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Proteasome subunit alpha type-8 (PSMA8) is a member of the peptidase T1A family. PSMA8 is a multicatalytic proteinase complex which is distinguished by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. The PSMA8 subunit may be testis-specific.

The Casein kinase 2 (EC2.7.11.1) is a serine/threonine-selective protein kinasethat is a tetramer of two alpha subunits and two beta subunits. The alpha subunits have the catalytic kinase domain. Casein kinase 2 has been implicated in cell cyclecontrol, DNA repair, regulation of the circadian rhythmand other cellular processes.
Casein kinase 2 activity has been reported to be activated following Wnt signaling pathwayactivation. A Pertussis toxin-sensitive G proteinand Disheveled appear to be an intermediary between Wnt-mediated activation of the Frizzled receptor and activation of casein kinase 2.

Epoxide Hydrolase 1 Microsomal (EPHX1) is a vital biotransformation enzyme which transfers epoxides from the degradation of aromatic compounds to trans-dihydrodiols that can be conjugated and excreted from the body. Epoxide hydrolase plays a role in both activation and detoxification of epoxides. Mutations in EPHX1 trigger preeclampsia, epoxide hydrolase deficiency or increased epoxide hydrolase activity.

TIMP2 belongs to the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases that take part in degradation of the extracellular matrix. Besides having an inhibitory role against metalloproteinases, the encoded protein has a exclusive part among TIMPfamily members in its capability to directly suppress the proliferation of endothelial cells. Consequently, the encoded protein is crucial to the conservation of tissue homeostasis by suppressing the production of quiescent tissues as an answer to angiogenic factors, and by inhibiting protease activity in tissues undergoing renovation of the extracellular matrix.

Thymidine kinase 2 mitochondrial (TK2) is a member of the DCK/DGK family. TK2 is an enzyme, a phosphotransferase (a kinase): 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase. Thymidine kinase is found in most living cells. Thymidine kinase is present in 2 forms in mammalian cells, TK1 and TK2. Thymidine kinases have a central function in the synthesis of DNA and thus in cell division, since they are part of the exceptional reaction chain to introduce deoxythymidine into the DNA. TK2 is a deoxyribonucleoside kinase which specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. TK2 localizes to the mitochondria and is essential for mitochondrial DNA synthesis. TK2 gene defects are a cause of mitochondrial DNA depletion syndrome type 2 (MTDPS2).

Nucleoside diphosphate kinase (Ndk) is an enzyme which catalyzes the exchange of phosphate groups between different nucleoside diphosphates. Ndk’s activity sustains equilibrium between the concentrations of various nucleoside triphosphates for example, when GTP is produced in the citric acid (Krebs) cycle is converted to ATP. Ndk has a key role in the synthesis of nucleoside triphosphates other than ATP.

Pin 1 is a peptidyl-prolyl cis/trans isomerase (PPIase) which interacts with NIMA and essential for cell cycle regulation Pin1 is nuclear PPIase containing a WW protein interaction domain, and is structurally and functionally related to Ess1/Ptf1, an essential protein in budding yeast. PPIase activity is necessary for Ess1/Pin1 function in yeast. Pin1 is thus an essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Substrates of Pin1 include the mitotic regulators (Cdc25 phosphatase and NIMA, PLK I, Wee, and Myt1 kinases), several transcription factors like b-Catenin, c-Jun, and the tumor suppressor protein p53, and some specific proteins like the RNA Pol II, the cytoskeleton protein tau, and the G1/S protein Cyclin D1.

GUK1 is part of the guanylate kinase family. GUK1 occurs as a monomer that catalyzes the ATP-dependent conversion of GMP to GDP, thus takes an important part in the recycling of GMP. Through its catalytic activity, GUK1 functions in regulation of the supply of guanine nucleotides to signal transduction pathways. GUK1 overexpression is related with pituitary adenocarcinomas, implicating that GUK1 is has a role in tumorigenesis.

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.

FBL is a significant small nucleolar protein in eukaryotes, which has an essential role in pre-rRNA processing during ribosomal biogenesis. Fibrillarin is a component of several ribonucleoproteins including a nucleolar small nuclear ribonucleoprotein (SnRNP) and one of the two classes of small nucleolar ribonucleoproteins (snoRNPs). Fibrillarin contains an N-terminal repetitive domain which is rich in glycine and arginine residues, like fibrillarins in other species. Fibrillarin’s central region is similar to an RNA-binding domain and contains an RNP consensus sequence. FBL is linked to the U3, U8, and U13 small nuclear RNAs and is positioned in the dense fibrillar component (DFC) of the nucleolus. Antisera from roughly 8% of humans with the autoimmune disease scleroderma recognize fibrillarin.

Kallikrein-15 (KLK15) is one of the 15 kallikrein subfamily members located in a cluster on chromosome 19. KLK15 contains numerous polyadenylation sites and alternative splicing results in multiple transcript variants encoding different isoforms. KLK15 is over expressed in prostate cancer and therefore uses as a diagnostic or prognostic marker for prostate cancer.

Methionyl Aminopeptidase 1D (METAP1D) is a part of the peptidase M24A family. METAP1D which is overexpressed in colon cancer cell lines participates in tumorigenesis. METAP1D eliminates methionine from the N-terminus of nascent proteins.

MMP-1 (interstitial collagenase) can break down a wide range of substrates including types I, II, III, VII, VIII, and X collagens as well as L-Selectin, pro-TNF, IGFBP-3, IGFBP-5, casein, gelatin, myelin basic protein, pro-MMP2 and pro-MMP9. A significant function of MMP-1 is the degradation of fibrillar collagens in extracellular matrix remodeling. MMP-1 is expressed in fibroblasts, keratinocytes, endothelial cells, monocytes and macrophages. MMP1 can be divided into a number of distinct domains: a prodomain which is cleaved on activation, a catalytic domain containing the zinc binding site and a short hinge region with a carboxyl terminal domain. MMP1 is part of a cluster of MMP genes which localize to chromosome 11q22.3.

Indoleamine 2,3-Dioxygenase 1 (IDO1) catalyzes the primary and rate-limiting stage in tryptophan catabolism to N-formyl-kynurenine. IDO1 affects on various tryptophan substrates including D-tryptophan, and serotonin and is expressed in dendritic cells, monocytes, and macrophages. IDO1 takes part in a range of pathophysiological processes like neuropathology, antimicrobial and antitumor defense, immunoregulation, and antioxidant activity. IDO1 regulates T-cell behavior by its pericellular catabolization of the necessary amino acid tryptophan.

STK17A belongs to the DAP kinase-associated apoptosis-inducing protein kinase family and encodes an autophosphorylated nuclear protein with a protein kinase domain. STK17A acts as a positive regulator of apoptosis. STK17A is greatly expressed in the placenta with lower levels in the heart, lung, skeletal muscle, kidney and pancreas.

Glutamate Decarboxylase 1 (GAD1) is one of several forms of glutamic acid decarboxylase. GAD1 is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for the GAD1 enzyme has been identified in the human pancreas since it has been detected as an autoantigen and an autoreactive T cell target type II diabetes. The GAD1 protein may also have a role in the stiff man syndrome. GAD1 enzyme deficiency leads to pyridoxine dependency with seizures. GAD1 also catalyzes the production of GABA.

Thyroid Peroxidase (TPO) represents one of the main autoantigenic targets in autoimmune thyroid disease of humans. Its identity with the formerly so-called `microsomal antigen` has been shown several years ago. As an integral membrane glycoprotein it is restricted to the apical plasma membrane of the follicular epithelial cells and comprises two identical subunits of approx. 100 kDa molecular weight. The hemoprotein TPO plays a key role in the thyroid hormone biosynthesis by catalysing both the iodination of tyrosyl residues and the coupling of iodotyrosyl residues in thyroglobulin (TG) to form precursors of the thyroid hormones T4 and T3.

PSMB5 belongs to the proteasome B-type family that has a 20S core beta subunit in the proteasome. This catalytic subunit is not present in the immunoproteasome and is substituted by catalytic subunit 3i (proteasome beta 8 subunit). A fundamental function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. PSMB5 exhibits an ATP dependent proteolytic activity and is involved in an ATP/ubiquitin dependent non lysosomal proteolytic pathway.

Peptidyl-prolyl cis-trans isomerase F, mitochondrial (Cyclophilin-F) accelerates the folding of proteins. Cyclophilin-F catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and involved in regulation of the mitochondrial permeability transition pore (mPTP). Cyclophilin-F, in cooperation with mitochondrial TP53, is involved in activating oxidative stress-induced necrosis. Cyclophilin-F is also involved in modulation of mitochondrial membrane F1F0 ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Furthermore, Cyclophilin-F has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.

Aldo-keto reductase family 1 member D1 (AKR1D1) belongs to the AKR superfamily. The AKR family proteins are soluble NADPH oxidoreductases, which have vital roles in the metabolism of drugs, carcinogens and reactive aldehydes. AKR1D1 is also responsible for the catalysis of the 5-beta-reduction of bile acid intermediates and steroid hormones that carry a delta (4)-3-1 structure. AKR1D1 is highly expressed in the liver, colon and testis. Deficiency of the AKR1D1 enzyme may contribute to hepatic dysfunction.

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins and leukotrienes. The same reaction also produces lysophosholipids, which represent another class of lipid mediators.
The secretory PLA2 (sPLA2) family, in which 10 isozymes have been identified, consists of low molecular weight, Ca2+-requiring secretory enzymes that have been implicated in a number of biological processes, such as modification of eicosanoid generation, inflammation, and host defense.This enzyme has been proposed to hydrolyze phosphatidylcholine (PC) in lipoproteins to liberate lyso-PC and free fatty acids in the arterial wall, thereby facilitating the accumulation of bioactive lipids and modified lipoproteins in atherosclerotic foci.
In mice, sPLA2 expression significantly influences HDL particle size and composition and demonstrate that an induction of sPLA2 is required for the decrease in plasma HDL cholesterol in response to inflammatory stimuli. Instillation of bacteria into the bronchi was associated with surfactant degradation and a decrease in large:small ratio of surfactant aggregates in rats.

Antioxidant enzyme Glutathione S- Transferase (GST) is thought to do the primary cellular defense mechanism against reactive oxygen species. GST reduces lipid hydroperoxides through its Se-independent glutathione peroxidase activity. The enzyme also detoxifies lipid peroxidation end products such as 4-hydroxynonenal (4-HNE).
The soluble GST is a 26 kDa protein which occurs as a dimer in all aerobic organisms. Each monomer has two domains, one that binds GSH and is an /-structure similar to thioredoxin and the other, all helical, that binds the hydrophobic substrate. The GST -fusion protein expression system is a widely used recombinant protein expression system that allows a peptide or a regulatory protein domain to be expressed as a fusion to the C-terminus of Schistosoma japonicum GST. Fusion proteins also possess GST -enzymatic activity and can undergo dimerization similar to in vivo. The fusion protein can be purified via GST -affinity column chromatography. In most cases, the desired peptides or domains are removed from GST by applying a specific protease that recognizes and cleaves the linker between the protein domain and GST. The technique has been widely used to generate different kinds of proteins for crystallization, molecular immunology studies, the production of vaccines and studies involving protein-protein and protein-DNA interactions.

GSTM3 belongs to the glutathione s-transferase (GST) family of proteins. There are eight GST proteins families, named alpha, kappa, mu, omega, pi, sigma, theta and zeta. Each one of the GST families has several proteins with different functions throughout the cell. The mu type of enzymes takes part in the detoxification of electrophilic compounds, including therapeutic drugs, carcinogens, environmental toxins and products of oxidative stress, by conjugation with glutathione.

Gltathione S-transferase PI 2, also known as GSTP2 is multifunctional enzyme which is involved in the protection of cellular components against anti-cancer drugs or peroxidative stress. Furthermore, down regulation of GSTP2 induces an increase of oxidative damage in the pyramidal cells of the CA1&CA3 regions as well as in the granular layer of the dentate gyrus, which at the end leads to structural and functional damage.