Affinage

TCAP

Telethonin · UniProt O15273

Length
167 aa
Mass
19.1 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TCAP (telethonin) is a small Z-disc protein that anchors titin filaments at the sarcomere periphery and serves as a mechanical and signaling hub coupling sarcomeric integrity to membrane organization and cardiomyocyte survival (PMID:9817758, PMID:21799151). Its defining biochemical activity is to cross-link two N-terminal titin Z1Z2 immunoglobulin domains into a palindromic antiparallel 2:1 (titin:telethonin) sandwich, with the C-terminus mediating dimerization of these complexes and being required for sarcomere assembly in vivo (PMID:12446666, PMID:16713295, PMID:20235223); single-molecule force spectroscopy shows this bond is mechanically anisotropic, resisting ultra-high force only along the physiological filament axis (PMID:19622741). Telethonin sits within a broader Z-disc interaction network, binding FATZ, calsarcin-1, MLP, and BMP10, and disease-associated mutations remodel these interactions in patterns that track with hypertrophic versus dilated cardiomyopathy (PMID:10984498, PMID:15582318, PMID:17921333). Beyond structural anchoring, telethonin bridges the sarcomere to membrane excitability by binding the minK IKs channel beta-subunit and modulating Nav1.5 sodium channel kinetics, with TCAP variants altering INa (PMID:11697903, PMID:18408010, PMID:32588437). Loss-of-function studies across zebrafish, Xenopus, and mouse establish that telethonin is dispensable for baseline titin anchoring but essential for T-tubule development, calcium-induced calcium release, and resistance to biomechanical stress, where its deficiency drives heart failure through elevated nuclear p53-mediated apoptosis (PMID:19679566, PMID:20235223, PMID:21799151, PMID:23100327). Constitutive bis-phosphorylation at Ser-157/Ser-161 by PKD and CaMKII maintains T-tubule organization and calcium transient fidelity (PMID:24280220). Telethonin abundance is dynamically controlled: it is a substrate of the MuRF1 and SCF-FBXL21 E3 ubiquitin ligases, with GSK-3beta-driven phosphodegron-dependent circadian degradation and CLOCK/BMAL1 transcriptional control conferring diurnal oscillation of its levels in muscle (PMID:18565784, PMID:25121604, PMID:29271608, PMID:32937135). TCAP loss is also linked to dystrophic skeletal muscle and impaired cardiac regeneration through elevated ROS and autophagy (PMID:20233748, PMID:39226992).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1998 High

    Established that telethonin binds the N-terminal titin Z1Z2 immunoglobulin domains and that this interaction is required for sarcomeric assembly, defining TCAP's core structural role.

    Evidence In vitro binding, yeast two-hybrid, and dominant-negative overexpression in cardiac myocytes

    PMID:9645487 PMID:9817758

    Open questions at the time
    • Stoichiometry and architecture of the complex not yet resolved
    • Whether the interaction directly anchors filaments versus assembling them not distinguished
  2. 2000 Medium

    Placed telethonin within a multiprotein Z-disc network by identifying FATZ as a direct binding partner, beginning the mapping of its interactome.

    Evidence GST overlay assay and yeast two-hybrid

    PMID:10984498

    Open questions at the time
    • Single binding method
    • Functional consequence of FATZ binding not tested
  3. 2001 Medium

    Extended telethonin's role from purely structural to membrane-coupling by showing it links myofibrillar components to the IKs channel via the minK cytoplasmic domain at T-tubular membranes.

    Evidence In vitro interaction mapping to C-terminal residues and confocal co-localization in cardiac muscle

    PMID:11697903

    Open questions at the time
    • Functional effect on IKs current not measured
    • Single lab
  4. 2002 High

    Resolved how telethonin organizes titin filaments by defining a 1:2 antiparallel cross-linking complex that can further dimerize, providing a structural basis for filament tethering at the Z-disc.

    Evidence Analytical ultracentrifugation and SAXS with ab initio modeling

    PMID:12446666

    Open questions at the time
    • No atomic-resolution structure yet
    • C-terminal organization unresolved
  5. 2004 Medium

    Connected TCAP biochemistry to disease by showing HCM- and DCM-associated mutations differentially remodel binding to titin, calsarcin-1, and MLP, linking phenotype to altered Z-disc interactions.

    Evidence Yeast two-hybrid and GST pull-down competition assays

    PMID:15582318

    Open questions at the time
    • No quantitative affinity measurements
    • In vivo validation of mutation effects absent
  6. 2006 Medium

    Revealed a nuclear/degradation dimension by showing MDM2 binds telethonin, alters its localization, and promotes ubiquitin-independent proteasomal degradation, antagonized by p14ARF.

    Evidence Yeast two-hybrid, reciprocal Co-IP, GST pull-down, and proteasome inhibitor assays

    PMID:16678796

    Open questions at the time
    • Physiological context of nuclear telethonin not established here
    • Single lab
  7. 2006 High

    Provided the high-resolution architecture of the titin-telethonin sandwich, confirming a palindromic 2:1 assembly and identifying the disordered C-terminus as the dimerization mediator.

    Evidence X-ray crystallography, SAXS, circular dichroism, and in vivo complementation

    PMID:16713295

    Open questions at the time
    • C-terminal structure undefined even when titin-bound
    • Mechanical behavior of the bond not addressed
  8. 2007 Medium

    Linked telethonin to stretch-sensing signaling through direct BMP10 binding, with a cardiomyopathy-associated BMP10 variant showing reduced Tcap binding and enhanced hypertrophic effect.

    Evidence Co-IP, co-localization, and cardiomyocyte hypertrophy assay with conditioned medium

    PMID:17921333

    Open questions at the time
    • Direct functional role of Tcap in BMP10 retention not isolated
    • Single lab
  9. 2008 Medium

    Demonstrated telethonin modulates cardiac/smooth-muscle excitability by co-immunoprecipitating with Nav1.5 and showing a patient mutation alters channel activation and window current.

    Evidence Co-IP, immunofluorescence, and patch-clamp in HEK293 cells

    PMID:18408010

    Open questions at the time
    • Mechanism of channel modulation not defined
    • Single lab
  10. 2008 Medium

    Identified telethonin as a proteasome substrate during muscle atrophy and as required for myoblast differentiation, beginning to define its turnover and developmental functions.

    Evidence Ubiquitin conjugate purification with mass spectrometry; siRNA knockdown in differentiating muscle cells

    PMID:18440815 PMID:18565784

    Open questions at the time
    • E3 ligase responsible for atrophy degradation not yet identified
    • Knockdown effect on differentiation is RNA-level only with no protein mechanism
  11. 2008 Low

    Linked telethonin to cardiomyocyte apoptosis during viral infection by identifying the proapoptotic protein Siva as a binding partner.

    Evidence Yeast two-hybrid screen and co-localization in CVB3-infected cardiomyocytes

    PMID:18849585

    Open questions at the time
    • No biochemical confirmation of direct interaction (no Co-IP)
    • Functional consequence not tested
    • Single lab
  12. 2009 High

    Defined the mechanical logic of the titin-telethonin bond, showing it is directionally optimized to resist ultra-high force only along the physiological filament axis.

    Evidence Single-molecule AFM force spectroscopy on reconstituted complex

    PMID:19622741

    Open questions at the time
    • In vivo relevance of anisotropy to Z-disc function inferred not directly tested
  13. 2009 Medium

    Separated telethonin's role in sarcomere assembly from membrane organization in vivo, showing Tcap integrates after Z-disc periodicity is set and is required for T-tubule development, and is mechanically inducible and ILK-regulated.

    Evidence Morpholino knockdown in zebrafish with EM, immunofluorescence, and ILK epistasis

    PMID:19679566

    Open questions at the time
    • Mechanism coupling Tcap to T-tubule development unresolved
    • Morpholino specificity caveats
  14. 2010 Medium

    Established the in vivo necessity of telethonin for muscle maintenance and the requirement of its C-terminus for sarcomere assembly, while linking Tcap loss to elevated myostatin.

    Evidence Tcap knockout mouse histology and biomechanics; Xenopus morpholino rescue with truncation and phospho-mutant constructs

    PMID:20233748 PMID:20235223

    Open questions at the time
    • Mechanism of myostatin regulation not defined
    • Context-dependence of phospho-mutant rescue noted by authors
  15. 2011 High

    Showed telethonin is dispensable for baseline titin anchoring but essential for stress tolerance, acting in the nucleus to modulate p53 turnover and limit cardiomyocyte apoptosis after biomechanical stress.

    Evidence Tcap KO mice with aortic banding, p53 turnover assays, and nuclear fractionation

    PMID:21799151

    Open questions at the time
    • Mechanism of stress-induced nuclear translocation not defined
    • Direct biochemical link between telethonin and p53 turnover not fully resolved
  16. 2012 High

    Identified telethonin as a load-sensitive regulator of T-tubule structure and calcium-induced calcium release, with KO causing progressive t-tubule loss and Ca2+ handling defects under overload.

    Evidence Tcap KO mice with confocal t-tubule imaging, Ca2+ transient/spark measurements, and aortic banding

    PMID:23100327

    Open questions at the time
    • Molecular link from telethonin to t-tubule maintenance machinery not defined
  17. 2013 High

    Defined post-translational control of telethonin's membrane/calcium function, showing constitutive bis-phosphorylation at Ser-157/Ser-161 by PKD and CaMKII is required for normal t-tubule organization and Ca2+ transient fidelity.

    Evidence In vitro kinase assays, MS phosphosite mapping, phospho-mutant adenoviral transfer, and Ca2+ imaging in cardiomyocytes

    PMID:24280220

    Open questions at the time
    • How phosphorylation mechanistically maintains t-tubules unresolved
    • Upstream signals controlling these kinases on telethonin not defined
  18. 2014 Medium

    Revealed transcriptional circadian control of Tcap, with CLOCK/BMAL1 directly driving rhythmic Tcap expression in the heart.

    Evidence ChIP, promoter binding, luciferase reporter, and RT-PCR in circadian-mutant mice

    PMID:25121604

    Open questions at the time
    • Physiological consequence of rhythmic Tcap not established
    • Single lab
  19. 2017 High

    Defined telethonin as a MuRF1 substrate that also stabilizes MuRF1-E2 (E2E1, E2J1) complexes and governs MuRF1-E2 affinity, integrating it into atrophy-associated ubiquitination.

    Evidence Surface plasmon resonance, yeast three-hybrid, split-GFP complementation, and HEK293T degradation assay

    PMID:29271608

    Open questions at the time
    • In vivo contribution of MuRF1-mediated turnover to muscle phenotype not isolated
  20. 2020 High

    Identified a circadian degradation axis in which GSK-3beta phosphorylates TCAP and FBXL21 to drive SCF-FBXL21 phosphodegron-dependent TCAP turnover, with loss impairing muscle fiber size and strength.

    Evidence Co-IP, in vivo phosphorylation assays, GSK-3beta inhibition/knockdown, and Psttm Fbxl21 hypomorph mouse functional testing

    PMID:32937135

    Open questions at the time
    • Interplay between MuRF1 and SCF-FBXL21 control of TCAP not reconciled
    • Phosphodegron residues' relationship to PKD/CaMKII sites unclear
  21. 2020 Medium

    Confirmed direct functional modulation of Nav1.5 by TCAP, showing variants p.E49K and p.R153H reduce peak INa with p.E49K shifting inactivation, establishing channel loss-of-function.

    Evidence Patch-clamp in HEK293 cells stably expressing hNav1.5 with wild-type versus variant TCAP

    PMID:32588437

    Open questions at the time
    • Mechanism by which TCAP couples to Nav1.5 gating not defined
    • Single lab heterologous system
  22. 2024 Medium

    Identified ROS and autophagy as downstream effectors of Tcap deficiency, with mitochondrial dysfunction, impaired cardiac regeneration, and stretch-sensing defects rescued by ROS scavengers or autophagy inhibitors.

    Evidence CRISPR/Cas9 knockout zebrafish with ROS and mitophagy measurement, cardiac regeneration assay, and pharmacological rescue

    PMID:39226992

    Open questions at the time
    • Molecular link from Tcap loss to ROS elevation not defined
    • Single lab zebrafish model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How biomechanical stress triggers telethonin nuclear translocation and the direct molecular mechanism by which it modulates p53 turnover remain undefined.
  • No defined translocation signal or trafficking mechanism
  • Direct telethonin-p53 biochemical relationship unresolved
  • Integration of structural anchoring, signaling, and degradation roles into one model incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2
Pathway
R-HSA-397014 Muscle contraction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9909396 Circadian clock 2
Partners
BMP10FATZFBXL21KCNE1MDM2SCN5ATRIM63TTN
Complex memberships
Z-disc (FATZ/calsarcin/MLP network)titin-telethonin Z-disc complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 The NH2-terminal titin Ig repeats Z1 and Z2 bind to telethonin (T-cap) at the periphery of the Z-line; dominant-negative expression of either titin Z1-Z2 domains or telethonin in cardiac myocytes disrupts sarcomeric integrity, indicating this interaction is required for sarcomeric assembly. In vitro binding studies, dominant-negative overexpression in cardiac myocytes, immunofluorescence The Journal of cell biology High 9817758
1998 Titin Z1 and Z2 domains interact specifically with telethonin in a conformation-dependent manner; longer titin fragments containing a serine-proline-rich phosphorylation site do not interact with telethonin, suggesting phosphorylation may regulate the interaction during myofibrillogenesis. Yeast two-hybrid analysis, protein binding assays, immunofluorescence on human myotubes FEBS letters Medium 9645487
2000 FATZ (filamin-, actinin-, and telethonin-binding protein) binds to telethonin at the Z-disc, identified by GST overlay assay, placing telethonin in a multi-protein interaction network at the Z-disc. Glutathione S-transferase (GST) overlay assay, yeast two-hybrid The Journal of biological chemistry Medium 10984498
2001 Telethonin specifically interacts with the cytoplasmic domain of minK (the potassium channel beta-subunit) via the sixteen C-terminal residues of telethonin; both proteins co-localize at the Z-line region in cardiac muscle on T-tubular membranes, suggesting telethonin functions as an adapter linking myofibrillar components to the IKs channel complex. In vitro interaction studies, immunofluorescence with confocal analysis, membrane-washing experiments Journal of molecular biology Medium 11697903
2002 Solution scattering and analytical ultracentrifugation reveal that telethonin acts as a central linker cross-linking two titin Z1Z2 molecules in an antiparallel 1:2 (telethonin:titin) complex; full-length telethonin dimerizes two such complexes at higher concentrations, suggesting a role in linking titin filaments at the Z-disc periphery. Analytical ultracentrifugation, synchrotron radiation X-ray scattering (SAXS), ab initio low-resolution modeling The Journal of biological chemistry High 12446666
2004 HCM-associated TCAP mutations (T137I, R153H) augment telethonin's interaction with titin and calsarcin-1, while DCM-associated mutations (E132Q, R87Q) impair telethonin's interaction with MLP, titin, and calsarcin-1, demonstrating that the clinical phenotype (HCM vs. DCM) correlates with altered binding properties among Z-disc components. Yeast two-hybrid, GST pull-down competition assays Journal of the American College of Cardiology Medium 15582318
2006 MDM2 specifically binds TCAP (telethonin), co-localizes with it in the nucleus, and promotes its degradation via the ubiquitin-independent proteasomal pathway; this degradation is inhibited by p14ARF, and elevated MDM2 expression can alter the subcellular localization of TCAP. Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, confocal microscopy, proteasome inhibitor experiments Biochemical and biophysical research communications Medium 16678796
2006 Crystal structure and SAXS data show telethonin assembles two titin N-terminal Z1Z2 domains into a palindromic antiparallel sandwich (2:1 titin:telethonin); the telethonin C-terminus does not form a defined structure even when bound to titin, but mediates dimerization of two titin/telethonin complexes. X-ray crystallography, small-angle X-ray scattering, circular dichroism, in vivo complementation Journal of structural biology High 16713295
2007 BMP10 physically interacts with telethonin at the Z-disc stretch-sensing region; a human BMP10 variant (Thr326Ile) associated with hypertensive dilated cardiomyopathy shows decreased binding to Tcap and increased extracellular secretion, with enhanced hypertrophic effect in neonatal cardiomyocytes. Co-immunoprecipitation, immunofluorescence co-localization, cell transfection and conditioned medium cardiomyocyte hypertrophy assay American journal of physiology. Heart and circulatory physiology Medium 17921333
2008 Telethonin is expressed in human gastrointestinal smooth muscle, co-localizes with Nav1.5, and co-immunoprecipitates with sodium channels; a TCAP mutation found in a patient with intestinal pseudo-obstruction, when co-expressed with SCN5A in HEK293 cells, alters steady-state activation kinetics of Nav1.5 resulting in a doubling of the window current. Co-immunoprecipitation, immunofluorescence, patch-clamp electrophysiology in HEK293 cells The Journal of biological chemistry Medium 18408010
2008 Telethonin is a substrate of the ubiquitin-proteasome system during muscle atrophy; purification of ubiquitin conjugates followed by deubiquitination identified telethonin as a 26S proteasome substrate in unloaded (atrophying) soleus muscle. Ubiquitin conjugate purification using S5a subunit, deubiquitination, mass spectrometry identification The international journal of biochemistry & cell biology Medium 18565784
2008 Telethonin knockdown by siRNA in differentiating skeletal muscle cells decreases expression of myogenic regulatory factors and prevents normal muscle cell phenotype development, indicating TCAP is required for myoblast differentiation. siRNA knockdown, Northern blots, real-time RT-PCR, cell morphology assessment Neuromuscular disorders : NMD Low 18440815
2008 Proapoptotic protein Siva specifically interacts with telethonin in cardiomyocytes during coxsackievirus B3 infection; Siva expression is increased in CVB3-infected mouse heart tissue and the proteins co-localize in cardiomyocytes. Yeast two-hybrid screen of human heart cDNA library, co-localization in infected cardiomyocytes Cardiovascular research Low 18849585
2009 Single-molecule force spectroscopy shows the titin-telethonin complex forms a highly directed molecular bond that resists ultra-high forces when loaded along its physiological direction (along the filament axis) but breaks easily in other directions, demonstrating the bond is mechanically anisotropic and optimized for the Z-disc's mechanical environment. Single-molecule force spectroscopy (AFM-based), reconstituted titin-telethonin complex Proceedings of the National Academy of Sciences of the United States of America High 19622741
2009 In zebrafish, Tcap depletion causes muscular dystrophy-like phenotypes; Tcap integrates into the sarcomere after Z-disc periodicity is established (sarcomere assembly remains intact in morphants), but sarcomere-plasma membrane interaction and T-tubule development are disrupted. Additionally, Tcap expression level is negatively regulated by integrin-linked kinase (ILK) and is inducible by mechanical stretch. Morpholino knockdown in zebrafish, immunofluorescence, electron microscopy, genetic epistasis with ILK Human molecular genetics Medium 19679566
2010 Tcap knockout mice develop dystrophic skeletal muscle histology (myofiber size variation, central nucleation) and show increased myostatin protein levels alongside Tcap loss, as well as increased muscle stiffness; this establishes Tcap as functionally important for muscle fiber maintenance and suggests a regulatory relationship with myostatin. Tcap knockout mouse model, muscle histology, Western blot for myostatin, force and stiffness assays of isolated muscles Human molecular genetics Medium 20233748
2010 In Xenopus, telethonin knockdown causes embryonic paralysis and sarcomeric disruption; these defects are rescued by full-length telethonin mRNA but not by C-terminal truncation or alanine substitution of four C-terminal phosphorylatable residues, establishing that the C-terminus of telethonin is required for sarcomere assembly. Morpholino knockdown in Xenopus, mRNA rescue with deletion and phospho-mutant constructs, sarcomere ultrastructure analysis Developmental dynamics : an official publication of the American Association of Anatomists Medium 20235223
2011 Telethonin knockout in mice does not impair baseline heart development or function, indicating it is not indispensable for titin anchoring per se (actin-titin cross-links via α-actinin are sufficient for Z-disc stability). However, telethonin deficiency leads to heart failure after biomechanical stress, partly through elevated p53-mediated apoptosis in cardiomyocytes; telethonin modulates turnover of the proapoptotic tumor suppressor p53 in the nuclear compartment following mechanical stress. Telethonin KO mouse model, mechanical stress (aortic banding), p53 turnover assays, nuclear fractionation, cardiac function measurements Circulation research High 21799151
2012 Telethonin knockout mice display progressive t-tubule loss, Ca2+ transient dysynchrony, elevated Ca2+ spark frequency, and depressed L-type Ca2+ channel activity with age and after aortic banding; this identifies telethonin as a critical load-sensitive regulator of t-tubule structure and calcium-induced calcium release. Tcap KO mice, confocal t-tubule imaging, Ca2+ transient and spark measurements, aortic banding mechanical overload model Human molecular genetics High 23100327
2013 Telethonin is constitutively bis-phosphorylated at Ser-157 and Ser-161 in adult rat and mouse ventricular myocardium; protein kinase D and CaMKII phosphorylate these sites in vitro. Expression of non-phosphorylatable S157A/S161A telethonin in cardiomyocytes disrupts t-tubule organization and prolongs/increases variance of intracellular Ca2+ transients, establishing that telethonin phosphorylation is required for normal t-tubule and calcium homeostasis. In vitro kinase assays, mass spectrometry, site-directed mutagenesis, phosphate affinity electrophoresis, adenoviral gene transfer, confocal imaging of t-tubules, Ca2+ transient measurements The Journal of biological chemistry High 24280220
2014 CLOCK and BMAL1 transcriptional activators directly target the Tcap promoter, driving circadian oscillation of Tcap mRNA and TCAP protein in the heart; Tcap mRNA rhythmicity is blunted in Clock-mutant hearts. ChIP assay, biotinylated oligonucleotide promoter binding, luciferase reporter assay, real-time PCR in circadian mutant mice PloS one Medium 25121604
2017 Telethonin is a substrate of MuRF1 E3 ubiquitin ligase; telethonin facilitates and stabilizes MuRF1-E2 (specifically E2E1 and E2J1) complexes, and its presence governs the affinity between MuRF1 and these E2 enzymes. Co-expression of MuRF1 with these E2s in HEK293T cells leads to increased telethonin degradation. Surface plasmon resonance, yeast three-hybrid, split-GFP complementation, HEK293T co-expression degradation assay Journal of cachexia, sarcopenia and muscle High 29271608
2020 FBXL21 interacts with TCAP in skeletal muscle in a circadian manner antiphasic to TCAP accumulation; GSK-3β phosphorylates both FBXL21 and TCAP to activate phosphodegron-dependent TCAP degradation via the SCF-FBXL21 complex. GSK-3β inhibition or knockdown diminishes FBXL21-Cul1 complex formation and delays TCAP degradation. Loss of this regulatory axis (Psttm Fbxl21 hypomorph mice) causes impaired skeletal muscle fiber size, exercise tolerance, and grip strength. Co-immunoprecipitation, in vivo phosphorylation assays, GSK-3β inhibition/knockdown, Psttm mouse model, skeletal muscle functional testing Cell reports High 32937135
2020 TCAP variants p.E49K and p.R153H reduce peak Nav1.5 sodium current density in HEK293 cells stably expressing hNav1.5, with p.E49K also shifting the voltage dependency of steady-state inactivation leftward; these findings demonstrate TCAP modulates Nav1.5 channel function and that specific mutations cause loss-of-function of INa. Patch-clamp electrophysiology in HEK293 cells, transfection of wild-type vs. variant TCAP Pacing and clinical electrophysiology : PACE Medium 32588437
2024 Tcap knockout zebrafish (CRISPR/Cas9) show muscular dystrophy phenotypes, abnormal mitochondria in skeletal muscle, inhibited stretch-sensing ability, altered cardiac morphology and function, increased ROS and mitophagy; impaired cardiac regeneration and cardiomyocyte proliferation after injury are rescued by ROS scavengers or autophagy inhibitors, identifying elevated ROS and autophagy as downstream effectors of Tcap deficiency. CRISPR/Cas9 knockout zebrafish, ROS measurement, mitophagy markers, cardiac regeneration assay, pharmacological rescue Biochimica et biophysica acta. Molecular basis of disease Medium 39226992

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. The Journal of cell biology 253 9817758
2000 Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nature genetics 241 10655062
2004 Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. Journal of the American College of Cardiology 224 15582318
2008 Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. Clinical and translational science 159 19412328
1997 Telethonin, a novel sarcomeric protein of heart and skeletal muscle. FEBS letters 150 9350988
2005 Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin. Molecular genetics and metabolism 147 16352453
1998 Two immunoglobulin-like domains of the Z-disc portion of titin interact in a conformation-dependent way with telethonin. FEBS letters 135 9645487
2000 FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle. The Journal of biological chemistry 133 10984498
2001 Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system. Journal of molecular biology 113 11697903
2009 The titin-telethonin complex is a directed, superstable molecular bond in the muscle Z-disk. Proceedings of the National Academy of Sciences of the United States of America 93 19622741
2001 Telethonin and other new proteins of the Z-disc of skeletal muscle. IUBMB life 85 11699871
2009 Depletion of zebrafish Tcap leads to muscular dystrophy via disrupting sarcomere-membrane interaction, not sarcomere assembly. Human molecular genetics 82 19679566
2011 Telethonin deficiency is associated with maladaptation to biomechanical stress in the mammalian heart. Circulation research 79 21799151
1999 Seven autosomal recessive limb-girdle muscular dystrophies in the Brazilian population: from LGMD2A to LGMD2G. American journal of medical genetics 76 10069710
2020 A Proposal for Multidisciplinary Tele-Rehabilitation in the Assessment and Rehabilitation of COVID-19 Survivors. International journal of environmental research and public health 67 32645876
2008 A mutation in telethonin alters Nav1.5 function. The Journal of biological chemistry 56 18408010
2004 Cloning and characterization of teneurin C-terminus associated peptide (TCAP)-3 from the hypothalamus of an adult rainbow trout (Oncorhynchus mykiss). General and comparative endocrinology 56 15158132
2012 A critical role for Telethonin in regulating t-tubule structure and function in the mammalian heart. Human molecular genetics 55 23100327
2005 Pharmacological modulation of cholinergic brain activity and its reflection in special EEG frequency ranges from various brain areas in the freely moving rat (Tele-Stereo-EEG). European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 53 16009538
2002 Acute and chronic effects of methamphetamine on tele-methylhistamine levels in mouse brain: selective involvement of the D(2) and not D(3) receptor. The Journal of pharmacology and experimental therapeutics 49 11805225
2017 A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate. Journal of cachexia, sarcopenia and muscle 45 29271608
2010 Functional muscle analysis of the Tcap knockout mouse. Human molecular genetics 43 20233748
1986 The bone marrow in urticaria pigmentosa and systemic mastocytosis. Cell composition and mast cell density in relation to urinary excretion of tele-methylimidazoleacetic acid. Archives of dermatology 43 3954410
2002 Solution scattering suggests cross-linking function of telethonin in the complex with titin. The Journal of biological chemistry 42 12446666
2008 Transcription-terminating mutation in telethonin causing autosomal recessive muscular dystrophy type 2G in a European patient. Neuromuscular disorders : NMD 41 18948002
2016 Implementation of a Tele-urology Program for Outpatient Hematuria Referrals: Initial Results and Patient Satisfaction. Urology 39 27450940
2013 Phosphoregulation of the titin-cap protein telethonin in cardiac myocytes. The Journal of biological chemistry 39 24280220
2007 Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy. American journal of physiology. Heart and circulatory physiology 38 17921333
2006 MDM2 interacts with and downregulates a sarcomeric protein, TCAP. Biochemical and biophysical research communications 38 16678796
1985 Morphometrical and immunocytochemical characterization of peri-insular and tele-insular acinar cells in the rat pancreas. European journal of cell biology 38 2581784
2015 Ancient interaction between the teneurin C-terminal associated peptides (TCAP) and latrophilin ligand-receptor coupling: a role in behavior. Frontiers in neuroscience 33 25964737
2011 Telethonin-deficiency initially presenting as a congenital muscular dystrophy. Neuromuscular disorders : NMD 32 21530252
2009 Teneurin C-terminal associated peptide (TCAP)-1 attenuates corticotropin-releasing factor (CRF)-induced c-Fos expression in the limbic system and modulates anxiety behavior in male Wistar rats. Behavioural brain research 32 19428634
2024 Multi-receptor skin with highly sensitive tele-perception somatosensory. Science advances 31 39259789
2007 Repeated intracerebral teneurin C-terminal associated peptide (TCAP)-1 injections produce enduring changes in behavioral responses to corticotropin-releasing factor (CRF) in rat models of anxiety. Behavioural brain research 31 18082275
2014 Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin): identification of cardiac clock-controlled genes using open access bioinformatics data. PloS one 30 25121604
2003 Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma. Journal of hepatology 30 12971961
1999 The novel sarcomeric protein telethonin exhibits developmental and functional regulation. Biochemical and biophysical research communications 30 10208846
1986 A quantitative immuno-electronmicroscopic study of amylase and chymotrypsinogen in peri- and tele-insular cells of the rat exocrine pancreas. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 30 2418099
2014 Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G. PloS one 27 25055047
2020 The GSK-3β-FBXL21 Axis Contributes to Circadian TCAP Degradation and Skeletal Muscle Function. Cell reports 26 32937135
2018 Tele-connecting China's future urban growth to impacts on ecosystem services under the shared socioeconomic pathways. The Science of the total environment 26 30380484
2016 Teneurins, TCAP, and latrophilins: roles in the etiology of mood disorders. Translational neuroscience 26 28123817
2006 Evidence for a dimeric assembly of two titin/telethonin complexes induced by the telethonin C-terminus. Journal of structural biology 25 16713295
2013 The genetics of dilated cardiomyopathy: a prioritized candidate gene study of LMNA, TNNT2, TCAP, and PLN. Clinical cardiology 22 24037902
2013 Origin of chordate peptides by horizontal protozoan gene transfer in early metazoans and protists: evolution of the teneurin C-terminal associated peptides (TCAP). General and comparative endocrinology 21 23453965
2010 Limb-girdle muscular dystrophy in a Portuguese patient caused by a mutation in the telethonin gene. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 20 22029105
2008 TCAP knockdown by RNA interference inhibits myoblast differentiation in cultured skeletal muscle cells. Neuromuscular disorders : NMD 20 18440815
1987 Immunohisto- and cytochemical studies of pancreatic enzymes in peri-insular and tele-insular acinar cells of streptozotocin-induced diabetic rats. Pancreas 20 2442746
1982 Ontogeny of subcellular distribution of rat brain tele-methylhistamine. Journal of neurochemistry 20 7077329
2019 Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion. Frontiers in endocrinology 19 30774623
1984 Normal levels of histamine and tele-methylhistamine in mast cell-deficient mouse brain. Brain research 19 6697200
2001 Early and selective disappearance of telethonin protein from the sarcomere in neurogenic atrophy. Journal of muscle research and cell motility 18 11763198
2014 Conserved expression of truncated telethonin in a patient with limb-girdle muscular dystrophy 2G. Neuromuscular disorders : NMD 17 25724973
2013 Teneurin C-terminal associated peptides (TCAP): modulators of corticotropin-releasing factor (CRF) physiology and behavior. Frontiers in neuroscience 17 24062636
2010 Distinct roles for telethonin N-versus C-terminus in sarcomere assembly and maintenance. Developmental dynamics : an official publication of the American Association of Anatomists 17 20235223
2008 Coordinate expression of the 19S regulatory complex and evidence for ubiquitin-dependent telethonin degradation in the unloaded soleus muscle. The international journal of biochemistry & cell biology 17 18565784
2004 Simultaneous fluorometric measurement of histamine and tele-methylhistamine levels in rodent brain by high-performance liquid chromatography. Analytical biochemistry 17 15464956
1992 Differences in secretory granule content in pancreatic acinar cells from peri-insular and tele-insular regions. Pancreas 17 1379368
2021 Effects of laser acupuncture tele-therapy for rheumatoid arthritis elderly patients. Lasers in medical science 16 33738615
2019 Clinical and genetic characterization of limb girdle muscular dystrophy R7 telethonin-related patients from three unrelated Chinese families. Neuromuscular disorders : NMD 16 32005491
2023 Characterization of TelE, a T7SS LXG Effector Exhibiting a Conserved C-Terminal Glycine Zipper Motif Required for Toxicity. Microbiology spectrum 15 37432124
2016 Novel mutation in TCAP manifesting with asymmetric calves and early-onset joint retractions. Neuromuscular disorders : NMD 15 27618135
1993 Morphometric studies on the juxta-insular and tele-insular acinar cells of the pancreas in normal and streptozotocin-induced diabetic rats. Journal of electron microscopy 15 8350023
2022 Tele-entomology and tele-parasitology: A citizen science-based approach for surveillance and control of Chagas disease in Venezuela. Parasite epidemiology and control 14 36118050
2017 Rare diagnosis of telethoninopathy (LGMD2G) in a Turkish patient. Neuromuscular disorders : NMD 14 28666572
2000 An acute i.c.v. infusion of leptin has no effect on hypothalamic histamine and tele-methylhistamine contents in Wistar rats. European journal of pharmacology 14 10794816
1999 Effects of selected histamine H3 receptor antagonists on tele-methylhistamine levels in rat cerebral cortex. Biochemical pharmacology 14 10796076
2012 A mathematical framework for combining decisions of multiple experts toward accurate and remote diagnosis of malaria using tele-microscopy. PloS one 13 23071544
2024 Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy. Biochimica et biophysica acta. Molecular basis of disease 12 39226992
1980 Tele-Methylhistamine is a specific MAO B substrate in man. Psychopharmacology 12 6774369
2025 Identification of splenic IRF7 as a nanotherapy target for tele-conditioning myocardial reperfusion injury. Nature communications 11 39994192
2018 Accuracy of tele-consultation on management decisions of lesions suspect for melanoma using reflectance confocal microscopy as a stand-alone diagnostic tool. Journal of the European Academy of Dermatology and Venereology : JEADV 11 30242916
2016 Expression and actions of corticotropin-releasing factor/diuretic hormone-like peptide (CDLP) and teneurin C-terminal associated peptide (TCAP) in the vase tunicate, Ciona intestinalis: Antagonism of the feeding response. General and comparative endocrinology 11 27292788
2015 Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet. BMC gastroenterology 11 25888445
2011 A study of FHL1, BAG3, MATR3, PTRF and TCAP in Australian muscular dystrophy patients. Neuromuscular disorders : NMD 11 21683594
2011 Identification of a novel brain derived neurotrophic factor (BDNF)-inhibitory factor: regulation of BDNF by teneurin C-terminal associated peptide (TCAP)-1 in immortalized embryonic mouse hypothalamic cells. Regulatory peptides 11 22209827
2022 Role of Teneurin C-Terminal Associated Peptides (TCAP) on Intercellular Adhesion and Communication. Frontiers in neuroscience 10 35585927
2019 Tele-Robotic Platform for Dexterous Optical Single-Cell Manipulation. Micromachines 10 31597299
2015 Characterization of the teneurin C-terminal associated peptide (TCAP) in the vase tunicate, Ciona intestinalis: A novel peptide system associated with energy metabolism and reproduction. General and comparative endocrinology 10 25687741
2020 Impact of a Primary Care Provider Tele-Mentoring and Community Health Worker Intervention on Utilization in Medicaid Patients with Diabetes. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 9 33471708
2019 Tele-glaucoma versus clinical evaluation: The New Jersey Health Foundation Prospective Clinical Study. Journal of telemedicine and telecare 9 31138016
2008 Proapoptotic protein Siva binds to the muscle protein telethonin in cardiomyocytes during coxsackieviral infection. Cardiovascular research 9 18849585
2023 Project T-SHARP: study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs. Trials 8 36750867
2023 Effects of the ECHO tele-mentoring program on HIV/TB service delivery in health facilities in Zambia: a mixed-methods, retrospective program evaluation. Human resources for health 8 36941682
2022 Content of Tele-Palliative Care Consultations with Patients Receiving Dialysis. Journal of palliative medicine 8 35254866
2022 Tcap Deficiency in Zebrafish Leads to ROS Production and Mitophagy, and Idebenone Improves its Phenotypes. Frontiers in cell and developmental biology 8 35372370
2020 Telethonin variants found in Brugada syndrome, J-wave pattern ECG, and ARVC reduce peak Nav 1.5 currents in HEK-293 cells. Pacing and clinical electrophysiology : PACE 8 32588437
2019 Utility of WhatsApp as a Tool for Tele-oncopathology for Oral Lesions. Indian journal of surgical oncology 8 31496588
2014 Molecular characterization, transcriptional regulation and association analysis with carcass traits of porcine TCAP gene. Gene 8 24462753
2020 Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy. Revista portuguesa de cardiologia 7 32565061
2019 Nomenclature and Comparative Morphology of the Teneurin/TCAP/ADGRL Protein Families. Frontiers in neuroscience 7 31130838
1983 The role of cytoplasmic aldehyde dehydrogenase in the metabolism of N-tele-methylhistamine. Pharmacology, biochemistry, and behavior 7 6634826
2023 Implementation evaluation of tiered tele-triage pathways for burn center consultations and transfers. The journal of trauma and acute care surgery 6 38147034
2022 Findings of limb-girdle muscular dystrophy R7 telethonin-related patients from a Chinese neuromuscular center. Neurogenetics 6 34982307
2022 Implementation and evaluation of a Tele-OSCE in oral and maxillofacial surgery - a pilot report. GMS journal for medical education 6 36540562
2020 tele-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials. The Journal of organic chemistry 6 32786609
2007 Titin-cap (TCAP) polymorphisms associated with marbling score of beef. Meat science 6 22061598
2022 Teneurin and TCAP Phylogeny and Physiology: Molecular Analysis, Immune Activity, and Transcriptomic Analysis of the Stress Response in the Sydney Rock Oyster (Saccostrea glomerata) Hemocytes. Frontiers in endocrinology 5 35784537
2015 Role of the teneurins, teneurin C-terminal associated peptides (TCAP) in reproduction: clinical perspectives. Hormone molecular biology and clinical investigation 5 26485751

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