Medical Knowledge Cockpit cardiomyopathy, dilated

SDHA

Somatic tumors

GIST, paraganglioma

Tumor types germline

paraganglioma

Cancer Syndrom

paragangliomas-5 (PGL5)

Translocation partner

Name

succinate dehydrogenase complex, subunit A, flavoprotein (Fp)

Chromosome banding

5p15

Cancer molecular gen.

Rec

Mutation type

Mis, N

Other syndrome disease

ACTN2

• Telethonin and other new proteins of the Z-disc of skeletal muscle
• Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11
• A (CA)n repeat polymorphism for the human skeletal muscle alpha-actinin gene ACTN2 and its localization on the linkage map of chromosome 1
• Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network
• Activation of human neutrophils induces an interaction between the integrin beta 2-subunit (CD18) and the actin binding protein alpha-actinin

• Leukocyte adhesion to vascular endothelium induces E-selectin linkage to the actin cytoskeleton

LDB3

• ZASP: a new Z-band alternatively spliced PDZ-motif protein
• Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C
• Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with alpha-actinin--analysis of patient mutations

LMNA

• Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins
• In vivo and in vitro interaction between human transcription factor MOK2 and nuclear lamin A/C
• Resveratrol Rescues SIRT1-Dependent Adult Stem Cell Decline and Alleviates Progeroid Features in Laminopathy-Based Progeria
• Review: nuclear lamins--structural proteins with fundamental functions
• The inner nuclear membrane

• The nuclear envelope in muscular dystrophy and cardiovascular diseases

DSG2

• Tandem arrangement of the closely linked desmoglein genes on human chromosome 18
• Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins
• Immunological identification and characterization of the desmosomal cadherin Dsg2 in coupled and uncoupled epithelial cells and in human tissues
• The fourth armadillo repeat of plakoglobin (gamma-catenin) is required for its high affinity binding to the cytoplasmic domains of E-cadherin and desmosomal cadherin Dsg2, and the tumor suppressor APC protein

TNNT2

• Protein kinase C phosphorylation of cardiac troponin T decreases Ca²⁺-dependent actomyosin MgATPase activity and troponin T binding to tropomyosin-F-actin complex
• Identification of sites phosphorylated in bovine cardiac troponin I and troponin T by protein kinase C and comparative substrate activity of synthetic peptides containing the phosphorylation sites
• Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region
• Deletion of the first 45 NH2-terminal residues of rabbit skeletal troponin T strengthens binding of troponin to immobilized tropomyosin
• Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene

• Troponin T: genetics, properties and function
• Raf-1: a novel cardiac troponin T kinase
• A troponin T mutation that causes infantile restrictive cardiomyopathy increases Ca²⁺ sensitivity of force development and impairs the inhibitory properties of troponin
• Long-term follow-up of R403WMYH7 and R92WTNNT2 HCM families: mutations determine left ventricular dimensions but not wall thickness during disease progression
• Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review

SCN5A

• Sodium channel mutations and susceptibility to heart failure and atrial fibrillation
• Ion channelopathies in functional GI disorders
• The role of the SCN5A-encoded channelopathy in irritable bowel syndrome and other gastrointestinal disorders
• Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome

MYH6

• Thick filament proteins and performance in human heart failure
• In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament
• Molecular mechanics of mouse cardiac myosin isoforms
• Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament
• The myosin power stroke

TNNI3

• The C terminus of cardiac troponin I stabilizes the Ca2+-activated state of tropomyosin on actin filaments
• Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury
• Cardiac troponin I is modified in the myocardium of bypass patients
• Transgenic mouse model of stunned myocardium
• Impaired diastolic function after exchange of endogenous troponin I with C-terminal truncated troponin I in human cardiac muscle

• Troponin I: inhibitor or facilitator
• To investigate protein evolution by detecting suppressed epitope structures

TTN

• Properties of titin immunoglobulin and fibronectin-3 domains
• Titin: an endosarcomeric protein that modulates myocardial stiffness in DCM
• A regular pattern of two types of 100-residue motif in the sequence of titin
• Titins: giant proteins in charge of muscle ultrastructure and elasticity
• Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils

SDHA

• Integration of cardiac proteome biology and medicine by a specialized knowledgebase
• Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes

BAG3

• BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis
• Regulation by heavy metals and temperature of the human BAG-3 gene, a modulator of Hsp70 activity
• CAIR-1/BAG-3 abrogates heat shock protein-70 chaperone complex-mediated protein degradation: accumulation of poly-ubiquitinated Hsp90 client proteins
• Large-scale characterization of HeLa cell nuclear phosphoproteins
• Immunoaffinity profiling of tyrosine phosphorylation in cancer cells

• Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry
• Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27
• CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins

DES

• Missense mutations in desmin associated with familial cardiac and skeletal myopathy
• De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy
• Desmin mutations and arrhythmogenic right ventricular cardiomyopathy

CRYAB

• Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay

EYA4

• Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus

LAMA4

• Tissue-specific expression of the human laminin alpha5-chain, and mapping of the gene to human chromosome 20q13.2-13.3 and to distal mouse chromosome 2 near the locus for the ragged (Ra) mutation
• The structural organisation of LAMA4, the gene encoding laminin alpha4

MYPN

• Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs

SGCD

• Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein
• Identification of a novel sarcoglycan gene at 5q33 encoding a sarcolemmal 35 kDa glycoprotein
• Generation and analysis of 280,000 human expressed sequence tags

PRDM16

• PRDM16 controls a brown fat/skeletal muscle switch

CSRP3

• Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle
• Decreased expression of the cardiac LIM domain protein MLP in chronic human heart failure
• Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc
• The muscle regulatory and structural protein MLP is a cytoskeletal binding partner of betaI-spectrin
• Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex

• Alterations at the intercalated disk associated with the absence of muscle LIM protein
• Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD

MYBPC3

• Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy
• Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction?
• Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome 11
• A molecular map of the interactions between titin and myosin-binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy
• Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy

• Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization Of cardiac transcript and protein
• Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene
• Identification of a new missense mutation in MyBP-C associated with hypertrophic cardiomyopathy
• Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy
• Double heterozygosity for mutations in the beta-myosin heavy chain and in the cardiac myosin binding protein C genes in a family with hypertrophic cardiomyopathy
• Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction?
• Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development
• Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy
• Integration of cardiac proteome biology and medicine by a specialized knowledgebase
• The ultrastructural location of C-protein, X-protein and H-protein in rabbit muscle
• A new protein of the thick filaments of vertebrate skeletal myofibrils. Extractions, purification and characterization
• A molecular map of the interactions between titin and myosin-binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy

TCAP

• MDM2 interacts with and downregulates a sarcomeric protein, TCAP
• Proapoptotic protein Siva binds to the muscle protein telethonin in cardiomyocytes during coxsackieviral infection
• Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin): identification of cardiac clock-controlled genes using open access bioinformatics data
• Telethonin protein expression in neuromuscular disorders
• Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives

• Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin
• Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy

ABCC9

• ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating

PLN

• Phospholamban: a key determinant of cardiac function and dysfunction

ACTC1

• Isolation and characterization of human actin genes
• There are approximately 20 actin gene in the human genome
• Molecular structure and evolutionary origin of human cardiac muscle actin gene
• Chromosomal location of the co-expressed human skeletal and cardiac actin genes

MYH7

• Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament

TMPO

• Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein
• Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins
• Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2

PSEN1

• Presenilin 1 facilitates the constitutive turnover of beta-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in the beta-catenin-signaling pathway
• Direct association of presenilin-1 with beta-catenin
• Isolation of human delta-catenin and its binding specificity with presenilin 1
• Interaction of presenilins with the filamin family of actin-binding proteins
• A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts with the presenilin proteins

• Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins

PSEN2

• Novel MITF targets identified using a two-step DNA microarray strategy
• Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death
• The presenilin 2 loop domain interacts with the mu-calpain C-terminal region
• A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein
• Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment

VCL

• Intact vinculin protein is Require for control of cell shape, cell mechanics, and rac-Dependent Lamellipodia Formation
• Structural and dynamic characterization of a vinculin binding site in the talin rod
• Co-existence of vinculin and a vinculin-like protein of higher molecular weight in smooth muscle
• Comparative biochemical analysis suggests that vinculin and metavinculin cooperate in muscular adhesion sites
• Variable and constant regions in the C-terminus of vinculin and metavinculin. Cloning and expression of fragments in E. coli

FKTN

• Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy

TPM1

• Refined localization of the human alpha-tropomyosin gene (TPM1) by genetic mapping

TNNC1

• Defining the binding site of levosimendan and its analogues in a regulatory cardiac troponin C-troponin I complex
• Drug binding to cardiac troponin C
• The effects of levosimendan and OR-1896 on isolated hearts, myocyte-sized preparations and phosphodiesterase enzymes of the guinea pig
• The inotropic effect of the active metabolite of levosimendan, OR-1896, is mediated through inhibition of PDE3 in rat ventricular myocardium
• A structural and functional perspective into the mechanism of Ca2+-sensitizers that target the cardiac troponin complex

• Computer-aided drug discovery approach finds calcium sensitizer of cardiac troponin
• Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil
• Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: the basis of W7 as an inhibitor of cardiac muscle contraction
• Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033

DMD

• Function and genetics of dystrophin and dystrophin-related proteins in muscle
• The 'spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families

• ECM-receptor interaction
  Homo sapiens (human) one gene

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• Wnt signaling pathway
  Homo sapiens (human) one gene

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• PI3K-Akt signaling pathway
  Homo sapiens (human) one gene

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