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GDF-5 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. Mutations in this gene are associated with acromesomelic dysplasia, Hunter-Thompson type; brachydactyly, type C; and chondrodysplasia, Grebe type. These associations confirm that the gene product plays a role in skeletal development.

SH2D1A acts as an inhibitor of the signaling lymphocyte activation molecule (SLAM) self-association. The SH2D1A protein is expressed at a high level in the thymus and the lung, with a lower level of expression in the spleen and the liver. The SH2D1A protein contains an SH2 domain and a short tail. SH2D1A has a key role in the bidirectional stimulation of T and B cells. Defects in the SH2D1A gene cause the X-linked lymphoproliferative disease (XLPD), aka Duncan disease. The XLPD is distinguished by a rare congenital immunodeficiency following an EBV infection (Epstein-Barr virus).

C3d is derived from human C3 after a series of proteolytic cleavages.C3d is prepared from purified human C3. The C3 is converted to C3b by treatment with the natural human C3 convertase and this C3b is converted to iC3b. Finally, this iC3b is cleaved with trypsin to yield C3d.If the C3b precursor was attached to a surface (as occurs during complement activation) the iC3b, C3dg and C3d fragments would remain covalently attached to that surface.C3d is able to attach to a surfaceonly during complement activation on a surface. Surface-bound C3d is linked to the target through an ester or an amide covalent bond. Ester bonds are unstable, thusC3d releasesfrom the particle.

Retinol Binding Protein-4 or RBP4, is the retinol currier protein in the plasma. RBP4 takes part on the conversion of retinol to the stable and soluble retinol complex in the plasma. RBP4 carries retinol from the liver tissue where its store to peripheral tissues. RBP-retinol complex has interactions with transthyretin in the plasma, thus prevents its loss by filtration in the kidney.

LYVE-1 has been identified as a major receptor for HA (extracellular matrix glycosaminoglycan hyaluronan) on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.

A 16-kDa peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores.

Mycobacterium antigen ESAT-6 has been isolated from low molecular weight fractions of the shot-term-culture filtrate (ST-CF) and it can easily be detected in tuberculosis patients.
The export of ESAT-6 which is a potent T-cell antigen, and related proteins requires a dedicated secretory apparatus that is encoded by a group of genes, several of which also code for proteins that are recognized strongly by T cells. The ESAT-6 systems can consequently be considered as immunogenicity islands and there is mounting evidence that the equivalent genes are subject to selective pressure imposed by the immune system of the host.
This antigen includes many epitopes detectable in the serum of most patients with tuberculosis (more than 90%). By the attempts to obtain the vaccine on the basis of ESAT-6 it was demonstrated that the optimization of adjuvant is very important when using the combination of dioctadecylammonium bromide and monophosphoryllipide.
Recently it was shown that ESAT-6 is very potential as diagnostic for differentiation between the mycobacterial infection and BCG vaccination. The main topic in ESAT-6 using is in antibody production and in test-systems for tuberculosis elaboration.

RARRES2 is a secreted chemotactic protein that initiates chemotaxis through the ChemR23 G protein-coupled seven-transmembrane domain ligand. RARRES2 is upregulated by the synthetic retinoid tazarotene and found in a vast variety of tissues. RARRES2 acts as an adipokine, and is truncated on both termini from the proprotein. RARRES2 is structurally related to the cathelicidin precursors, cystatin C and kininogens. RARRES2 promotes calcium mobilization and chemotaxis of immature dendritic cells and macrophages. RARRES2 is secreted as a precursor of little biological activity, which requires proteolytic cleavage of its COOH-terminal domain to be exchangeed into a potent and highly specific agonist of ChemR23. RARRES2 signals via its receptor, ChemR23 (CMKLR1), as a positive regulator of adipocyte differentiation and metabolic function. The Chemerin receptor acts as a coreceptor for SIV and some primary HIV-1 strains. The Chemerin receptor has another ligand, called tazarotene-induced gene.

ANGPTL3 and ANGPTL4 are angiopoietin-like proteins secreted and expressed mainly by the liver, their role being the regulation of triglyceride metabolism by inhibiting the lipolysis of triglyceride-rich lipoproteins. During different nutritional states (feeding/fasting) the levels of the circulating triglycerides are regulated by Angptl3 and Angptl4 through differential inhibition of Lipoprotein lipase (LPL) as shown by the experimental data. The molecular structure of ANGPTL3 is similar to that of the angiopoietins (vascular endothelial growth factors). Deletion mutants of human Angiopoietin 5 were used in order to demonstrate that the N-terminal domain (fragment 17-207) and not the C-terminal fibrinogen-like domain (fragment 207-460) increased the plasma triglyceride levels in mice.

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.

ESM1, also knows as, Endothelial cell-specific molecule 1 is a protein encoded by a gene called ESM1 in humans. ESM1 is a secreted protein that is highly expressed in human kidney and lung tissues (in the endothelial cells). There are suggestions regarding the protein’s involvement in endothelium-dependent pathological diseases, due to his regulation that is performed by cytokines.

Fibroblast Growth Factor 17 (FGF17) belongs to the fibroblast growth factor (FGF) family. FGF family members have broad mitogenic and cell survival activities, and are involved in various biological processes including embryonic development cell growth, morphogenesis, tissue repair, tumor growth and invasion. The FGF17 gene is highly expressed in the cerebellum and cortex. The mouse homolog of the FGF17 gene is localized to specific sites in the midline structures of the forebrain, the midbrain-hindbrain junction, developing skeleton and developing arteries, suggesting a role in central nervous system, bone and vascular development.

TUBG1 belongs to the tubulin superfamily. TUBG1 localizes to the centrosome and binds to microtubules to create the gamma-tubulin ring complex. TUBG1 facilitates the microtubule nucleation and is essential for microtubule formation and progression of the cell cycle.

Chromgranin-A is part of the neuroendocrine secretory protein family. CHGA is located in secretory vesicles of neurons and endocrine cells. Chromgranin-A is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Other peptides, including chromostatin, beta-granin, WE-14 and GE-25, are also derived from the full-length protein. Chromgranin-A has numerous biological activities on some tissues and organs and exerts a large spectrum of homeostatic actions, including antifungal and antimicrobial effect, modulation of cell adhesion, and inhibition of parathyroid hormone secretion.

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.

Tubulin, beta 3 class III (TUBB3), which is the major constituent of microtubules, is primarily Expressed in neurons and is involved in neurogenesis and in axon guidance and maintenance. TUBB3 binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha-chain.

SRGN is identified as a hematopoietic cell granule proteoglycan. Proteoglycans stored in the secretory granules of various hematopoietic cells also hold a protease-resistant peptide core, and is vital for neutralizing hydrolytic enzymes. SRGN is related to the macromolecular complex of granzymes and perforin that acts as a intermediary of granule-mediated apoptosis.

NusA is an important player in both prevention and enhancement of transcriptional termination. NusA is important both in Rho-dependent and intrinsic termination, as well as in lambda and other phage antitermination systems. The NusA gene was first identified by isolation of the nusAl mutation, which limits bacteriophage-l growth by preventing the antitermination activity of the l N protein. NusA plays a role in transcriptional antitermination in the cell. It has been shown to specifically aid in read-through of the RNA polymerase genes rpoB and rpoC, as well as in successful synthesis of the ribosomal RNA genes. Additionally to its anti-termination role, NusA is needed for both Rho-dependent and intrinsic transcriptional termination. NusA is obligatory for Rho-dependent termination in lambda phage and in the cell. NusA plays a role in intrinsic termination and the inhibition of RNA elongation. However NusA interacts with all three subunits of RNA polymerase, its termination activity primarily depends on its interaction with the carboxy-terminus of RpoA. NusA induces conformational change in RNA polymerase & prevents RNA interaction with RpoA. This binding sequentially activates NusA, allowing it to bind RNA and promote formation of hairpins at intrinsic termination sites. NusA binds Rho, and participates with sigma70 for binding to the core RNA polymerase complex. NusA does not compete with NusG for binding to either Rho or the polymerase, despite modulating the same process as NusG in both cases.

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8) is a receptor for TNFSF8/CD30L. TNFRSF8 has a role in the regulation of cellular growth and transformation of activated lymphoblasts. In addition, the TNFRSF8 protein regulates gene expression via activation of NF-kappa-B. TNFRSF8 being a regulator of apoptosis, induces cell death or proliferation, depending on the cell type.

HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 5 (HERC5) is a member of the HERC family of ubiquitin ligases, found in a cluster of HERC family genes on chromosome 4. HERC5 is a protein with a HECT domain and 5 RCC1 repeats. The HERC5 protein localizes to the cytoplasm and perinuclear region and serves as an INF-induced E3 protein ligase that mediates ISGylation of protein targets. HERC5 exhibits antiviral activity towards HIV-1, influenza A virus and human papillomavirus. HERC5 is a major E3 ligase for ISG15 conjugation. HERC5 also serves as a positive regulator of innate antiviral response in cells induced by INF. Pro-inflammatory cytokines upregulate HERC5 in endothelial cells. HERC5 is physically connected with polyribosomes, broadly modifies recently synthesized proteins in a cotranslational fashion.

Translational activator of mitochondrially encoded cytochrome c oxidase I (TACO1) belongs to the TACO1 family. TACO1 is a mitochondrial protein which functions as a translational activator of mitochondrially-encoded cytochrome c oxidase 1. Mutations in this gene are associated with Leigh syndrome.

JAZF zinc finger 1 (JAZF1) is a nuclear protein with 3 C2H2-type zinc fingers, which functions as a transcriptional repressor. Chromosomal anomalies involving the JAZF1 are linked with endometrial stromal tumors. Alternatively spliced variants which encode different protein isoforms have been described; though, not all variants have been fully characterized.

Leucine zipper down-regulated in cancer 1-like (LDOC1L) is a member of the LDOC1 family. LDOC1L is a nuclear protein containing a leucine zipper-like motif and a proline-rich region that shares noticeable similarity with an SH3-binding domain. LDOC1L localizes to the nucleus and is downregulated in certain cancer cell lines. LDOC1L is believed to regulate the transcriptional response mediated by the nuclear factor kB (NFkB).

UBL3 - a member of the ubiquitin-like family is found in the membrane. UBL3 holds two N-glycosylation sites, a C-terminal prenylation site and a protein kinase C phosphorylation site. Even though Ubiquitin-like proteins are not directly involved in protein degradation, it seems they have several mechanistic similarities to the ubiquitin pathway.