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Inositol monophosphatase1 (IMPA1) is responsible for the provision of inositol essential for synthesis of phosphatidylinositol and polyphosphoinositides. IMPA1 has a central role in the phosphatidylinositol signaling pathway by catalyzing the hydrolysis of inositol monophosphates. IMPA1 has been recognized as the pharmacological target for lithium action in the brain. The IMPA1 enzyme has a magnesium-dependent phosphatase activity and is inhibited by therapeutic concentrations of lithium. Inhibition of inositol monophosphate hydroylosis and ensuing depletion of inositol for phosphatidylinositol synthesis may perhaps explain the anti-manic and anti-depressive effects of lithium administered to treat bipolar disorder.

Thiamin pyrophosphokinase 1 (TPK1) is a homodimer which catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. TPK1 is found in the heart, kidney, testis, small intestine and peripheral blood leukocytes, and at very low levels in a variety of tissues. TPK1 gene defects cause the thiamine metabolism dysfunction syndrome type 5, episodic encephalopathy type (THMD5), which is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism.

UBE2T is part of the E2 ubiquitin-conjugating enzyme family that participates in the protein degradation pathway. UBE2T catalyzes the ATP-dependent attachment of ubiquitin to target proteins, thus tagging them for subsequent destruction by the proteasome. UBE2T is an important factor of the Faconi anemia pathway of DNA damage repair and, upon self-inactivation, may negatively regulate the Faconi pathway.

Clusterin also named Apolipoprotein J (APO-J) is a 75-80 kD disulfide-linked heterodimeric protein containing about 30% of N-linked carbohydrate rich in sialic acid but truncated forms targeted to the nucleus have also been identified.
The precursor polypeptide chain is cleaved proteolytically to remove the 22-mer secretory signal peptide and subsequently between residues 227/228 to generate the a and b chains. These are assembled in anti-parallel to give a heterodimeric molecule in which the cysteine-rich centers are linked by five disulfide bridges and are flanked by two predicted coiled-coil a-helices and three predicted amphipathic a-helices.
Across a broad range of species clusterin shows a high degree of sequence homology ranging from 70% to 80%. It is nearly ubiquitously expressed in most mammalian tissues and can be found in plasma, milk, urine, cerebrospinal fluid and semen.
It is able to bind and form complexes with numerous partners such as immunoglobulins, lipids, heparin, bacteria, complement components, paraoxonase, beta amyloid, leptin and others. Clusterin has been ascribed a plethora of functions such as phagocyte recruitment, aggregation induction, complement attack prevention, apoptosis inhibition, membrane remodeling, lipid transport, hormone transport and/or scavenging, matrix metalloproteinase inhibition.
A genuine function of clusterin has not been defined. One tempting hypothesis says that clusterin is an extracellular chaperone protecting cells from stress induced insults caused by degraded and misfolded protein precipitates.
Clusterin is up- or down regulated on the mRNA or protein level in many pathological and clinically relevant situations including cancer, organ regeneration, infection, Alzheimer disease, retinitis pigmentosa, myocardial infarction, renal tubular damage, autoimmunity and others.

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.
Reg I was found to be expressed mainly in pancreatic beta and acinoductular cells as well as gastric fundic enterochromaffin-like (ECL) cells. Reg I production in ECL cells is stimulated by gastrin, as well as by the proinflammatory cytokine, cytokine-induced neutrophil chemoattractant (CINC)-2Beta. In patients with chronic hypergastrinemia, Reg production is stimulated, with the increased proliferation of gastric mucosal cells. Patients with Helicobacter pylori infection also showed increased Reg production in the gastric mucosa, partly via increased plasma gastrin concentration and partly via increased proinflammatory cytokine production. The serum concentration of the reg-protein was significantly higher in patients with various pancreatic diseases than in normal controls, and was also significantly higher in patients with acute pancreatitis or chronic relapsing pancreatitis than in patients with chronic pancreatitis. Furthermore, the serum PSP/reg-protein concentration was also significantly increased in liver cirrhosis, choledocholithiasis, and various cancers of the digestive system.

Cartilage-associated protein (CRTAP) is a secreted protein localizing to the extracellular space which takes part in collagen post-translational modifications, extracellular fibril assembly and intracellular trafficking. CRTAP which is mainly expressed with predominant expression in articular chondrocytes is essential for efficient 3-hydroxylation of fibrillar collagen prolyl residues. Mutations in the gene encoding CRTAP might cause to autosomal recessive osteogenesis imperfecta (OI) type 7 and type 2B.

Neutral endopeptidase (NEP) is an enzyme located in the cell membrane (bound to it) that is able to dissolve biologically active proteins and is expressed on the surface of lymphoid progenitors, human podocytes, syncytiotrophoblastic cells, and many other epithelial cells including polymorphonuclear leukocytes.

Treponema pallidum is a gram-negative spirochaete bacterium and is considered to be metabolically crippled. There are at least four known subspecies: T. pallidum pallidum, T. pallidum pertenue, T. pallidum carateum and T. pallidum endemicum. The helical structure of T. pallidum pallidum allows it to move in a corkscrew motion through viscous mediums such as mucus. Treponema pallidum subsp. pallidum has one of the smallest bacterial genomes at 1.14 million base pairs (Mb) and has limited metabolic capabilities, reflecting its adaptation through genome reduction to the rich environment of mammalian tissue.

AHCY is an enzyme that catalyzes the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to adenosine (Ado) and L-homocysteine (Hcy). AHCY controls the intracellular S-adenosylhomocysteine (SAH) concentration that is crucial for transmethylation reactions. AHCY deficiency causes hypermethioninemia.

Tropomyosin beta chain isoform 2 is affiliate to the actin filament binding protein family which primarily expressed in slow, type 1 muscle fibers. Mutations in TPM2 can change the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes.

BDNF promotes the survival of neuronal populations that are all located either in the central nervous system or directly connected to it. BDNF is a major regulator of synaptic transmission and plasticity at adult synapses in many regions of the cns. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (ltp), long-term depression (ltd), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability.

Arginase-1 is part of the urea cycle, it catalyzes the hydrolysis of arginine to ornithine and urea. There are two isoforms of mammalian arginase which differ in their tissue location, subcellular localization, immunologic crossreactivity & physiologic role. Arginase-1is a cytosolic enzyme and expressed primarily in the liver tissue. Inherited deficiency in this enzyme may lead toargininemia, which is an autosomal recessive disease in which hyperammonemia is detected.

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.

Dual specificity phosphatase 13 (DUSP13) is a member of the protein-tyrosine phosphatase family. DUSP13 cooperates with protein kinases to control cell proliferation and differentiation. DUSP13 is engaged in the regulation of meiosis and/or differentiation of testicular germ cells in the course of spermatogenesis. DUSP13 demonstrates intrinsic phosphatase activity towards both phospho-seryl/threonyl and -tyrosyl residues of myelin basic protein, with similar specific activities in vitro.

Iduronate 2-Sulfatase also known as IDS, belongs to the highly-conserved sulfatase family of enzymes which catalyze the hydrolysis of O-sulfate and N-salfate esters from a variety of substrates. IDS is essential for the lysosomal degradation of the glycosaminoglycans (GAG) heparan sulfate as well as dermatan sulfate. Furthermore, IDS hydrolyzes the 2-sulfate group of the IDS units of the GAG.

ElaC Ribonuclease Z 1, also known as ELAC1 is a member of the RNase Z family. Zinc phosphodiesterase, which shows some tRNA 3'-processing endonuclease activity. In addition, ELAC1 is implicated in tRNA maturation, by removing a 3'-trailer from precursor tRNA.

NSE is the ?? isoform of the glycolytic enzyme enolase and is expressed primarily in neurons, in normal and neoplastic neuroendocrine cells. NSE is a highly soluble cytoplasmic protein that is readily secreted into the CSF and serum following tissue damage. NSE shows neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons and binds in a calcium-dependent manner to cultured neocortical neurons promoting cell survival.

Ornithine decarboxylase is the preliminary and rate-limiting enzyme in the biosynthetic pathway of polyamines and it takes part in the alteration of ornithine to putrescine. ODC1 is a key member of various biological processes, such as cell growth, transformation, differentiation and apoptosis. Overexpression of the ODC1 gene has a vital part in cell proliferation and the progress of cancer.

PAPPA is a large zinc binding protein, which acts as a metalloprotease and specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. PAPP-A can also act as a regulator of IGF bioactivity in a number of biological systems, including the human ovary and cardiovascular systems. It was shown that PAPP A levels are elevated in patients with unstable angina or acute myocardial infarction. Furthermore, PAPPA is believed to be involved in local proliferative processes such as wound healing and bone remodeling. Moreover, PAPP-A is produced in high concentrations during pregnancy and is released into the maternal circulation. In placenta, PAPP A is expressed in X cells in septa and anchoring villi, and in syncytiotrophoblasts in the chorionic villi.
Lower levels of PAPPA are found in an array of other tissues including kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow, colon, fibroblasts and osteoblasts. PAPP-A is present in serum and placenta during pregnancy; with levels increasing throughout pregnancy. Low levels of PAPP A are associated with a number of foetal chromosomal abnormalities, as well as pre-eclampsia and stillbirth.
PAPPA levels may be a potentially highly specific marker for heart disease.
PAPP-A proteolytic activity is inhibited by targeting substrate exosite binding.

Thrombomodulin, also referred to THBD, is an endothelial cell-expressed, transmembrane glycoprotein that can form a complex with the coagulation factor, thrombin. This complex increasethe activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. Thrombomodulinbound thrombin has procoagulant effect at the same time by inhibiting fibrinolysis by cleaving thrombinactivatable fibrinolysis inhibitor (TAFI) into its active form. Reduced levels of thrombomodulin or increased serum levels of THBD can correlate with pathogenesis of certain cardiovascular diseases, such as atherosclerosis and thrombosis. Furthermore, it associated with, diabetes mellitus, liver cirrhosis, cerebral & myocardial infarction, and multiple sclerosis.

Alpha-galactosidase A (GLA) is a homodimeric glycoprotein which hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. GLA catalyzes the hydrolysis of melibiose into galactose and glucose. Various mutations in the GLA gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry disease (a rare lysosomal storage disorder which results from a failure to catabolize alpha-D-galactosyl glycolipid moieties).

Thiosulfate sulfurtransferase like domain containing 1 (TSTD1) is a member of a family of transferases, specifically the sulfurtransferases, which transfer sulfur-containing groups. TSTD1 is localized around the nuclear membranes. TSTD1 is expressed in a number of human tissues, including the kidney, liver, skeletal muscle, heart, colon, thymus, spleen, placenta and lung. TSTD1 may participate in cyanide detoxification, the formation of iron-sulfur proteins, and the modification of sulfur-containing enzymes.

PSMA6 belongs to the peptidase T1A family, which is a 20S core alpha subunit. The proteasome is a multicatalytic proteinase complex with an extremely organized ring-shaped 20S core structure. The core structure consists of 4 rings of 28 non-identical subunits; 2 rings consist of 7 alpha subunits and 2 rings consist of 7 beta subunits. PSMA6 is spread all over eukaryotic cells in large quantities and cleave peptides in an ATP/ubiquitin-dependent procedure in a non-lysosomal pathway.