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The secreted polypeptide noggin, encoded by the NOG gene, binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signaling proteins, such as bone morphogenetic protein-4 (BMP4). By diffusing through extracellular matrices more efficiently than members of the TGF-beta superfamily, noggin may have a principal role in creating morphogenic gradients. Noggin appears to have pleiotropic effect, both early in development as well as in later stages. It was originally isolated from Xenopus based on its ability to restore normal dorsal-ventral body axis in embryos that had been artificially ventralized by UV treatment. The results of the mouse knockout of noggin suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation. Recently, several dominant human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1) were identified; both SYM1 and SYNS1 have multiple joint fusion as their principal feature, and map to the same region (17q22) as NOG. All NOG mutations altered evolutionarily conserved amino acid residues. The amino acid sequence of human noggin is highly homologous to that of Xenopus, rat and mouse.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) induces proliferation, migration, and fenestration in capillary endothelial cells derived from endocrine glands. Its expression is induced by hypoxia and is restricted to the steroidogenic glands (ovary, testis, adrenal, and placenta). Its expression is often complementary to the expression of VEGF (MIM 192240), suggesting that these molecules function in a coordinated manner. EG-VEGF potently contracts gastrointestinal (gi) smooth muscle. Induces proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. Has little or no effect on a variety of other endothelial and non-endothelial cell types.

Troponin I, (TNNI1) is a member of the troponin I family. Troponin complex has 3 subunits, TNNI1 known as the inhibitory Subunit which prevents the actin-myosin interactions and thus mediating striated muscle relaxation. TNNI1 combines with tropomyosin and regulates calcium sensitivity of striated muscles by structural modifications in actin-myosin complexes.

Geminin is a 25 kDa nuclear protein, which inhibits DNA replication and is degraded during the mitotic phase of the cell cycle. Geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. In addition, Geminin directly interacts with Six3 and Hox homeodomain proteins during embryogenesis and inhibits their functions. Geminin can also promote DNA replication. Geminin has 2 roles in 2 different stages of the cell cycle: Geminin is a negative regulator of DNA replication during the “S phase” of the cell cycle. Inhibition of Geminin during the “S phase” (by RNAi) results in an additional round of replication of portions of the genome. During the “M phase” of the cell cycle (mitosis) Geminin stabilizes the replication factor Cdt1 promoting DNA replication during the next cell cycle. Moreover, inhibition of Geminin during mitosis (by RNAi) causes destabilization of Cdt1 protein and impairment of DNA replication during the next cell cycle. Geminin thus guarantees that only one round of replication occurs during each cell cycle. It was discovered that Geminin is overexpressed in a number of malignancies and cancer cell lines. This maintains the concept that Geminin has also a positive role in DNA replication and cell cycle progression. Geminin accumulates through S, G2 and M phases of the cell cycle but is absent during the G1 phase. During the metaphase/anaphase transition of mitosis Geminin levels decrease.

SNRPD3 is a small nuclear ribonucleoprotein (snRNPs) that contains the spliceosome in eukaryotes. SNRPD3 is essential for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Alternative splicing happens in this locus and two transcript variants encoding the same protein were branded.

AKAP7 is a member of the A-kinase anchoring protein (AKAP) family, a group of functionally related proteins which bind to a regulatory subunit (RII) of cAMP-dependent protein kinase A (PKA) and target the enzyme to specific subcellular sections. AKAP7 is expressed in heart, brain, pancreas, lung and skeletal muscle. AKAP7 binds PKA to the plasma membrane, and allows efficient coupling to the L-type calcium channel.

SAR1A is a member of the small GTPase superfamily. SAR1A is a vital component of COPII vesicle coats involved in export of cargo from the ER (Endoplasmic Reticulum). The GTPase activity of SAR1A serves as a molecular switch to control protein-protein and protein-lipid interactions which dictate vesicle budding from the ER. SAR1A, while GDP-bound interacts with the membrane-bound exchange factor Sec12 and trades its bound GDP for GTP. SAR1A is also involved in the transport from the ER to the Golgi apparatus. SAR1A is required to maintain SEC16A localization at distinct locations on the ER membrane possibly by preventing its dissociation. SAR1A-GTP-dependent compilation of SEC16A on the ER membrane creates a structured scaffold defining endoplasmic reticulum exit sites.

MYCBP is a member of the AMY1 family. MYCBP (c-Myc binding protein) binds to the transactivation domain of c-Myc and stimulates the activation of E-box-dependent transcription. MYCBP translocates from the cytoplasm to the nucleus during S phase when increased expression of c-Myc occurs. MYCBP also associates with AKAP 149 and AKAP 84 in mitochondria of somatic cells and sperm, suggesting a role for MYCBP in spermatogenesis. MYCBP is highly expressed in the heart, placenta, pancreas, skeletal muscle and kidney. It is also present at low levels in the lung.

MAPK3 is a part of the MAP kinase family which is recognized as extracellular signal-regulated kinases (ERKs), that function in a signaling cascade that controls various cellular procedures such as proliferation, differentiation, and cell cycle progression in reaction to a variety of extracellular signals. MAPK3 is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets.

Secreted frizzled-related protein 4 (SFRP4) belongs to the SFRP family which contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs serve as soluble modulators of Wnt signaling. SFRP4 may serve as a regulator of adult uterine morphology and function. SFRP4 increases apoptosis during ovulation possibly via modulation of FZ1/FZ4/WNT4 signaling. SFRP4 also has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake. SFRP4 is expressed in proliferative endometrium and several types of ovarian, endometrial and Brest tumors. SFRP4 is expressed in mesenchymal cells and in cardiomyocytes. SFRP4 expression in ventricular myocardium correlates with apoptosis related gene expression. SFRP4 is up-regulated in failing myocardium.

SUMO1 is a protein that belongs to the SUMO (small ubiquitin-like modifier) protein family. SUMO1 functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. Still, unlike ubiquitin which targets proteins for degradation, SUMO1 is involved in a variety of cellular processes, for example nuclear transport, transcriptional regulation, apoptosis, and protein stability. SUMO1 is not active until the last four amino acids of the carboxy-terminus are cleaved off.

CRP is an acute phase protein that correlates with inflammatory disease and is synthesized by hepatocytes during the acute phase response by certain cytokines (IL-1 and TNF Alpha and Beta). CRP levels increase dramatically (up to 1,000 fold) and serve as a useful marker of inflammation in such conditions as bacterial infection, rheumatoid arthritis, viral infections, transplantation rejection, meningitis, myocardial infarction, septicemia, osteomyelitis and others. CRP is also highly correlated to Serum Amyloid A levels.

Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a broadly expressed PTP membrane protein with high expression levels in pancreatic beta cells. The PTPMT1 protein is completely restricted to the matrix face of the inner membrane of the mitochondrion. PTPMT1 is responsible for dephosphorylating mitochondrial proteins and thus has a major role in the production of ATP. PTPMT1 exhibits a specific preference for the lipid signaling molecule phosphatidylinositol 5-phosphate as substrate.

RAB31 Member RAS Oncogene Family (RAB31) is a 194 amino lipid-anchored protein which localizes to the cytoplasmic side of the cell membrane and is a member of the Ras related GTPase superfamily. RAB31 is expressed at high levels in the lung, brain and heart. RAB31 functions in a similar mode to other Rab proteins, namely playing a part in protein transport. Small GTP-binding proteins of the RAB family, for example RAB31, play critical roles in vesicle and granule targeting. RAB31 gas the highest expression in the placenta and brain with lower levels in the heart and lung. However, RAB31 is not detected in liver, skeletal muscle, kidney or pancreas.

SLAMF1 is a member of the immunoglobulin gene superfamily and is involved in T-cell stimulation. The SLAMF1 protein is constitutively expressed on peripheral blood memory T cells, T-cell clones, immature thymocytes, and a fraction of B cells, and is swiftly induced on naive T cells after activation. There are probably 2 modes of SLAM signaling: one in which the inhibitor SH2D1A serves as a negative regulator and another in which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal transduction functions.

COL4A3BP is a kinase that particularly phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, recognized as the Goodpasture antigen that is the outcome of an autoimmune reaction directed at COL4A3BP. One isoform of COL4A3BP participates in ceramide intracellular transport.

Ribosomal Protein 4X (RPS4X) is ribosomal protein S4, a component of the 40S subunit which is a part from the S4E family of ribosomal proteins. Ribosomal protein S4 is the only ribosomal protein known to be encoded by more than one gene, that is RPS4X and ribosomal protein S4, Y-linked (RPS4Y). Both isoforms encoded by these genes are not the same, but are functionally alike.

N-Myc Downstream Regulated 3, also known as NDRG3, is a protein coding gene which is a part of the NDRG family and is expressed greatly in brain. NDRG2 is an important paralog of NDRG3.

Syntaxin-11 (STX11) belongs to the t-SNARE family. Syntaxin-11 regulates protein transport between late endosomes and the trans-Golgi network. STX11 interacts with the SNARE proteins SNAP-23 and VAMP. STX11 gene mutations are linked with familial hemophagocytic lymphohistiocytosis.

Podocalyxin (PODXL) is a greatly glycosylated transmembrane sialoprotein in the CD34 and endoglycan family. The PODXL protein is involved in the regulation of both adhesion and cell morphology and cancer progression. PODXL functions as an anti-adhesive molecule, which retains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Moreover, PODXL serves as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner.

Regucalcin (RGN) is a member of the SMP-30/CGR1 family. Regucalcin is a Ca (2+)-binding protein which does not contain EF-hand motif of Ca (2+)-binding domain. RGN has a critical role in the keep of intracellular Ca2+ homeostasis due to activating of Ca2+ pump enzymes in the plasma membrane (basolateral membrane), microsomes (endoplasmic reticulum) and mitochondria of many cells. Moreover, RGN plays a multifunctional role in the regulation of cell functions in the liver, kidney cortex, heart and brain and a suppressor protein for cell signaling systems in many cell types.

Protein Tyrosine Phosphatase Non Receptor Type-11 or PTPN11 has 2 Src homology 2 domains and part of the tyrosine phosphatase group of proteins. PTPN11 is responsible for the catalyzation of tyrosine residues dephosphorylation in proteins and takes part in the stimulation and activation of Erk/MAP kinase transduction via signals from tyrosine kinase. Noonan syndrome and acute myeloid leukemia can be caused from mutations in PTPN11.

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 IFN-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to IFN-based treatment than are the other genotypes (2, 3, 5 and 6).