Affinage

LDB3

LIM domain-binding protein 3 · UniProt O75112

Length
727 aa
Mass
77.1 kDa
Annotated
2026-06-10
47 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LDB3 (ZASP/Cypher) is a striated-muscle-specific Z-disc scaffold protein that organizes the sarcomeric cytoskeleton and serves as a hub for mechanical and signaling complexes in cardiac and skeletal muscle (PMID:10427098). Its PDZ domain directly binds the C-terminal calmodulin-like domain of alpha-actinin-2 through a surface distinct from the titin-binding site, forming a ternary ZASP/alpha-actinin-2/titin complex, while a ZASP-like (ZM) motif provides a second contact with the alpha-actinin rod (PMID:15062084, PMID:15084604, PMID:16476425). ZASP additionally binds G- and F-actin through an alternatively spliced actin-binding region between the PDZ and LIM domains, with isoform- and exon-dependent affinity, and this actin engagement underlies its role in Z-disc integrity and F-actin organization (PMID:24668811, PMID:28349680). Beyond structural scaffolding, ZASP acts as an A-kinase anchoring protein that binds the PKA RIIalpha subunit and calcineurin, tethers and promotes PKA-mediated phosphorylation of the L-type calcium channel Cav1.2, and is required for normal beta-adrenergic regulation of cardiac Ca2+ current (PMID:23996002, PMID:29743299). It integrates additional signaling axes through the Cav1.2/Nav1.5 channel complex, PGM1, PKCalpha, filamin C and its chaperone HSPA8, an Ankrd2/p53 SUMOylation complex, and actin-dependent MRTFA-SRF signaling that drives cardiomyocyte maturation (PMID:19377068, PMID:20852297, PMID:24647531, PMID:33742095, PMID:39113806). ZASP is the major O-GlcNAcylated protein of human heart myofibrils, with modification increased in failing hearts (PMID:23271734). Mutations in ZASP cause dilated cardiomyopathy, cardiac conduction defects, and myofibrillar myopathy (zaspopathy) by disrupting these scaffolding and signaling interactions and triggering Z-disc disassembly and protein aggregation (PMID:14662268, PMID:15668942, PMID:20852297, PMID:33742095).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Established the molecular identity of ZASP as a Z-disc PDZ protein anchored to the sarcomere, answering where it acts and through what scaffolding partner.

    Evidence PDZ domain characterization, alpha-actinin-2 binding assay, and immunoelectron microscopy in heart and skeletal muscle

    PMID:10427098

    Open questions at the time
    • Did not define which other Z-disc partners or signaling roles ZASP carries
    • Functional consequence of the interaction in vivo not tested
  2. 2003 Medium

    Linked ZASP mutations to cardiomyopathy phenotypes by showing they perturb cytoskeletal organization and alter PKC affinity, framing the disease mechanism as disrupted scaffolding/signaling.

    Evidence Cell transfection with mutant constructs; yeast two-hybrid and pull-down for the D626N LIM-domain/PKC interaction

    PMID:14660611 PMID:14662268

    Open questions at the time
    • In vitro transfection phenotype not validated in muscle tissue
    • Causal chain from increased PKC affinity to cardiomyopathy not demonstrated
  3. 2004 High

    Resolved the structural basis of the ZASP-alpha-actinin interaction, showing the PDZ domain and ZM motif engage distinct alpha-actinin surfaces compatible with a ternary titin complex.

    Evidence NMR structure of the PDZ domain with affinity measurement; SPR with purified ZM/ALP and alpha-actinin rod plus cell localization

    PMID:15062084 PMID:15084604

    Open questions at the time
    • Stoichiometry and dynamics of the full ternary complex in vivo not established
    • Role of LIM domains in the assembly not addressed
  4. 2005 Medium

    Identified exon-6 ZM-motif residues as critical for ZASP function in vivo by linking them to myofibrillar myopathy (zaspopathy).

    Evidence Genetic screening and clinical-pathological correlation in patient families

    PMID:15668942

    Open questions at the time
    • No biochemical reconstitution of how the mutations impair function
    • Mechanism connecting the mutated residues to myofibrillar disruption unknown at this stage
  5. 2006 Medium

    Showed ZASP and ALP compete for the same alpha-actinin rod site and that cardiomyopathy mutations spare alpha-actinin co-localization, indicating disease mechanisms beyond simple loss of alpha-actinin binding.

    Evidence Co-localization in myoblasts and competition binding assays with purified proteins

    PMID:16476425

    Open questions at the time
    • The actual affected function of these mutations remained undefined
    • Physiological consequence of ZASP/ALP competition not tested
  6. 2007 High

    Defined an organism-level requirement for ZASP in Z-line assembly and integrin adhesion using the Drosophila ortholog, showing it recruits alpha-actinin and is needed for muscle structure.

    Evidence RNAi knockdown, physical interaction, and integrin genetic epistasis with larval phenotype analysis in Drosophila

    PMID:18166658

    Open questions at the time
    • Whether human ZASP regulates integrin adhesion in muscle not established
    • Direct molecular link between ZASP and integrin activation not defined here
  7. 2009 High

    Connected ZASP to muscle maintenance and metabolic enzyme positioning, identifying PGM1 as a stress-dependent Z-disc partner and confirming ortholog requirement for muscle integrity.

    Evidence Y2H and endogenous Co-IP in rat cardiomyocytes for PGM1; dsRNAi knockdown with ultrastructural/behavioral analysis in Drosophila

    PMID:19377068 PMID:19603185

    Open questions at the time
    • Functional role of Z-disc-anchored PGM1 in energy metabolism not measured
    • Whether PGM1 mislocalization drives DCM in vivo unknown
  8. 2010 High

    Demonstrated that ZASP physically complexes with cardiac ion channels and that a DCM mutation alters ionic currents in vivo, establishing an electrophysiological dimension to ZASP disease.

    Evidence S196L transgenic mouse, cardiomyocyte electrophysiology, and pull-down of Cav1.2/Nav1.5

    PMID:20852297

    Open questions at the time
    • Mechanism by which ZASP modulates channel gating/trafficking not defined here
    • Direct vs indirect nature of channel binding not resolved
  9. 2012 High

    Identified ZASP as a post-translationally modified Z-disc protein, the major O-GlcNAcylated myofibrillar protein, with disease-associated increases pointing to a regulatory role in heart failure.

    Evidence Enzymatic labeling, antibody detection, and MALDI-MS/MS on human heart myofibrils; integrin co-activation assays for the Drosophila ortholog

    PMID:22992465 PMID:23271734

    Open questions at the time
    • Functional consequence of ZASP O-GlcNAcylation on its interactions not tested
    • O-GlcNAc sites and their regulation not mapped
  10. 2013 High

    Defined ZASP as a Z-disc AKAP that scaffolds PKA (RIIalpha) and calcineurin and promotes Cav1.2 phosphorylation, recasting it from passive scaffold to active signaling organizer.

    Evidence Co-IP, in vitro phosphorylation, site-directed mutagenesis, and functional assays in Cypher-null cardiomyocytes

    PMID:23996002

    Open questions at the time
    • Whether calcineurin tethering opposes PKA signaling locally not quantified
    • In vivo physiological output of the AKAP function not yet shown here
  11. 2014 High

    Established direct ZASP-actin binding through an alternatively spliced region and connected ZASP to p53/SUMO regulation and disease splicing, broadening its mechanistic repertoire.

    Evidence In vitro actin binding and mouse muscle expression (#14); Co-IP, transactivation and SUMO assays for Ankrd2/p53 (#15); exon array and minigene analysis in DM1 (#16)

    PMID:24647531 PMID:24668811 PMID:24878509

    Open questions at the time
    • Physiological relevance of ZASP-p53 regulation in muscle unclear
    • How actin binding and signaling functions are coordinated by splicing not resolved
  12. 2017 High

    Quantified isoform- and exon-dependent affinity of ZASP for G- and F-actin and showed ZM disease mutations do not impair actin binding, separating actin engagement from the zaspopathy mechanism.

    Evidence SPR, electron microscopy, NMR HSQC, and circular dichroism with recombinant ZASP isoforms and mutants

    PMID:28349680

    Open questions at the time
    • The molecular defect of ZM mutations remained unidentified
    • In vivo significance of differential isoform actin affinity not tested
  13. 2018 High

    Showed in vivo that the long ZASP isoform is required for Cav1.2 surface density and beta-adrenergic potentiation of L-type Ca2+ current, providing the physiological output of its AKAP function.

    Evidence Long-Cypher knockout mice with patch-clamp electrophysiology and channel protein quantification

    PMID:29743299

    Open questions at the time
    • Whether reduced channel density reflects trafficking or stability not resolved
    • Contribution to arrhythmia phenotypes in patients not directly linked
  14. 2021 Medium

    Defined the molecular mechanism of A165V zaspopathy as disrupted mechanosensing signaling, with early filamin C/chaperone aggregation preceding mutant protein aggregation, and revealed a PKA/beta-catenin proliferative axis.

    Evidence Ldb3 A165V knock-in mice with Co-IP and pathway Western blots (#19); phosphoproteomics and reporter assays in Cypher-knockout cardiac tissue (#20)

    PMID:33742095 PMID:34966794

    Open questions at the time
    • Temporal order of filamin C aggregation versus PKCalpha/mTOR dysregulation not fully causal
    • Beta-catenin axis validated in single lab without independent replication
  15. 2024 High

    Established a developmental role for ZASP in cardiomyocyte maturation via actin-controlled MRTFA-SRF transcription, with SRF re-expression rescuing maturation and function in vivo.

    Evidence Cypher knockout mice, RNA-seq, G/F-actin fractionation, nuclear-cytoplasmic extraction, and AAV-SRF rescue with electron microscopy

    PMID:39113806

    Open questions at the time
    • How ZASP-dependent F-actin stability links to the AKAP and channel functions mechanistically not integrated
    • Relevance of the maturation pathway to adult cardiomyopathy onset unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZASP's distinct functions — Z-disc scaffolding, actin organization, AKAP-mediated channel regulation, mechanosensing, and transcriptional control — are coordinated by isoform splicing and post-translational modification into a unified mechanism remains unresolved.
  • No integrated model linking O-GlcNAcylation, splicing, and the multiple signaling axes
  • Structural basis for simultaneous engagement of alpha-actinin, actin, channels, and PKA undefined
  • Genotype-to-mechanism map for the full mutation spectrum incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2
Partners
ACTN2ANKRD2CACNA1CFLNCPGM1PKCPRKAR2ASCN5A
Complex memberships
Z-discZASP/Ankrd2/p53 complexZASP/alpha-actinin-2/titin ternary complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 ZASP (LDB3) was identified as a novel Z-band protein containing a PDZ domain that directly binds to the C-terminal region of alpha-actinin-2; it is specifically expressed in heart and skeletal muscle and localizes to the Z-band of the sarcomere as shown by immunoelectron microscopy. PDZ domain characterization, co-immunoprecipitation/binding assay with alpha-actinin-2, immunoelectron microscopy, Western blot The Journal of cell biology High 10427098
2003 Mutations in ZASP/Cypher cause cytoskeleton disarray in transfected cells, establishing a mechanistic basis for dilated cardiomyopathy and left ventricular non-compaction. Cell transfection with mutant ZASP constructs, in vitro cytoskeletal analysis Journal of the American College of Cardiology Medium 14662268
2003 A D626N mutation in the third LIM domain of Cypher/ZASP, associated with dilated cardiomyopathy, increases the affinity of the LIM domain for protein kinase C (PKC) as demonstrated by yeast two-hybrid and pull-down assays. Yeast two-hybrid assay, pull-down assay The Journal of biological chemistry Medium 14660611
2004 The solution structure of the ZASP PDZ domain was determined by NMR, showing it is a classical class 1 PDZ domain that recognizes the carboxy-terminal sequence of alpha-actinin-2 calmodulin-like domain with micromolar affinity; the alpha-actinin-2/ZASP PDZ interaction involves a binding surface distinct from that recognized by titin Z repeats, forming a ternary ZASP/alpha-actinin-2/titin complex. NMR structure determination, binding affinity measurement Structure (London, England : 1993) High 15062084
2004 The ZASP-like motif (ZM) in the related protein ALP (actinin-associated LIM protein) is required for interaction with the alpha-actinin rod region and for targeting to the muscle Z-line; this is the first evidence that the ZM motif has a direct role in protein-protein interaction, and the same motif in ZASP/Cypher was confirmed to interact with alpha-actinin. Surface plasmon resonance with purified recombinant proteins, cell localization assays The Journal of biological chemistry High 15084604
2005 Mutations in ZASP exon 6 (A147T and A165V) at or within a motif important for Z-disk linking cause myofibrillar myopathy (zaspopathy), establishing these residues as critical for ZASP function in vivo. Genetic screening, clinical-pathological correlation in patients Annals of neurology Medium 15668942
2006 ZASP/Cypher internal fragments containing either ZM exon 4 or ZM exon 6 co-localize with alpha-actinin in cultured cells; ZASP/Cypher directly interacts with the alpha-actinin rod and competes with ALP for the same binding site on the rod. Patient cardiomyopathy mutations in the internal domain did not affect co-localization with alpha-actinin or protein stability. Co-localization in myoblasts and non-muscle cells, direct binding assay (competition assay with purified proteins) Experimental cell research Medium 16476425
2007 Drosophila Zasp (ortholog of human ZASP/LDB3) localizes to integrin adhesion sites and muscle Z-lines; depletion of Zasp by RNAi disrupts integrin adhesion sites, prevents Z-line formation, and blocks recruitment of alpha-actinin to the Z-line. Zasp also physically interacts with alpha-actinin and interacts genetically with integrins, showing it regulates integrin function. RNAi knockdown, co-localization, physical interaction (pulldown), genetic epistasis with integrins, fly larval phenotype analysis The Journal of cell biology High 18166658
2009 Phosphoglucomutase 1 (PGM1), a glycolytic enzyme, was identified as a binding partner of ZASP/Cypher at domains encoded by exons 4 and 10; PGM1 localizes to Z-discs under stress conditions. DCM-associated mutations Ser189Leu, Thr206Ile (exon 4), and Ile345Met (exon 10) reduce ZASP binding to PGM1, suggesting ZASP anchors PGM1 to the Z-disc under stress. Yeast two-hybrid, co-immunoprecipitation of endogenous proteins in rat cardiomyocytes, stress-dependent localization assay Cardiovascular research High 19377068
2009 Post-transcriptional silencing of Drosophila dzasp (ortholog of human ZASP/LDB3) causes locomotor defects and disruption of muscle structure and ultrastructure, consistent with a role in maintenance of muscular integrity. UAS/Gal4-driven dsRNAi knockdown in Drosophila, behavioral and ultrastructural analysis Cell and tissue research Medium 19603185
2010 The ZASP S196L mutation in transgenic mice causes hemodynamic dysfunction consistent with DCM and cardiac conduction defects; ZASP4 physically complexes with both L-type calcium channel (Cav1.2) and sodium channel (Nav1.5), and S196L cardiomyocytes show altered L-type Ca2+ and Na+ currents. Transgenic mouse model, electrophysiology on isolated cardiomyocytes, pull-down assay for channel interactions Circulation. Arrhythmia and electrophysiology High 20852297
2012 Drosophila Zasp cooperates with talin to activate α5β1 integrins in mammalian tissue culture and αPS2βPS integrins in Drosophila, establishing Zasp as the first protein shown to co-activate α5β1 integrins together with talin, acting by a mechanism distinct from known αIIbβ3 co-activators. Cell spreading assays in mammalian tissue culture, Drosophila genetic assays, integrin activation assays Journal of cell science Medium 22992465
2012 ZASP is the major O-linked β-N-acetylglucosamine (O-GlcNAc)-modified protein in human heart myofibrils, identified by MALDI-MS/MS; O-GlcNAcylation of ZASP is increased in diseased (failing) heart compared to donor hearts. SDS-PAGE, enzymatic conjugation assay with UDP-GalNAz and fluorescent tagging, monoclonal antibody detection (CTD110.6, RL2), MALDI-MS/MS, immunofluorescence co-localization The Journal of biological chemistry High 23271734
2013 Cypher/ZASP acts as an A-kinase anchoring protein (AKAP) in cardiomyocytes: it interacts specifically with the type II regulatory subunit RIIα of PKA; Cypher/ZASP itself is phosphorylated by PKA at Ser265 and Ser296; its PDZ domain interacts with the L-type calcium channel (Cav1.2) C-terminal PDZ binding motif; Cypher/ZASP facilitates PKA-mediated phosphorylation of Cav1.2; and Cypher/ZASP interacts with the phosphatase calcineurin. Co-immunoprecipitation, in vitro phosphorylation assay, site-directed mutagenesis, cardiomyocyte functional assays in Cypher-null cells The Journal of biological chemistry High 23996002
2014 ZASP directly interacts with skeletal actin filaments through an actin-binding domain located between the PDZ and LIM domains; this domain is alternatively spliced, and the exon 6-encoded ZM motif (mutated in zaspopathy) and the exon 8-11 junction peptide (exclusive to long isoform ZASP-LΔex10) both contribute to actin binding. MFM-associated mutations in the actin-binding domain of ZASP-LΔex10 cause Z-disc disruption and F-actin accumulation in mouse skeletal muscle. In vitro binding assay, expression in mouse skeletal muscle with phenotypic readout (Z-disc disruption, F-actin accumulation), isoform-specific analysis The Journal of biological chemistry High 24668811
2014 ZASP interacts with the mechanosensing protein Ankrd2 and tumor suppressor p53, forming a triple complex that facilitates poly-SUMOylation of p53; ZASP acts as a negative regulator of p53 in transactivation experiments with p53-responsive promoters (MDM2 and BAX). The PDZ domain of ZASP binds directly to both Ankrd2 and p53. Disease-associated mutations A165V and A171T in the ZM-motif abolish Ankrd2 binding and impair alpha-actinin2 binding. Co-immunoprecipitation, luciferase transactivation assays, SUMO modification assays, domain-deletion and mutagenesis analysis PloS one High 24647531
2014 Aberrant inclusion of LDB3 exon 11 in myotonic dystrophy type 1 (DM1) skeletal muscle is mediated by MBNL1 sequestration; the exon 11-positive LDB3 isoform has reduced affinity for PKC compared to the exon 11-negative isoform, potentially contributing to CUG-BP1 upregulation through altered PKC binding. Exon array, RT-PCR, Western blot, minigene transfection with CTG repeat expansion, PKC binding affinity comparison Neurobiology of disease Medium 24878509
2017 Recombinant ZASP isoforms (ZASP-S, ZASP-LΔex10) bind to G-actin with high affinity (Kd ≈ 10^-8 to 10^-9 M) as measured by surface plasmon resonance; isolated actin-binding region lacking exon 10 (ABRΔex10) binds with lower affinity (Kd ≈ 10^-7 M), while ABR+10 binds only weakly (Kd ≈ 10^-5 M). ZASP-S and ABRΔex10 also induce F-actin and array formation. Disease-causing ZM mutations A147T and A165V do not affect actin binding affinity. Surface plasmon resonance, electron microscopy, NMR HSQC spectroscopy, circular dichroism Biochemistry High 28349680
2018 The long form of Cypher/Zasp is required for normal β-adrenergic regulation of cardiac CaV1.2 L-type Ca2+ channels in vivo; cardiomyocytes from long Cypher knockout (LCyphKO) mice show reduced cell-surface density of CaV1.2, reduced basal Ca2+ current, and significantly reduced β-adrenergic/PKA stimulation of L-type Ca2+ current (net β-adrenergic Ca2+ current reduced to 39±12% of wild type at 100 nM isoproterenol). Knockout mouse model (LCyphKO), patch-clamp electrophysiology, protein quantification in isolated ventricular myocytes The Journal of general physiology High 29743299
2021 LDB3 modulates mechanical stress signaling through interactions with the mechanosensing domain of filamin C, its chaperone HSPA8, and PKCα in the muscle Z-disc; the myopathy-associated A165V mutation triggers early aggregation of filamin C and its chaperones at the Z-disc before aggregation of the mutant protein itself. The mutation impairs PKCα and TSC2-mTOR signaling pathways, causing protein aggregation and Z-disc disruption. Ldb3 Ala165Val/+ knock-in mice, co-immunoprecipitation, immunofluorescence, Western blot for pathway analysis Communications biology High 33742095
2021 Cypher/ZASP facilitates PKA-mediated phosphorylation of β-catenin at Ser675, promoting β-catenin transcriptional activity and cardiomyocyte proliferative capacity; Cypher co-localizes with β-catenin at intercalated discs. Cypher deletion also suppresses phosphorylation of vimentin Ser72 and troponin I Ser23/24. Quantitative phosphoproteomics on Cypher-knockout mouse cardiac tissue, PKA activation assays, immunofluorescence, reporter assays for β-catenin transcriptional activity Frontiers in cardiovascular medicine Medium 34966794
2024 Cypher/ZASP plays a role in cardiomyocyte maturation through actin-mediated MRTFA-SRF signaling: Cypher deletion destabilizes F-actin and increases G-actin levels, thereby impeding nuclear localization of MRTFA and suppressing SRF-mediated transcription of genes critical for sarcomere isoform switching, mitochondrial metabolism, and electrophysiology. Re-expression of SRF during the critical postnatal period rescues CM maturation defects and improves cardiac function in Cypher-depleted mice. Cypher knockout mice, RNA-sequencing, G-actin/F-actin fractionation, nuclear-cytoplasmic extraction, actin disassembly and co-sedimentation assays, adenovirus/AAV rescue experiments with SRF, transmission electron microscopy Theranostics High 39113806

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. Journal of the American College of Cardiology 392 14662268
2005 Mutations in ZASP define a novel form of muscular dystrophy in humans. Annals of neurology 207 15668942
1999 ZASP: a new Z-band alternatively spliced PDZ-motif protein. The Journal of cell biology 180 10427098
2003 A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C. The Journal of biological chemistry 117 14660611
2007 Zasp is required for the assembly of functional integrin adhesion sites. The Journal of cell biology 99 18166658
2004 The ZASP-like motif in actinin-associated LIM protein is required for interaction with the alpha-actinin rod and for targeting to the muscle Z-line. The Journal of biological chemistry 70 15084604
2009 Impaired binding of ZASP/Cypher with phosphoglucomutase 1 is associated with dilated cardiomyopathy. Cardiovascular research 61 19377068
2006 Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with alpha-actinin--analysis of patient mutations. Experimental cell research 47 16476425
2014 Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP) mutations in the actin-binding domain cause disruption of skeletal muscle actin filaments in myofibrillar myopathy. The Journal of biological chemistry 43 24668811
2013 Cypher/ZASP is a novel A-kinase anchoring protein. The Journal of biological chemistry 43 23996002
2004 Solution structure of ZASP PDZ domain; implications for sarcomere ultrastructure and enigma family redundancy. Structure (London, England : 1993) 43 15062084
2007 Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 genes. American journal of medical genetics. Part A 35 17394203
2021 Myopathy associated LDB3 mutation causes Z-disc disassembly and protein aggregation through PKCα and TSC2-mTOR downregulation. Communications biology 29 33742095
2010 A ZASP missense mutation, S196L, leads to cytoskeletal and electrical abnormalities in a mouse model of cardiomyopathy. Circulation. Arrhythmia and electrophysiology 29 20852297
2014 LDB3 splicing abnormalities are specific to skeletal muscles of patients with myotonic dystrophy type 1 and alter its PKC binding affinity. Neurobiology of disease 28 24878509
2014 ZASP interacts with the mechanosensing protein Ankrd2 and p53 in the signalling network of striated muscle. PloS one 27 24647531
2014 A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy. Clinical genetics 25 25041374
2018 The AKAP Cypher/Zasp contributes to β-adrenergic/PKA stimulation of cardiac CaV1.2 calcium channels. The Journal of general physiology 21 29743299
2019 RNA sequencing reveals abnormal LDB3 splicing in sudden cardiac death. Forensic science international 18 31419596
2012 Zasp regulates integrin activation. Journal of cell science 18 22992465
2009 Post-transcriptional silencing of the Drosophila homolog of human ZASP: a molecular and functional analysis. Cell and tissue research 16 19603185
2016 A novel mutation in the PDZ-like motif of ZASP causes distal ZASP-related myofibrillar myopathy. Neuropathology : official journal of the Japanese Society of Neuropathology 15 27546599
2014 Combination of genetic screening and molecular dynamics as a useful tool for identification of disease-related mutations: ZASP PDZ domain G54S mutation case. Journal of chemical information and modeling 14 24730657
2021 Young and early-onset dilated cardiomyopathy with malignant ventricular arrhythmia and sudden cardiac death induced by the heterozygous LDB3, MYH6, and SYNE1 missense mutations. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 13 33949037
2022 Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy. European journal of human genetics : EJHG 12 36253531
2017 Coexistence of congenital left ventricular aneurysm and prominent left ventricular trabeculation in a patient with LDB3 mutation: a case report. Journal of medical case reports 11 28821295
2012 Z-band alternatively spliced PDZ motif protein (ZASP) is the major O-linked β-N-acetylglucosamine-substituted protein in human heart myofibrils. The Journal of biological chemistry 11 23271734
2017 Expression and Purification of ZASP Subdomains and Clinically Important Isoforms: High-Affinity Binding to G-Actin. Biochemistry 10 28349680
2010 Identification of ZASP, a novel protein associated to Zona occludens-2. Experimental cell research 10 20868680
2015 D117N in Cypher/ZASP may not be a causative mutation for dilated cardiomyopathy and ventricular arrhythmias. European journal of human genetics : EJHG 9 26419279
2023 Expression of LIM domain-binding 3 (LDB3), a striated muscle Z-band alternatively spliced PDZ-motif protein in the nervous system. Scientific reports 8 36609526
2022 Lim Domain Binding 3 (Ldb3) Identified as a Potential Marker of Cardiac Extracellular Vesicles. International journal of molecular sciences 7 35806378
2019 Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy. Journal of Zhejiang University. Science. B 7 31379146
2024 Divergent Regulatory Roles of Transcriptional Variants of the Chicken LDB3 Gene in Muscle Shaping. Journal of agricultural and food chemistry 6 38764183
2021 Phosphoproteomic Analysis Reveals Downstream PKA Effectors of AKAP Cypher/ZASP in the Pathogenesis of Dilated Cardiomyopathy. Frontiers in cardiovascular medicine 6 34966794
2024 ZASP: A Highly Compatible and Sensitive ZnCl2 Precipitation-Assisted Sample Preparation Method for Proteomic Analysis. Molecular & cellular proteomics : MCP 4 39243857
2022 Case Report: Novel LIM domain-binding protein 3 (LDB3) mutations associated with hypertrophic cardiomyopathy family. Frontiers in pediatrics 4 36452351
2013 [Myofibrillary myopathy due to the ZASP mutation Ala147Thr : two cases with exclusively distal leg involvement]. Der Nervenarzt 4 23263837
2010 Markesbery disease: autosomal dominant late-onset distal myopathy: from phenotype to ZASP gene identification. Neuromolecular medicine 4 20809097
2024 A rare form of LIM domain-binding protein 3 (LDB3) mutation causes hypertrophic cardiomyopathy and myofibrillar myopathy type 4. Clinical genetics 3 38992921
2024 Cypher/ZASP drives cardiomyocyte maturation via actin-mediated MRTFA-SRF signalling. Theranostics 3 39113806
2016 Left ventricular non-compaction revealed by aortic regurgitation due to Kawasaki disease in a boy with LDB3 mutation. Pediatrics international : official journal of the Japan Pediatric Society 3 27553890
2002 A cellular mechanism that reversibly inactivates pancaspase inhibitor zAsp-CH(2)-DCB: a potential pitfall causing discrepancy between in vitro and in vivo caspase assays. Biochemical and biophysical research communications 3 11866468
2025 ZASP/LDB3-related atypical distal myopathy with subtle cardiac impairment unveiled after COVID-19 infection: a short report. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 1 40626683
2024 Association between ZASP/LDB3 Pro26Ser and Inclusion Body Myopathy. International journal of molecular sciences 1 38928252
2026 Anaesthetic Management of a Patient With LDB3-Associated Myopathy Undergoing Prostate Biopsy Under Total Intravenous Anaesthesia: A Case Report. Cureus 0 41798484
2024 Myofibrillar myopathies due to a novel mutation in exon 8 of the LDB3 gene. International journal of rheumatic diseases 0 38333999

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