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Glycoprotein Nmb (GPNMB) is a member of the PMEL/NMB family. GPNMB is a type I transmembrane glycoprotein which exhibits homology to the pMEL17 precursor, a melanocyte-specific protein. GPNMB is expressed in the lowly metastatic human melanoma cell lines and xenografts but has no expression in the highly metastatic cell lines. GPNMB might be involved in growth delay and reduction of metastatic potential. GPNMB is up-regulated in a number of cancer cells, including in glioblastoma multiforme. GPNMB is expressed in many melanoma cells, as well as in tissue macrophages, including liver Kuppfer cells and lung alveolar macrophages, in podocytes and in some cells of the ciliary body of the eye (at protein level). GPNMB is hardly detectable in the healthy brain.

GRAP2 belongs to the GRB2/Sem5/Drk family. GRAP2 is an adaptor-like protein has a part in leukocyte-specific protein-tyrosine kinase signaling. Similar to related family member, GRB2-related adaptor protein contains an SH2 domain flanked by two SH3 domains and it interacts with other proteins, for example GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains.

CD8B encodes the CD8 beta chain isoforms of the CD8 antigen. CD8 is a cell surface glycoprotein which facilitates efficient cell-cell interactions within the immune system and is located on most cytotoxic T lymphocytes. The T-cell receptor on the T lymphocyte and the co-receptor CD8 antigen identify antigens exposed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional co-receptor is either a heterodimer composed of one alpha and one beta chain or a homodimer composed of two alpha chains. Both alpha and beta chains share substantial homology to immunoglobulin variable light chains.

Killer Cell Lectin-like Receptor Subfamily G, Member 1 (KLRG1) is a member of the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Natural killer (NK) cells are lymphocytes which mediate lysis of certain tumor cells and virus-infected cells without previous activation. NK cells can also regulate specific humoral and cell-mediated immunity. The cell surface expression of KLRG1 is up-regulated by MHC class I molecules expression.

Neuropilin 1 (Nrp1) is a transmembrane glycoprotein which functions as a co-receptor for several extracellular ligands including class III/IV semaphorins, some isoforms of vascular endothelial growth factor and transforming growth factor beta. Nrp1 binds vascular endothelial growth factor (VEGF)-A and is believed to serve as a coreceptor for kinase insert domain-containing receptor (KDR) by connecting with KDR and enhancing VEGF signaling. Nrp1 is a marker of regulatory T cells.

CD5 is a suitable immunohistochemical marker for T-cells, though not as sensitive as CD3. Approximately 76% of T-cell neoplasms are reported to express CD5, and it is also observed in chronic lymphocytic leukemia, hairy cell leukemia, and mantle cell lymphoma cells. CD5 is commonly lost in cutaneous T-cell lymphoma, and its deficiency can be used as an indicator of malignancy in this condition. CD5’s absence in T cell acute lymphoblastic leukemia, though relatively rare, is linked with a poor prognosis. CD5 serves as a receptor in regulating T-cell proliferation.

T-cell surface glycoprotein CD3 zeta chain (CD247) is a member of the CD3Z/FCER1G family. CD247 is T-cell receptor zeta, which along with T-cell receptor alpha/beta and gamma/delta heterodimers, and also with CD3-gamma, -delta and -epsilon, creates the T-cell receptor-CD3 complex. The zeta chain has a central role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the CD247 antigen causes impaired immune response.

ATPaseTransporting Beta 2 (ATP1B2) is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na+ and K+ ions across the plasma membrane. The precise function of the beta-2 subunit is not known. The ATP1B2 protein is composed of 3 subunits: alpha (catalytic), beta and gamma.

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.

Cytohesin 3 (CYTH3) belongs to the PSCD family, whose members have identical structural organization which consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain, and seem to mediate the regulation of protein sorting and membrane trafficking. CYTH3 is involved in the regulation of Golgi structure and function, and it might have a physiological role in regulating ADP-ribosylation factor protein 6 (ARF) functions, in addition to acting on ARF1.

CD84 belongs to the signaling lymphocyte activation molecule (SLAM) family which forms a subset of the greater CD2 cell-surface receptor Ig superfamily. CD84, a membrane glycoprotein, is a homophilic adhesion molecule found in various immune cells types and takes part in regulating receptor-mediated signaling in those cells.

PLGF is a growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration. It binds to receptor vegfr-1/flt1.

GMCSF is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13.
GM-CSF stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

CD5 is a suitable immunohistochemical marker for T-cells, though not as sensitive as CD3. Approximately 76% of T-cell neoplasms are reported to express CD5, and it is also observed in chronic lymphocytic leukemia, hairy cell leukemia, and mantle cell lymphoma cells. CD5 is commonly lost in cutaneous T-cell lymphoma, and its deficiency can be used as an indicator of malignancy in this condition. CD5’s absence in T cell acute lymphoblastic leukemia, though relatively rare, is linked with a poor prognosis. CD5 serves as a receptor in regulating T-cell proliferation.

CD276, belongs to the B7 family of immunoregulatory transmembrane glycoproteins expressed by T cells. CD276 is a costimulatory molecule for T cell activation in addition to IFN-gamma production. Furthermore CD276 upregulates BRCC3 expression, preventing DNA defects caused by 5-Fu. CD276 is correlated with TNM stage of NSCLC and act as a potential biomarker for NSCLC-derived MPEs. CD276 inhibits natural-killer mediated cell lysis in tumor cells, and act as a marker for detection of neuroblastoma cells. CD276 is implicated in the development of acute as well as chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. In addition, CD276 provides the placenta & fetus a proper immunological environment during the course of pregnancy.

Matrix metalloproteinases are a family of zinc and calcium-dependent endopeptidases that break down extracellular matrix proteins. The MMP9 is secreted as a 92kDa zymogen. Cleavage of ProMMP-9 results in the active enzyme, having a molecular weight of approximately 82kDa. MMP9 is composed of the following domains: a gelatin-binding domain consisting of three fibronectin type II units, a catalytic domain containing the zinc-binding site, a proline-rich type V collagen-homologous domain and a hemopexin-like domain. MMP9 is produced by the several cell types: monocytes, macrophages, neutrophils, keratinocytes, fibroblasts, osteoclasts and endothelial cells. MMP9 is involved in inflammatory responses, tissue remodeling, wound healing, tumor growth and metastasis. MMP9 may also play an important part in local proteolysis of the extracellular matrix and in leukocyte migration, as well as in bone osteoclastic resorption. MMP9 cleaves type IV and type V collagens into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. MMP9 can also degrade fibronectin but not laminin or Pz-peptide.
MMP9 defects may be a cause of susceptibility to intervertebral disc disease (IDD), also known as lumbar disk herniation (LDH).

CD8B encodes the CD8 beta chain isoforms of the CD8 antigen. CD8 is a cell surface glycoprotein which facilitates efficient cell-cell interactions within the immune system and is located on most cytotoxic T lymphocytes. The T-cell receptor on the T lymphocyte and the co-receptor CD8 antigen identify antigens exposed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional co-receptor is either a heterodimer composed of one alpha and one beta chain or a homodimer composed of two alpha chains. Both alpha and beta chains share substantial homology to immunoglobulin variable light chains.

CD27 belongs to the TNF-receptor superfamily. CD27 is necessary for initiation and long-term maintenance of T cell immunity. CD27 binds to ligand CD70, and has a crucial role in regulating B-cell activation and immunoglobulin synthesis. The CD27 receptor transduces signals which result in the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 mediate the signaling process of CD27. CD27-binding protein (SIVA), which is a proapoptotic protein, can bind to the CD27 receptor and is believed to have a significant role in the apoptosis induced by CD27.

Synaptotagmin-11 (SYT11) protein may be involved in Ca2+-dependent exocytosis of secretory vesicles through Ca2+ and phospholipid binding to the C2 domain or may function as Ca2+ sensors in the process of vesicular trafficking and exocytosis.

HMOX1 cleaves the heme ring at the alpha methene bridge to form Biliverdin. Biliverdin is then converted to Bilirubin by Biliverdin reductase. In physiological state, the highest activity of HMOX1 is found in the spleen, where senescent erythrocytes are sequestrated and destroyed. Heme Oxygenase-1 is involved in the regulation of cardiovascular function and its adaptive response to a variety of stressors. HMOX1 is induced in the colon of ulcerative colitis. HMOX1 is found to overexpress with a higher extent of intraplaque angiogenesis implies a multi-faceted role for HMOX1 in modulating the progression of atherosclerosis. HMOX1 expression reduced LPS-stimulated secretion of MCP-1, IL-6, IL-10, and TNF-alpha in murine and human macrophages.

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, insulin resistance, and cancer.

CD163 is an acute phase-regulated receptor which participates in the removal and endocytosis of hemoglobin/haptoglobin complexes by macrophages and thus keeps tissues from free hemoglobin-mediated oxidative damage. Furthermore, CD163 partakes in the uptake and recycling of iron, through endocytosis of hemoglobin/haptoglobin and ensuing breakdown of heme. In addition, CD163 binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent way. CD163 demonstrates greater affinity for complexes of hemoglobin and multimeric haptoglobin of HP-1F phenotype than for complexes of hemoglobin and dimeric haptoglobin of HP-1S phenotype. Moreover, CD163 stimulates a cascade of intracellular signals which involves tyrosine kinase-dependent calcium recruitment, inositol triphosphate formation and secretion of IL-6 & CSF-1.

CST9 belongs to the CRES (cystatin-related epididymal spermatogenic) subfamily. The CRES (cystatin-related epididymal spermatogenic) protein outlines a new subgroup in the family 2 cystatins of the cystatin superfamily. A few members are active cysteine protease inhibitors, however others have lost or possibly never developed this inhibitory activity. CST9 takes part in hematopoietic differentiation or inflammation and is expressed in heart, placenta, lung, liver, skeletal muscle and pancreas. CST9 is upregulated by LPS in several cancer cell lines, such as promyelocytic leukemia (HL-60) and myelomonocytic leukemia.

CD69 is a type 2 transmembrane glycoprotein which belongs to the C-type lectin family. CD69 is a very early activation Ag of T lymphocytes. The expression of CD69 is induced upon activation of T lymphocytes, and CD69 takes part in proliferation. Moreover, CD69 acts to transmit signals in natural killer cells as well as platelets. CD69 functions in the pathogenesis of allergen induced eosinophilic airway inflammation and responsiveness. Among the diseases which are associated with CD69: cd3gamma deficiency and mast cell disease.