cardiac

Cardiac phospholamban/PLN Protein, Human, Recombinant (GST) is expressed in yeast with N-GST tag. The predicted molecular weight is 33.1 kDa and the accession number is P26678.

Muscle contraction. Myosin-6/MYH6 Protein, Human, Recombinant (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 76.8 kDa and the accession number is P13533.

Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm. Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm. Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.

Muscle contraction. Myosin-6/MYH6 Protein, Human, Recombinant (E. coli, His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 80.8 kDa and the accession number is P13533.

Regulatory light chain of myosin. Does not bind calcium. MYL3 Protein, Human, Recombinant (GST) is expressed in E. coli expression system with N-GST tag. The predicted molecular weight is 48.8 kDa and the accession number is P08590.

CSRP3 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli.

Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. TNNI3 Protein, Mouse, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 40.1 kDa and the accession number is P48787.

Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role. MYBPC3 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 50.8 kDa and the accession number is Q14896.

Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. TnTc Protein, Rat, Recombinant (His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 41.6 kDa and the accession number is P50753.

Desmin is a cytoplasmic protein and belongs to the intermediate filament family. interacts with DST and MTM1. Desmin is only expressed in vertebrates, however homologous proteins are found in many organisms. Desmin is the main intermediate filament in mature skeletal, cardiac and smooth-muscle cells. DES founctions as homopolymers to form a stable intracytoplasmic filamentous network connecting myofibrils to each other and to the plasma membrane. .Defects in DES are cause of the myopathy myofibrillar type 1, cardiomyopathy dilated type 1I, and neurogenic scapuloperoneal syndrome Kaeser type.

Butyrophilin-Like Protein 9 (BTNL9) is single-pass type I membrane protein member of the BTN/MOG family that belongs to the immunoglobulin superfamily. BTNL9 consists of two domains: one B30.2/SPRY domain and one Ig-like V-type (immunoglobulin-like) domain. Human BTNL9 mRNA has been identified in adipose, lung, thymus, spleen, colon, and cardiac tissues, but its highest levels of expression were found in B cells. BTNL9 expression has also been found to be down-regulated in colon cancer tumors. BTNL9 Protein, Mouse, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-Fc tag. The predicted molecular weight is 60-70 KDa and the accession number is Q8BJE2.

Transforming growth factor beta 2 (TGF-β2) is a member of TGF-beta superfamily that shares a characteristic cysteine knot structure. Mice with TGF-β2 gene deletion show defects in development of cardiac, lung, craniofacial, limb, spinal column, eye, inner ear and urogenital systems. All TGF-β isoforms signal via the same heteromeric receptor complex, consisting of a ligand binding TGF-β receptor type II (TβR-II), and a TGF-β receptor type I (TβR-I). Signal transduction from the receptor to the nucleus is mediated via SMADs. TGF-β expression is found in cartilage, bone, teeth, muscle, heart, blood vessels, haematopoitic cells, lung, kidney, gut, liver, eye, ear, skin, and the nervous system.

Platelet-Activating Factor Acetylhydrolase (PAFAH) is a secreted enzyme which belongs to the AB hydrolase superfamily and Lipase family and catalyzes the degradation of platelet-activating factor to biologically inactive products. PAFAH is produced by inflammatory cells and hydrolyzes oxidised phospholipids in LDL. PAFAH has been implicated in the development of atherosclerosis and has also been identified as a marker for cardiac disease. PAFAH might have a major physiologic effect in the presence of inflammatory bodily responses. PAFAH alters the action of PAF by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. PAFAH has specificity for substrates with a short residue at the sn-2 position.

Aggrecan is a large proteoglycan that forms giant hydrated aggregates with hyaluronan in the extracellular matrix (ECM). The extraordinary resistance of these aggregates to compression explains their abundance in articular cartilage of joints where they ensure adequate load-bearing. In the brain, they provide mechanical buffering and contribute to formation of perineuronal nets, which regulate synaptic plasticity. Aggrecan is also present in cardiac jelly, developing heart valves, and blood vessels during cardiovascular development. Whereas aggrecan is essential for skeletal development, its function in the developing cardiovascular system remains to be fully elucidated.

S100B, a calcium-binding protein of the EF-hand type exerts both intracellular and extracellular functions.The intracellular, and extracellular, roles of S100B are attractive therapeutic targets for the treatment of both cardiac and vascular disease.

Promotes dimerization of NF-kappa-B subunits and regulates NF-kappa-B transcription factor activity. Promotes growth of cardiomyocytes, but not cardiomyocyte proliferation. Promotes cardiac muscle hypertrophy. Plays a role in the regulation of the growth of actin filaments. Inhibits the activity of the F-actin-capping protein complex formed by the CAPZA1 and CAPZB heterodimer. Myotrophin Protein, Bovine, Recombinant (His) is expressed in yeast with N-10xHis tag. The predicted molecular weight is 15.2 kDa and the accession number is Q3T0F7.

E3 ubiquitin ligase. Mediates the ubiquitination and subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. Regulates the proteasomal degradation of muscle proteins under amino acid starvation, where muscle protein is catabolized to provide other organs with amino acids. Inhibits de novo skeletal muscle protein synthesis under amino acid starvation. Regulates proteasomal degradation of cardiac troponin I/TNNI3 and probably of other sarcomeric-associated proteins. May play a role in striated muscle atrophy and hypertrophy by regulating an anti-hypertrophic PKC-mediated signaling pathway. May regulate the organization of myofibrils through TTN in muscle cells.

TPM4, also known as tropomyosin 4, is a member of the tropomyosin family. Members of this family are actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. TPM4 is expressed in cardiac tissue and platelets. It is highly expressed in the platelets of hypertensive patients. TPM4 plays a central role, in association with the troponin complex, in the calcium-dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells, it is implicated in stabilizing cytoskeleton actin filaments.

v-akt murine thymoma viral oncogene homolog 1 (AKT1), or protein kinase B-alpha (PKB-ALPHA) is a serine-threonine protein kinase, belonging to the Protein Kinase Superfamily. AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. AKT1 activity is required for physiologic cardiac growth in response to IGF1 stimulation or exercise training. In contrast, AKT1 activity was found to antagonize pathologic cardiac growth that occurs in response to endothelin 1 stimulation or pressure overload. AKT1 selectively promotes physiological cardiac growth while AKT2 selectively promotes insulin-stimulated cardiac glucose metabolism. AKT1 deletion prevented tumor initiation as well as tumor progression, coincident with decreased Akt signaling in tumor tissues. AKT1 is the primary Akt isoform activated by mutant K-ras in lung tumors, and that AKT3 may oppose AKT1 in lung tumorigenesis and lung tumor progression. A number of separate studies have implicated AKT1 as an inhibitor of breast epithelial cell motility and invasion. AKT1 may have a dual role in tumorigenesis, acting not only pro-oncogenically by suppressing apoptosis but also anti-oncogenically by suppressing invasion and metastasis.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Alteration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expression has been studied for various cardiac diseases, including dilated cardiomyopathy (DCM), with the significance of surrogate markers of extracellular matrix (ECM) remodeling. MMP-8 was identified only in myocardiocytes, while MMP-9 and TIMP-2 were present in both myocardiocytes and stroma, but with different intensity. The increasing intensity of MMP-8 and TIMP-2 immunoreactions was significantly associated with low HCS.

Myoglobin(MB) is a cytoplasmic protein expressed in myocytes of the heart and skeletal muscle that reversibly binds oxygen. It belongs to the globin family. Functions of myoglobin include oxygen storage and transport, as well as scavenging of NO and reactive oxygen species. MB serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Myoglobin also serves as a sensitive marker for muscle injury resulting from cardiac infarction. Surprisingly, mice in which myoglobin has been removed by gene targeting are able to perform extensive exercise and respond normally to hypoxic challenge.

Fatty Acid Binding Protein 3 (FABP3) is a small cytoplasmic protein (15 kDa) that is released from cardiac myocytes following an ischemic episode. Like the nine other distinct FABPs that have been identified, FABP3 is involved in active fatty acid metabolism where it transports fatty acids from the cell membrane to mitochondria for oxidation. FABPs are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-types. They form 14-15 kDa proteins and are thought to participate in the uptake, intracellular metabolism and/or transport of long-chain fatty acids. They may also be responsible in the modulation of cell growth and proliferation. The FABP3 gene contains four exons and its function is to arrest growth of mammary epithelial cells. This gene is also a candidate tumor suppressor gene for human breast cancer. FABP3 is a sensitive biomarker for myocardial infarction and can be detected in the blood within one to three hours of onset of pain.

Activin RIA, also known as ALK-2, TSK-7L, SKR1, TSR-I, and ACTR-I, is a glycosylated 65 kDa type I receptor in the TGF-beta serine/threonine kinase receptor family. Binding of TGF-beta superfamily ligands induces formation of a heterotetrameric complex that contains two chains each of a type I and a type II receptor in multiple combinations. The type II receptors phosphorylate the type I receptors which then phosphorylate and activate Smad signal transduction proteins. Activin RIA functions in a wide variety of growth and differentiation processes including gastrulation, skeletal system development, and cardiac morphogenesis. BMP signaling through Activin RIA is enhanced by the direct interaction between Activin RIA and RGM-B/DRAGON, a BMP coreceptor that also associates with other type I and type II receptors. Activin RIA can additionally phosphorylate the coreceptor Endoglin and is required for the inhibitory effect of Endoglin on prostate cancer cell motility.

Butyrophilin-Like Protein 9 (BTNL9) is single-pass type I membrane protein member of the BTN/MOG family that belongs to the immunoglobulin superfamily. BTNL9 consists of two domains: one B30.2/SPRY domain and one Ig-like V-type (immunoglobulin-like) domain. Human BTNL9 mRNA has been identified in adipose, lung, thymus, spleen, colon, and cardiac tissues, but its highest levels of expression were found in B cells. BTNL9 expression has also been found to be down-regulated in colon cancer tumors. BTNL9 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with C-6xHis tag. The predicted molecular weight is 18-30 KDa and the accession number is Q6UXG8.

Butyrophilin-Like Protein 9 (BTNL9) is single-pass type I membrane protein member of the BTN/MOG family that belongs to the immunoglobulin superfamily. BTNL9 consists of two domains: one B30.2/SPRY domain and one Ig-like V-type (immunoglobulin-like) domain. Human BTNL9 mRNA has been identified in adipose, lung, thymus, spleen, colon, and cardiac tissues, but its highest levels of expression were found in B cells. BTNL9 expression has also been found to be down-regulated in colon cancer tumors. BTNL9 Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-Fc tag. The predicted molecular weight is 55-70 KDa and the accession number is Q6UXG8.

LMCD1 is transcriptional cofactor which contains a cysteine-rich domain in the N-terminal region and 2 LIM domains in the C-terminal region. It also has several potential phosphorylation and N-myristoylation sites and a single potential N-glycosylation site. LMCD1 is expressed in many tissues with highest abundance in skeletal muscle. LMCD1 restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. It plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway.

Surfactant Pulmonary-Associated Protein D (SP-D) is a 43 kDa member of the collectin family of innate immune modulators. Its principal components consist of a collagen-like region and a C-terminal carbohydrate recognition domain (CRD), a structure that places it in a subset of pattern recognition proteins termed defense collagens. SP-D is constitutively secreted by alveolar lining cells and epithelium associated with tubular structures and induced in cardiac smooth muscle and endothelial cells. It binds both secreted and transmembrane proteins that transduce its function. It binds human neutrophil defensins, modulating influenza anti-viral defense. It binds MD-2/LY96, a secreted protein that cooperates with Toll-like receptors (TLRs) in the response of macrophages to bacterial lipopolysaccharides (LPS) or cell wall components. It also binds macrophage CD14 and TLRs directly, blocking binding of LPS and down-regulating TNF-α secretion. SP-D binding of both SIRPα and the calreticulin/CD91 complex on macrophages allows for a graded response to environmental challenge.

Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.

Catalyzes the de novo synthesis of acetyl-CoA in vitro. Promotes acetylation of CTTN, possibly by providing the acetyl donor, ensuring correct dendritic spine morphology and synaptic transmission. Binds to follistatin-related protein FSTL1 and may act as a cell surface receptor for FSTL1, contributing to AKT activation and subsequent FSTL1-induced survival and function of endothelial cells and cardiac myocytes.

Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and cooperatively to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription in vivo in a cell-specific manner. The activation function appears to be mediated by a limiting cell-specific transcriptional intermediary factor (TIF). Involved in cardiac development. Binds to the M-CAT motif.

E3 ubiquitin ligase. Mediates the ubiquitination and subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. Regulates the proteasomal degradation of muscle proteins under amino acid starvation, where muscle protein is catabolized to provide other organs with amino acids. Inhibits de novo skeletal muscle protein synthesis under amino acid starvation. Regulates proteasomal degradation of cardiac troponin I/TNNI3 and probably of other sarcomeric-associated proteins. May play a role in striated muscle atrophy and hypertrophy by regulating an anti-hypertrophic PKC-mediated signaling pathway. May regulate the organization of myofibrils through TTN in muscle cells.

Relaxin-1, also known as Prorelaxin H1 and RLN1, is a secreted protein that belongs to the insulin family. It is a peptide hormone that was first described in 1926 by Frederick Hisaw. Since its discovery as a reproductive hormone 8 years ago, relaxin has been implicated in a number of pregnancy-related functions involving extracellular matrix (ECM) turnover and collagen degradation. It is now becoming evident that relaxin's ability to reduce matrix synthesis and increase ECM degradation has important implications in several nonreproductive organs, including the heart, lung, kidney, liver and skin. The relaxin-like peptide family belongs in the insulin superfamily and consists of 7 peptides of high structural but low sequence similarity; relaxin-1 (RNL1), relaxin-2 (RNL2) and relaxin-3 ( RNL3), and the insulin-like (INSL) peptides, INSL3, INSL4, INSL5 and INSL6. The functions of relaxin-3, INSL4, INSL5, INSL6 remain uncharacterised. Relaxin-1 / RLN1 is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. Relaxin-1 / RLN1 may be involved in remodeling of connective tissues during pregnancy, promoting growth of pubic ligaments and ripening of the cervix. Relaxin and estrogen appear to play protective roles against airway fibrosis, airway SM thickening, and cardiac hypertrophy. Relaxin may also provide a means to regulate excessive collagen deposition during kidney development and in diseased states characterized by renal fibrosis.

PDE1C belongs to the cyclic nucleotide phosphodiesterase family, PDE1 subfamily. Phosphodiesterases (PDEs) are a family of related phosphohydrolyases that selectively catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). They regulate the cellular levels, localization and duration of action of these second messengers by controlling the rate of their degradation. PDEs are expressed ubiquitously, with each subtype having a specific tissue distribution. These enzymes are involved in many signal transduction pathways and their functions include vascular smooth muscle proliferation and contraction, cardiac contractility, platelet aggregation, hormone secretion, immune cell activation, and they are involved in learning and memory. PDE1C has a high affinity for both cAMP and cGMP. It is expressed in several tissues, including brain and heart. As a cyclic nucleotide phosphodiesterase, PDE1C has a dual-specificity for the second messengers cAMP and cGMP.

cGMP-dependent 3',5'-cyclic phosphodiesterase, also known as cyclic GMP-stimulated phosphodiesterase and PDE2A, is a peripheral membrane protein that belongs to the cyclic nucleotide phosphodiesterase family and PDE2 subfamily. Phosphodiesterases (PDEs) comprise a family of enzymes that regulate the levels of cyclic nucleotides, key second messengers that mediate a diverse array of functions. Phosphodiesterases (PDEs) modulate signaling by cyclic nucleotides in diverse processes such as cardiac contractility, platelet aggregation, lipolysis, glycogenolysis, and smooth muscle contraction. PDE2A is an evolutionarily conserved cGMP-stimulated cAMP and cGMP PDE. PDE2A contains two GAF domains. PDE2A is expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas. PDE2A is a cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. PDE2A is involved in the regulation of blood pressure and fluid homeostasis by the atrial natriuretic peptide (ANP), making PDE2-type enzymes important targets for drug discovery.

NRG4 (neuregulin 4) is a member of the neuregulin protein family. The neuregulins consist of four structurally-related proteins that are part of the EGF family of proteins. It has been shown that these proteins have diverse functions in the development of the nervous system and play multiple essential roles in vertebrate embryogenesis including cardiac development, Schwann cell, and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscular synapses. NRG4 contains 1 EGF-like domain. It activates type-1 growth factor receptors to initiating cell-to-cell signaling through tyrosine phosphorylation. NRG4 is a low-affinity ligand for the ERBB4 tyrosine kinase receptor. It concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. However, it does not bind to the ERBB1, ERBB2, and ERBB3 receptors.

CD38, also called ADP-ribosyl cyclase, is a Type II integral membrane protein with 301 amino acids in length that belongs to the ADP-ribosyl cyclase family.It synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion. And also moonlights as a receptor in cells of the immune system. CD38 is expressed in B and T lymphocytes, osteoclasts, and in cardiac, pancreatic, liver and kidney cells. Through its production of cyclic ADP-ribose, CD38 modulates calcium-mediated signal transduction in many types of cells, including neutrophils and pancreatic beta cells.

GTP-Binding Protein Rheb (RHEB) is a member of the small GTPase superfamily and encodes a lipid-anchored, cell membrane protein with five repeats of the RAS-related GTP-binding region. Highest levels of RHEB can be found in the skeletal and cardiac muscle, and it is vital in the regulation of growth and cell cycle progression due to its role in the Insulin/TOR/S6K signaling pathway. RHEB stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling, and it activates the protein kinase activity of mTORC1. RHEB has GTPase activity and shuttles between a GDP-bound form and a GTP-bound form, farnesylation of the protein is required for this activity.

Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:135300]; also known as GINGF1. Gingival fibromatosis is a rare overgrowth condition. Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:610733]. NS4 is an autosomal dominant disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common. characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.

Troponin I, also known as TNI, is a 24 kDa component of a protein complex on striated muscle thin filaments.Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments. Troponin I inhibits the calcium-dependent muscle contraction mediated by Troponins C and T. The expression of cardiac Troponin I (TNNI3) is restricted to cardiac muscle, while TNNI1 and TNNI2 (encoded by distinct genes) are expressed in skeletal muscle. Mutations of cardiac Troponin I are associated with heriditary cardiomyopathy. Human cardiac Troponin I shares 93% amino acid sequence identity with mouse and rat cardiac Troponin I.

Granulocyte colony-stimulating factor (G-CSF) is a growth factor and an essential cytokine which belongs to the IL-6 superfamily. Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. G-CSF binding to its receptor G-CSF-R which belongs to the cytokine receptor type I family depends on the interaction of alpha-helical motifs of the former and two fibronectin type III as well as an immunoglobulin-like domain of the latter. G-CSF is a cytokine that have been demonstrated to improve cardiac function and perfusion in myocardial infarction. And it was initially evaluated as a stem cell mobilizer and erythropoietin as a cytoprotective agent.

E3 ubiquitin ligase. Mediates the ubiquitination and subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. Regulates the proteasomal degradation of muscle proteins under amino acid starvation, where muscle protein is catabolized to provide other organs with amino acids. Inhibits de novo skeletal muscle protein synthesis under amino acid starvation. Regulates proteasomal degradation of cardiac troponin I/TNNI3 and probably of other sarcomeric-associated proteins. May play a role in striated muscle atrophy and hypertrophy by regulating an anti-hypertrophic PKC-mediated signaling pathway. May regulate the organization of myofibrils through TTN in muscle cells.

SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as FOS). Together with MRTFA transcription coactivator, controls expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration. The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. Required for cardiac differentiation and maturation.

Fibroblast growth factor 16 (FGF16) is preferentially expressed in the heart after birth, suggesting its regulation is associated with tissue-specific chromatin remodeling and DNA-protein interactions. Mutation of the MEF2 site resulted in a blunting of FGF16 promoter activity in transfected neonatal rat cardiac myocytes, that chromatin remodeling and MEF2 binding in the FGF16 promoter contribute to expression in the postnatal heart. FGF16 involvement in the fine tuning of the human skeleton of the hand. Impaired FGF16 function may also be responsible for connective tissue symptoms in MF4 patients. FGF16 expression is markedly increased in ovarian tumors, and FGF16 in conjunction with Wnt pathway contributes to the cancer phenotype of ovarian cells and suggests that modulation of its expression in ovarian cells might be a promising therapeutic strategy for the treatment of invasive ovarian cancers.

CCL18 is a chemotactic cytokine involved in the pathogenesis and progression of various disorders, including cancer. Proof showed high levels of CCL18 in the serum of epithelial ovarian carcinoma patients suggesting its potential as a circulating biomarker. CCL18 chemokine has an important role in chemokine-mediated tumor metastasis, and may serve as a potential predictor for poor survival outcomes for ovarian cancer. (CCL18) is predominantly secreted by M2-tumor associated macrophages (TAMs) and promotes malignant behaviors of various human cancer types. CCL18 has a correlation with cardiac function in patients with AAMI and it might be considered as an indicator of poor LVEF in patients with AAMI. Circulating and WAT-secreted CCL18 correlates with insulin resistance and metabolic risk score. Because CCL18 is macrophage-specific and associates with adipose immune gene expression, it may constitute a marker of WAT inflammation. Macrophages are thought to be the main source of CCL18, and the effect of pirfenidone, an anti-fibrotic agent for idiopathic pulmonary fibrosis, on the expression of CCL18 in macrophages warrants investigation.

Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors ( Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. Studies point to the potential role of the (pituitary) adenylate cyclase activating polypeptide receptor 1 (ADCYAP1R1) gene, which has been implicated in stress response, in posttraumatic stress disorder (PTSD). Pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate PAC1 receptor (Adcyap1r1) are expressed in peripheral nociceptive pathways, participate in anxiety-related responses and have been have been linked to posttraumatic stress disorder and other mental health afflictions. Recent studies revealed the role of the PAC1 (ADCYAP1R1) gene variability in vulnerability to posttraumatic stress disorder in women. Due to the relatively high comorbidity of posttraumatic stress disorder and substance use disorder, we hypothesized about possible associations between PAC1 gene and problematic alcohol use.

Calsequestrin-1 is an isoform of calsequestrin. Calsequestrin is a calcium-binding protein of the sarcoplasmic reticulum. It helps hold calcium in the cisterna of the sarcoplasmic reticulum after a muscle contraction, even though the concentration of calcium in the sarcoplasmic reticulum is much higher than in the cytosol. Two forms of calsequestrin have been identified: Calsequestrin-2 and Calsequestrin-1. Calsequestrin-1 is found in fast skeletal muscle. The release of calsequestrin-bound calcium (through a calcium release channel) triggers muscle contraction. The active protein is not highly structured, more than 5% of it adopting a random coil conformation. When calcium binds there is a structural change whereby the alpha-helical content of the protein increases from 3 to 11%. Both forms of calsequestrin are phosphorylated by casein kinase 2, but the cardiac form is phosphorylated more rapidly and to a higher degree. Calsequestrin-1 is also secreted in the gut where it deprives bacteria of calcium ions.

Gelsolin is a calcium-activated actin filament severing and capping protein found in many cell types and as a secreted form in the plasma of vertebrates. Gelsolin is composed of six of these domains, termed G1-6. Some reaseraches show that gelsolin can act as a transcriptional cofactor in signal transduction and its own expression and function can be influenced by epigenetic changes. The difference in the expression levels of cytoplasmic and plasma gelsolin suggests that these two different forms of gelsolin may play different roles after cardiac injury. Plasma gelsolin, as an important component of the EASS, may have evolved to rapidly clear actin filaments from the circulation that are released by injured or dead cells.

Catalyzes the de novo synthesis of acetyl-CoA in vitro. Promotes acetylation of CTTN, possibly by providing the acetyl donor, ensuring correct dendritic spine morphology and synaptic transmission. Binds to follistatin-related protein FSTL1 and may act as a cell surface receptor for FSTL1, contributing to AKT activation and subsequent FSTL1-induced survival and function of endothelial cells and cardiac myocytes.

SerpinB6, also known as Cytoplasmic antiproteinase, Peptidase inhibitor 6, Placental thrombin inhibitor, SERPINB6 and PI-6, is a cytoplasm protein that belongs to the serpin family and Ov-serpin subfamily. SerpinB6 / PI-6 is an inhibitor of cathepsin G, kallikrein-8 and thrombin. It may play an important role in the inner ear in the protection against leakage of lysosomal content during stress and loss of this protection results in cell death and sensorineural hearing loss. SerpinB6 / PI-6 is expressed in keratinocytes (at protein level). It is also found in placenta, cardiac muscle, lung, liver, kidney and pancreas. SerpinB6 / PI-6 is expressed in the inner ear hair cells. It’s expressed abundantly by normal mast cells in different tissues and by mast cells in mastocytoma lesions. SerpinB6 / PI-6 may be involved in the regulation of serine proteinases present in the brain or extravasated from the blood. Defects in SerpinB6 are the cause of deafness autosomal recessive type 91 which is a form of non-syndromic deafness characterized by progressive and age-dependent sensorineural hearing loss. Vestibular function is normal.

C-Kit/SCF R is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). c-Kit contains 5 Ig-like C2-type (immunoglobulin-like) domains and 1 protein kinase domain. It belongs to the protein kinase superfamily and CSF-1/PDGF receptor subfamily. SCF R expression on mast cells enables them to infiltrate SCF-secreting tumors where they promote tumor growth and induce local immune suppression. SCF R is up-regulated on dendritic cells by Th2-orTh17-biasing stimuli, and it is required for subsequent dendritic cell induction of Th2 and Th17 responses. SCF R protects vascular smooth muscle cells from apoptosis and assists in the recovery of cardiac function following myocardial infarction.