm, M., Mues, A., Young, P., Fürst, D.O., Wilmanns, M., Gautel, M. Nature (1998) [Pubmed]
  11. The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. Gregorio, C.C., Trombitás, K., Centner, T., Kolmerer, B., Stier, G., Kunke, K., Suzuki, K., Obermayr, F., Herrmann, B., Granzier, H., Sorimachi, H., Labeit, S. J. Cell Biol. (1998) [Pubmed]
  12. 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. (2000) [Pubmed]
  13. 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., Knöll, R., Hoshijima, M., Chien, K.R., Kimura, A. J. Am. Coll. Cardiol. (2004) [Pubmed]
  14. Cellular expression, localization and interactions of the product of the human MOST-1 gene associated with breast and prostate cancers. Tan, J.M., Chow, V.T. Int. J. Oncol. (2007) [Pubmed]
  15. 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., Young, P., Fürst, D.O., Gautel, M. FEBS Lett. (1998) [Pubmed]
  16. Treatment of hypertrophic cardiomyopathy: relation to pathological mechanisms. Kaltenbach, M., Hopf, R. J. Mol. Cell. Cardiol. (1985) [Pubmed]
  17. The present and future of telemedicine in Japan. Takahashi, T. International journal of medical informatics. (2001) [Pubmed]
  18. Reduction of functional capillary density in human brain after stroke. Gjedde, A., Kuwabara, H., Hakim, A.M. J. Cereb. Blood Flow Metab. (1990) [Pubmed]
  19. The seizures of frontal lobe epilepsy. A study of clinical manifestations. Geier, S., Bancaud, J., Talairach, J., Bonis, A., Szikla, G., Enjelvin, M. Neurology (1977) [Pubmed]
  20. Continuous hemofiltration with polyethersulfone membranes evaluated by tele-monitoring. Pacitti, A., Cantaluppi, V., Fenoglio, R., De Nitti, C., Tetta, C. Contributions to nephrology. (2003) [Pubmed]
  21. Tele-affiliation in medical education: experience from the international program at Yale Office of Telemedicine. Condos, S.G., Stamkopoulos, T., Selles, J.M., Merrell, R.C. Methods of information in medicine. (2002) [Pubmed]
  22. Radiation protection in radionuclide therapies with (90)Y-conjugates: risks and safety. Cremonesi, M., Ferrari, M., Paganelli, G., Rossi, A., Chinol, M., Bartolomei, M., Prisco, G., Tosi, G. Eur. J. Nucl. Med. Mol. Imaging (2006) [Pubmed]
  23. Biomedical program of the ALTAIR french russian flight onboard the MIR station. Andre-Deshays, C., Haignere, J.P., Guell, A., Marsal, O., Suchet, L., Kotovskaya, A., Gratchev, V., Noskin, A., Grigoriev, A. Acta astronautica. (1995) [Pubmed]
  24. Preparation of biological samples in space: the experiment preparation unit. Deceuninck, H., Pastor, M., Bois, J.M. Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology. (2002) [Pubmed]
  25. The hydrophilic domain of small ankyrin-1 interacts with the two N-terminal immunoglobulin domains of titin. Kontrogianni-Konstantopoulos, A., Bloch, R.J. J. Biol. Chem. (2003) [Pubmed]
  26. Early and selective disappearance of telethonin protein from the sarcomere in neurogenic atrophy. Schröder, R., Reimann, J., Iakovenko, A., Mues, A., Bönnemann, C.G., Matten, J., Gautel, M. J. Muscle Res. Cell. Motil. (2001) [Pubmed]
  27. 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. (2006) [Pubmed]
  28. Solution scattering suggests cross-linking function of telethonin in the complex with titin. Zou, P., Gautel, M., Geerlof, A., Wilmanns, M., Koch, M.H., Svergun, D.I. J. Biol. Chem. (2003) [Pubmed]
  29. Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system. Furukawa, T., Ono, Y., Tsuchiya, H., Katayama, Y., Bang, M.L., Labeit, D., Labeit, S., Inagaki, N., Gregorio, C.C. J. Mol. Biol. (2001) [Pubmed]
  30. 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. (1997) [Pubmed]
  31. Virtual reality in behavioral neuroscience and beyond. Tarr, M.J., Warren, W.H. Nat. Neurosci. (2002) [Pubmed]
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