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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.

GMCSF is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13.
GM-CSF stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. Granulocyte Macrophage Colony Stimulating Factor is a potent species-specific growth factor produced by a variety of cell types including T cells, B cells, macrophages, mast cells and endothelial cells. GM-CSF is produced in response to cytokine or immune stimulation and has been shown to stimulate the proliferation, maturation and function of hematopoietic cells.

Apolipoprotein-D is mainly associated with high density lipoproteins in human plasma. Apolipoprotein-D is an atypical apolipoprotein and, based on its primary structure, Apolipoprotein-D is a member of the lipocalin family. Lipocalins adopt a beta-barrel tertiary structure and transport small hydrophobic ligands. Apolipoprotein-D binds cholesterol, progesterone, pregnenolone, bilirubin and arachidonic acid.
Apolipoprotein-D is expressed in numerous tissues having high levels of expression in spleen, testes and brain. Apolipoprotein-D is present at high concentrations in the cyst fluid of women with gross cystic disease of the breast, a condition associated with increased risk of breast cancer. Apolipoprotein-D accumulates in regenerating peripheral nerves and in the cerebrospinal fluid of patients with neurodegenerative conditions, such as Alzheimer's disease. Apolipoprotein-D participates in maintenance and repair within the central and peripheral nervous systems. Apolipoprotein-D is a multi-ligand, multi-functional transporter and transports a ligand from 1 cell to another within an organ, scavenge a ligand within an organ for transport to the blood or could transport a ligand from the circulation to specific cells within a tissue.

BCL2 gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends.

Zinc-alpha-2-glycoprotein (ZAG) is found in body fluids such as serum, sweat, and seminal and breast cyst fluids. It is identical in amino acid sequence to tumor-derived lipid mobilizing factor (LMF), a protein associated with the dramatic loss of adipose body stores in cancer cachexia, and has been shown to stimulate lipolysis by adipocytes in vivo and in vitro. A role for ZAG has been proposed in the regulation of body weight, and age-dependent changes in genetically influenced obesity, and also it regulates melanin production by normal and malignant melanocytes. It has also recently been classified as a novel adipokine in that it is produced by both white and brown fat adipocytes and may act in a local autocrine fashion in the reduction of adiposity in cachexia. Controlling ZAG/LMF's activity could be life-saving in the management of certain cancers and other cachexiainducing conditions, and its possible normal role in body fat store homeostasis is deserving of understanding in its own right. ZAG exhibits a class I major histocompatibility complex (MHC) fold but is a soluble protein rather than being anchored to plasma membranes and does not associate with alpha-2-microglobulin in humans. Like antigen-presenting MHC class I proteins, ZAG has an open apical groove, and X-ray crystallography of human derived ZAG revealed an unidentifiable electron density in a similar position to that occupied by antigenic peptides in classical MHC proteins and glycolipids in isoforms of CD1. This presumptive ligand is not a peptide, and the groove is too small to hold a glycolipid such as is presented by CD1 isoforms. By analogy with all other MHC class I-related proteins that have an open apical groove [some do not ], occupancy by a ligand is probably crucial to ZAG's biological function. Despite all of the structural and biochemical evidence that ZAG binds a ligand, none has so far been found by extraction from protein isolated from biological fluids. This difficulty could be because the ligand is labile, heterogeneous, or readily lost during purification procedures. Knowing more about how ZAG interacts with the compounds it has been found to bind, both natural and artificial, will inform searches for the elusive ligand(s) and its/their role in ZAG's signaling function.

ST6GAL1 also known as ST6 Beta-Galactosamide Alpha-2,6-Sialyltranferase 1, is part of the glycosyltransferase family 29. ST6GAL1 is a type II membrane protein which catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. Furthermore, ST6GAL1 is normally found in the Golgi however it can be proteolytically processed to a soluble form, ST6GAL1 is also involved in the generation of the cell-surface carbohydrate determinants as well differentiation antigens HB-6, CD75, and CD76.

IL3RA, also known as Interleukin 3 Receptor Subunit Alpha, is a single-pass type 1 membrane protein which is a member of the type 1 cytokine receptor family as well as type 5 subfamily. IL3RA is a pleiotropic cytokine which is produced mainly by activated T cells or mast cells. Moreover, the specific alpha subunit of the interleukin 3 receptor is strongly expressed in a variety of leukemic blasts as well as leukemic stem cells and appears to be a great target for the therapy of leukemias.

PRDX3 is part of the peroxiredoxin family of antioxidant enzymes, that reduces hydrogen peroxide and alkyl hydroperoxides. PRDX3 is particularly located in the mitochondria and involved in the regulation of cellular redox status by serving as a primary line of defense against H2O2 produced during respiration. PRDX3 is a significant regulator of the abundance of mitochondrial H(2)O(2), which itself promotes apoptosis in cooperation with other mediators of apoptotic signaling. PRDX3 mitochondrial protein is significantly decreased in Alzheimer Disease and Down Syndrome.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that takes part in mammalian growth and development. IGF1 mediates various growth-promoting effects of growth hormone (GH; MIM 139250). Early studies showed that growth hormone did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as 'somatomedin' (Daughaday et al., 1972). 3 main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

CCL-20 is a chemotactic factor that draws lymphocytes & neutrophils, rathar than monocytes. MIP-3 alpha inhibits proliferation of myeloid progenitors in colony formation assays. MIP3A plays a role in the formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. CCL-20 holdes antibacterial activity e.coli atcc 25922 and s.aureus atcc 29213. CCL-20 gene transcription is activated by H. pylori, which activates NF-kappaB through intracellular signal pathway which involves IkappaB kinase and NF-kappaB-inducing kinase. MIP-3 alpha is invloved in chemokine-mediated lymphocyte trafficking during gastric inflammation in Helicobacter infection. CCL-20 expression is involved in the recruitment of CD45R0-positive T cell subsets into the intestinal lamina propria.
MIP-3A is in charge of the advancement of pulpal inflammation through the recruitment of C-C motif Receptor 6-expressing lymphocytes Vaginal epithelial cells respond to factors present in semen by secreting MIP-3 alpha, which increases langerhans cells recruitment during HIV transmission.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

HRASLS3 is a tumor suppressor that takes part in dependent cell death. HRASLS3 is part of the class II tumor suppressor gene family and is involved in the regulation of differentiation and survival. HRASLS3 protein is expressed in a number of human tumors including ovarian carcinomas, lung carcinomas.

GDF-11 belongs to the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. GDF-11 is a central developmental factor which controls muscular and neural development. In adults, GDF-11 encourages cardiac hypertrophy reverse by the revival of cardiomyocytes.

Interleukin-3 is a pleiotropic cytokine produced primarily by activated T cells.
IL-3 is thought to function via specific cell surface receptors to stimulate the proliferation, differentiation and survival of haematopoietic cell lines. IL-3 has also been shown to affect the functional activity of a variety of other cell types including mast cells, eosinophils, megakaryocytes and basophils.

Epidermal growth factor has a profound effect on the differentiation of specific cells in vivo and is a potent mitogenic factor for a variety of cultured cells of both ectodermal and mesodermal origin. The EGF precursor is believed to exist as a membrane-bound molecule which is proteolytically cleaved to generate the 53-amino acid peptide hormone that stimulates cells to divide. EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Long EGF is a recombinant analog of Human EGF developed as a replacement for use in therapeutic cell culture applications as a like-for-like supplement for Recombinant Human or native EGF. It includes the Human EGF amino acid sequence plus a 53 amino acid N-terminal extension peptide.

TGFB2 is a 27.08 kDa protein having two identical 118 amino acid peptide chains linked by a single disulfide bond. TGFB2 is part of a family of five related cytokines that have an extensive variation of normal and neoplastic cells, indicating the importance of these homo-dimmer proteins as multi-functional regulators of cellular activity. The three mammalian isoforms of TGF-beta (TGFb1, TGFb2 and TGFb3) signal through the same receptor and stimulate similar biological responses. They are involved in physiological processes as embryogenesis, tissue remodelling and wound healing.

CD81 antigen isoform 1, also known as CD81, is part of the tetraspanin family. CD81 interacts directly with immunoglobulin superfamily member 8 (IGSF8, CD316) and CD36. In B cells, CD81 is part of a complex with CD21, CD19 and Leu13. Furthermore, this complex decreases the threshold for B cell activation through B cell receptors by linking Ag specific recognition and CD21 mediator recognition. While on T cells CD81 connects with CD4 and CD8 and provides a costimulatory signal with CD3.

Interleukin 13 Receptor, Alpha 2 (IL13RA2) is a member of the type I cytokine receptor family, Type 5 subfamily. IL13RA2 is related to l13RA1, a subunit of the interleukin 13 receptor complex. IL13RA2 binds IL13 with high affinity, though lacking the cytoplasmic domain, and does not appear to function as a signal mediator. IL13RA2 plays a role in the internalization of IL13.

HSP90B1 is an abundant molecular chaperone resident endoplasmic reticulum (ER) lumenal stress protein which is part of the Hsp90 family. HSP90B1 is involved in maintaining protein homeostasis in the secretory pathway as well as functioning in the intracellular trafficking of peptides from the extracellular space to the MHC class I antigen processing pathway of antigen presentation cells. HSP90B1 has key roles in signal transduction, protein folding, protein degradation, and morphologic evolution. HSP90B1 protein associates with numerous cochaperones and involved in folding of newly synthesized proteins or stabilizing and refolding denatured proteins after stress. HSP90B1 is highly expressed in human gastric carcinoma BGC-823 cells during the whole cell cycle.

Glycerol dehydrogenase (GldA) catalyzes the NAD-dependent oxidation of glycerol to dihydroxyacetone (glycerone). The GldA protein allows microorganisms to use glycerol as a source of carbon under anaerobic conditions. Furthermore, in E.coli GldA has an imperative role by regulating the intracellular level of dihydroxyacetone by catalyzing the reverse reaction, i.e. the conversion of dihydroxyacetone into glycerol. GldA possesses an extensive substrate specificity, due to its ability to oxidize 1,2-propanediol and to reduce glycolaldehyde, methylglyoxal and hydroxyacetone into ethylene glycol, lactaldehyde and 1,2-propanediol, respectively.

RELM-beta (Resistin-Like Molecule-beta) is a member of a recently identified family of secreted proteins containing a conserved cystein-rich C-terminus. The RELM family consists of resistin (also called FIZZ3), RELM-alfa (FIZZ1), RELM-beta (FIZZ2) and RELM-gamma. Only resisistin and RELM-beta were found in humans whereas all four RELM family members were identified in rodents.
RELM-beta appears to be produced as a homodimer exclusively by intestinal goblet cells and can be found in high quantities in stool. Remarkably, stool of germ-free mice displaying sterile intestinal tract does not contain RELM-beta until bacterial colonization takes place after pathogen-free mice entered natural environment. Some, but not all, colon carcinoma cell lines secrete RELM-beta into the cell culture supernatant.
The physiological function of RELM-beta is not known. High doses of recombinant RELM-beta showed hyperglycemic effects including lowered glucose disposal and increased hepatic glucose production in mice.

Epidermal growth factor has a profound effect on the differentiation of specific cells in vivo and is a potent mitogenic factor for a variety of cultured cells of both ectodermal and mesodermal origin. The EGF precursor is believed to exist as a membrane-bound molecule which is proteolytically cleaved to generate the 53-amino acid peptide hormone that stimulates cells to divide.
EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.