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Heparan Sulfate 3-O-Sulfotransferase 1 (HS3ST1), is sulfotransferase which uses 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan. HS3ST1 catalyzes the rate limiting step in the biosynthesis of heparan sulfate (HSact). This modification is a vital part in the biosynthesis of anticoagulant heparan sulfate since it concludes the structure of the antithrombin pentasaccharide binding site.

EPGN is an EGF-related polypeptide growth factor that signals through the ErbB receptor-1. EPGN is produced in numerous tissues, including the testis, liver, heart and in certain tumor cells. EPGN is mitogenic for fibroblasts and epithelial cells. Human EPGN is originally synthesized as a glycosylated 14.7 kDa transmembrane precursor protein, which is processed by proteolytic cleavage to produce a mature soluble sequence.

STMN3 is a neuronal specific protein which belongs to the stathmin/oncoprotein 18 family of microtubule-destabilizing phosphoproteins. It is similar to the SCG10 protein and is involved in signal transduction and regulation of microtubule dynamics.

Small VCP/p97-interacting protein (SVIP) is involved in various cellular processes, including membrane fusion and ubiquitin-dependent protein degradation. SVIP functions as an inhibitor of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. On the other hand, SVIP overexpression increased the levels of p62 protein and enhanced starvation-activated autophagy as well as stimulated sequestration of polyubiquitinated proteins and p62 in autophagosomes.

Programmed cell death 1 ligand 2 (PDCD1LG2) which takes part in the costimulatory signal, is necessary for T-cell proliferation. PDCD1LG2 is also involved in IFNG production in a PDCD1-independent way. The interaction with PDCD1 inhibits T-cell proliferation by preventing cytokine production and cell cycle progression.

Acidic fibroblast growth factor is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described. The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.

GAPDH is a catalytic enzyme normally known to play a role in glycolysis. GAPDH exists as a tetramer composed of 36-kDa subunits and has a range of intracellular functions. GAPDH catalyzes the reversible reduction of 1,3-bisphosphoglycerate to glyceraldehyde 3-phosphophate in the presence of NADPH. Besides functioning as a glycolytic enzyme in cytoplasm, GAPDH has function in intracellular processes such as membrane fusion, microtubule bundling, phosphotransferase activity, nuclear RNA export, DNA replication and DNA repair. GAPDH catalyzes a vital energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD). The enzyme exists as a tetramer of identical chains.

Tyrosylprotein Sulfotransferase 2 (TPST2) is a member of the protein sulfotransferase family. TPST2 is a widely expressed protein, which catalyzes the O-sulfation of tyrosine residues within acidic regions of proteins. The TPST2 protein is a type II integral membrane protein located in the Golgi body.

Cytosolic and membrane-bound types of GST are encoded by 2 different supergene families. There are 8 classes of the soluble cytoplasmic mammalian GST: alpha, kappa, mu, omega, pi, sigma, theta and zeta. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are arranged in a gene cluster on chromosome 1p13.3 and aare highly polymorphic. These genetic differences can change an individual's resistance to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with the rise in a number of cancers.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/ macrophagemigration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/ macrophagemigration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Haptoglobin or HP is encoded by the HP gene in humans. Haptoglobin binds free hemoglobin (which is released from erythrocytes) in the blood plasma, therefore inhibits the Hb oxidative activity. The complex that contains Haptoglobin and hemoglobin will then be eliminated mostly through the spleen.

Acidic fibroblast growth factor is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described. The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.

Hepatocyte Growth Factor (HGF) is a multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. HGF synergizes with Interleukin-3 and GM-CSF to stimulate colony formation of hematopoietic progenitor cells in vitro and may, therefore, also modulate hematopoiesis. HGF is secreted as a single inactive polypeptide which is cleaved by serine proteases into a 69kDa Alpha chain and 34kDa Beta chain. A disulfide bond linking the alpha and beta chains produces the active heterodimeric molecule.

HDHD2 is a member of the HAD-like hydrolase superfamily which includes L-2-haloacid dehalogenase, epoxide hydrolases and phosphatases. There are two active sites in HDHD2 - an L-2-haloacid dehalogenase and a carboxylate group. The L-2-haloacid dehalogenase active site catalyzes the hydrolytic dehalogenation of D- and L-2-haloalkanoic acids, producing L- and D-2-hydroxyalkanoic acids.

ADH1C is a member of the zinc-containing alcohol dehydrogenase family which metabolizes a large assortment of substrates, such as ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. ADH1 is a monomorphic and a key factor in fetal and infant livers, becoming less active in gestation and only weakly active during adulthood.

Hypoxia-inducible factor-1 (HIF-1), identified as one of the transcription factors, has been found to play an essential role in cellular and systemic oxygen homeostasis. HIF-1 is a heterodimer composed of HIF-1b subunit and one of three subunits (Hif-1a, Hif-2 (or Hif-3)). The activation of Hif-1 (is closely associated with a variety of tumors and oncogenic pathways. Hif-1 (consists of DNA binding domain (DBD domain), Dimerization domain and C-terminal regulatory domains, including two transactivation domains (TAD), an oxygen-dependent degradation (ODD) domain, and inhibitory domains. Under hypoxic conditions HIF1A activates the transcription of more than 40 genes, including, erythropoietin, glucose transporters, glycolytic enzymes, VEGF, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1A also plays a crucial role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. It binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation involves recruitment of transcriptional coactivators such as CREBPB and EP300. Its activity is improved by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX appears to activate CTAD and potentiates activation by NCOA1 and CREBBP. The induction is under reduced oxygen tension. HIF1A is also induced by a variety of receptor-mediated factors such as growth factors, cytokines, and circulatory factors for example PDGF, EGF, FGF-2, IGF-2, TGF-1 beta, HGF, TNF alpha, IL-1 beta, angiotensin-2 and thrombin. Nevertheless, this induction is less intense than that stimulated by hypoxia.

Overexpression of the HIF1AN is linked with tumor aggressiveness in pancreatic endocrine tumors. HIF1AN hydroxylates Notch ICD at two residues that are crucial for the function of Notch ICD as a transactivator within cells and during neurogenesis and myogenesis. HIF1AN is commonly expressed in invasive breast carcinoma. The hypoxic response and survival recommends that tumour regulation of HIF1AN is an additional important mechanism for HIF pathway activation. HIF1AN is an asparaginyl hydroxylase enzyme that controls the transcriptional activity of hypoxia-inducible factor. FIH1 is a part of the Fe2+ and 2-oxoglutarate-dependent dioxygenase superfamily, FIH1 is protein that hydoxylates a specific asparagine residue (Asn-803) within the HIF1A C-terminal transactivation domain. In normoxia, the HIF1AN-mediated hydroxylation of the HIF1? transactivation domain which results in blockage of the HIF1A-p300/CBP interaction and represses transcriptional activity of HIF1A targeted genes.

ALDH1A1 is part of the aldehyde dehydrogenases family.
Aldehyde dehydrogenase is the 2nd protein of the main oxidative pathway of alcohol metabolism. Cytosolic and mitochondrial are 2 main liver isoforms of ALDH that are differentiateed by their electrophoretic mobility, kinetic property, & subcellular localization. The majority of Caucasians have two main isozymes, whereas just about 50% of Orientals have only the cytosolic form, excluding the mitochondrial form. ALDH1A1 is also a member of the group of corneal crystallins that assist the transparency of the cornea.
(Retinal + NAD+ + H2O = retinoate + NADH).

HMGB1 is an abundant chromatin-binding protein found in eukaryotic cell nucleus and acts in the assembly of nucleoprotein complexes. Inside the cell, HMGB1 binds to DNA and is involved in transcriptional regulation. Outside the cell, HMGB1 acts as a cytokine with activities that resemble those of tumor necrosis factor (TNF). HMGB1 is elevated significantly in chronic kidney disease patients and correlates with glomerular filtration rate as well as with markers of inflammation and malnutrition. HMGB1 is involved in Gram-negative sepsis by catalyzing movement of LPS monomers from LPS aggregates to CD14 to initiate a TLR4-mediated proinflammatory response. HMGB1 plays an important role in the relationship between necrosis and malignancy in glioma tumours. HMG1 protein is induced by Mycobacterium bovis BCG. Overexpression of HMGB1 is common in gastrointestinal stromal tumors and is related to the KIT mutation. HMG1 induces growth inhibition and apoptosis in macrophages through RAGE intracellular signaling pathway. The increase of extracellular HMGB1 observed in salivary glands of Sjogren's syndrome patients indicates that HMGB-1 is involved in the inflammatory process of the disease. HMGB-1 together with estrogen increase cell cycle progression in tumor cell lines.

SGTA is a ubiquitously expressed protein that contains three TPR protein-protein interaction duplicates. SGTA takes part as a component of the androgen receptor (AR)-chaperone-cochaperone complex, functions as a cochaperone and participates in androgen signaling. SGTA binds directly to HSC70 and HSP70 and mediates their ATPase activity. SGTA gene encodes a protein that is able to interact with the chief nonstructural protein of parvovirus H-1 and 70-kDa heat shock cognate. In addition, SGTA interacts with Vpu and Gag from HIV-1, SARS-CoV accessory protein 7a, DNAJC5 and DNAJC5B. Since this transcript is expressed universally in several tissues, SGTA serves a housekeeping function. While being involved in apoptosis and androgen signaling, SGTA is a possible molecule for polycystic ovary syndrome, a disorder characterized by androgen excess, obesity and menstrual disturbances.

HSPH1 analysis is used as an indicator and as a diagnostic aid in problematic lesions.
HSPH1 chaperones the responses to endoplasmic reticulum (ER) stress during its interactions with GRP78 and GSK3, and without HSP105 cell death following ER stress proceeds by a non-caspase-3-dependent process.
HSPH1 is highly expressed in a variety of human tumors.
HSPH1 is a mammalian member of the HSP105/110 family, a diverged subgroup of the HSP70 family. HSP105 has 2 isoforms, alpha and beta. Hsp105a associates with Hsp70/Hsc70 as complexes in vivo and regulates the chaperone activity of Hsp70/Hsc70 negatively in vitro and in vivo.

Dsb proteins are in charge for the formation and rearrangement of disulfide bonds during the folding of secreted and membrane proteins in bacteria. DsbG has disulfide bond isomerase and chaperone activity. DsbG interacts with refolding intermediates of chemically denatured citrate synthase and prevents their aggregation in vitro. DsbG shares sequnce homology with DsbC. DsbG forms a stable periplasmic dimer and displays an equilibrium constant with glutathione comparable with DsbA and DsbC. DsbG is expressed at roughly 25% level of DsbC.

ASF1 Anti-Silencing Function 1 Homolog B (ASF1B) belongs to the H3/H4 family of histone chaperone proteins and is similar to the anti-silencing function-1 protein in yeast. ASF1B is the substrate of the tousled-like kinase family of cell cycle-regulated kinases, and may have a crucial role in modulating the nucleosome structure of chromatin by guaranteeing a regular supply of histones at sites of nucleosome assembly. ASF1B cooperates with CAF-1 (chromatin assembly factor 1) to stimulate replication-dependent chromatin assembly. ASF1B is highly expressed in the testis and at lower levels in colon, small intestine and thymus. ASF1B is necessary for spermatogenesis.