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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.

Listeriolysin O (aka LLO) is a hemolysin produced by Listeria monocytogenes bacteria, the pathogen responsible for causing listeriosis. The toxin may be regarded as a virulence factor, since it is crucial for the virulence of L. monocytogenes. LLO is a single polypeptide protein encoded by the hlyA gene and composed of 529 residues. LLO is a thiol-activated cholesterol-dependent pore forming toxin protein; therefore, it is activated by reducing agents and inhibited by oxidizing agents. Still, LLO differs from other thiol-activated toxins, as its cytolytic activity is maximized at a pH of 5.5. Inside the acidic phagosomes (average pH ~ 5.9) of cells that have phagocytosed L. monocytogenes, LLO is selectively activated by maximizing activity at a pH of 5.5. Following the phagosome lysis by LLO, the bacterium breaks out into the cytosol, where it is able to grow intracellularly, and the toxin has reduced activity in the more basic cytosol. Thus, LLO permits L. monocytogenes to break out from the phagosomes into the cytosol without harming the plasma membrane of the infected cell, which allows the bacteria to live intracellularly, where they are sheltered from extracellular immune system factors such as the complement system and antibodies. LLO also brings about dephosphorylation of histone H3 and deacetylation of histone H4 in the early phases of infection, before entry of L. monocytogenes into the host cell. The pore-forming activity is not implicated in causing the histone modifications. The modifications of the histones affect the down regulation of genes encoding proteins involved in the inflammatory response. Therefore, LLO may be significant in subverting the host immune response to L. monocytogenes. At its NH2-terminus it possesses a 25 residues long typical signal sequence excited during the secretion process. Moreover, in its NH2-terminus there is also a 19 amino acids PEST- like sequence that may target this toxin for degradation. The PEST-like sequence found in LLO and is considered crucial for virulence, given that mutants lacking the sequence lysed the host cell. Nevertheless, contrary to PEST's supposed role in protein degradation, evidence implies that the PEST-like sequence may control LLO production in the cytosol rather than increase degradation of LLO.

SPINT2 is a transmembrane protein acts as an inhibitor of HGF activator. SPINT2 inhibits plasmin, plasma and tissue kallikrein, and factor XIa. SPINT2 has two extracellular Kunitz domains that inhibit few serine proteases. SPINT2 is assumed tumor suppressor, mutations in SPINT2 leads to a congenital sodium diarrhea.

Aprotinin inhibits the activity of several proteolytic enzymes such as chymotrypsin, kallikrein, plasmin and trypsin. Aprotinin is present in blood and in most tissues, with a high concentration in lung. Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa), while in granulocytes it prevents the expression of pro-inflammatory adhesive glycoproteins (e.g., CD11b).

ANXA1 is part of the family of Ca(2+)-dependent phospholipid binding proteins which have a Mw between 35kDa-40kDa and are situated on the cytosolic face of the plasma membrane. ANXA1 protein has a Mw of 40kDa, with phospholipase A2 inhibitory activity to bind from two to four calcium ions with high affinity. Since phospholipase A2 is necessary for the biosynthesis of the potent mediators of inflammation, prostaglandins and leukotrienes, ANXA1 might have potential anti-inflammatory activity. ANXA1 promotes membrane fusion and iplays a role in exocytosis. The recognition of ANXA1 protein by immunocytochemical leads a simple, highly sensitive and specific assay for diagnosis of hairy cell leukemia.

ASCC1 is a subunit of the triggering signal cointegrator 1 (ASC-1) complex which is a transcriptional coactivator. ASC-1 complex takes a vital part in gene transactivation using various transcription factors such as activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). ASCC1 has an N-terminal KH-type RNA-binding motif, essential for AP-1 transactivation by the ASC-1 complex. Alterations in ASCC1 result in Barrett esophagus and esophageal adenocarcinoma.

Cadherin-5 (CDH5) belongs to the atypical/type 2 subgroup of Cadherin homophilic adhesion proteins. Cadherin-5 is a calcium-dependent cell-cell adhesion molecule, which is comprised of 5 extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Cadherin-5 protein plays a role in the formation, maturation and remodeling of the vascular wall. CDH5 is generally considered to be specific for vascular endothelia in which it is either the sole or the predominant cadherin, often co-existing with N-cadherin. Moreover, the CDH5 protein regulates or is regulated by VEGF R2, type 1 and type 2 TGF-beta receptors, and other endothelial junction proteins such as JAM-C, Claudin-5, and N-Cadherin. CDH5 also connects with alpha-catenin forming a link to the cytoskeleton. CDH5 functions jointly with KRIT1 to create and maintain correct endothelial cell polarity and vascular lumen. Furthermore, Cadherin-5 is essential for activation of PRKCZ and for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction. The CDH5 gene is located in a gene cluster in a region on the long arm of chromosome 16 which is involved in loss of heterozygosity events in breast and prostate cancer.

Low affinity immunoglobulin gamma Fc region receptor III-A (FCGR3A) is a receptor for the Fc portion of immunoglobulin G, and is involved in the elimination of antigen-antibody complexes from the circulation, as well as other antibody-dependent responses. FCGR3A needs to associate with the gamma subunit of Fc epsilon. The FCGR3A receptor is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, while FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. In addition, FCGR3A is expressed on macrophages, subpopulation of T-cells, immature thymocytes and placental trophoblasts. FCGR3A mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis. FCGR3A gene mutations are linked with susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia.

XCL1 is a small cytokine belongs to the XC chemokine family that is also known as lymphotactin. XCL1 is found in high levels in spleen, thymus, intestine and peripheral blood leukocytes, and at lower levels in lung, prostate gland and ovary. Cellular sources for XCL1 include activated thymic and peripheral blood CD8+ T cells. This chemokine attracts T cells. In humans, XCL1 is closely related to XCL2, whose gene is found at the same locus on chromosome 1. XCL1 induces it chemotactic function by binding to a chemokine receptor called XCR1.

Inhibitor of DNA Binding 2 (ID2) is a part of the inhibitor of DNA binding family, whose members are transcriptional regulators that contain a helix-loop-helix (HLH) domain but not a basic domain. Members of the ID family inhibit the functions of basic helix-loop-helix transcription factors in a dominant-negative way by suppressing their heterodimerization partners through the HLH domains. ID2 play a role in negatively regulating cell differentiation and may be an inhibitor of tissue-specific gene expression.

Anamorsin, ( CIAPIN) is a member of anamorsin family. CIAPIN mainly expressed in the cytoplasm of liver, pancreas and heart tissue cells and does not show any homology to known apoptosis regulatory molecules of the Bcl-2 or CASP families, or to signal transduction molecules. CIAPIN1 Expression is reliant on growth factor stimulation. It is a ubiquitously expressed protein, and when it is overexpressed, it grants apoptotic resistance.

WNT1-inducible-signaling pathway protein 2 (WISP2) belongs to the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. The CTGF family members are characterized by 4 conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like (CT) domain. WISP2 protein lacks the CT domain which is implicated in dimerization binding. WISP2 is possibly involved in bone remodeling. WISP2 is expressed in primary osteoblasts and fibroblasts. WISP2 stimulates osteoblast adhesion and inhibits osteocalcin production. WISP2 expression in colon tumors is reduced while the other 2 WISP members are overexpressed in colon tumors. WISP2 may play an imperative role in modulating bone turnover.

CFI cleaves and inactivates C3b and C4b. CFI is inactive without a cofactor such as the soluble factor H and C4b binding protein. CFI cleaves the alpha-peptide chain of C3b and C4b when these binds1 of the cofactors. This cleavage inactivates all of the complement activating functions of these proteins producing iC3b and iC4b.CFI cleaves the alpha chain of C3b twice and this releases a small fragment called C3f. CFI can cleave iC3b releasing C3c from C3dg in the presence of CR1.C4b is cleaved rapidly at 2 sites separating C4c from C4d.

Type IV collagen is a major structural component of basement membranes. It is a multimeric protein composed of 3 alpha subunits, which are encoded by 6 different genes, alpha 1 through alpha 6. Each of these alpha subunits can form a triple helix structure with 2 other subunits to form type IV collagen. The Goodpasture syndrome is a condition in which autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are restricted basically to the non-collagenous C-terminal domain of the protein. There are numerous alternative transcripts that appear to be unique to the human COL4A3 and alternative splicing is limited to the six exons that encode this C-terminal domain. COL4A3 is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to the Alport syndrome are also situated within the exons that encode this C-terminal region. COL4A3 is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Several exons of COL4A3 are interspersed with exons of an uncharacterized gene which is on the opposite strand.

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.

WIF1 binds to wnt proteins and inhibits their activities. WIF1 plays a role in mesoderm segmentation. WNT proteins are extracellular signaling molecules that take part in the control of embryonic development & cancer. WIF1 protein contains a WNT inhibitory factor (WIF) domain and 5 epidermal growth factor (EGF)-like domains. WIF1 takes part in mesoderm segmentation. WIF1 protein is found to be present in fish, amphibia and mammals. WIF1 is a recurrent target in human salivary gland oncogenesis. Downregulation of WIF1 takes part in the development and progression of pleomorphic adenomas. WIF1 is a tumor suppressor, specifically in nonfunctioning pituitary tumors.

Chemokine (C-X-C motif) ligand 11 (CXCL11) is a small cytokine belonging to the CXC chemokinen family that is also called inducible T-cell alpha chemoattractant (I-TAC) and (IP-9). I-TAC is highly expressed in peripheral blood leukocytes, pancreas and liver, with moderate levels in thymus, spleen and lung and low expression levels were in small intestine, placenta and prostate. Gene expression of CXCL11 is strongly induced by IFN-g and IFN-b, and weakly induced by IFN-a. The I-TAC chemokine elicits its effects on its target cells by interacting with the cell surface chemokine receptor CXCR3, with a higher affinity than do the other ligands for this receptor, CXCL9 and CXCL10. I-TAC is chemotactic for activated T cells. The CXCL11 gene is located on human chromosome 4 along with many other members of the CXC chemokine family.

Plasminogen activator inhibitor-1 is the principal inhibitor of tissue plasminogen activator(tPA) and uPA, the activators of plasminogenand hence fibrinolysis(the physiological breakdown of blood clots). It is a serine protease inhibitor(serpin) protein (SERPINE1). The other PAI, plasminogen activator inhibitor-2(PAI-2) is secreted by the placentaand only present in significant amounts during pregnancy. In addition, protease nexinacts as an inhibitor of tPA. SERPINE1, however, is the main inhibitor of the plasminogen activators.

Galectin-3 mediates with the alpha-3, beta-1 integrin the stimulation by cspg4 of endothelial cells migration. Galectin-3 plays an necessary part during the acquisition of vasculogenic mimicry and angiogenic properties associated with melanoma progression. LGALS3 overexpression is highly expressed in early stages of papillary carcinoma, and its expression intensity declines during tumor progression. Serum levels of LGALS3 are high in patients with thyroid malignancy but there is considerable overlap in serum LGALS3 concentrations between those with benign and malignant nodular thyroid disease. LGLAS3 takes part as an immune regulator to inhibit T-cell immune responses and promote tumor growth, as a result providing a new mechanism for tumor immune tolerance.

Nectin Cell Adhesion Molecule 2, also known as NECTIN2, is a Ca(2+)-independent cell-cell adhesion molecule which is one of the plasma membrane components of adherens junctions. NECTIN2 takes a vital part in the establishment of homotypic as well as heterotypic cell to cell contacts. NECTIN2 is essential for resisting herpes simplex virus type 2 infection in transfected cells. NECTIN2 is also a possible target for antibody therapy of breast & ovarian cancers. NECTIN2 might be related with human longevity. Two diseases which have been associated with NECTIN2 are Herpes Simplex and Ovarian Cystic Teratoma.

Fc Fragment Of IgG Receptor And Transporter also known as FCGRT is a transmembrane glycoprotein with structural homology to MHC class 1 proteins. FCGRT is widely expressed in endothelial and epithelial cells and takes a vital part in IgG homeostasis. Moreover, FCGRT is expressed in neutrophils in addition myeloid antigen presenting cells. FCGRT can enhance IgG-meditated phagocytosis as well as antigen presentation by heses cells, however it promotes the degradation of opsonizing IgG rather than returning it to the circulation.

Tubulointerstitial Nephritis Antigen Like 1 also known as TINAGL1 is similar in sequence to tubulointerstitial nephritis antigen, a secreted glycoprotein which is identified by antibodies in several types of immune-related tubulointerstitial nephritis. Three transcript variants encoding different isoforms are known for TINAGL1.

Type IV collagen is a major structural component of basement membranes. It is a multimeric protein composed of 3 alpha subunits, which are encoded by 6 different genes, alpha 1 through alpha 6. Each of these alpha subunits can form a triple helix structure with 2 other subunits to form type IV collagen. The Goodpasture syndrome is a condition in which autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are restricted basically to the non-collagenous C-terminal domain of the protein. There are numerous alternative transcripts that appear to be unique to the human COL4A3 and alternative splicing is limited to the six exons that encode this C-terminal domain. COL4A3 is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to the Alport syndrome are also situated within the exons that encode this C-terminal region. COL4A3 is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Several exons of COL4A3 are interspersed with exons of an uncharacterized gene which is on the opposite strand.