Search results

Neuregulin is a signaling protein for ErbB2/ErbB4 receptor heterodimers on the cardiac muscle cells, playing an important role in heart structure and function through inducing ErbB2/ErbB4 receptor phosphorylation and cardiomyocyte differentiation. Research on molecular level discovered that neuregulin recombinant could make disturbed myocardial cell structure into order and strengthen the connection between myocardial cells by intercalated discs re-organization. Pharmacodynamic experiments in animals showed that neuregulin (NRG1) recombinant can reduce the degree of damage on myocardial cells caused by ischemia, hypoxia and viral infection.

SPARC, an acronym for “secreted protein, acidic and rich in cysteine”, is also known as osteonectin or BM-40. It is the founding member of a family of secreted matricellular proteins with similar domain structure. The 303 amino acid, 43 kDa protein contains a 17 aa signal sequence, an N-terminal acidic region that binds calcium, a follistatin domain containing Kazal-like sequences, and a C-terminal extracellular calcium (EC) binding domain with two EF-hand motifs. SPARC is produced by fibroblasts, capillary endothelial cells, platelets and macrophages, especially in areas of tissue morphogenesis and remodeling. SPARC shows context-specific effects, but generally inhibits adhesion, spreading and proliferation, and promotes collagen matrix formation. For endothelial cells, SPARC disrupts focal adhesions and binds and sequesters PDGF and VEGF. SPARC is abundantly expressed in bone, where it promotes osteoblast differentiation and inhibits adipogenesis.

BDH1 belongs to the short-chain dehydrogenase/reductase gene family. BDH1 forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific necessity for phosphatidylcholine for optimal enzymatic activity. BDH1 catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the 2 main ketone bodies formed during fatty acid catabolism.

Coiled-Coil Domain Containing 90B (CCDC90B) is a member of the CCDC90 family. The CCDC90B protein is distinguished by the presence of a domain of unknown function, DUF1640. The DUF1640 domain is a characteristic of the entire protein with excluding of the first 23 amino acid residues which are a mitochondrial targeting site and the cleaved CCDC90B is expected to be a mitochondrial protein with no transmembrane spans or segments. CCDC90B is predicted to contain at least 3 specific phospohorylation sites.

ITGB4 (integrin beta-4 isoform 1) belongs to the Integrin beta family. ITGB4 forms noncovalent heterodimers with Integrin alpha 6 and takes part in the formation of epithelial hemidesmosomes. ITGB4 has a vital structural role in the hemidesmosome of epithelial cells and is needed for the regulation of keratinocyte motility & polarity. ITGB4 leans towards the association with alpha 6 subunit and is expected to take a key role in the biology of invasive carcinoma.

Lactate dehydrogenase (LDH) is an enzyme(EC1.1.1.27) present in a wide variety of organisms, including plants and animals.
A tetrameric enzyme that catalyses the interconversion of pyruvateand lactate with concomitant interconversion of NADH and NAD+. At high concentrations of pyruvate, the enzyme exhibits feedback inhibition and the rate of conversion of pyruvate to lactate is decreased. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.

GLRX2 is a multifunctional enzyme with glutathione-dependent oxidoreductase, glutathione peroxidase and glutathione S-transferase (GST) activity. The disulfide bond functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. In addition, it is also involved in reducing cytosolic protein- and non-protein-disulfides in a coupled system with glutathione reductase. Required for resistance to reactive oxygen species (ROS) by directly reducing hydroperoxides and for the detoxification of ROS-mediated damage. Glutaredoxins are a family of glutathione-dependent hydrogen donors that participate in a variety of cellular redox reactions.

TXNDC12 is a member of the thioredoxin super family. This Family members have a thioredoxin fold with a consensus active-site sequence (CxxC) and take part in redox regulation, protection against oxidative stress, refolding of disulfide-containing proteins, and regulation of transcription factors.

CAMP Responsive Element Binding Protein 3-Like 2, also known as CREB3L2 belongs to the oasis bZIP transcription factor family. Members of this family are able to dimerize however from homodimers only. CREB3L2 is a transcriptional activator. Translocations between CREB3L2 on chromosome 7 and the gene fused in sarcoma on chromosome 16 can be found in some tumors. One disease which is associated with CREB3L2 is myxofibrosarcoma.

Stanniocalcin 1 (STC1) is the mammalian homologue of STC, which was originally identified as a calcium/phosphate-regulating hormone in bony fishes. In contrast, STC1 may play an autocrine and paracrine role with pleiotropic effects in mammals. It is expressed in a wide variety of tissues, but unexpectedly is not detected in the circulation under normal circumstances, which is possibly caused by its attaching to soluble and tethered forms of a high-affinity binding protein. STC-1 can affect calcium homeostasis, bone and muscle mass and structure, and angiogenesis through effects on osteoblasts, osteoclasts, myoblasts/myocytes, and endothelial cells in mouse model. Differential regulation of myocardial STC1 protein expression was reported in heart failure. In addition, STC1 may regulate calcium currents in cardiomyocytes and may contribute to the alterations in calcium homeostasis of the failing heart. STC1 was found to be a selective modulator of hepatocyte growth factor (HGF)-induced endothelial migration and morphogenesis, an inhibitor of macrophage chemotaxis and chemokinesis, suppressor of progesterone and luteinization inhibitor. Together with STC-2, it may play important roles in the processes of implantation and decidualization in the rat. In terminally differentiated adipocytes, it may function as a "survival factor", which contributes to the maintenance of the integrity of mature adipose tissue. In context with its possible role in gestation, a Big STC, a three highermolecular- mass variant has been described. STC1 was identified as one of hypoxia-responsive genes coupled to hypoxia-driven angiogenesis.
Current research indicates that STC-1 might be a useful molecular marker to detect tumor cells in blood and bone marrow from patients with various types of malignancies.

Mammalian crystallins which are water soluble structural proteins located in the vertebrate eye are classified in three forms, labeled alpha, beta and gamma. Crystallins, the primary components of the lens, raise the refractive index of the eye all through the accommodation by creating high-molecular weight aggregates that maintain transparency. CRYGS is a monomer that does not aggregate. CRYGS encodes the most substantial gamma-crystallin in adult eye lens tissue. Gamma-crystallins has a part in cataract formation due to aging or mutations in specific genes,

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1a and MIP-1b that are now officially named CCL3 and CCL4 respectively. Both are major factors produced by macrophages after they are stimulated with bacterial endotoxins. They activate human granulocytes (neutrophils, eosinophilsand basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-a from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17.

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1a and MIP-1b that are now officially named CCL3 and CCL4 respectively. Both are major factors produced by macrophages after they are stimulated with bacterial endotoxins. They activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-a from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17.

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1a and MIP-1b that are now officially named CCL3 and CCL4 respectively. Both are major factors produced by macrophages after they are stimulated with bacterial endotoxins. They activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-a from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17.

Collagen triple helix repeat-containing protein 1 (CTHRC1) functions as a negative regulator of collagen matrix deposition. CTHRC1 is a secreted 28kDa protein which is glycosylated and highly conserved from lower chordates to mammals. CTHRC1 is highly connected with calcified tissues and cartilaginous matrix, but not with endothelial cells. CTHRC1 is detected qualitatively in plasma of healthy human subjects. CTHRC1 plasma levels are also significantly elevated during pregnancy, in diabetes, in inflammatory and infectious conditions, in subjects with acute myeloid leukemia but not in subjects with solid cancers. The hormonal functions of CTHRC1 include regulation of lipid storage and cellular glycogen levels with potentially far-reaching implications for cell metabolism and physiology. CTHRC1 gene deletion leads to fatty liver (steatosis) formation in mice while others exhibited inactivation of the CTHRC1 gene also results in low bone mass.

Agouti-related protein is an endogenous antagonist of hypothalamic alpha-melanocortin receptors MC3R and MC4R with potent orexigenic activity. Although a complete deletion of the AGRP gene does not produce any significant metabolic phenotypes, reduction in AGRP expression by RNA interference is associated with increased metabolic rate along with reduced weight gain. In hypothalamus, it is produced by neurons in the medial portion of arcuate nucleus, which produce also the potent orexigenic peptide Neuropeptide Y (NP-Y). Another site of central AGRP production is the hypothalamic nucleus. AGRP encompasses 132 amino acid residues and its alpha-melanocortin inhibiting activity results in a 34 amino acid cystine knot domain within the C-terminal (87-132) portion of the protein. Both AGRP and NP-Y expression was shown to be suppressed by leptin. Central administration of AGRP induces hyperphagia and increased gain in body weight in rodents, but may also exert metabolic effects even when hyperphagia is prevented. In the absence of hyperphagia, intracerebralventricular administration of AGRP caused significant increases in plasma leptin and insulin concentrations (twofold and 1.5-fold, respectively) and fat pad mass.
In the periphery, AGRP mRNA was found in adrenal glands, lung, testis, ovary, skeletal muscle and adipose tissue in humans or rodents. In the adrenals, it was shown that AGRP antagonizes glucosteroid production mediated by MC4R. AGRP could then modulate locally the functions of some peripheral tissues such as adrenals.
In human and rat serum, detectable levels of AGRP-like activity were reported in the lower picogram range. The serum AGRP levels were elevated in obese humans compared to lean controls and increased with fasting in rats.

SCO Cytochrome Oxidase Deficient Homolog 1, also known as SCO1 is a member of the SCO1/2 family. Mammalian cytochrome c oxidase (COX) catalyzes the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Furthermore, in yeast, two related COX assembly genes, SCO1 & SCO2 which are synthesis of cytochrome c oxidase, enable subunits 1 as well as 2 to be incorporated into the holoprotein. This gene is the human homolog to the yeast SCO1 gene. Among the diseases associated with SCO1 are hepatic failure, early-onset, neurologic disorder due to cytochrome c oxidase deficiency and fatal infantile cytochrome c oxidase deficiency.

DCXR catalyzes the NADPH-dependent reduction of numerous pentoses, tetroses, trioses, alpha-dicarbonyl molecules and L-xylulose. DCXR takes part in the uronate cycle of glucose metabolism. DCXR participates in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thus preventing osmolytic stress from occurring in the renal tubules.

DEAD Box Protein 56 (DDX56) belongs to the DEAD box protein family. DEAD box proteins, categorized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. DEAD box proteins are implicated in several cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based upon their distribution patterns, certain members of this family are assumed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. DDX56 exhibits ATPase activity in the presence of polynucleotides and associates with nucleoplasmic 65S preribosomal particles.

Myosin Light Chain 6B (MYL6B) is a heavy chain regulator located in smooth muscle and non-muscle Myosin complexes. Contractile activity in the smooth muscle is regulated by the calcium/calmodulin-dependent phosphorylation of Myosin light chain by Myosin light chain kinase. MYL6B doesn’t bind calcium during contraction. MYL6B is mostly found as a hexamer consisting of 4 light chains and 2 heavy chains. MYL6B usually interacts with Myosin Va, an Actin based motor which moves in large steps. MYL6B is expressed in the majority of tissues with neurons, while smooth muscle tissue having the highest expression.

Dehydrogenase/reductase SDR family member 8 (HSD17B11) is a member of the HSD17B family of proteins, which regulate the availability of steroids within various tissues throughout the body. HSD17B11 is widely expressed with the highest levels found in the retina, pancreas, kidney, liver, lung, adrenal, small intestine, ovary and heart as well as in steroidogenic cells. HSD17B11 converts androstan-3-?,17-?-diol (3-?-diol) to androsterone, suggesting it may participate in androgen metabolism during steroidogenesis.

DTD2 is e member of the DTD family. DTD2 protein hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr) as a defense mechanism against a harmful effect of D-tyrosine.

Actin-related protein 2/3 complex subunit 3 (ARPC3) which Belongs to the ARPC3 family is one of 7 subunits of the human Arp2/3 protein complex. The Arp2/3 complex is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. ARPC3 which is localized to the cytoplasm and cytoskeleton, interacts with p20-ARC and takes part in the structural integrity of the protein complex.