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Growth/differentiation factors (GDF1-GDF15) belong to the BMP family of TGF-beta superfamily proteins. These factors are produced as inactive preproproteins which are subsequently cleaved and assembled into active secreted homodimers. BMP13 is a growth factor which controls proliferation and cellular differentiation in the retina and bone formation. BMP13 has a central role in regulating apoptosis during retinal development. GDF proteins are vital during embryonic development, particularly in the skeletal, nervous, and muscular systems. BMP13 gene mutations result in colobomata, which are congenital abnormalities in ocular development, and in Klippel-Feil syndrome (KFS), which is a congenital disorder of spinal segmentation.

Glutamyl-TRNA Amidotransferase, Subunit C also known as GATC allows the formation of properly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction occurs in the attendance of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). In addition, GATC is subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (QRSL1), B (PET112) and C (GATC) subunits.

Granulocyte/Macrophage Colony-Stimulating Factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. MCSF induces cells of the monocyte/macrophage lineage. MCSF plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.

Natriuretic Peptide A (NPPA) is a part of the natriuretic peptide family and is involved in cardiovascular homeostasis through regulation of natriuresis, diuresis, and vasodilation. NPPA is synthesized as a great precursor which releases a peptide from the N-terminus with similarity to vasoactive peptide, cardiodilatin, and another peptide from the C-terminus with natriuretic-diuretic activity. In female pregnancy, NPPA is promoting trophoblast invasion and spiral artery remodeling in uterus.

HB-EGF is an EGF related growth factor which signals via the EGF receptor, and stimulates the proliferation of SMC (smooth muscle cells), fibroblasts, epithelial cells and keratinocytes. HB-EGF is expressed in various cell types and tissues, including vascular endothelial cells and SMC, macrophages, skeletal muscle, keratinocytes and particular tumor cells. HB-EGF’s ability to explicitly bind HPR sulfate proteoglycans is dissimilar from other EGF-like molecules, and might be related to the enhanced mitogenic activity, relative to EGF, that HB-EGF exerts on smooth muscle cells.

HB-EGF is an EGF related growth factor which signals via the EGF receptor, and stimulates the proliferation of SMC (smooth muscle cells), fibroblasts, epithelial cells and keratinocytes. HB-EGF is expressed in various cell types and tissues, including vascular endothelial cells and SMC, macrophages, skeletal muscle, keratinocytes and particular tumor cells. HB-EGF’s ability to explicitly bind heparin and heparin sulfate proteoglycans is dissimilar from other EGF-like molecules, and might be related to the enhanced mitogenic activity, relative to EGF, that HB-EGF exerts on smooth muscle cells.

Active IL-12 is a p70 disulphide-linked dimer composed of p35 and p40 subunits. The protein is a pleiotropic cytokine produced primarily by antigen presenting cells and has multiple effects on T lymphocytes and natural killer cells in terms of stimulating cytotoxicity, proliferation, production of other cytokines and Th1 subset differentiation.

PLGF is a growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration. It binds to receptor vegfr-1/flt1.
PLGF-2 binds neuropilin-1 and 2 in a heparin-dependent manner.

GMFG is a hematopoietic-specific protein that mediates the pluripotentiality and lineage commitment of human hematopoietic stem cells. Glia maturation factor gamma is a cytokine-responsive protein in EPO-induced and G-CSF-induced hematopoietic lineage development. Glia maturation factor also acts as a Nerve Growth Factor in nervous system development, angiogenesis and immune function. GMFG possesses hematopoietic tissue-specific gene expression, a promoter concentrated with high-score hematopoiesis-specific transcription factors, and molecular coevolution with a rudimentary blood/immune system.

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.

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), VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes, dendritic cells and on trophoblast cells. The flt-1 gene was first described in 1990. The receptor contains seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular splited tyrosine kinase domain. Compared to VEGFR-2 the Flt-1 receptor has a higher affinity for VEGF but a weaker signaling activity. VEGFR-1 thus leads not to proliferation of endothelial cells, but mediates signals for differentiation. Interestingly a naturally occuring soluble variant of VEGFR-1 (sVEGFR-1) was found in HUVE supernatants in 1996, which is generated by alternative splicing of the flt-1 mRNA. The biological functions of sVEGFR-1 still are not clear, but it seems to be an endogenous regulator of angiogenesis, binding VEGF with the same affinity as the full-length receptor.

Cystatin E/M or CST6 is part of the cystatin type 2 family. Part of the cystatin type 2 family members can act as cysteine protease inhibitors, whereas cystatin E/M regulates cathepsin B inhibitors and not cathepsin C. cystatin E/M is a protein the when secreted, has an effect on osteogenesis and bone resorption, insulin regulation, response to systemic inflammation & hepatocyte growth factor receptors.

Eukaryotic translation elongation factor 1 delta (EEF1D) is a subunit of the elongation factor-1 complex that is responsible for the enzymatic transport of aminoacyl tRNAs to the ribosome. EEF1D functions as guanine nucleotide exchange factor. EEF1D interacts with HIV-1 Tat, and consequently represses the translation of host-cell, but not HIV-1, mRNAs. EEF1D overexpression is linked to oesophageal carcinoma and may negatively influence the outcome of medulloblastomas.

TGF-beta receptor-associated protein 1 also known as TGFBRAP1 takes part in the TGF-beta/activin signaling pathway. TGFBRAP1 is related with inactive heteromeric TGF-beta and activin receptor complexes, mainly through the type II receptor, and is released upon activation of signaling. TGFBRAP1recruits SMAD4 to the vicinity of the receptor complex and smoothes the progress of its interaction with receptor-regulated Smads, such as SMAD2.

CST4 is a member of the cystatin superfamily which contains proteins that hold multiple cystatin-like sequences. Several family members are active cysteine protease inhibitors, whereas others have lost or possibly never attained this inhibitory activity. CST4 strongly inhibits papain (non-competitively) and ficin, partially inhibits stem bromelain and bovine cathepsin C, however does not inhibit porcine cathepsin B or clostripain.

NAA10 is a member of the acetyltransferase family. NAA10 interacts with NAA15, HIF-1 and with the ribosome. In its binding to HIF-1, NAA10 functions as a protein acetyltransferase by regulating its stability. In various cell lines, NAA10 is downregulated in response to hypoxia. NAA10 is expressed during the course of the development of the brain.

NF-kappa-B inhibitor beta (NFKBIB) is a member of the NF-kappa-B inhibitor family, which inhibit NF-kappa-B by complexing with, and trapping it in the cytoplasm. Phosphorylation of serine residues on these proteins by kinases marks them for destruction via the ubiquitination pathway, thus allowing activation of the NF-kappa-B, which translocates to the nucleus to act as a transcription factor.

TGFBI is an extracellular matrix protein induced by transforming growth factor (TGF)-beta 1. TGFBI protein is involved in cell growth, cell differentiation, wound healing and cell adhesion. In addition, some missense mutations of TGFBI were identified in families affected with human autosomal dominant corneal dystrophies. TGFBI gene encodes for a 683 amino-acid protein containing an RGD motif and four internal repeated domains which have highly conserved sequences founded in several species (Fasciclin domain).

CCN1 is a part of the extremely conserved cyclin family, whose members are characterized by a remarkable periodicity in protein abundance through the cell cycle. Cyclins which function as regulators of CDK kinases, shows the highest similarity with cyclin G. Different cyclins display diverse expression and degradation patterns which contribute to the chronological coordination of every mitotic event. The transcript of CCN1was found to be expressed continually during cell cycle progression.

Complement Factor Properdin (CFP) which is a plasma glycoprotein, is a positive regulator of the alternative complement pathway of the innate immune system. CFP binds and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that eventually ends with formation of the membrane attack complex and lysis of the target cell. Mutations in CFP lead to 2 forms of properdin deficiency that cause high susceptibility to meningococcal infections.

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.

Tetratricopeptide repeat protein 33 (TTC33) is comprised of 3 TPR repeats.

LFA-3 is ligand of the t-lymphocyte cd2 glycoprotein. This interaction is important in mediating thymocyte interactions with thymic epithelial cells, antigen-independent and dependent interactions of t-lymphocytes with target cells and antigen- presenting cells and the t-lymphocyte rosetting with erythrocytes. In addition, the lfa-3/cd2 interaction may prime response by both the cd2+ and lfa-3+ cells.

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), VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes, dendritic cells and on trophoblast cells. The flt-1 gene was first described in 1990. The receptor contains seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular splited tyrosine kinase domain. Compared to VEGFR-2 the Flt-1 receptor has a higher affinity for VEGF but a weaker signaling activity. VEGFR-1 thus leads not to proliferation of endothelial cells, but mediates signals for differentiation. Interestingly a naturally occuring soluble variant of VEGFR-1 (sVEGFR-1) was found in HUVE supernatants in 1996, which is generated by alternative splicing of the flt-1 mRNA. The biological functions of sVEGFR-1 still are not clear, but it seems to be an endogenous regulator of angiogenesis, binding VEGF with the same affinity as the full-length receptor.