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TNFSF12 is a cytokine that is part of the TNF ligand family. TNFSF12 is a ligand for the FN14/TWEAKR receptor. TNFSF12 has overlapping signaling functions with TNF, but displays a much wider tissue distribution. TNFSF12 induces apoptosis through multiple pathways of cell death in a cell type-specific manner. TNFSF12 promotes proliferation and migration of endothelial cells, and therefore acts as a regulator of angiogenesis. TNFSF12 is expressed in adult heart, pancreas, skeletal muscle, small intestine, spleen and peripheral blood lymphocytes. TWEAK h induces NFkB and chemokine secretion. TNFSF12 exerts an apoptotic activity in HT-29 human adenocarcinoma cells whilst cultured in the presence of IFN-?. TNFSF12 promotes proliferation and migration of endothelial cells.

Tissue factor is well-known as the main cellular initiator of blood coagulation. The Tissue factor gene encodes coagulation factor III which is a cell surface glycoprotein that enables cells to initiate the blood coagulation cascades, and functions as the high-affinity receptor for the coagulation factor VII. Following vessel injury, the Tissue Factor and Factor VIIa complex activates the coagulation protease cascade, which leads to fibrin deposition and activation of platelets. The ensuing complex presents a catalytic event, which is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. Therefore, Tissue factor has a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. Tissue Factor can also be stimulated by the inflammatory mediators interleukin 1 and TNF, as well as by endotoxin, to appear on monocytes and vascular endothelial cells as a component of cellular immune response.
Tissue factor is the only one in the coagulation pathway for which a congenital deficiency has not been described. Certain levels of Tissue Factor are essential for the maintained viability and growth of endothelium and Tissue Factor-expressing tumor cells. Additionally, abnormal Tissue Factor expression inside the vasculature initiates life threatening thrombosis in various diseases, for example sepsis, atherosclerosis, and cancer. Alternative spliced Tissue Factor expression advances tumor growth, and is linked to increased tumor cell proliferation and angiogenesis in pancreatic cancer.

NFATC2, also known as nuclear factor of activated T-cells 2, belongs to the nuclear factor of activated T cells family. NFATC2 takes a significant part in the course of T helper cell differentiation, activation, and effector function. Even though KO of an individual NFAT isoform in T cells directs to rather minor effects, T cells lacking for NFATC1 and 2 totally fail to produce T helper cell effector cytokines, for instance the interleukins IL-4 and IL-2. Moreover, NFATC2 is highly phosphorylated and kept in the cytoplasm. Next T cell receptor stimulation, dephosphorylation via calcium-activated calcineurin induces a conformational modification of NFATC2 which reveals a few nuclear localization sequences.

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.

Coagulation factor VII is a vitamin K-dependent factor which is essential for hemostasis. It circulates in the blood as a zymogen which is later converted to an active form by factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of factor VII, a heavy chain with a catalytic domain and a light chain with 2 EGF-like domains are generated, and the two chains are held together by a disulfide bond. The presence of factor III and calcium ions further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Alternative splicing of factor VII results in 2 transcripts. Defects in coagulation factor VII can cause coagulopathy. Coagulation factor VII initiates the extrinsic pathway of blood coagulation. Minor proteolysis converts factor VII to factor VIIa by factors Xa, XIIa, IXa, or thrombin. Factor VIIa also converts factor IX to factor IXa in the presence of tissue factor and calcium.

Spermine synthase (SMS) is amember of the spermidine/spermine synthase family. SMS is an enzyme which converts spermidine into spermine. The SMS enzyme is essential for normal viability, growth and fertility involved in polyamine metabolism. Defects in the SMS gene are the cause of Snyder-Robinson syndrome (SRS), also known as X-linked mental retardation Snyder-Robinson type. SRS is categorized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry, its transmission is X-linked recessive.

Branched Chain Amino-Acid Transaminase 2 (BCAT2) is a member of the class-IV pyridoxal-phosphate-dependent aminotransferase family. BCAT2 is a branched chain aminotransferase found in mitochondria. BCAT2 forms a dimer which catalyzes the first step in the production of the branched chain amino acids leucine, isoleucine, and valine. In addition, BCAT2 may actn as a transporter of branched chain alpha-keto acids.

PCK1 is a central regulating point for the regulation of gluconeogenesis. PCK1 has a vital part in this process by stimulating hepatic glucose production. The expression of PCK1 is controlled by cAMP, glucocorticoids, diet etc. Modulation of the signals controlling PCK1 levels offers a possible therapeutic tactic to the treatment of Diabetes and subsequently obesity.

PGLS is an enzyme in the second step pentose phosphate pathway. 6-Phosphogluconolactonase is crucial for the synthesis of nucleotide sugars and NADPH, the key cause for decreasing power. PGLS transforms 6-phosphogluconolactone to 6-phosphogluconate.

PSME3 is a member of the PA28 family. The 26S proteasome is an extremely organized multicatalytic proteinase complex composed of 2 complexes, a 20S core and a 19S regulator. Proteasomes are spread all over the eukaryotic cells in large quantities and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. PSME3 stimulates the trypsin-like catalytic subunit of the proteasome and inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. PSEM3 enables the MDM2-p53/TP53 collaboration that encourages ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, restricting its growth and causing inhibited apoptosis after DNA damage.

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis.

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.

SAT-1 is a member the acetyltransferase family, and is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. SAT1 catalyzes the acetylation of spermidine and spermine, and is involved in the regulation of the intracellular concentration of polyamines and their transport out of cells. Therefore, SAT-1’s role is essential in polyamine homoeostasis, given that acetylated products are either excreted from the cell or oxidized by acetylpolyamine oxidase. Increased SAT1 activity causes variety of other effects which include pancreatic cells death, obstruction of regenerative tissue growth, behavioral changes, keratosis follicularis spinulosa decalvans (KFSD), and hair loss.
Defects in the SAT1 gene are linked to KFSD (keratosis follicularis spinulosa decalvans), which is a rare X-linked disorder affecting the skin and the eye. The KFSD affected men show thickening of the skin of the neck, ears, and extremities, particularly the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration. Even though the majority of the affected families are compatible with an X-linked inheritance, KFSD are found to be clinically and genetically heterogeneous.

Profilin-1 also known as Pfn1 is a ubiquitous actin monomer-binding protein which is a member of the profilin family. Pfn1 significantly enhances skin wound healing in-vitro as well as in-vivo which is mediated by purinergic receptors. Furthermore, Pfn1 is also active in endothelial cell migration and vessel sprouting. Pfn1 is considered to regulate actin polymerization in response to extracellular signals.

The protein kinase A holoenzyme is a heterotetramer composed of two types of subunits: Catalytic and Regulatory. The Catalyticsubunit contains the enzyme's active site. It also contains a domain that binds ATP and a domain that binds the regulatory subunit. The Regulatory subunit consists oftwo molecules which bind one another in an anti-parallel orientation to form a homodimer; for type I subunits- this binding is covalent via disulfide bonds. This subunit also has has two domains that bind cyclic AMP, a domain that interacts with a catalytic subunit, and an "auto-inhibitory" domain that serves as a substrate or pseudosubstrate for the catalytic subunit. Regulatory subunits may also have biologic activity distinct from their role in modulating catalytic subunit activity. Regulatory subunits exist in two major forms, RI and RII, with each form having two subtypes designated alpha and beta. Each of the four isotypes of the regulatory subunit is encoded by a different gene. In addition, three isotypes of the catalytic subunit have been identified (alpha, beta and gamma). The different isotypes tend to have different distributions within cells and among tissues. Type I enzymes inhabit cytoplasmic, soluble fractions of the cell, whereas type II enzymes tend to associate with cellular membranes.

Proteasome 26S Subunit, Non-ATPase 5, also known as PSMD5 is a member of the proteasome subunit S5B/HSM3 family. The 26S proteasome is an enzymatic complex which degrades ubiquitinated proteins in eukaryotic cells. Furthermore, PSMD5 acts as a chaperones which is involved in the assembly of the 26s proteasome, particularly of the base subcomplex of the PA700/19S regulatory complex. PSMD5 is full of dileucine repeats, which have been involved in trafficking of various transmembrane proteins.

PSMD9 is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. PSMD9 acts as a chaperone through the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). During the base subcomplex compilation, PSMD9 is part of an intermediate PSMD9:PSMC6:PSMC3 module, also called modulator trimer complex. PSMD9 is released during the further base assembly process.

KGF is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF7 is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis.

Stem cell factor / KIT ligand (SCF) is a cytokine which binds CD117 (c-Kit). SCF is also known as "steel factor" or "c-kit ligand". SCF exists in two forms, cell surface bound SCF and soluble (or free) SCF. Soluble SCF is produced by the cleavage of surface bound SCF by metalloproteases.
SCF is a growth factor important for the survival, proliferation, and differentiation of hematopoietic stem cells and other hematopoietic progenitor cells. One of its roles is to change the BFU-E (burst-forming unit-erythroid) cells, which are the earliest erythrocyte precursors in the erythrocytic series, into the CFU-E (colony-forming unit-erythroid).

ADP-ribosylation factor 3 (ARF3) belongs to the human ARF gene family. This family encodes small guanine nucleotide-binding proteins which stimulate the ADP-ribosyltransferase activity of cholera toxin and have a role in vesicular trafficking and as activators of phospholipase D. ARF3 functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. ARF3 is involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus. The ARF3 gene is comprised of 5 exons and 4 introns.

GDF8 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. This gene is thought to encode a secreted protein which negatively regulates skeletal muscle growth.

TNFRSF6B is a member of the Tumor necrosis factor receptor superfamily. TNFRSF6B performs as a decoy receptor which races against death receptors for ligand binding. TNFRSF6B has a regulatory role in suppressing FasL- and LIGHT-mediated cell death and T cell activation in addition to inducing angiogenesis via neutralization of TL1A.

FGF8 is part of the fibroblast growth factor family. FGF family members have wide mitogenic and cell survival activities, and participate in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF8 supports androgen and anchorage independent growth of mammary tumor cells. FGF8 over expression increases tumor growth and angiogensis. The adult expression of FGF-8 gene is restricted to testes and ovaries. FGF8 functions as an embryonic epithelial factor. FGF8 takes part in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination.