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The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins are implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. WNT3A is a member of the WNT gene family. WNT3A is a protein which shows 96% amino acid identity to mouse Wnt3A protein, and 84% to human WNT3 protein, another WNT gene product. The WNT3A gene is clustered with WNT14 gene, another family member, in chromosome 1q42 region.

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets. Its major physiologic role appears to be neutralization of molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair. Oncostatin-A is a member of the CXC chemokine family. Furthermore it is used as an inhibitor in the angiogenesis during tumor therapy.

Cytotoxic and Regulatory T Cell Molecule, also known as CRTAM belongs to the immunoglobulin superfamily which complies with the structural characteristics of the JAM family and is phylogenetically more closely related to nectin-like proteins. CRTAM is implicated in epithelial cell adhesion. Furthermore, CRTAM interacts with CADM1 as well as promotes natural killer (NK) cell cytotoxicity.

Collagen triple helix repeat-containing protein 1 (CTHRC1) functions as a negative regulator of collagen matrix deposition. CTHRC1 is a secreted 28kDa protein which is glycosylated and highly conserved from lower chordates to mammals. CTHRC1 is highly connected with calcified tissues and cartilaginous matrix, but not with endothelial cells. CTHRC1 is detected qualitatively in plasma of healthy human subjects. CTHRC1 plasma levels are also significantly elevated during pregnancy, in diabetes, in inflammatory and infectious conditions, in subjects with acute myeloid leukemia but not in subjects with solid cancers. The hormonal functions of CTHRC1 include regulation of lipid storage and cellular glycogen levels with potentially far-reaching implications for cell metabolism and physiology. CTHRC1 gene deletion leads to fatty liver (steatosis) formation in mice while others exhibited inactivation of the CTHRC1 gene also results in low bone mass.

IL13 is an immunoregulatory cytokine produced primarily by activated Th2 cells. IL-13 is involved in several stages of B-cell maturation and differentiation. It up-regulates CD23 and MHC class II expression, and promotes IgE isotype switching of B cells. This cytokine down-regulates macrophage activity, thereby inhibits the production of pro-inflammatory cytokines and chemokines. This cytokine is found to be critical to the pathogenesis of allergen-induced asthma but operates through mechanisms independent of IgE and eosinophils. This gene, IL3, IL5, IL4, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL4.

C1QTNF3 also called Cartducin is a novel angiogenic factor in the formation of neointima following angioplasty. C1QTNF3 a paralog of Acrp30 (adiponectin). C1QTNF3 is a secretory protein produced by chondrogenic precursors & proliferating chondrocytes, and belongs to a novel C1q family of proteins. Cartducin promotes the growth of mesenchymal chondroprogenitor cells & chondrosarcoma-derived chondrocytic cells in vitro. Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways. C1QTNF3 promotes proliferation & the migration of endothelial cells.

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. CSF-1 induces cells of the monocyte/macrophage lineage. It plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.

Cystatin C is part to the cystatin protein family, which has members with various cystatin-like sequences. Part of the proteins has the ability to act as active cysteine protease inhibitors, other members has lost or never had the ability. Three sub members of the cystatin protein family are the type 1 cystatins, type 2 cystatins & kininogens. The locus in chromosome twenty holds the most type 2 cystatin genes. Cystatin C can be found in the cystatin locus, it is the most common extracellular inhibitor of cysteine proteases, that is available in big volumes in biological fluids and exist in every tissue in the body.

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.

Fibroblast Growth Factors (FGFs) comprise a family of at least eighteen structurally realted proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentation, angiogenesis, wound healing and tumorgenesis. The biological activities of the FGFs are mediated by a family if type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGFR-1to -4 are known. Multiple forms of FGFR-1 to -3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGFR-1 and -2 results in receptors containing all three Ig domains, referred to as the alpha isoform, or only IgII and IgIII, referred to as the ? isoform. Only the alpha isoform has been identified for FGFR-3 and FGFR-4. Additional splicing events for FGFR-1 to -3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. Mutations in FGFR-1 to -3 have been found in patients with birth defects involving craniosynostosis.

CD3-epsilonpolypeptide (CD3E) along with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, creates the T-cell receptor-CD3 complex. This complex has an imperative role in coupling antigen recognition to a number of intracellular signal-transduction pathways. The genes encoding the epsilon, gamma delta polypeptides are found in the same cluster on chromosome 11. The epsilon polypeptide plays a vital role in T-cell development. CD3E gene defects cause immunodeficiency. CD3E is also linked to a susceptibility to type I diabetes in women.

PRDX3 is part of the peroxiredoxin family of antioxidant enzymes, that reduces hydrogen peroxide and alkyl hydroperoxides. PRDX3 is particularly located in the mitochondria and involved in the regulation of cellular redox status by serving as a primary line of defense against H2O2 produced during respiration. PRDX3 is a significant regulator of the abundance of mitochondrial H(2)O(2), which itself promotes apoptosis in cooperation with other mediators of apoptotic signaling. PRDX3 mitochondrial protein is significantly decreased in Alzheimer Disease and Down Syndrome.

C3 is central to the activation of all 3 pathways of complement activation. Initiation of each pathway generates proteolytic enzyme complexes which binds the target surface. These enzymes cleave a peptide bond in C3 releasing the anaphylatoxin C3a and activating C3b. Most of the C3 activated during complement activation never attaches to the surface due to its thioester reaction with water forming fluid phase C3b which is rapidly inactivated by factors H and I forming iC3b. Surface-bound C3b is necessary in all 3 pathways for efficient activation of C5 and formation of C5b-9 complexes that lyse the target cell membrane.

C3 is central to the activation of all 3 pathways of complement activation. Initiation of each pathway generates proteolytic enzyme complexes which binds the target surface. These enzymes cleave a peptide bond in C3 releasing the anaphylatoxin C3a and activating C3b. Most of the C3 activated during complement activation never attaches to the surface due to its thioester reaction with water forming fluid phase C3b which is rapidly inactivated by factors H and I forming iC3b. Surface-bound C3b is necessary in all 3 pathways for efficient activation of C5 and formation of C5b-9 complexes that lyse the target cell membrane.

Native human C3a is created by cleavage of human C3 protein by a human C3 convertase. C3a is a member of the anaphylatoxin family of three proteins (C3a, C4a and C5a) created by the activation of complement. C3a mediates various inflammatory responses including smooth muscle contraction, increased vascular permeability, vasodilation and release of histamine from mast cells and basophils. C3a (In contrast to C5a) does not exhibit significant neutrophil stimulating activities and does not induce chemotaxis, granule release or superoxide production. C3a acts through the C3a Receptor which is a G-protein coupled receptor found mainly on peripheral tissues, lymphoid cells and in the central nervous system. These activities of C3a are inactivated by removal of the C-terminal arginine which happens rapidly in plasma due to the action of carboxypeptidase N.

Formiminotransferase cyclodeaminase is an enzyme which catalyzes the conversion of formiminoglutamateand tetrahydrofolateinto formiminotetrahydrofolateand glutamate.
Formiminotransferase cyclodeaminase, a bifunctional enzyme of tetrahydrofolate synthesis, is the target antigen of anti-LC1 (liver cytosol antigen type 1) autoantibodies. Presence of LC1 autoantibodies is a marker for type 2 autoimmune hepatitis (for which anti-LKM 1/cytochrome P450 2D6 autoantibodies are a further marker).
Serum LC1 autoantibody concentrations appear to fluctuate in parallel with aminotransferase levels, a particularly intriguing observation that suggests a possible role of LC1 autoreactivity in the pathogenic mechanism leading to hepatocyte injury.

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.

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.

Eotaxin-2, also called MPIF2 & Ckb6, is a novel CC chemokine produced by activated monocytes and T lymphocytes. Eotaxin-2 selectively chemoattracts cells expressing CCR3 including eosinophils, basophils, Th2 T cells, mast cells, and certain subsets of dendritic cells. Furthermore, Eotaxin-2 inhibits the proliferation of multipotential hematopoietic progenitor cells. The mature protein, which includes C-terminal truncation, contains 78 amino acids (92 amino acids for the mouse homolog, without C-terminal truncation).
CCL24 functions as a chemotactic chemokine for resting t-lymphocytes, and eosinophils. CCL24 has lower chemotactic activity for neutrophils but none for monocytes and activated lymphocytes. CCL24 is a strong suppressor of colony formation by a multipotential hematopoietic progenitor cell line and binds to CCR3.

Human interleukin family 1, member 7 (IL1F7) belongs to the interleukin 1 cytokine family. There are 5 alternatively spliced transcript variants encoding distinct isoforms with distinct expression profiles. The longest IL-1F7 transcript, named IL1F7b or IL1F7 isoform 1, encodes a 218 aa residues proprotein and containing a 45 aa propeptide which is cleaved to produce a mature protein. IL1F7b binds to IL18 Rb with low affinity however it doesn’t exert any IL18 agonistic or antagonistic effects. IL1F7b also binds IL18BP (interleukin 18 binding protein), which is an inhibitory binding protein of interleukin 18 (IL18), and afterward forms a complex with IL18 receptor beta subunit, and through which it inhibits the activity of IL18.

CCL-20 is a chemotactic factor that draws lymphocytes & neutrophils, rathar than monocytes. MIP-3 alpha inhibits proliferation of myeloid progenitors in colony formation assays. MIP3A plays a role in the formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. CCL-20 holdes antibacterial activity e.coli atcc 25922 and s.aureus atcc 29213. CCL-20 gene transcription is activated by H. pylori, which activates NF-kappaB through intracellular signal pathway which involves IkappaB kinase and NF-kappaB-inducing kinase. MIP-3 alpha is invloved in chemokine-mediated lymphocyte trafficking during gastric inflammation in Helicobacter infection. CCL-20 expression is involved in the recruitment of CD45R0-positive T cell subsets into the intestinal lamina propria. MIP-3A is in charge of the advancement of pulpal inflammation through the recruitment of C-C motif Receptor 6-expressing lymphocytes Vaginal epithelial cells respond to factors present in semen by secreting MIP-3 alpha, which increases langerhans cells recruitment during HIV transmission.

The IL1RL1 gene is a member of the IL-1 receptor family, encoding a transmembrane protein with a structure similar to IL-1R1. IL1RL1 is a receptor for interleukin-33, its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. IL1RL1 may possibly be involved in helper T-cell function. IL1RL1 is highly expressed in kidney, lung, placenta, stomach, skeletal muscle, colon and small intestine.A soluble form of the IL1RL1 is produced from the same gene by alternative splicing and was shown to be expressed in several cell types including fibroblasts and mast cells. Soluble IL1RL1 also acts as a negative regulator of Th2 cytokine production and high levels have been reported in several disease states and conditions including asthma, sepsis and myocardial infarction.Analysis of the similar gene in mouse suggested that the IL1RL1 receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells.

Serpin Peptidase Inhibitor, Clade B Member 3, also known as SERPINB3 is a papain-like cysteine protease inhibitor which modulates the host immune response versus tumor cells. SERPINB3 is a protein coding gene which acts as an inhibitor of UV-induced apoptosis by suppressing the activity of c-Jun NH(2)-terminal kinase (JNK1).