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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.

Cathepsin-A (CTSA) is a protective protein which is crucial for both the activity of beta-galactosidase and neuraminidase, CTSA associates with these enzymes and exerts a protective function required for their stability and activity. The CTSA protein is also a carboxypeptidase and can deamidate tachykinins. CTSA is a component of the lysosomal multienzyme complex along with beta-galactosidase and sialidase Neu1. CTSA is a multicatalytic enzyme with deamidase and esterase in addition to carboxypeptidase activities.

This gene is a member of the EPO/TPO family and encodes a secreted, glycosylated cytokine composed of four alpha helical bundles. The protein is found in the plasma and regulates red cell production by promoting erythroid differentiation and initiating hemoglobin synthesis. This protein also has neuroprotective activity against a variety of potential brain injuries and antiapoptotic functions in several tissue types.

Interleukin-7 is a potent lymphoid cell growth factor produced primarily by stromal cells. IL-7 has been shown to support the proliferation and differentiation of pre B- and early T cells as well as displaying a biological effect on cells of NK and myeloid lineages.

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.

Tissue plasminogen activator (abbreviated PLAT or tPA) is a secreted serine proteasewhich converts the proenzymeplasminogento plasmin, a fibrinolyticenzyme. Plasminogen is synthesized as a single chain which is cleaved by PLAT into the two chain disulfide linked plasmin.
This enzyme plays a role in cell migrationand tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding; decreased activity leads to hypofibrinolysiswhich can result in thrombosisor embolism.

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.

Connective Tissue Growth Factor belongs to the CCN family of proteins. The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). The CCN genes encode secreted proteins associated with the Extracellular Matrix (ECM) and cell membrane. CCN proteins are matricellular proteins which are involved in the regulation of various cellular functions including: proliferation, differentiation, survival, adhesion and migration. They are expressed in derivatives of the three embryonic sheets and are implicated in the development of kidney, nervous system, muscle, bone marrow, cartilage and bone. During adulthood, they are implicated in wound healing, bone fracture repair, and pathologies such as: fibrosis, vascular ailments and tumorigenesis.
Full length secreted CCN proteins can show an antiproliferative activity, whereas truncated isoforms are likely to stimulate proliferation and behave as oncogenes. The full length protein consists of four modulesModule I shares partial identity with the N-terminal part of the Insulin-like Growth Factor Binding Proteins (IGFBPs).
Module II includes a stretch of 70amino acid residues – which shares sequence identity with the Von Willebrand Factor Type C repeat (VWC).
Module III contains sequences sharing identity with the Thrombospondin type 1 repeat (TSP1) (WSXCSXXCG), which is thought to be implicated in the binding of sulfated glycoconjugates and to be important for cell adhesion. Module IV, also designated CT, is encoded by exon5. It is the leasts conserved one of the four domains at the level of nucleotide sequence, but it appears to be critical for several of the biological functions attributed to the CCN proteins. Module IV resembles the CT domain of several extracellular protein including, Von Willebrand's factor and mucins. Sequence similarities to heparin-binding motifs are also found within this domain.
Proteolysis of the secreted full-length CCN proteins that has been reported in the case of CCN2 and CCN3 might result in the production of CCN-derived peptides with high affinity for ligands that full-length CNN proteins bind only poorly. Amino-truncated CCN2 isoforms were biologically active whereas no specific biological activity has been attributed to the truncated CCN3. Although the molecular processes underlying the production of these secreted isoforms is presently unknown, it is important to note that proteolysis occur at the same amino acid residues in both CCN2 and CCN3. An elevated expression of CCN2 has also been detected by Northern blotting in human invasive mammary ductal carcinomas, dermatofibromas, pyogenic granuloma, endothelial cells of angiolipomas and angioleiomyomas, and in pancreatic tumors. A study performed with chondrosarcomas representative of various histological grades established that CCN2 expression was closely correlated with increasing levels of malignancy. In agreement with CCN2 playing a role in brain tumor angiogenesis, immunocytochemistry studies indicated that both glioblastoma tumor cells and proliferating endothelial cells stained positive for CCN2. In astrocytomas, CCN2 expression was particularly elevated in high grade tumors, with a marked effect of CCN2 on cell proliferation. Downregulation of CCN2 expression in these cells was associated with a growth arrest at the G1/S transition while over-expression of CCN2 induced a two-fold increase of the number of cells in the G1 phase. Gene profiling analysis allowed to identify a set of about 50 genes whose expression might account for the proliferative activity of CCN2 in these cells. CCN2 was seen in a higher proportion of mononuclear cells of patients with acute lymphoblastic leukemia.

TNFRSF13B (TACI) is a transmembrane receptor protein found predominantly on the surface of B cells (a significant part of the immune system). TACI was at first discovered owing to its ability to interact with calcium-modulator and cyclophilin ligand (CAML). Later on, it was found that TACI plays a key role in humoral immunity by interacting with two members of the TNF family. Also, TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis.

IL-17F having an accession number of Q96PD4 is a cytokine that shares sequence similarity with IL17. IL-17F is expressed by activated T cells, and has been shown to stimulate the production of several other cytokines, including IL6, IL8, and CSF2/GM_CSF. IL-17F inhibits the angiogenesis of endothelial cells and induce endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1. IL-17F induces stromal cells to produce proinflammatory and hematopoietic cytokines. Intestinal IL17F gene expression is increased in active CD.
IL-17A & IL-17F alleles influence the susceptibility to and pathophysiological features of ulcerative colitis independently. IL-17F and MIF gene polymorphisms are significantly associated with the development of functional dyspepsia.
The initiation of IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. IL-17F induces expression of IFN-gamma-inducible protein 10 (IP-10) by activating Raf1-mitogen-activated protein kinase 1/2-extracellular-regulated kinase 1/2-p90 ribosomal S6 kinase-cyclic AMP response element-binding protein signaling pathway.

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, and cancer.

TNFR1 belongs to the TNF-receptor superfamily. TNFR1 is a receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.
TNFR1 is capable of signaling both cell survival and apoptosis. TNFR1-induced apoptosis requires 2 sequential signaling complexes. TNFR1 is capable of activating NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNFR1 contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Human TNFR1 has a major region which controls cell surface expression. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women.
Germline mutations of the extracellular domains of TNFR1 are linked to the autosomal dominant periodic fever syndrome. The impaired receptor clearance is believed to be a mechanism of the disease. Familial hibernian fever (FHF) is caused by defects in TNFRSF1A gene.

Interleukin-4 is a pleiotropic cytokine produced primarily by activated T lymphocytes, basophils and mast cells. Multiple immune response-modulating functions are performed by IL-4 on a variety of cell types and it has an important role in the regulator of isotype switching, induction of IgE production in B lymphocytes and differentiation of precursor T helper cells. IL-4 binds to both membrane-bound and secreted soluble IL-4 receptors.

Cytohesin 2 (CYTH2) is an ARF-1 guanine nucleotide exchange factor (GEF). ARF (ADP ribosylation factor) proteins are a part of a group within the RAS superfamily and bindes GTP-b proteins central to the process of vesicle budding. CYTH2 promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Furthermore, CYTH2 promotes the activation of ARF factors through replacement of GDP with GTP. The protein encoded by CYTH2 is a member of the PSCD family. Members of PSCD family appear to mediate the regulation of protein sorting and membrane trafficking. The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane.

E-selectin (SELE) is a part of a family of divalent cation-dependent carbohydrate-binding glycoproteins or adhesion molecules. E-selectin is expressed on the surface of endothelial cells and mediates the interaction of leukocytes and platelets with endothelial cells during an inflammatory response. E-selectin is present in single copy in the human genome and contains 14 exons spanning about 13 kb of DNA.

Recombinant Human Sonic Hedgehog is part of a small group of secreted proteins that are vital for development in both vertebrates and invertebrates. 3 mammalian hedgehog genes (sonic, desert, Indian) share about 60% homology. The Human Sonic Hedgehog is 99% homologous to the mouse gene. Sonic HedgeHog is a protein that is vital in guding the early embryo. It has been associated as the major inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Sonic HedgeHog binds to the patched receptor, which functions in association with smoothened, to activate the transcription of target genes. In the absence of sonic HedgeHog, patched receptor represses the constitutive signaling activity of smoothened. Sonic HedgeHog also regulates another factor, the gli oncogene. Sonic HedgeHog intercellular signal is essential for a various patterning events during development: signal produced by the notochord that induces ventral cell fate in the

SNF8 belongs to the SNF8 family of vacuolar sorting proteins and is restricts to both the nucleus and the cytoplasm. SNF8 is a subunit of the endosomal sorting complex essential for transport II (ESCRT-II), which is necessary for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway facilitates transfer of transmembrane proteins into the lumen of the lysosome for degradation. Additionally, the ESCRT-II complex takes part in transcription regulation by contributing to derepression of transcription by RNA polymerase II, probably by its interface with ELL.

FAS / CD95 is a 36kDa transmembrane type I receptor, which belongs to the NF/NGF receptor super-family. It is a potent inducer of apoptosis in cells of the immune system upon interaction with its natural ligand, CD95L. Although the CD95/CD95L system could play a role in tumor regression, tumor cells seem to down-regulate CD95 expression as a mechanism of resistance to CD95L-induced killing by T lymphocytes and NK cells. The Fas antigen is expressed on the surface of various cell types, including activated T and B lymphocytes and T lymphoblastoid cell line. CD95 is also expressed in a broad panel of non-transformed cells outside the immune system.

TIE-1 (tyrosine kinase with Ig and EGF homology domains 1) and TIE-2/Tek comprise a receptor tyrosine kinase (RTK) subfamily with unique structural characteristics: two immunoglobulin-like domains flanking three epidermal growth factor (EGF)-like domains and followed by three fibronectin type III-like repeats in the extracellular region and a split tyrosine kinase domain in the cytoplasmic region. These receptors are expressed primarily on endothelial and hematopoietic progenitor cells and play critical roles in angiogenesis, vasculogenesis and hematopoiesis. Human TIE-1 cDNA encodes a 1122 amino acid (aa) residue precursor protein with an 18 residue putative signal peptide, a 726 residue extracellular domain and a 353 residue cytoplasmic domain. Two ligands, angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2), which bind TIE-2 with high-affinity have been identified. Ang2 has been reported to act as an antagonist for Ang1. Mice engineered to overexpress Ang2 or to lack Ang1 or Tie-1 display similar angiogenic defects.

CALR is a multifunctional protein that acts as a main Ca(2+)-binding (storage) protein in the lumen of the endoplasmic reticulum. Calreticulin is localized in the nucleus, and participates in transcription regulation. Calreticulin binds to the synthetic peptide KLGFFKR, which is nearly identical to an amino acid sequence in the DNA-binding domain of the superfamily of nuclear receptors. CALR binds to antibodies in specific sera of systemic lupus and Sjogren patients which have anti-Ro/SSA antibodies, it is well conserved among species, and it is positioned in the endoplasmic and sarcoplasmic reticulum where it binds calcium. The amino terminus of CALR interacts with the DNA-binding domain of the glucocorticoid receptor and prevents the receptor from binding to its specific glucocorticoid response element. CALR reduces the binding of androgen receptor to its hormone-responsive DNA element and inhibits androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. Therefore, CALR acts as a significant modulator of the regulation of gene transcription by nuclear hormone receptors.

Cytokeratin 8 (KRT8) belongs to the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. KRT8 typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. KRT8 has a role in retaining cellular structural integrity and also functions in signal transduction and cellular differentiation. KRT8 gene mutations cause cryptogenic cirrhosis.