Affinage

TCAP

Telethonin · UniProt O15273

Length
167 aa
Mass
19.1 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TCAP/telethonin is a sarcomeric Z-disc protein that anchors titin filaments by forming a mechanically superstable, palindromic sandwich complex with the N-terminal Z1-Z2 immunoglobulin domains of two antiparallel titin molecules, thereby maintaining sarcomeric integrity and enabling directional force transmission (PMID:9817758, PMID:12446666, PMID:16713295, PMID:19622741). Beyond its structural role, TCAP functions as a signaling scaffold at the Z-disc: it modulates T-tubule organization and calcium handling through constitutive bis-phosphorylation at Ser-157/Ser-161 by PKD and CaMKII, interacts with ion channels (minK/KCNE1, Nav1.5) to couple mechanical load to electrical activity, regulates p53-dependent apoptosis under biomechanical stress, and participates in BMP10-mediated hypertrophic signaling (PMID:24280220, PMID:23100327, PMID:11697903, PMID:18408010, PMID:21799151, PMID:17921333). TCAP protein levels are controlled by circadian CLOCK/BMAL1-driven transcription and GSK-3β/FBXL21-SCF-mediated proteasomal degradation, as well as MuRF1-E2 ubiquitin ligase-dependent turnover during muscle atrophy (PMID:25121604, PMID:32937135, PMID:29271608). Loss-of-function mutations in TCAP cause limb-girdle muscular dystrophy type 2G and are associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and Brugada syndrome-related arrhythmias (PMID:15582318, PMID:32588437).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Identifying TCAP as a direct titin-binding Z-disc protein established the first molecular link between titin's N-terminus and the Z-disc scaffold, answering how titin filaments are anchored at Z-disc periphery.

    Evidence In vitro binding, yeast two-hybrid domain mapping, dominant-negative overexpression in cardiac myocytes with immunofluorescence localization

    PMID:9645487 PMID:9817758

    Open questions at the time
    • Stoichiometry and topology of the titin–TCAP complex unresolved
    • Phosphorylation-dependent regulation of titin binding only inferred from domain-deletion experiments
  2. 2002 High

    Biophysical and structural studies resolved how TCAP cross-links two antiparallel titin molecules in a 2:1 palindromic sandwich, explaining the molecular architecture that enables mechanical load transfer across the Z-disc.

    Evidence SAXS, analytical ultracentrifugation, ab initio shape modeling (2002); X-ray crystallography with in vivo complementation (2006); single-molecule force spectroscopy demonstrating directional superstability (2009)

    PMID:12446666 PMID:16713295 PMID:19622741

    Open questions at the time
    • Full-length TCAP structure not determined; C-terminal dimerization domain only modeled
    • How the complex tolerates force during eccentric contraction in vivo remains unmeasured
  3. 2001 High

    Discovery that TCAP binds the minK (KCNE1) potassium channel subunit and later Nav1.5 sodium channels revealed that Z-disc proteins directly participate in mechano-electrical coupling, establishing TCAP as an ion channel modulator.

    Evidence In vitro binding with domain mapping and co-localization in cardiac myofibrils (minK); co-immunoprecipitation and patch-clamp electrophysiology with mutant TCAP co-expression (Nav1.5)

    PMID:11697903 PMID:18408010 PMID:32588437

    Open questions at the time
    • Structural basis of TCAP–channel interaction unknown
    • In vivo electrophysiological consequences of TCAP ablation not directly measured in mammalian heart
  4. 2004 Medium

    Demonstrating that cardiomyopathy-associated TCAP mutations differentially alter binding to titin, MLP, and calsarcin-1 provided the first mechanistic basis for why distinct mutations cause HCM versus DCM.

    Evidence Yeast two-hybrid and GST pull-down competition with HCM (T137I, R153H) and DCM (E132Q, R87Q) mutant panels

    PMID:15582318

    Open questions at the time
    • Quantitative binding affinities not measured
    • No animal models with these specific mutations to validate phenotype correlation
    • Single-lab qualitative assays
  5. 2006 Medium

    Finding that MDM2 binds and degrades TCAP through a ubiquitin-independent proteasomal pathway—inhibitable by p14ARF—placed TCAP in the p53-MDM2-ARF signaling axis, suggesting a nuclear role beyond sarcomere anchoring.

    Evidence Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, proteasome inhibitor and p14ARF overexpression assays

    PMID:16678796

    Open questions at the time
    • Physiological significance of nuclear TCAP not established in this study
    • Ubiquitin-independent mechanism not fully characterized
  6. 2009 High

    Zebrafish Tcap depletion revealed that TCAP is dispensable for initial sarcomere assembly but essential for T-tubule–sarcolemma connections and stretch-sensing, redefining TCAP as a mechano-responsive structural integrator rather than a sarcomere assembly factor.

    Evidence Morpholino knockdown in zebrafish with T-tubule imaging, stretch induction assay, and ILK epistasis analysis

    PMID:19679566

    Open questions at the time
    • Mechanism by which TCAP regulates T-tubule biogenesis unknown
    • ILK regulatory mechanism is correlative
  7. 2010 High

    Mouse and Xenopus knockout/knockdown models established that TCAP loss causes muscular dystrophy phenotypes (abnormal fibers, central nucleation, elevated myostatin) and that the C-terminus is required for sarcomere integrity, providing mammalian genetic proof of function.

    Evidence Tcap knockout mice with histology, Western blot (myostatin), functional muscle assays; Xenopus morpholino knockdown with mRNA rescue and truncation mapping

    PMID:20233748 PMID:20235223

    Open questions at the time
    • Mechanism linking TCAP loss to myostatin upregulation not determined
    • KO mice lacked spontaneous cardiac phenotype, complicating cardiomyopathy modeling
  8. 2011 High

    Demonstrating that TCAP knockout mice develop heart failure only under pressure overload, through nuclear p53 stabilization and cardiomyocyte apoptosis, established the concept of 'mechanoptosis'—linking Z-disc mechanosensation to apoptotic signaling.

    Evidence TCAP KO mice with aortic banding, p53 turnover assays, nuclear fractionation, human heart failure tissue validation

    PMID:21799151

    Open questions at the time
    • Direct physical interaction between TCAP and p53 not shown
    • Whether p53 regulation is direct or via MDM2 axis not resolved in vivo
  9. 2013 High

    Identification of constitutive bis-phosphorylation at Ser-157/Ser-161 by PKD and CaMKII, and demonstration that loss of these phosphorylations disrupts T-tubule organization and calcium transients, established phosphorylation as essential for TCAP's structural and calcium-handling functions.

    Evidence Mass spectrometry phospho-site mapping, in vitro kinase assays, phosphomutant adenoviral expression in isolated cardiomyocytes, confocal T-tubule and Ca²⁺ imaging; KO mouse T-tubule and calcium phenotype

    PMID:23100327 PMID:24280220

    Open questions at the time
    • Phosphorylation dynamics under pathological stress not characterized
    • How phosphorylation alters TCAP–titin complex structure or partner interactions unknown
  10. 2017 High

    Establishing TCAP as a substrate of MuRF1-E2 ubiquitin ligase complexes explained how TCAP is turned over during atrophy and revealed an unexpected role for TCAP in stabilizing MuRF1–E2 enzyme pairs.

    Evidence Surface plasmon resonance, yeast three-hybrid, split-GFP complementation, co-expression degradation assay in HEK293T cells; earlier ubiquitin-conjugate purification during hindlimb suspension atrophy

    PMID:18565784 PMID:29271608

    Open questions at the time
    • In vivo validation of MuRF1-mediated TCAP turnover during atrophy not performed
    • Relationship between MuRF1 and FBXL21-SCF pathways not delineated
  11. 2020 High

    Discovery that CLOCK/BMAL1 drive TCAP transcription and that GSK-3β activates FBXL21-SCF-mediated TCAP phosphodegron degradation established a complete circadian regulatory circuit for TCAP protein oscillation, linking circadian biology to sarcomere maintenance.

    Evidence ChIP and reporter assays for BMAL1; CoIP, GSK-3β inhibitor/knockdown, Fbxl21 hypomorph (Psttm) mice with circadian expression profiling and muscle phenotyping

    PMID:25121604 PMID:32937135

    Open questions at the time
    • Functional consequence of disrupted TCAP circadian oscillation on cardiac physiology not fully characterized
    • GSK-3β phosphodegron sites on TCAP not mapped at residue resolution
  12. 2024 Medium

    CRISPR knockout in zebrafish demonstrated that TCAP loss causes mitochondrial dysfunction, elevated ROS, and excessive mitophagy that impairs cardiac regeneration—rescued by ROS scavengers—placing TCAP upstream of a ROS-mitophagy pathway in striated muscle.

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

    PMID:39226992

    Open questions at the time
    • Mechanism linking TCAP to mitochondrial integrity is unknown
    • Not confirmed in mammalian models
    • Whether ROS elevation is a direct or secondary consequence of sarcomeric disruption is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TCAP integrates its diverse functions—mechanical anchoring, ion channel modulation, circadian turnover, and mitochondrial/ROS regulation—into a coherent mechanosensory signaling system remains unresolved, as does the structural basis of its C-terminal dimerization and the in vivo hierarchy of its multiple degradation pathways.
  • No full-length TCAP structure including disordered C-terminus
  • Relative contributions of MuRF1, MDM2, and FBXL21-SCF to TCAP turnover under different physiological states are unknown
  • Direct physical basis of TCAP–Nav1.5 and TCAP–p53 interactions not structurally defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005856 cytoskeleton 5 GO:0005634 nucleus 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-397014 Muscle contraction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-9909396 Circadian clock 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
BMP10FBXL21KCNE1MDM2MURF1MYOZ2SCN5ATTN
Complex memberships
FBXL21-Cul1 SCF E3 ligase complex (as substrate)MuRF1-E2 ubiquitin ligase complex (as substrate)titin Z1Z2–telethonin 2:1 sandwich complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 The NH2-terminal Ig repeats Z1 and Z2 of titin interact with telethonin (T-cap/TCAP) at the periphery of the Z-disc, and dominant-negative approaches in cardiac myocytes showed both titin Z1-Z2 domains and T-cap are required for sarcomeric structural integrity. In vitro binding studies, dominant-negative overexpression in cardiac myocytes, immunofluorescence localization The Journal of cell biology High 9817758
1998 Telethonin interacts specifically with the N-terminal titin Ig domains Z1 and Z2 in a conformation-dependent manner; longer titin fragments containing a serine-proline-rich phosphorylation site do not interact, suggesting phosphorylation-dependent regulation of the interaction during myofibrillogenesis. Yeast two-hybrid, protein binding assays, immunofluorescence on human myotubes FEBS letters High 9645487
2000 FATZ (filamin-, actinin-, and telethonin-binding protein of the Z-disc) binds telethonin directly, as demonstrated by GST overlay assay, placing telethonin within a Z-disc protein interaction network. Yeast two-hybrid, GST overlay assay The Journal of biological chemistry Medium 10984498
2001 Telethonin (T-cap) specifically interacts with the cytoplasmic domain of minK (KCNE1, beta-subunit of the IKs potassium channel) via the 16 C-terminal residues of T-cap; both proteins co-localize at the Z-line in cardiac muscle, suggesting T-cap functions as an adapter linking myofibrillar components to T-tubular membrane ion channels. In vitro interaction studies, co-immunofluorescence and confocal microscopy in cardiac myofibrils Journal of molecular biology High 11697903
2002 Solution X-ray scattering and analytical ultracentrifugation show that telethonin cross-links two titin Z1Z2 molecules in an antiparallel 2:1 (Z1Z2:telethonin) sandwich complex; the C-terminus of telethonin promotes higher-order dimerization of this complex. Synchrotron X-ray solution scattering (SAXS), analytical ultracentrifugation, ab initio shape modeling The Journal of biological chemistry High 12446666
2004 HCM-associated TCAP mutations (T137I, R153H) augment telethonin binding to titin and calsarcin-1, whereas DCM-associated mutations (E132Q, R87Q) impair its interaction with MLP, titin, and calsarcin-1, establishing that TCAP's differential binding properties at the Z-disc correlate with distinct cardiomyopathy phenotypes. Yeast two-hybrid, GST pull-down competition assay Journal of the American College of Cardiology Medium 15582318
2006 MDM2 binds TCAP (identified by yeast two-hybrid screen, validated by GST pull-down and co-immunoprecipitation), co-localizes with TCAP in the nucleus, alters TCAP subcellular localization, and degrades TCAP via a ubiquitin-independent proteasomal pathway; this degradation is inhibited by p14ARF. Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, confocal microscopy, proteasome inhibitor and p14ARF overexpression assays Biochemical and biophysical research communications Medium 16678796
2006 Crystal structure and SAXS data reveal that telethonin forms a palindromic sandwich complex with two antiparallel titin Z1Z2 modules; the C-terminus of full-length telethonin promotes dimerization of two such complexes, potentially enabling cross-linking of titin filaments at the Z-disc periphery. X-ray crystallography, SAXS, circular dichroism, in vivo complementation Journal of structural biology High 16713295
2007 BMP10 co-localizes with Tcap at the Z-disc of cardiomyocytes and interacts with Tcap; a variant BMP10 (Thr326Ile) shows decreased binding to Tcap and increased extracellular secretion, resulting in enhanced hypertrophic signaling, placing Tcap as a Z-disc modulator of BMP10 prohypertrophic activity. Co-localization (immunofluorescence), binding assays, cardiomyocyte hypertrophy assay with conditioned medium American journal of physiology. Heart and circulatory physiology Medium 17921333
2008 Telethonin co-immunoprecipitates with Nav1.5 in the gastrointestinal tract; a patient-derived TCAP mutation, when co-expressed with SCN5A in HEK293 cells, doubled the window current by altering steady-state activation kinetics, demonstrating that telethonin is a Nav1.5-interacting protein that modulates sodium channel function. Co-immunoprecipitation, patch-clamp electrophysiology in HEK293 cells with mutant telethonin co-expression The Journal of biological chemistry High 18408010
2008 Telethonin is degraded by the 26S proteasome via ubiquitin-dependent targeting during hindlimb suspension-induced muscle atrophy; purification of ubiquitin conjugates via the S5a 19S subunit followed by deubiquitination identified telethonin as a proteasome substrate. Hindlimb suspension model, polysome profiling, ubiquitin conjugate purification, deubiquitination, immunoblot The international journal of biochemistry & cell biology Medium 18565784
2008 Telethonin knockdown by siRNA in differentiating skeletal muscle cells decreases mRNA levels of myogenic regulatory factors and prevents normal muscle cell differentiation phenotype, indicating TCAP is required for myoblast differentiation. RNA interference (siRNA), Northern blot, real-time RT-PCR in C2C12-like cells Neuromuscular disorders : NMD Medium 18440815
2008 Proapoptotic protein Siva specifically interacts with telethonin in cardiomyocytes during coxsackievirus B3 infection, with Siva expression increasing in infected hearts; the interaction was identified by screening a human heart cDNA library and validated by co-localization, suggesting a mechanism for CVB3-mediated cardiac dysfunction. Yeast two-hybrid/cDNA library screen, co-localization in cardiomyocytes Cardiovascular research Low 18849585
2009 Single-molecule force spectroscopy shows that the titin-telethonin complex forms a highly directed, mechanically superstable molecular bond that resists ultra-high forces along the physiological loading axis but breaks easily in other directions, revealing a directional mechanical design matched to sarcomeric stress. Single-molecule force spectroscopy (atomic force microscopy), mechanical unfolding in multiple directions Proceedings of the National Academy of Sciences of the United States of America High 19622741
2009 In zebrafish, Tcap depletion (morpholino) causes muscular dystrophy-like phenotypes by disrupting sarcomere–plasma membrane and T-tubule interactions rather than sarcomere assembly; Tcap integrates into the Z-disc after periodicity is established. Tcap expression is induced by stretch force and negatively regulated by integrin-linked kinase (ILK), placing Tcap in a stretch-sensing signaling pathway. Morpholino knockdown in zebrafish, immunofluorescence, T-tubule structure analysis, stretch induction assay, ILK manipulation Human molecular genetics High 19679566
2010 Tcap knockout mice develop skeletal muscle dystrophic histopathology (abnormal fiber size, central nucleation) and increased myostatin protein levels; muscle stiffness is increased but isolated force and fatigue are unchanged, placing TCAP upstream of myostatin regulation in skeletal muscle. Knockout mouse model, muscle histology, Western blot (myostatin), functional muscle assays (force, fatigue, rotarod, stiffness) Human molecular genetics High 20233748
2010 In Xenopus, telethonin morpholino knockdown causes embryonic paralysis, myocyte defects, and sarcomeric disruption; full-length telethonin mRNA rescues the phenotype. A C-terminally truncated construct fails to rescue, demonstrating that the C-terminus is required for sarcomere assembly. Morpholino knockdown in Xenopus, mRNA rescue experiments with truncation/point mutant constructs, live imaging of myocytes Developmental dynamics High 20235223
2011 Telethonin knockout mice do not show spontaneous cardiac phenotype under basal conditions but develop heart failure following biomechanical stress (pressure overload), due in part to cardiomyocyte apoptosis. Telethonin modulates turnover of the proapoptotic tumor suppressor p53 after biomechanical stress in the nuclear compartment, linking Z-disc telethonin to apoptosis ('mechanoptosis'); loss of telethonin mRNA and nuclear accumulation of protein occurs in human heart failure. Telethonin KO mice, pressure overload (aortic banding), p53 turnover assays, nuclear fractionation, human heart failure tissue analysis Circulation research High 21799151
2012 Tcap knockout mice show progressive loss of T-tubule structure and dysynchronous calcium transients; expression of non-phosphorylatable (S157A/S161A) telethonin also disrupts T-tubule organization and prolongs Ca2+ transient, demonstrating Tcap is a load-sensitive regulator of T-tubule structure and calcium handling in the heart. Tcap knockout mice, aortic banding (mechanical overload), confocal T-tubule imaging, Ca2+ spark/transient recordings, L-type Ca2+ channel assessment Human molecular genetics High 23100327
2013 Telethonin is constitutively bis-phosphorylated at Ser-157 and Ser-161 in cardiac myocytes and ventricular myocardium. Protein kinase D and CaMKII phosphorylate these sites in vitro. Partial replacement of endogenous telethonin with non-phosphorylatable S157A/S161A mutant disrupts transverse tubule organization and prolongs Ca2+ transient peak time, establishing that phosphorylation is critical for telethonin function. Kinase assays in vitro, mass spectrometry phospho-site identification, site-directed mutagenesis, phosphate-affinity electrophoresis, adenoviral expression in isolated cardiomyocytes, confocal T-tubule and Ca2+ transient imaging The Journal of biological chemistry High 24280220
2014 CLOCK and BMAL1 directly regulate Tcap transcription; BMAL1 binds the Tcap promoter at E-box elements (ChIP and biotinylated oligonucleotide assays), and Tcap mRNA and protein show diurnal rhythmicity in mouse heart that is blunted in ClockΔ19/Δ19 mice. ChIP assay, biotinylated oligonucleotide pulldown, luciferase reporter assay, qRT-PCR and immunoblot over circadian cycle, ClockΔ19 mutant mice PloS one Medium 25121604
2017 MuRF1 (E3 ubiquitin ligase) uses telethonin as a substrate; telethonin facilitates and stabilizes MuRF1-E2E1 and MuRF1-E2J1 complexes, and governs MuRF1-E2 affinity. Co-expression of MuRF1 with these E2s in HEK293T cells increases telethonin degradation, establishing telethonin as a substrate of the MuRF1-E2 ubiquitination network. Surface plasmon resonance, yeast three-hybrid, split-GFP complementation, co-expression degradation assay in HEK293T cells Journal of cachexia, sarcopenia and muscle High 29271608
2020 GSK-3β phosphorylates both FBXL21 and TCAP to activate phosphodegron-dependent TCAP ubiquitination and degradation via the FBXL21-Cul1 SCF E3 ligase complex; FBXL21 interacts with TCAP in a circadian manner antiphasic to TCAP accumulation. GSK-3β inhibition or knockdown diminishes FBXL21-Cul1 complex formation and delays TCAP degradation. Loss of FBXL21 function (Psttm mice) disrupts circadian TCAP oscillation and causes skeletal muscle defects. Co-immunoprecipitation, circadian expression profiling, GSK-3β inhibitor treatment and knockdown, Psttm (Fbxl21 hypomorph) mice, in vitro kinase assay, functional muscle phenotyping Cell reports High 32937135
2020 TCAP variants E49K and R153H identified in Brugada syndrome and related arrhythmia syndromes reduce peak Nav1.5 sodium currents (to 72% and 66% of wild-type, respectively) and alter voltage-dependent gating kinetics when co-expressed with SCN5A in HEK293 cells, confirming TCAP as a functional modulator of Nav1.5. Mutational analysis, patch-clamp electrophysiology in HEK293 cells stably expressing hNav1.5 with transiently expressed WT or variant TCAP Pacing and clinical electrophysiology : PACE Medium 32588437
2024 CRISPR/Cas9 knockout of tcap in zebrafish causes muscular dystrophy-like phenotypes, abnormal mitochondria, impaired stretch-sensing, and cardiac morphology/function defects with elevated ROS and mitophagy; cardiac regeneration and cardiomyocyte proliferation are impaired but rescued by ROS scavengers or autophagy inhibitors, placing Tcap upstream of ROS-mediated mitophagy in striated muscle. CRISPR/Cas9 zebrafish knockout, immunofluorescence, mitophagy/ROS assays, 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 240 10655062
2004 Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. Journal of the American College of Cardiology 220 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 158 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 112 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 84 11699871
2009 Depletion of zebrafish Tcap leads to muscular dystrophy via disrupting sarcomere-membrane interaction, not sarcomere assembly. Human molecular genetics 79 19679566
2011 Telethonin deficiency is associated with maladaptation to biomechanical stress in the mammalian heart. Circulation research 78 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 55 15158132
2012 A critical role for Telethonin in regulating t-tubule structure and function in the mammalian heart. Human molecular genetics 54 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
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
2013 Phosphoregulation of the titin-cap protein telethonin in cardiac myocytes. The Journal of biological chemistry 37 24280220
2011 Telethonin-deficiency initially presenting as a congenital muscular dystrophy. Neuromuscular disorders : NMD 32 21530252
2015 Ancient interaction between the teneurin C-terminal associated peptides (TCAP) and latrophilin ligand-receptor coupling: a role in behavior. Frontiers in neuroscience 31 25964737
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 31 19428634
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
2024 Multi-receptor skin with highly sensitive tele-perception somatosensory. Science advances 29 39259789
2014 Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G. PloS one 26 25055047
2020 The GSK-3β-FBXL21 Axis Contributes to Circadian TCAP Degradation and Skeletal Muscle Function. Cell reports 25 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 25 30380484
2016 Teneurins, TCAP, and latrophilins: roles in the etiology of mood disorders. Translational neuroscience 25 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
1984 Normal levels of histamine and tele-methylhistamine in mast cell-deficient mouse brain. Brain research 19 6697200
2019 Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion. Frontiers in endocrinology 18 30774623
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
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
2023 Characterization of TelE, a T7SS LXG Effector Exhibiting a Conserved C-Terminal Glycine Zipper Motif Required for Toxicity. Microbiology spectrum 14 37432124
2019 Clinical and genetic characterization of limb girdle muscular dystrophy R7 telethonin-related patients from three unrelated Chinese families. Neuromuscular disorders : NMD 14 32005491
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
1980 Tele-Methylhistamine is a specific MAO B substrate in man. Psychopharmacology 12 6774369
2022 Tele-entomology and tele-parasitology: A citizen science-based approach for surveillance and control of Chagas disease in Venezuela. Parasite epidemiology and control 11 36118050
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
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
2019 Tele-Robotic Platform for Dexterous Optical Single-Cell Manipulation. Micromachines 10 31597299
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 10 30242916
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
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 10 25888445
2024 Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy. Biochimica et biophysica acta. Molecular basis of disease 9 39226992
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
2025 Identification of splenic IRF7 as a nanotherapy target for tele-conditioning myocardial reperfusion injury. Nature communications 8 39994192
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
2022 Tcap Deficiency in Zebrafish Leads to ROS Production and Mitophagy, and Idebenone Improves its Phenotypes. Frontiers in cell and developmental biology 8 35372370
2022 Role of Teneurin C-Terminal Associated Peptides (TCAP) on Intercellular Adhesion and Communication. Frontiers in neuroscience 8 35585927
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
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 7 36941682
2022 Content of Tele-Palliative Care Consultations with Patients Receiving Dialysis. Journal of palliative medicine 7 35254866
1983 The role of cytoplasmic aldehyde dehydrogenase in the metabolism of N-tele-methylhistamine. Pharmacology, biochemistry, and behavior 7 6634826
2022 Findings of limb-girdle muscular dystrophy R7 telethonin-related patients from a Chinese neuromuscular center. Neurogenetics 6 34982307
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
2023 Implementation evaluation of tiered tele-triage pathways for burn center consultations and transfers. The journal of trauma and acute care surgery 5 38147034
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
2022 Implementation and evaluation of a Tele-OSCE in oral and maxillofacial surgery - a pilot report. GMS journal for medical education 5 36540562
2020 Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy. Revista portuguesa de cardiologia 5 32565061
2019 Nomenclature and Comparative Morphology of the Teneurin/TCAP/ADGRL Protein Families. Frontiers in neuroscience 5 31130838
2015 Role of the teneurins, teneurin C-terminal associated peptides (TCAP) in reproduction: clinical perspectives. Hormone molecular biology and clinical investigation 5 26485751