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Tumor protein p53 responds to various cellular stresses by regulating target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. p53 is a tumor suppressor gene expressed in a wide variety of tissue types and is involved in regulating cell growth, replication, and apoptosis. p53 is a DNA-binding protein containing transcription activation, DNA-binding & oligomerization domains.
p53 binds to mdm2, SV40 T antigen and human papilloma virus E6 protein p53 senses DNA damage and possibly facilitating repair. p53 protein is a transcription factor which is encoded in humans by the TP53 gene. Alterations of TP53 occur not only as somatic mutations in human malignancies, but also as germline mutations in some cancer-prone families with Li-Fraumeni syndrome. p53 mutants that often occur in many different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Mutation involving p53 is found in a wide variety of malignant tumors, including breast, ovarian, bladder, colon, lung, and melanoma. The p53 expression in normal cells is low and in an assortment of transformed cell lines is high, which may contribute to transformation and malignancy. Multiple p53 variants encode distinct isoforms, which can regulate p53 transcriptional activity. p53’s significance in multicellular organisms is in cell cycle regulation therefore it functions as a tumor suppressor that is involved in preventing cancer. p53’s role in conserving stability by preventing genome mutation has earned it descriptions such as "the guardian of the genome," "the guardian angel gene," and the "master watchman.” The name p53 refers to its evident molecular mass: it migrates as a 53kDa protein on SDS-PAGE. However, based on calculations from its amino acid residues, p53's mass is in fact only 43.7kDa. This difference is attributed to the high number of proline residues in the protein which slow its migration on SDS-PAGE, consequently making it appear larger than it actually is.

Lipopolysaccharides (LPS) are a type of glycolipids on the outer cell wall of Gram-negative bacteria. Lipopolysaccharide binding protein (aka LBP) is a plasma protein which facilitates the diffusion of bacterial LPS (endotoxin). LBP is involved in the acute-phase immunologic response to gram-negative bacterial infections. In cooperation with bactericidal permeability-increasing protein (BPI), LBP binds LPS and interacts with the CD14 receptor, most likely playing a role in regulating LPS-dependent monocyte responses. LBP belongs to a family of structurally and functionally related proteins, including BPI, plasma cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). The LBP gene is found on chromosome 20, directly downstream of the BPI gene. LBP catalyzes the transfer of LPS monomers from LPS aggregates to HDL particles, to phospholipid bilayers, and to a binding site on soluble CD14 (sCD14). sCD14 is capable of speeding up the transfer by receiving an LPS monomer from an LPS aggregate, and then yielding it to an HDL particle, therefore acting as a soluble "shuttle" for an insoluble lipid.

Erythropoietin or EPO is a hormone (glycoprotein), part of the type I cytokine group of proteins. EPO is found mainly in the kidney tissue, produced from fibroblast-like cortical interstitial cells near the proximal tubules. EPO is also present in the blood, where it acts as red cell production regulator, by the promotion of differentiation of erythroid and thereby starts hemoglobin synthesis. Furthermore, EPO has neuroprotective activity towards brain injuries & anti-apoptotic activity in different tissues.

Factor IX is a glycoprotein, which is synthesized in the liver. The domain structure of factor IX is similar to that of the other vitamin K dependent coagulation factors. The NH2-terminal region contains 12 g-carboxyglutamic acid (gla) residues, which facilitate the calcium dependent binding of factor IX to negatively charged phospholipid surfaces. Two domains which are homologous to epidermal growth factor (EGF) span the region between the NH2-terminal gla domain and the activation peptide (Ala-146 to Arg-180). Factor IX is activated by either factor XIa or the factor VIIa/tissue factor/phospholipid complex. Cleavage at site A yields the intermediate IXa, which is subsequently converted to the fully active form IXab by cleavage at site B. The NH2-terminal light chain (GLA and EGF domains) remains covalently attached to the COOH-terminal heavy chain by a disulfide bond. The serine protease catalytic triad (Ser-365, His 221, Asp-269) is located in the heavy chain. Factor IXab is the catalytic component of the “intrinsic factor Xase complex” (factor VIIIa/IXa/Ca2+/phospholipid) which proteolytically activates factor X to factor Xa.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

THYN1, is greatly conserved among vertebrates and plant types. TYHN1 takes part in the induction of apoptosis. THYN1 in the thymocytes was primarily found in the nucleus, as shown in lymphoma cells, demonstrating that the THYN1 is localized in the nucleus, regardless of the cyclic or resting stage of the cell cycle.

GH is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the gGH locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five GHs, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the GH locus. Mutations in or deletions of the gene lead to GH deficiency and short stature.

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.

Human T-lymphotropic virus (HTLV) is a human, single-stranded RNA retrovirus that causes T-cell leukemia and T-cell lymphoma. The virus activates a subset of T-helper cellscalled Th1cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-gamma and TNF-alpha). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly IL-4, IL-5, IL-10 and IL-13). The end result is a reduction in the ability of the infected host to mount an adequate immune response to invading organisms that require a predominantly Th2 dependant response (these include parasitic infections and production of mucosal and humoral antibodies).

Complement factor H (CFH) is an important regulatory component of the alternative pathway of complement. CFH is prevents complement activation on host cells and tissues, mainly the kidney. CFH controls the formation and decay of the alternative pathway C3/C5 convertase and acts as a cofactor for factor I which proteolytically inactivates C3b when C3b is bound to factor H. The N-terminal 5 domains of CFH bind to C3b and inhibit binding of factor B thus reducing the formation of C3/C5 convertase. CFH also binds to preformed C3/C5 convertases and causes quick release of the catalytic subunit Bb. These activities are necessary for controlling the spontaneous activation of the alternative pathway amplification process in plasma. In addition, CFH controls the formation and decay of these enzymes when C3b is attached to the surface of particles.

EPO is a member of the EPO/TPO family and encodes a secreted, glycosylated cytokine composed of 4 alpha helical bundles. EPO is found in the plasma and regulates red cell production by promoting erythroid differentiation and initiating hemoglobin synthesis. EPO also has neuroprotective activity against a variety of potential brain injuries and antiapoptotic functions in several tissue types.

A 16kDa peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores.

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.

Lysyl Oxidase also known as LOX is an extracellular copper enzyme which initiates the crosslinking of collagens and elastin. LOX catalyzes oxidative deamination of the epsilon-amino group in certain lysine and hydroxylysine residues of collagens and lysine residues of elastin. Adding up to crosslinking extracellular matrix proteins, LOX plays a part in tumor suppression. Moreover, defects in LOX are the cause of autosomal recessive cutis laxa type I, CL type I. Two transcript variants encoding dissimilar isoforms have been found for LOX.

Adiponectin is a hormone exclusively expressed from adipose tissue.
Many studies demonstrate that Adiponectin has direct anti-diabetic, anti-atherogenic and anti-inflammatory functions. APM-1 can increase insulin sensitivity of skeletal muscle. Attenuate hepatic lipogenesis and gluconeogenesis, regulate NO production in endothelial cells, inhibit proliferation of smooth muscle cells and prevent lipid accumulation of macrophage cells.
In the circulation, Adiponectin is present as three different oligomeric complexes, including the high molecular weight (HMW), the middle molecular weight (MMW, also called hexamer) and low molecular weigh (MMW, also called trimer) forms 8. Different oligomeric complex of Adiponectin activates different signaling pathways and exerts distinct functions.

ALAD form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins) by catalyzing the compression of 2 molecules of delta-aminolevulinate. ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is vital for enzymatic activity. ALAD has 8 identical subunits and its enzymatic activity is inhibited by lead. Mutations in the ALAD structural gene are the source for high sensitivity to lead poisoning and acute hepatic porphyria.

Sex-hormone-binding globulin (SHBG) is a beta-globulin which specifically binds steroid hormones; it is involved in the transport of sex steroids in plasma. The main site of SHBG synthesis is assumed to be the hepatocytes. The production of SHBG is regulated by androgen/estrogen balance, thyroid hormones, and dietary factors, among others. The concentration of SHBG is a key factor regulating their distribution between protein-bound and free states. SHBG concentration determination is primarily significant in the evaluation of mild disorders of androgen metabolism and it allows detection of women with hirsutism who are likely to react to estrogen therapy. Testosterone/SHBG-ratios correlate well with both measured and calculated values for free testosterone thus aid to distinguish between subjects with excessive androgen activity and normal individuals. SHBG gene polymorphisms are linked with polycystic ovary syndrome and type 2 diabetes mellitus.

P4HB is a multifunctional and highly abundant enzyme that is part of the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, P4HB has a role in hydroxylation of prolyl residues in preprocollagen. P4HB is a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds.

Human Fatty Epidermal Acid Binding Protein FABP also called FABP-5 is a 15 kD member of the intracellular fatty acid binding protein (FABP) family, which is known for the ability to bind fatty acids and related compounds ( bile acids or retinoids). In an internal cavity. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mal1 (EFABP) are closely related and both are expressed in adipocytes. Absence of EFABP/mal1 resulted in increased systemic insulin sensitivity in two models of obesity and insulin resistance. Adipocytes isolated from mal1-deficient mice also exhibited enhanced insulin-stimulated glucose transport capacity. In contrast, mice expressing high levels of mal1 in adipose tissue display reduced systematic insulin activity.

TREM2 is a membrane protein that forms a receptor signaling complex with TYROBP. TREM2 may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in the TREM2 gene are a source of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL).

GHBP is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. A common alternate allele of this gene, called GHRd3, lacks exon three and has been well-characterized. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature. Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized.

REG protein was shown to be stimulated during the regeneration of pancreatic islets. Since then, many Reg-related proteins have been identified in humans and other animals. In human, the four REG family genes, i.e., REG 1 alpha, REG 1 beta, REG-related sequence (RS) and HIP/PAP, have so far been isolated. These Reg-related proteins are classified into four subfamilies according to their amino-acid sequences, but they share a similar structure and physiological function. Reg protein is a growth factor for pancreatic beta cells and also suggests that the administration of Reg protein could be used as another therapeutic approach for diabetes mellitus. Human REG cDNA which encodes a 166-amino acid protein with a 22-amino acid signal peptide. The amino acid sequence of human REG protein has 68% homology to that of rat Reg protein.

Migration And Invasion Enhancer 1 (MIEN1) is a member of the SelWTH family. MIEN1 enhances cell migration by stimulating filopodia formation at the leading edge of migrating cells and takes parts in regulation of apoptosis, probably via control of CASP3. MIEN1 participates in a redox-related process as well.