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Human interleukin family 1, member 5 (IL-1F5 / FIL1-delta) belongs to the interleukin 1 cytokine family. IL1F5 is expressed by a variety of cells including monocytes, Bcells, dendritic cells/Langerhans cells, keratinocytes,and gastric fundus Parietal and Chief cells. IL1F5 is an antagonist of IL1F9; however IL1F5 activity related to receptor binding remains unclear. Human and mouse IL1F5 share 90% amino acid sequence identity.

Plasma fibronectin level is elevated in severe coronary artery disease. Increased plasma fibronectin levels are related with venous thromboembolism (VTE) particularly in males, and extend the probable association between biomarkers and risk factors for arterial atherothrombosis and VTE. Fibronectin plays a role in several cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. Fibronectin consists in two main forms: 1) as an insoluble glycoprotein dimer that serves as a linker in the extracellular matrix and 2) as a soluble disulphide linked dimer found in the plasma. The plasma form is produced by hepatocytes, and the ECM form is synthesized by fibroblasts, chondrocytes, endothelial cells, macrophages, as well as certain epithelial cells. Fibronectin also takes part as a general cell adhesion molecule by anchoring cells to collagen or proteoglycan substrates. Fibronectin organizes cellular interaction with the ECM by binding to different components of the extracellular matrix and to membrane-bound Fibronectin receptors on cell surfaces.

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.

Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2) which is mostly expressed in mesenchymal cells is a part of the discoidin-like domain containing subfamily of receptor tyrosine kinases. DDR2 whose ligand is fibrillar collagen rather than a growth factor-like peptide is unique among RTKs. DDR2 regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. DDR2 is also essential for normal bone development.

IL20 is a cytokine structurally related to interleukin 10 (IL10). IL20 cytokine has been shown to transduce its signal through signal transducer and activator of transcription 3 (STAT3) in keratinocytes. A specific receptor for this cytokine is found to be expressed in skin and upregulated dramatically in psoriatic skin, suggesting a role for this protein in epidermal function and psoriasis.

Fractalkine soluble form is chemotactic for t-cells and monocytes, but not for neutrophils. Fractalkine membrane-bound form promotes adhesion of those leukocytes to endothelial cells. Fractalkine regulates leukocyte adhesion and migration processes at the endothelium and binds to CX3CR1. Natural Human Fractalkine is produced as a long protein (373-amino acid) with an extended mucin-like stalk and a chemokine domain on top. The mucin-like stalk permits it to bind to the cell surface. Fractalkine gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.

Thrombopoietin is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets.

CETN1 is an EF-hand type Ca2+-binding protein. CETN1 is localized to the centrosome of interphase cells, and reorganizes the region of the spindle poles during mitosis, reflecting the dynamic behavior of the centrosome during the cell cycle. CETN1 has a vital part in the determination of centrosome position and isolation, and in the course of microtubule separating.

Chromogranin A is a 439 amino acid protein which is encoded on chromosome 14 and is present in neuroendocrine cells throughout the body, including the neuroendocrine cells of the large and small intestine, adrenal medulla and pancreatic islets. It is an excellent marker for carcinoid tumors, phenochromocytomas, paragangliomas, and other neuroendocrine tumors.
Coexpression of chromogranin A and neuron specific enolase (NSE) is common in neuroendocrine neoplasms.

Resistin, a product of the RSTN gene, is a peptide hormone belonging to the class of cysteine-rich secreted proteins which is termed the RELM family, and is also described as ADSF (Adipose Tissue- Specific Secretory Factor) and FIZZ3 (Found in Inflammatory Zone). Human resistin contains 108 amino acids as a prepeptide, and its hydrofobic signal peptide is cleaved before its secretion. Resistin circulates in human blood as a dimeric protein consisting of two 92 amino acid polypeptides, which are disulfide-linked via Cys26.
Resistin may be an important link between obesity resistance. Mouse resistin, specifically produced and secreted by adipocyte, acts on skeletal muscle myocytes, hepatocytes and adipocytes themselves so that it reduces their sensitivity. They have also suggested that resistin is present at elevated levels in blood of obese mice, and is down regulated by fasting and antidiabetic drugs. Way et al., on the other hand, have found that resistin expression is severly suppressed in obesity and is stimulated by several antidiabetic drugs.
Other studies have shown that mouse resistin increases during the differentiation of adipocytes, but it also seems to inhibit adipogenesis. In contrast, the human adipogenic differentiation is likely to be associated with a down regulation of resistin gene expression.

IL11 is a member of the gp130 family of cytokines. These cytokines drive the assembly of multisubunit receptor complexes, all of which contain at least one molecule of the transmembrane signaling receptor IL6ST (gp130). IL-11 is shown to stimulate the T-cell-dependent development of immunoglobulin-producing B cells. It is also found to support the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells.

IL-16 is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of IL-16 is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. IL-16 functions exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Two transcript variants encoding different isoforms have been found for this gene.
IL-16 stimulates a migratory response in cd4+ lymphocytes, monocytes, and eosinophils. Also induces t-lymphocyte expression of interleukin 2 receptor. ligand for cd4.

IL-36gamma belongs to the IL-1 family which includes IL-1b, IL-1a, IL-1ra, IL-18, IL-36 Ra (IL-1F5), IL-36a (IL-1F6), IL-36b (IL-1F8), IL-37 (IL-1F7) and IL-1F10. ). The IL-1 family members display a 12 b-strand, b-trefoil configuration, and are thought to have ascended from a mutual ancestral gene. IL-36g is an 18-22 kDa, 169aa intracellular and secreted protein which holds no signal sequence, no prosegment and no potential N-linked glycosylation sites. Human IL-36g shares 58%- 69% aa sequence homology with mouse, rat, bovine and equine IL-36g, and 23 - 57% aa sequence homology with other family members. The IL-36g receptor is a mixture of IL-1 Rrp2, mostly located in epithelia and keratinocytes, and the extensively expressed IL-1 RAcP. All IL-36 (a, b and g) activate N F-?B and MAPK pathways in an IL-1 Rrp2 dependent reaction. Additionally, IL-36g induces production of inflammatory cytokines and chemokines like CXCL8/IL-8.

Resistin, a product of the RSTN gene, is a peptide hormone belonging to the class of cysteine-rich secreted proteins which is termed the RELM family, and is also described as ADSF (Adipose Tissue- Specific Secretory Factor) and FIZZ3 (Found in Inflammatory Zone). Human resistin contains 108 amino acids as a prepeptide, and its hydrofobic signal peptide is cleaved before its secretion. Resistin circulates in human blood as a dimeric protein consisting of two 92 amino acid polypeptides, which are disulfide-linked via Cys26.
Resistin may be an important link between obesity and insulin resistance. Mouse resistin, specifically produced and secreted by adipocyte, acts on skeletal muscle myocytes, hepatocytes and adipocytes themselves so that it reduces their sensitivity to insulin. Steppan et al. have suggested that resistin suppresses the ability of insulin to stimulate glucose uptake. They have also suggested that resistin is present at elevated levels in blood of obese mice, and is down regulated by fasting and antidiabetic drugs. Way et al., on the other hand, have found that resistin expression is severly suppressed in obesity and is stimulated by several antidiabetic drugs.
Other studies have shown that mouse resistin increases during the differentiation of adipocytes, but it also seems to inhibit adipogenesis. In contrast, the human adipogenic differentiation is likely to be associated with a down regulation of resistin gene expression.

Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) is a member of the FAH family. FAHD1 is considered to have hydrolase activity and it uses Magnesium and Calcium as cofactors. It seems quite likely that the metal binding sites are involved in an enzymatic activity connected to the catabolism of aromatic amino acids.

MAPK14 belongs to the MAP kinase family and is most associated with p38 MAP kinases(MAPKs). MAPKs are activated mainly as a reaction to cellular stress and inflammatory cytokines, and inhibitors that target the MAPK14 and MAPK11 have demonstrated ability to cure inflammatory disease. The substrates of this kinase contain transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which demonstrate the parts of MAPK14 in stress-related transcription, cell cycle regulation and genotoxic stress response.

IL17D modulates immune responses indirectly by stimulating the production of myeloid growth factors and chemokines, as well as suppressing the proliferation of myeloid progenitors. IL17D is expressed in the skeletal muscle, heart, adipose tissue, lung, pancreas, and nervous system. Among IL-17 family members, IL17D is most closely related to IL17B, sharing 27% aa sequence identity. The treatment of endothelial cells with IL17D cytokine stimulates the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by IL17D cytokine is NF-kappa B-dependent.

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.

IL-17 family members are glycoproteins secreted as dimers which induce local cytokine production and recruit granulocytes to sites of inflammation. The IL-17 family is comprised of at least six pro-inflammatory cytokines that share a conserved cysteine-knot structure but diverge at the N-terminus. IL-17 is induced by IL-15 and IL-23, mostly in activated CD4+ T cells distinct from Th1 or Th2 cells. IL-17B binds the IL-17B receptor, but not the IL-17 receptor; it is most homologous with IL-17D, which is expressed by resting CD4+ T cells and CD19+ B cells. IL17B Diseases associated with IL17B include spondyloarthropathy, and neuronitis, and among its related super-pathways are Mucin expression in CF via IL-6, IL-17 signaling pathways and STAT3 Pathway.

Human IL-17A/F is a 40kDa glycoprotein which is secreted as a disulfide-linked heterodimer. IL-17A/F consists of two proteins of the IL-17 family, IL-17A and IL17F. Proteins of the 6 homodimeric IL17 family show a cysteine knot motif that contains two disulfide-bonds. Human IL17A is produced as a 155 a.a precursor that includes a 23 amino acids signal sequence and a 132 amino acid chain that includes an N-linked glycosylation site. Human IL17F is produced as a 153 amino acid precursor with a 20 amino acid signal sequence and a 133 amino acid region. Similar to IL17A, IL17F also has an N-linked glycosylation site. Both proteins (IL17A & IL17F) share 50% amino acid sequence identity. Human IL17A & IL17F show approximately 60% homology in their amino acid sequence to mouse IL-17A and IL-17F. Interleukin-17A/F and IL17A, IL17F homodimers are manufactured by activted CD4+ T cells, called Th17. IL-23 causes Th17 lymphocytes to manufacture IL-17A/F. IL17RA and IL17RC form a heterodimer for the binding of IL17A and IL17F. IL-17A/F binds IL-17RA. Interleukin-17A/F induces chemokine production and airway neutrophilia with intermediate potency between IL17A (most potent) and IL17F (least potent).

Nectin-1, also referred to as ED4, is a poliovirus receptor- related 1 protein is a part of the Nectin family. Nectin-1 endorses cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions among PVRL1/nectin-1 & PVRL4/nectin-4 and among PVRL1/nectin-1 & PVRL3/nectin-3 have been found. Nectin-1 acts as an entry receptor for herpes simplex virus & pseudorabies virus as well. Likewise, Neurite outgrowth-promoting activity has been shown by Nectin-1.

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.

BTC is a potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells. The effects of betacellulin are mediated by the EGF receptor and other related receptors.

Calmodulin Like 5, also known as CALML5 is a part of the calmodulin family of calcium binding proteins. CALML5 undergoes a conformational change as a result of binding calcium. CALML5 is taking part in terminal differentiation of keratinocytes and encodes a calcium binding protein expressed in the epidermis.