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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.

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.

Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes. All VEGF-receptors have seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. VEGFR-2 has a lower affinity for VEGF than the Flt-1 receptor, but a higher signalling activity. Mitogenic activity in endothelial cells is mainly mediated by VEGFR-2 leading to their proliferation. Differential splicing of the flt-1 gene leads to the formation of a secreted, soluble variant of VEGFR-1 (sVEGFR-1). No naturally occurring, secreted forms of VEGFR-2 have so far been reported. The binding of VEGF165 to VEGFR-2 is dependent on heparin.

Human interleukin family 1, member 10 (IL1F10) belongs to the interleukin 1 cytokine family. IL1F10 is expressed in the fetal skin, spleen and tonsil, generally in the basal epithelia of skin and in proliferating B-cells of the tonsil. IL1F10 binds soluble IL1 receptor type 1 and may be implicated in the regulation of adapted and innate immune responses.

LGALS8 is a prostate-specific antigen that is solely overexpressed in malignant tumors and thus is a supplementary specific identifier of malignancies. LGALS8 is part of the galectin gene family which facilitates both cell-cell and cell matrix interactions in a method parallel to the selectin subgroup of C-type lectins.

Mitochondrial Ribosome Recycling Factor (MRRF) is a member of the RRF family. MRRF attaches to the large ribosomal subunit in the cleft which has a peptidyl transferase center. MRRF controls the release of ribosome from messenger RNA at the termination of protein biosynthesis. Also, it may intensify the efficacy of translation by recycling ribosome from one round of translation to another.

Excess adiposity is the most important risk in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Adipose tissue produces several proteins (adipocytokines) such as leptin, adiponectin, resistin, tumor necrosis factor-?, and IL-6, that modulate insulin sensitivity and appear to play an important role in the pathogenesis of insulin resistance, diabetes, dyslipidemia, inflammation, and atherosclerosis. However, the mechanisms by which fat tissue induces insulin resistance and the role of adipocytokines in the pathogenesis of T2DM have not been well established.
Visfatin, also known as pre-B cell colony-enhancing factor (PBEF), is a cytokine that is highly expressed in visceral fat and was originally isolated as a secreted factor that synergizes with IL-7 and stem cell factors to promote the growth of B cell precursors. Visfatin homologs have been identified in carp, invertebrate mollusks, and bacteria, as well as in vertebrates, including humans and the mouse. It has been postulated to play a role in innate immunity.
Visfatin exerts insulin-mimetic effects that are dose-dependent and quantitatively similar to those of insulin in stimulating muscle and adipocyte glucose transport, and in inhibiting hepatocyte glucose production. Intravenous injection of recombinant visfatin in mice decreased plasma glucose in a dose-dependent fashion. In keeping with its insulin-mimetic effects, visfatin was as effective as insulin in reducing hyperglycemia in insulin-deficient diabetic mice. Visfatin was also found to be bound to and activate insulin receptor, causing receptor phosphorylation and the activation of downstream signaling molecules. However, visfatin and insulin did not compete for binding to the insulin receptor, indicating that the two proteins were recognized by different regions of the receptor. Thus, visfatin might play a role in glucose homeostasis and dysregulation in biosynthesis or signal transduction, and might contribute to the pathogenesis of diabetes.

Eukaryotic translation initiation factor 3 subunit J (EIF3J) is a member of the EIF-3 subunit J family. EIF3 has a crucial role in binding of initiator methionyl-tRNA and mRNA to the 40S ribosomal subunit to produce the 40S initiation complex. EIF3J binds to the aminoacyl (A) site and mRNA access channel of the 40S subunit, setting EIF3J directly in the ribosomal decoding center. In addition, EIF3J interacts with eIF1A and reduces 40S subunit affinity for mRNA. An elevated affinity for mRNA is restored upon enlistment of initiator tRNA, despite the fact EIF3J remains in the mRNA-binding cleft in the presence of tRNA.

The Melanoma Inhibitory protein (MIA) was identified as an inhibitor of in vitro growth of malignant melanoma cells. The protein contains a SH3 domain. MIA acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas, in an autocrine fashion. In a study of human melanoma cell lines with different metastatic capacity MIA mRNA expression appeared to be inversely correlated with pigmentation. MIA has been shown to represent a very sensitive and specific serum marker for systemic malignant melanoma that might be useful for staging of primary melanomas, detection of progression from localized to metastatic disease during follow-up, and monitoring therapy of advanced melanomas.

CTLA-4 is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases.

LGLAS9 binds galactosides and has high affinity for the Forssman pentasaccharide. LGLAS9 participates in thymocyte-epithelial interactions relevant to the biology of the thymus and Inhibits cell proliferation. LGLAS9 is a ligand for HAVCR2/TIM3. LGLAS9 Induces T-helper type 1 lymphocyte (Th1) death. LGLAS9 performs as an eosinophil chemoattractant LGLAS9 is an S-type lectin which is over-expressed in Hodgkin's disease tissue and takes part in the interaction between the H&RS cells with their surrounding cells.

EIF2B1 is one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), which is a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Phosphorylation of eIF2 inhibits GEF activity of EIF2B, an inhibition which requires the eIF2B1 subunit. Defects in eIF2B1 are a cause of leukoencephalopathy with vanishing white matter (VWM), a brain disease which is characterized by head trauma and motor deterioration.

Stromal Cell-Derived Factor 2 (SDF2) is a secretory protein which is partly similar to the hydrophilic segments of yeast mannosyltransferases. SDF2 protein’s expression is ubiquitous and the gene is rather conserved among mammals. SDF2is a protein-coding gene whose alternative splicing results in coding and non-coding variants.

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, INS resistance, and cancer.

Dickkopf-related protein 3 (DKK3) belongs to the DKK protein family including Dkk-1, 2, 3 and -4. DKK3 is a 350 amino acid secreted glycoprotein which is comprised of an N-terminal signal peptide and 2 conserved cysteine-rich domains that are separated by a 12 amino acid linker region. DKK3 is involved in embryonic development through its inhibition of the WNT signaling pathway. DKK3 gene expression is decreased in a variety of cancer cell lines and it may act as a tumor suppressor gene.

ARF1 is a small guanine nucleotide-binding protein that increases the enzymatic activities of cholera toxin. ARF1 is necessary and ubiquitous in eukaryotes. ARF1 takes part in vesicular transport and functioning via phospholipase D activation. ARF1 is involved in membrane traffic and organelle integrity which are closely tied to their reversible association with membranes and distinct interactions with membrane phospholipids.

IL2 is a secreted cytokine that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine is a heterotrimeric protein complex whose gamma chain is also shared by interleukin 4 (IL4) and interleukin 7 (IL7). The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli.

Stromal Cell-Derived Factor 2 (SDF2) is a secretory protein which is partly similar to the hydrophilic segments of yeast mannosyltransferases. SDF2 protein’s expression is ubiquitous and the gene is rather conserved among mammals. SDF2 is a protein-coding gene whose alternative splicing results in coding and non-coding variants.

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.

GHBP is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. A common alternate allele of this gene, called GHRd3, lacks exon three and has been well-characterized. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature. Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized.

S100A8 is a part of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a broad range of cells, and participate in the regulation of cellular processes such as cell cycle progression and differentiation. S100A8 plays a role in the inhibition of casein kinase and as a cytokine. S100A8 altered expression is related with cystic fibrosis disease. S100A8 is a calcium-binding protein that has antimicrobial activity against bacteria and fungi.S100A8 is crucial for resistance towards invasion by pathogenic bacteria. S100A8 up-regulates transcription of genes that are under the control of NF-kappa-B. S100A8 plays a role in the development of endotoxic shock in response to bacterial lipopolysaccharide. S100A8 endorses tubulin polymerization and promotes phagocyte migration and infiltration of granulocytes at sites of wounding. S100A8 takes part as a pro-inflammatory mediator in acute and chronic inflammation and up-regulates the release of IL8 and cell-surface expression of ICAM1.

Prolactin is a neuroendocrine hormone synthesized primarily by the pituitary gland but also a variety of other cell types including the placenta, brain and uterus. Its primary function is to promote and maintain lactation but has also been shown to have a role in breast cancer development, regulation of reproductive function and immunoregulation.

Pleiotrophin (Osteoblast-Specific Factor-1, OSF-1) contains 136 amino acid residues. The sequence is very rich in cationic amino acids (24% of the residues); lysine cluster sequences are found in the N-terminal and C-terminal ends of the structure.
The OSF-1 gene was shown by Northern blotting analysis to be expressed in mouse calvarial osteoblast-enriched cells and in mouse brain tissues, but not in thymus, spleen, kidney, liver, lung, testis or heart. Pleiotrophin has the ability to promote adhesion, migration, expansion, and differentiation of human osteoprogenitor cells. In addition to certain types of cancer, the embryonic growth and differentiation factor pleiotrophin is found also in adults in inflammatory diseases. In osteoarthritis, pleiotrophin is especially expressed in early stages, and its concentrations in the synovial fluid could serve as a marker for the progress of the disease. Pleitrophin might be involved in cartilage repair in osteoarthritis, in particular, in earlier stages.

Osteoprotegerin acts as decoy receptor for rankl and thereby neutralizes its function in osteoclastogenesis. OPG inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local rankl/opg ratio. Osteoprotegerin may also play a role in preventing arterial calcification. May act as decoy receptor for trail and protect against apoptosis. Trail binding blocks the inhibition of osteoclastogenesis.