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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.

IL2 is a secreted cytokine that is essential 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 and interleukin 7. The expression of IL2in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the exact expression of a single gene.

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.

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.

CNTF is a polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. The protein is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. In addition to the predominant monocistronic transcript originating from this locus, the gene is also co-transcribed with the upstream ZFP91 gene. Co-transcription from the two loci results in a transcript that contains a complete coding region for the zinc finger protein but lacks a complete coding region for ciliary neurotrophic factor.
CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.

GMFB is part of the GMF subfamily of the larger actin-binding protein ADF family. GMFB is phosphorylated after phorbol ester stimulation, and is crucial for the nervous system. GMFB causes brain cell differentiation, stimulates neural regeneration and inhibits tumor cell proliferation. GMFB overexpression in astrocytes results in the increase of BDNF production. GMFB expression is increased by exercise, thus BDNF is important for exercise-induction of BDNF.

The gene for TNFRSF12A was initially recognized as a fibroblast growth factor inducible immediate early response gene Fn14 in mouse NIH 3T3 fibroblasts. Human TNFRSF12A cDNA encodes a 129 amino acid residue type I transmembrane protein with a 27 aa signal peptide, a 53 aa extracellular domain, a 21 aa transmembrane domain and a 28 aa cytoplasmic domain. Human and mouse TNFRSF12A hold 82% aa sequence identity. TNFRSF12 is the tiniest member of the TNF receptor superfamily and has only one cysteine rich region in its extracellular domain. The TNFRSF12A cytoplasmic domain holds one TRAF binding motif which binds TRAFs 1, 2, and 3. TNFRSF12A binds its ligand TWEAK/TNFSF12A with high affinity to initiate a signal transduction cascade which subject to the cell type, causes different cellular responses such as cell death, cell proliferation, and angiogenesis.

Coagulation factor VIII participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder.

The Trefoil Factor peptides (TFF1, TFF2 and TFF3) are stable secretory proteins expressed in the gastrointestinal tract (gastric mucosa), and are involved in intestinal mucosal defense and repair. TFF1 is an essential protein for normal differentiation of the antral and pyloric gastric mucosa and functions as a gastric-specific tumor suppressor gene. TFF1 is a stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. TFF1 protects the mucosa from isults, stabilizes the mucus layer, & affects healing of the epithelium. TFF1 is commonly expressed in tumors. TFF1 is related with the cell membrane of MCF-7 cells. High levels of TFF1 and TFF2 are found in serum from inflammatory bowel disease.

Osteopontin is a glycoprotein that was first identified in osteoblasts and is involved in bone remodeling, immune functions in fibroblasts, macrophages, and lymphocytes during inflammation and wound healing. SPP1 binds tightly to hydroxyapatite. SPP1 forms an integral part of the mineralized matrix. SPP1 is vital to cell-matrix interaction.
Secreted Phosphoprotein-1 protects against cardiac ischemia-reperfusion injury via late preconditioning. Expression of both Ostepontin and CD44 in hepatocellular carcinoma is linked with advanced tumor stage and contributes to prognosis information. SPP1 is the most over-expressed gene in intrahepatic cholangiocarcinoma. Secreted Phosphoprotein-1 overexpression is related with interstitial lung diseases.

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.

Erythropoietin or EPO is a hormone (glycoprotein), part of the type I cytokine group of proteins. EPO is found mainly in the kidney tissue, produced from fibroblast-like cortical interstitial cells near the proximal tubules. EPO is also present in the blood, where it acts as red cell production regulator, by the promotion of differentiation of erythroid and thereby starts hemoglobin synthesis. Furthermore, EPO has neuroprotective activity towards brain injuries & anti-apoptotic activity in different tissues.

Thyrotroph embryonic factor (TEF) is a nuclear transcription factor which is a part of the bZIP (basic region/leucine zipper) family and PAR subfamily. TEF binds DNA as either a homodimer or heterodimer, and is known to transactivate the TSH beta promoter. TEF accumulates according to a robust circadian rhythm and is also inhibits cell growth by down-regulating beta chain expression of cytokine receptors.

Intrinsic Factor is a member of the cobalamin transport protein family. It encodes a glycoprotein secreted by parietal cells of the gastric mucosa and is required for adequate absorption of vitamin B12 in the terminal ileum. Vitamin B12 is essential for erythrocyte maturation and mutations in the Intrinsic Factor may lead to congenital pernicious anemia. Upon entry into the stomach, vitamin B12 binds to one of two B12 binding proteins present in the gastric fluid. In the less acidic environment of the small intestine, these proteins dissociate from the vitamin, allowing it to bind to intrinsic factor and enter the portal circulation through a receptor in the ileal mucosa specific for the B12-intrinsic factor complex.

Osteopontin is a glycoprotein that was first identified in osteoblasts and is involved in bone remodeling, immune functions in fibroblasts, macrophages, and lymphocytes during inflammation and wound healing. SPP1 binds tightly to hydroxyapatite. SPP1 forms an integral part of the mineralized matrix. SPP1 is vital to cell-matrix interaction.
Secreted Phosphoprotein-1 protects against cardiac ischemia-reperfusion injury via late preconditioning. Expression of both Ostepontin and CD44 in hepatocellular carcinoma is linked with advanced tumor stage and contributes to prognosis information. SPP1 is the most over-expressed gene in intrahepatic cholangiocarcinoma. Secreted Phosphoprotein-1 overexpression is related with interstitial lung diseases.

Retinol binding protein 4(RBP4) belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. This protein was found to be expressed and secreted by adipose tissue, and was strongly associated with insulin resistance. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin which prevents its loss by filtration through the kidney glomeruli.
RBP4 delivers retinol from the liver to the peripheral tissues. In plasma, the rbp-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli.

Krueppel-like factor 12 (KLF12) belongs to the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a particular site in the AP-2 alpha gene promoter. AP-2 alpha (Activator protein-2 alpha) is a developmentally-regulated transcription factor and vital regulator of gene expression during vertebrate development and carcinogenesis. KLF12 gene repression entails binding with a corepressor, CtBP1.

Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.

Transcription Elongation Factor A (SII)-Like 7 (TCEAL7) has a role in the negative regulation of NF-kappa-B signaling at the basal level by controlling transcriptional activity of NF-kappa-B on its target gene promoters. TCEAL7 links with cyclin D1 promoter containing Myc E-box sequence and transcriptionally inhibits cyclin D1 expression. TCEAL7 regulates telomerase reverse transcriptase expression and telomerase activity in both alternative lengthening of telomeres (ALT) and telomerase-positive cell lines. TCEAL7 is highly expressed in normal and fetal brain tissues, and weakly expressed in the uterus and ovary. TCEAL7 is down-regulated in epithelial ovarian, cervical, prostate, breast, brain and lung cancer cell lines and in the brain and ovarian tumors.

Chemokine (C-X-C motif) ligand (CXCL7) is a small cytokine belonging to the CXC chemokine family. It is a protein that is released in large amounts from platelets following their activation. It stimulates various processes including mitogenesis, synthesis of extracellular matrix, glucose metabolism and synthesis of plasminogen activator.

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.