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Sex-hormone-binding globulin (SHBG) is a beta-globulin which specifically binds steroid hormones; it is involved in the transport of sex steroids in plasma. The main site of SHBG synthesis is assumed to be the hepatocytes. The production of SHBG is regulated by androgen/estrogen balance, thyroid hormones, insulin and dietary factors, among others. The concentration of SHBG is a key factor regulating their distribution between protein-bound and free states. SHBG concentration determination is primarily significant in the evaluation of mild disorders of androgen metabolism and it allows detection of women with hirsutism who are likely to react to estrogen therapy. Testosterone/SHBG-ratios correlate well with both measured and calculated values for free testosterone thus aid to distinguish between subjects with excessive androgen activity and normal individuals. SHBG gene polymorphisms are linked with polycystic ovary syndrome and type 2 diabetes mellitus.

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).

Uteroglobin (SCGB1A1) which belongs to the Secretoglobin (SCGBs) superfamily, is a multifunctional protein that exerts anti-inflammatory and anti-tumorigenic effects by binding small hydrophobic molecules such as phospholipids and prostaglandins. Uteroglobin is involved in numerous functions including anti-inflammation, inhibition of phospholipase A2 and the sequestering of hydrophobic ligands. SCGB1A1 is expressed by Clara cells, the non-ciliated, non-mucous secretory cells predominant in lung bronchioles, and by other epithelia which communicate with the external environment. On top of sequestering pro-inflammatory mediators and carcinogens, Uteroglobin is implicated in the inhibition of cell migration and invasion, platelet aggregation, and T cell differentiation. SCGB1A1 gene defects are associated with a susceptibility to asthma.

SERF2 (small EDRK-rich factor 2) is a member of the SERF family. SERF2 is a protein-coding gene. Among the diseases associated with SERF2 are spinal muscular atrophy, and muscular atrophy.

KLF4 is a transcription factor that performs as both an activator and repressor. KLF4 is expressed mainly in erythroid tissues and found mostly in gut. KLF4 is takes part in the differentiation of epithelial cells in addition to skeletal and kidney development.

Human T-lymphotropic virus (HTLV) is a human, single-stranded RNA retrovirus that causes
T-cell leukemia and T-cell lymphoma. The virus activates a subset of T-helper cellscalled Th1cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-gamma and TNF-alpha). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly
IL-4, IL-5, IL-10 and IL-13). The end result is a reduction in the ability of the infected host to mount an adequate immune response to invading organisms that require a predominantly
Th2 dependant response (these include parasitic infections and production of mucosal and humoral antibodies).
HTLV-1 p24 is usually used for clinical diagnosis and forms both monomer and dimer on
SDS-PAGE gel but the majority of protein is a dimer.

Human T-lymphotropic virus (HTLV) is a human, single-stranded RNA retrovirus that causes T-cell leukemia and T-cell lymphoma. The virus activates a subset of T-helper cellscalled Th1cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-gamma and TNF-alpha). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly IL-4, IL-5, IL-10 and IL-13). The end result is a reduction in the ability of the infected host to mount an adequate immune response to invading organisms that require a predominantly Th2 dependant response (these include parasitic infections and production of mucosal and humoral antibodies).

The FGFs are a family of more than 20 small (~17–26 kDa) secreted peptides. The initial characterization of these proteins focused on their ability to stimulate fibroblast proliferation. This mitogenic activity was mediated through FGF receptors (FGFRs) 1, 2, or 3. A fourth closely related tyrosine kinase receptor (FGFR4) was able to bind the FGFs but did not lead to a mitogenic response.
FGFs modulate cellular activity via at least 5 distinct subfamilies of high-affinity FGF receptors (FGFRs): FGFR-1, -2, -3, and -4, all with intrinsic tyrosine kinase activity and, except for FGFR-4, multiple splice isoforms, and FGFR-5, which lacks an intracellular kinase domain. There is growing evidence that FGFRs can be important for regulation of glucose and lipid homeostasis. The overexpression of a dominant negative form of FGFR-1 in ? cells leads to diabetes in mice, which thus implies that proper FGF signaling is required for normal ? cell function and glycemia maintenance. FGFR-2 appears to be a key molecule during pancreatic development. Moreover, FGFR-4 has been implicated in cholesterol metabolism and bile acid synthesis.
FGF-21 is preferentially expressed in liver, but an exact knowledge of FGF-21 bioactivity and its mode of action have been lacking to date. FGF-21 is a potent activator of glucose uptake on adipocytes, protects animals from diet-induced obesity when overexpressed in transgenic mice, and lowers blood glucose and triglyceride levels when therapeutically administered to diabetic rodents.

HCV is a small 50nm, enveloped, single-stranded, positive sense RNAvirus in the family Flaviviridae.
HCV has a high rate of replication with approximately one trillion particles produced each day in an infected individual. Due to lack of proofreading by the HCV RNA polymerase, the HCV has an exceptionally high mutation rate, a factor that may help it elude the host's immune response. Hepatitis C virus is classified into six genotypes(1-6) with several subtypes within each genotype. The preponderance and distribution of HCV genotypes varies globally. Genotype is clinically important in determining potential response to interferon-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to interferon-based treatment than are the other genotypes (2, 3, 5 and 6).

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid. CXCL12 is strongly chemotactic for lymphocytes and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

GH is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature.

MANF is a 20kDa protein which belongs to the ARMET family. MANF was originally known as an arginine-rich region protein which was extremely mutated in a large number of tumors. MANF Expression is induced during ER stress, signifying that MANF takes part in protein quality control during ER stress.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/ macrophagemigration, neurons, cancer cells, kidney epithelial cells ). VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Human chorionic gonadotropin (hCG) is a peptide hormoneproduced in pregnancy, that is made by the embryosoon after conceptionand later by the syncytiotrophoblast(part of the placenta). Its role is to prevent the disintegration of the corpus luteumof the ovaryand thereby maintain progesteroneproduction that is critical for a pregnancyin humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testinggenerally is based on the detection or measurement of hCG.

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.

PSG5 belongs to the PSG family, which are a highly connected group of secreted glycoproteins, vastly expressed in fetal placental syncytiotrophoblast cells. PSGs are can be found in serum from the first 2-3 weeks of pregnancy and at higher levels as the pregnancy progresses, up to e point where they are the highest fetal protein found in maternal blood at term. PSG5’s role is inducing secretion of TH2-type cytokines from monocytes and modulating the maternal immune system throughout the pregnancy, thus defending the semi-allotypic fetus from rejection.

Histamine N-Methyltransferase or HNMT, is located in the cell cytosol. Sadenosyl-L-methionine acts as a methyl donor for HNMT which inactivates histamine. By inactivation of histamine, it affects the immune system’s response. HNMT acts on histamine in body tissues such as kidney, central nervous system and bronchus. The protein has a crucial part in the airway response to histamine & histamine degradation process and regulation.

The somatomedins, or IGFs, comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of GH. Early studies showed that GH 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). Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.

Granulocyte Colony Stimulating Factor is a growth factor and/or cytokine produced by the endothelium, macrophages and a number of other immune cells. GCSF stimulates the bone marrow to produce granulocytes and also to stimulate the survival, proliferation, differentiation and function of neutrophil granulocyte progenator cells and mature neutrophils.

Adiponectin is a recently discovered 244 amino acid protein, the product of the apM1 gene, which is physiologically active and specifically and highly expressed in adipose cells (Adipokine). The protein belongs to 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.

Dysbindin domain-containing protein 2 (DBNDD2) is a member of the dysbindin family. DBNDD2 regulates the activity of casein kinase-1 and inhibits CSNK1D autophosphorylation (in vitro). DBNDD2 also interacts with CSNK1D and CSNK1E. DBNDD2 is detected in brain.