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Sclerostin (SOST) is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Sclerostin functions as a negative regulator of bone growth, by inhibiting bone formation. SOST is widely expressed at low levels, with highest levels in the bone, cartilage, kidney, liver, bone marrow and primary osteoblasts differentiated for 21 days. SOST gene defects cause sclerosteosis and bone dysplasia.

Ebolavirus (EVD) belongs to the Filoviridae family of proteins which is comprised of a single-strand, non-infectious RNA genome. EVD genome is about 19,000 base pairs long and covers 7 genes in the order 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR. There are 4 different ebolaviruses such as: Zaire (EBO-Z), Sudan (EBO-S), Cote d’Ivoire (EBO-CI) and Reston (EBO-R) that differ in amino acid sequence and location of where the gene overlaps. Similar to filoviruses and ebolavirions, EVD is a filamentous element that could appear in 3 forms: shepherd's crook, U shape or a 6 shape. Ebolaviruses may be coiled, toroid, or branched. Most ebolavirions are 80nm wideand 14,000nm long.

The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms that have been identified in mammals. The 14-3-3gamma, a subtype of the 14-3-3 family of proteins, was thought to be brain and neuron-specific. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways.

Alpha 1 ACT is an early-stage acute-phase plasma protein and a serpin that preferentially inactivates chymotrypsin, cathepsin G, and chymase. Alpha-1-ACT, a serine protease inhibitor, is tightly associated with amyloid plaques in Alzheimer's disease (AD) and in normal aged human and monkey brain.
Regulation of the serine proteases and serine protease inhibitors plays an important role in neuromuscular differentiation. Prostate specific antigen (PSA), a chymotrypsin-like serine protease, is predominantly complexed to Alpha-1-ACT.

Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryosoon after conception and later by the syncytiotrophoblast(part of the placenta). Its role is to prevent the disintegration of the corpus luteumof the ovaryand thereby maintain progesterone production that is critical for a pregnancy in humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG.

Yersinia enterocolitica is a Gram-negative bacillus-shaped bacterium, which is a member of the Enterobacteriaceae family. Y.Enterocolitica is motile at temperatures between 22-29°C, however becomes non-motile at normal human body temperature. Y. Enterocolitica infection causes the yersiniosis disease, which is an animal-borne disease occurring in humans, as well as in a various groups of animals such as cattle, deer, pigs, and birds. Yersinia enterocolitica is a heterogeneous group of strains, which are conventionally classified by bio-typing into six bio-groups on the basis of phenotypic characteristics, and by serotyping into more than 57 “O” serogroups, on the basis of their O (lipopolysaccharide or LPS) surface antigen. Five of the six biogroups (1B and 2–5) are considered as pathogens. Nevertheless, only a few of these serogroups have been linked with disease in either humans or animals. Strains which belong to serogroups O:3 (biogroup 4), O:5,27 (biogroups 2 and 3), O:8 (biogroup 1B), and O:9 (biogroup 2) are most frequently isolated worldwide from human samples. Still, the main Y. enterocolitica serogroup in many European countries is serogroup O:3 followed by O:9, whereas the serogroup O:8 is mostly detected in the United States.

Matrix metalloproteinase-7 (MMP-7) also known as matrilysin and PUMP (EC 3.4.24.23) cleaves a number of substrates including collagen types IV and X, elastin, fibronectin, gelatin, laminin and proteoglycans. MMP-7 is closely related to the stromelysin family members but is encoded by a different gene. MMP-7 is the smallest of all the MMPs consisting of a pro-peptide domain and a catalytic domain. It lacks the hemopexin-like domain common to other members of the MMPs. MMP-7 is secreted as a 28 kDa proenzyme and can be activated in vitro by organomercurials and trypsin and in vivo by MMP-3 to a 18 kDa active MMP-7 enzyme. Once activated, MMP-7 can activate pro-MMP-1 and pro-MMP-9 but not pro-MMP-2. MMP-7 is widely expressed having been reported in elevated levels in cycling endometrium as well as in colorectal cancers and adenomas, hepatocellular carcinomas, rectal carcinomas, and approximately 50% of gliomas.

S100A10 is a member of the S100 family of proteins contains two EF-hand calcium-binding motifs and is thought to be involved in the regulation of a number of cellular processes including cell cycle progression and differentiation. S100 proteins are localized either in the cytoplasm or the nucleus of a wide range of cells. There are at least 13 members in the S100 gene family, which are located as a cluster on chromosome 1q21. S100A10 may function in exocytosis and endocytosis.

Fibrinogen Beta Chain 9 (FGB) is the beta component of fibrinogen, a blood-borne glycoprotein composed of 3 pairs of nonidentical polypeptide chains. When vascular injury accrues, fibrinogen is cleaved by thrombin to form fibrin which is found in abundance in blood clots.

Integrins are heterodimeric proteins consist of alpha and beta subunits. There are more than 18 alpha and 8 beta subunits discovered in mammals. Integrin family members are membrane receptors that participates in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. ITGB1 encodes a beta subunit.

Prorelaxin H2 (RLN2) is a member of a family which is produced by the ovary, targets the mammalian reproductive system to ripen the cervix, elongate the pubic symphysis and inhibit uterine contraction. It may also have other roles in boosting sperm motility, regulating blood pressure, controlling heart rate and releasing vasopressin. RLN2 is a peptide hormone linked to several therapeutically relevant physiological effects, including regulation of collagen metabolism and multiple vascular control pathways. The active form of the RLN2 protein consists of an A chain and a B chain linked by disulfide bonds.

Plasma protease C1 inhibitor (SERPING1) is a part of the serpin superfamily of serine protease inhibitors. SERPING1 plays an important role in regulating activation of both the complement and contact systems. That isdue to the fact that SERPING1 regulates the activation of complement factor C1 in addition to the activity of activated C1 by coupling with the active catalytic site at the light chains of C1r and C1s. SERPING1 insufficiency results in hereditary angioedema, which is characterized by recurrent episodes of localized angioedema of the skin, gastrointestinal mucosa or upper respiratory mucosa.

SKP1 is a F-box enzyme which functions as a substrate recognition component of the SCF ubiquitin ligase complex which controls the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SKP1 binds to proteins containing an F-box motif, such as cyclin F, S-phase kinase-associated protein 2, and other regulatory proteins involved in ubiquitin dependent proteolysis. SKP1 takes part in the control of beta-catenin levels and the activity of beta-catenin dependent TCF transcription factors. SKP1 serves as an adapter that links the F-box protein to CUL1 in the SCF complex.

Keratin 8 and 18 (K8/18) are the major components of intermediate filament (IF) proteins of simple or single-layered epithelia.

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.

The adipose tissue exclusively expresses and secretes Adiponectin (Acrp30). Acrp30 is involved in various physiological processes such as energy homeostasis, insulin sensitivity, hormonal processes, fatty acid metabolism and obesity.
Adiponectin circulates in the plasma. Decreased levels of Adiponectin are associated with insulin resistance and hyperinsulinemia, as seen in people with obesity insulin resistance, and diabetes type 2, whose plasma levels of adiponectin are reduced.
The modular structure of Acrp30 is comprised of N-terminal collagenous domain followed by a C-terminal globular domain.
Acrp30 also acts as a significant negative regulator in hematopoiesis and immune systems; it may be involved in ending inflammatory responses through its inhibitory functions. Adiponectin inhibits endothelial NF-kappa-b signaling through a cAMP-dependent pathway, it also inhibits TNF-alpha- induced expression of endothelial adhesion molecules.

SLPI is a secreted inhibitor which guards epithelial tissues from serine proteases. SLPI is localized in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. SLPI inhibitory effect contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes. SLPI protein has broad-spectrum anti-biotic activity. SLPI is an acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. SLPI prevents elastase-mediated damage to oral and mucosal tissues.

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.

Sclerostin Domain Containing 1 (SOSTDC1) belongs to the sclerostin family and an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. The SOSTDC1 protein acts as a bone morphogenetic protein (BMP) antagonist. Specifically, SOSTDC1 directly associates with BMPs, prohibiting them from binding their receptors, thus regulating BMP signaling throughout cellular proliferation, differentiation, and programmed cell death. SOSTDC1 may also be involved in the onset of endometrial receptivity for implantation/sensitization for the decidual cell reaction Enhances Wnt signaling and hinders TGF-beta signaling. In addition, SOSTDC1 directly antagonizes the activity of BMP2, BMP4, BMP6 and BMP7 in a dose-dependent manner.

Chondrosarcoma Associated Gene 1 (CSAG1) belongs to a family of tumor antigens. The CSAG1 protein is expressed in chondrosarcomas, but may also be expressed in normal tissues such as testis.

CASQ2 belongs to the calsequestrin family and is localized to the sarcoplasmic reticulum in cardiac and slow skeletal muscle cells. CASQ2 is a calcium binding protein that stores calcium for muscle function. The discharge of calcium bound to CASQ2 through a calcium release channel activates muscle contraction. CASQ2 binds 40 to 50 moles of calcium. CASQ2 mutations result in stress-induced polymorphic ventricular tachycardia, also called catecholaminergic polymorphic ventricular tachycardia 2 which is known fir its bidirectional ventricular tachycardia that causes cardiac arrest.

Natriuretic Peptide Precursor B acts as a cardiac hormone with a variety of biological actions including natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. It is thought to play a key role in cardiovascular homeostasis. Helps restore the body's salt and water balance. Improves heart function.

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.

Zinc-alpha-2-glycoprotein (ZAG) is found in body fluids such as serum, sweat, and seminal and breast cyst fluids. It is identical in amino acid sequence to tumor-derived lipid mobilizing factor (LMF), a protein associated with the dramatic loss of adipose body stores in cancer cachexia, and has been shown to stimulate lipolysis by adipocytes in vivo and in vitro. A role for ZAG has been proposed in the regulation of body weight, and age-dependent changes in genetically influenced obesity, and also it regulates melanin production by normal and malignant melanocytes. It has also recently been classified as a novel adipokine in that it is produced by both white and brown fat adipocytes and may act in a local autocrine fashion in the reduction of adiposity in cachexia. Controlling ZAG/LMF's activity could be life-saving in the management of certain cancers and other cachexiainducing conditions, and its possible normal role in body fat store homeostasis is deserving of understanding in its own right. ZAG exhibits a class I major histocompatibility complex (MHC) fold but is a soluble protein rather than being anchored to plasma membranes and does not associate with alpha-2-microglobulin in humans. Like antigen-presenting MHC class I proteins, ZAG has an open apical groove, and X-ray crystallography of human derived ZAG revealed an unidentifiable electron density in a similar position to that occupied by antigenic peptides in classical MHC proteins and glycolipids in isoforms of CD1. This presumptive ligand is not a peptide, and the groove is too small to hold a glycolipid such as is presented by CD1 isoforms. By analogy with all other MHC class I-related proteins that have an open apical groove [some do not ], occupancy by a ligand is probably crucial to ZAG's biological function. Despite all of the structural and biochemical evidence that ZAG binds a ligand, none has so far been found by extraction from protein isolated from biological fluids. This difficulty could be because the ligand is labile, heterogeneous, or readily lost during purification procedures. Knowing more about how ZAG interacts with the compounds it has been found to bind, both natural and artificial, will inform searches for the elusive ligand(s) and its/their role in ZAG's signaling function.