Search results

Procalcitonin is a peptide hormone mainly produced by the C cells of the thyroid and certain endocrine cells of the lung. Under normal expression conditions, procalcitonin is immediately cleaved into three specific fragments, an N terminal residue, calcitonin and katacalcin. Levels of unprocessed procalcitonin rise significantly after bacterial infection, trauma or shock.

MORC Family CW-Type Zinc Finger 3 (MORC3) localizes to the nuclear matrix. MORC3 takes part in the regulation of the tumor suppressor protein p53. MORC3may indicate on dermatomyositis (DM) as autoantibodies against this protein have been found in patients.

Cystatins are a superfamily of cysteine proteinase inhibitors found in both plants and animals. They comprise a group of proteinase inhibitors, widely distributed in tissues and body fluids, and form tight complexes with cysteine proteases such as cathepsin B, H, L and S. Cystatin C, a secreted molecule of this family, is of interest from biochemical, medicine and evolutionary points of view. Cystatin C, with molecular weight of 13260 Da, is composed of 120 amino acids, lacks carbohydrate and has two disulfide bridges located near the carboxyl terminus. Cystatin C is increased in patients with malignant diseases, and is related to the insufficiency of renal function and appears to be a better marker than creatinine. On the other hand, low levels of cystatin C involve cause the breakdown of the elastic laminae and, subsequently, the atherosclerosis and abdominal aortic aneurysm.

Adiponectin, also known as Acrp30, AdipoQ and GBP-28, is a 244 amino acid protein, the product of the apM1 gene, which is physiologically active and specifically and highly expressed in adipose cells (Adipokine). Adiponectin is a part of the soluble defense collagen super family; it has a collagen-like domain structurally homologous with collagen VIII and X and complement factor C1q-like globular domain. APM-1 forms homotrimers, which are the building blocks for higher order complexes found circulating in serum.

Cyclophilin-C belongs to the peptidyl-prolyl cis-trans isomerase (PPIase)) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. Like other PPIases, the Cyclophilin-C protein can bind immunosuppressant cyclosporin A.

The mammaglobin gene was first identified using a differential screening approach directed at the isolation of novel, human breast cancer-associated genes. Mammaglobin encodes a 10 kDa glycoprotein and is distantly relaetd to a family of epithelial secretory proteins that includes rat estramustine-binding protein/prostatein and human Clara cell 10 kDa protein (CC10)/uteroglobin. Mammaglobin, a mammary-specific member of the uterglobin family, is known to be overexpressed in human breast cancer. Studies suggest that mammaglobin is one of the first relatively mammary-specific and mammary-sensitive markers (85%). Mammaglobin may be valuable used in a panel with BRST-2 (GCDFP-15) and ER in evaluating tumors of unknown primary sites.
SCGB2A2 (the mammaglobin gene) is located on chromosome 11, at locus 11q13. SCGB2A2 is member of the secretoglobin superfamily of which is a group of small dimeric secreted and sometimes glycosylated proteins. Expressed mainly in mucosa, secretoglobins appear to be involved in cell signalling, immune response, chemotaxis, and might also serve as transporters for steroid hormones in humans.

Decorin (DCN) is a small cellular or pericellular matrix proteoglycan which is closely related in structure to biglycan protein. Decorin is a secreted protein which binds to collagen and fibronectin in extracellular matrix. Decorin appears in different glycoforms, substituted with chondroitin sulfate or dermatan sulfate consistent with the original tissue. DCN contains one attached glycosaminoglycan chain. Decorin influences the rate of fibril formation. Decorin is capable of suppressing the growth of various tumor cell lines. DCN gene defects cause corneal dystrophy. The DCN gene is a candidate gene for Marfan syndrome.

GDF8 is a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site which is cleaved to produce a mature protein containing seven conserved cysteine residues. The members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. This gene is thought to encode a secreted protein which negatively regulates skeletal muscle growth.

Serine peptidase inhibitor Kazal type 7 (SPINK7) which includes one Kazal-like domain is most likely serine protease inhibitor. Diseases linked with SPINK7 include esophageal cancer, and oral squamous cell carcinoma

Calmodulin Like 5, also known as CALML5 is a part of the calmodulin family of calcium binding proteins. CALML5 undergoes a conformational change as a result of binding calcium. CALML5 is taking part in terminal differentiation of keratinocytes and encodes a calcium binding protein expressed in the epidermis.

Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. The single FST gene encodes two isoforms, FST317 and FST344 containing 317 and 344 amino acids respectively, resulting from alternative splicing of the precursor mRNA. In a study in which 37 candidate genes were tested for linkage and association with polycystic ovary syndrome (PCOS) or hyperandrogenemia in 150 families, evidence was found for linkage between PCOS and follistatin. Follistatin binds directly to activin and functions as an activin antagonist. specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (fsh).

Galectins are a family of animal lectins with an affinity for beta-galactosides. This family has at least 14 identified members. Galectins share similarities in the CRD (the carbohydrate recognition domain). Galectins are synthesized as cytosolic proteins. Though localized principally in the cytoplasm and lacking a classical signal peptide, galectins can also be stimulated to secretion by non-classical pathways or alternatively targeted to the nucleus. Galectins are involved in modulating cell-cell and cell-matrix interactions. Galectin-8 is a tandem-repeat-type member of the galectin family, consisting of 2 CRDs attached by a linker peptide. Galectin-8 is greatly expressed in lung carcinomas, a number of forms of prostate carcinomas, in addition to other tumor cells. Galectin-8 attaches to a subset of cell surface integrins to modulate ECM-integrin interactions. Once immobilized, Galectin-8 promotes cell adhesion by ligation and clustering of cell surface integrin receptors. On the other hand, as a soluble ligand, Galectin-8 can inhibit cell adhesion.

Mediator Complex Subunit 27 (MED27) is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, together with TFIID, is necessary for efficient activation by SP1. MED27 is a component of the Mediator complex, a coactivator involved in the regulated transcription of virtually all RNA polymerase II-dependent genes. MED27 protein is also a component of other multisubunit complexes such as the thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. The activation of MED27 gene transcription is a multistep process, which is triggered by factors that identify transcriptional enhancer sites in DNA.

Insemination involves of a series of specific cell-cell interactions concluding in the fusion of the sperm and egg plasma membranes. Recognition, binding, and fusion take place through the interface of complementary molecules which are localized to specific domains of the sperm and egg plasma membranes. In the sperm, the postacrosomal region or equatorial segment is involved in sperm-egg plasma membrane fusion. The protein encoded by this gene belongs to the cysteine-rich secretory protein (CRISP) family. CRISP1 is expressed in the epididymis, is secreted into the epididymal lumen, and binds to the postacrosomal region of the sperm head, where it takes part in sperm-egg fusion.

Reg protein was shown to be stimulated during the regeneration of pancreatic islets. Since then, many Reg-related proteins have been identified in humans and other animals. In human, the four REG family genes, i.e., REG 1 alpha, REG 1 beta, REG-related sequence (RS) and HIP/PAP, have so far been isolated. These Reg-related proteins are classified into four subfamilies according to their amino-acid sequences, but they share a similar structure and physiological function. Reg protein is a growth factor for pancreatic beta cells and also suggests that the administration of Reg protein could be used as another therapeutic approach for diabetes mellitus. Human REG cDNA which encodes a 166-amino acid protein with a 22-amino acid signal peptide. The amino acid sequence of human REG protein has 68% homology to that of rat Reg protein.
Reg I was found to be expressed mainly in pancreatic beta and acinoductular cells as well as gastric fundic enterochromaffin-like (ECL) cells. Reg I production in ECL cells is stimulated by gastrin, as well as by the proinflammatory cytokine, cytokine-induced neutrophil chemoattractant (CINC)-2Beta. In patients with chronic hypergastrinemia, Reg production is stimulated, with the increased proliferation of gastric mucosal cells. Patients with Helicobacter pylori infection also showed increased Reg production in the gastric mucosa, partly via increased plasma gastrin concentration and partly via increased proinflammatory cytokine production. The serum concentration of the reg-protein was significantly higher in patients with various pancreatic diseases than in normal controls, and was also significantly higher in patients with acute pancreatitis or chronic relapsing pancreatitis than in patients with chronic pancreatitis. Furthermore, the serum PSP/reg-protein concentration was also significantly increased in liver cirrhosis, choledocholithiasis, and various cancers of the digestive system.

Casein Kinase 2 also called CK2 (also called PKCK2) is a ubiquitous Ser/Thr kinase expressed in all eukaryotes. CK2 is a tetramer composed of two catalytic kinase domains, alpha subunits, and two identical regulatory beta subunits. It has been implicated in cell cycle control, DNA repair, regulation of the circadian rhythm, and other cellular processes. The beta subunit itself does not have kinase activity, but confers stability to the CK2 alpha subunit and is involved in activity and substrate specificity.

Human thyrostimulin ranks among the glycoprotein hormone family. These hormones consist of two subunits, the common alpha- and specific beta-subunits, which associate noncovalently to form a heterodimer. The alpha-subunit combines with four distinct beta-subunits giving rise to four biologically active hormones in human: FSH, LH, TSH, and CG. FSH, LH, and TSH, mainly expressed in the anterior pituitary, are essential for coordinated endocrine regulation in the hypothalamus- pituitary axis and show to activate specific G protein–coupled receptors in the thyroid (TSH receptor) and gonads (LH and FSH receptors), respectively.
The heterodimeric glycoprotein hormones have only been identified in vertebrates and are highly conserved in organisms from primitive rayfin fish (Chondrostei) to human in both primary sequences and functional characteristics.
Corticotroph-derived glycoprotein hormone (CGH), also referred to as thyrostimulin, is a noncovalent heterodimer of glycoprotein hormone alpha 2 (GPHA2) and glycoprotein hormone beta 5 (GPHB5).
Recombinant A2/B5 heterodimeric glycoproteins activates human TSH receptors, but not LH and FSH receptors, and shows high affinity to TSH receptors in a radioligand receptor assay. The heterodimer also stimulates cAMP production and thymidine incorporation by cultured thyroid cells and increases serum thyroxine levels in TSH-suppressed rats in vivo. This new heterodimeric glycoprotein hormone was named as thyrostimulin based on its thyroid-stimulating activity. The expression of thyrostimulin in the anterior pituitary known to express TSH receptors suggested a paracrine mechanism.

Carboxypeptidase A4 (CPA4) belongs to the carboxypeptidase A/B subfamily, and it is located in a cluster with 3 other family members on chromosome 7. CPA4 is a secreted, zinc-dependent metallocarboxypeptidase, which removes the C-terminal amino acid from peptides having a free C-terminal carboxyl group. CPA4 is a metalloprotease which may be involved in the histone hyperacetylation pathway. CPA4 are synthesized as zymogens which are activated by proteolytic cleavage.

Resistin, a product of the RSTN gene, is a peptide hormone belongs to the class of cysteine-rich secreted proteins (monomeric peptide contains 11 cysteine residues) referred to as the RELM family, and is also described as ADSF (Adipose Tissue-Specific Secretory Factor) or FIZZ3 (Found in Inflammatory Zone 3). Resistin may be an important link between obesity. Mouse resistin, specifically produced and secreted by adipocyte, acts on skeletal muscle myocytes, hepatocytes and adipocytes themselves so that it reduces their sensitivity. Steppan et al. have suggested that resistin suppressed the ability to stimulate glucose uptake. They have also suggested that resistin was present at elevated levels in blood of obese mice, and was down regulated by fasting and by antidiabetic drugs. Way et al., on the other hand, have found that resistin expression is severely suppressed in obesity.
Other studies have shown that mouse resistin increases during the differentiation of adipocytes, but it also seems to inhibit adipogenesis. In contrast, the human adipogenic differentiation is likely to be associated with a down regulation of resistin gene expression.

Cystatin-SN (CST1) belongs to the type 2 salivary cystatin family found in a variety of fluids and secretions, including plasma, tears, and saliva. The cystatin superfamily includes proteins which contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, whereas others have lost or possibly never developed this inhibitory activity. CST1 is up-regulated in cancerous lesions of gastric cancer tissues compared to noncancerous regions, in addition clinicopathological analysis revealed a significant correlation between high expression of CST1.

Midkine (MK) is the product of a retinoic acid responsive gene, MK, and is a member of a family of heparin binding factors. It contains 121 amino acid residues including 10 conserved cysteine residues, all of which appear to be disulphide linked.
Midkine is expressed during embryogenesis, showing an expression pattern that suggests functions in neurogenesis, cell migration, secondary organogenetic induction, and mesoderm-epithelial interaction.
The widespread downregulation of MK in the adult human is reverted in a number of cancers, in which polypeptides are able to act as both transforming growth factors and promoters of angiogenesis.
Midkine (MK), induces chemotaxis of human neutrophils and was found to trigger mobilization of intracellular calcium of these cells.
Midkine induces histamine release from rat peritoneal mast cells with a rapid response in a dose dependent manner.
Midkine is also a potent stimulator of collagen and glycosaminoglycan synthesis.

Cystatins are a superfamily of cysteine proteinase inhibitors found in both plants and animals. They comprise a group of proteinase inhibitors, widely distributed in tissues and body fluids, and form tight complexes with cysteine proteases such as cathepsin B, H, L and S. Cystatin C, a secreted molecule of this family, is of interest from biochemical, medicine and evolutionary points of view. Cystatin C, with molecular weight of 13260 Da, is composed of 120 amino acids, lacks carbohydrate and has two disulfide bridges located near the carboxyl terminus. Cystatin C is increased in patients with malignant diseases, and is related to the insufficiency of renal function and appears to be a better marker than creatinine. On the other hand, low levels of cystatin C involve cause the breakdown of the elastic laminae and, subsequently, the atherosclerosis and abdominal aortic aneurysm.

Cystatin-A is the intracellular inhibitor of cysteine proteinase cathepsin B (CatB) and belongs to family 1 of the cystatin superfamily of inhibitor proteins. CSTA is a stefin that functions as a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. It has been proposed that extracellular CatB together with other classes of proteinases are all subjected to a cascade-like manner of activation. CatB and its inhibitor Cystatin-A are involved in degradation of extracellular matrix proteins during tissue remodeling. CSTA is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Cystatin-A has been reported to be found in high concentrations in epithelial cells, polymorphonuclear leukocytes and lymphoid tissue. Stefins may be used as prognostic and diagnostic tools for cancer.