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Gltathione S-transferase PI 2, also known as GSTP2 is multifunctional enzyme which is involved in theprotection of cellular components against anti-cancer drugs or peroxidative stress. Furthermore, down regulation of GSTP2induces an increase of oxidative damage in the pyramidal cells of the CA1&CA3 regions as well as in the granular layer ofthe dentate gyrus, which at the end leads to structural and functional damage.

General control of amino acid synthesis protein 5 like 2 (KAT2A) is a member of the GCN5 family. KAT2A functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Acetylation of histones gives a specific tag for epigenetic transcription activation. KAT2A interacts with Ku70, TAF9, transcription initiation protein SPT3 homolog, TADA2L, Ku80 and DDB1.

Glucagon is an important hormone involved in carbohydrate metabolism. The hormone is synthesized and secreted from alpha cells (a-cells) of the islets of Langerhans, which are located in the endocrine portion of the pancreas. Glucagon is released when the glucose level in the blood is low (hypoglycemia), causing the liver to convert stored glycogen into glucose and release it into the bloodstream. The action of glucagon is thus opposite to that of insulin, which instructs the body's cells to take in glucose from the blood in times of satiation.
Glucagon is beneficial for the culture of some cell types. It has been used in some biochemical regulation studies of glycogenolysis in hepatocytes. It has been also been found to induce DNA replication in primary cultures of adult rat hepatocytes when used in combinations with EGF and Insulin. Glucagon increases the blood glucose concentration by promoting rapid breakdown of liver glycogen, and also acts to relax smooth muscle such as the gastrointestinal tract.

Cathepsin-Z (CTSZ) is a lysosomal cysteine proteinase and member of the peptidase C1 family. CTSZ, which has been also known as cathepsin X and cathepsin P, exhibits carboxy-monopeptidase and carboxy-dipeptidase activities. CTSZ is expressed ubiquitously in cancer cell lines and primary tumors and, similar to other members of this family, takes part in tumorigenesis.

Disulfide Oxidoreductase or DsbA is a protein, found in the plasma. It is part of the thioredoxin protein family. The protein creates disulfide bonds in the target proteins by contributing disulfide bond from its Cys30-Pro31-His32-Cys33 active site to a couple of cysteine residues.

Ubiquitin-conjugating enzyme E2 J2 (UBE2J2) is a member of the ubiquitin-conjugating enzyme family. UBE2J2 catalyzes the covalent attachment of ubiquitin to other proteins. UBE2J2 is located in the membrane of the endoplasmic reticulum. UBE2J2 participates in the selective degradation of misfolded membrane proteins from the endoplasmic reticulum (ERAD).

Dual Specificity Phosphatase 22, also known as DUSP22, is a part of the protein-tyrosine phosphatase family which holds 1 tyrosine-protein phosphatase domain. DUSP22 activates the Jnk signaling pathway and dephosphorylates and deactivates p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). DUSP22 interacts with MAPK1 and MAPK8.

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.

Tryptase alpha/beta-1 (TPSAB1) is a tryptase which is the key neutral protease present in mast cells and is discharged upon the coupled activation-degranulation response of this cell type. TPSAB1 is enzymatically active only as a heparin-stabilized tetramer, and is resistant to all known endogenous proteinase inhibitors. TPSAB1 is implicated as a mediator in the pathogenesis of asthma and other allergic and inflammatory disorders.

Prostaglandin Reductase 2 (PTGR2) is a member of the medium-chain dehydrogenase/reductase superfamily. PTGR2 is an enzyme involved in the metabolism of prostaglandins. PTGR2 catalyzes an NADPH-dependent reduction of the conjugated alpha, beta-unsaturated double bond of 15-keto-PGE(2), which is a fundamental step in terminal inactivation of prostaglandins and suppression of PPARgamma-mediated adipocyte differentiation. PTGR2 may also be involved in controlling activation of the peroxisome proliferator-activated receptor.

M2 autoantigen is a key mark of antimitochondrial autoantibodies (AMA), a typical serological feature in patients suffering from primary biliary cirrhosis (PBC) which is a serious autoimmune liver disease accompanied by damage to intrahepatic bile ducts. Molecular definition of the M2 antigen has displayed it as no less than 3 separate target proteins. The M2 role is like the so-called E2 subunits (or dihydrolipoamide transferases) of different mitochondrial dehydrogenase complexes:
*pyruvate dehydrogenase complex.
*branched chain 2-oxo-acid dehydrogenase complex.
*2-oxoglutarate dehydrogenase complex.
Biochemically, these complexes catalyze the oxidative decarboxylation of various alpha-keto-acid substrates and systematically engage with a prosthetic lipoamide group; they are situated in the mitochondrial matrix in association with the inner membrane. The most well-known reactivity of AMA positive PBC sera is against PDC-E2. Some patients have AMA which reacts with PDC-E2 alone (95%), but most patients also show reactivity against OGDC-E2 (39-88%) and/or BCOADC-E2 (53-55%). Actually, patients can be found with reactivity only against OGDC-E2 and/or BCOADC-E2 and no PDC-E2 autoantibodies. These patients will be overlooked in assays based on natural source-derived, predominantly PDC-E2-containing M2 antigen preparations.

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.

TOP1 is an important nuclear enzyme that interconverts supercoiled DNA to the necessary topological conformations for standard DNA replication and transcription. TOP1 is the target antigen for TOP1 autoantibodies. TOP1 antibodies are a specific marker in scleroderma patients (specificity 98-100%) and are related with the existence of diffuse skin involvement and pulmonary fibrosis. In human tissues top1 enzyme is primarily synthesized as a protein with a molecular weight of 100-kDa. Most of this precursor is then proteolytically processed to a 70-kDa size, from which the TOP1 antigen has derived its name.

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.

AK1 is a small ubiquitous enzyme which is essential for maintenance and cell growth. It is involved in the regulation of adenine nucleotide composition within a cell by catalyzing the reversible transfer of the terminal phosphate group between ATP and AMP. The AK1 protein is found in the cytosol of skeletal muscle, brain and erythrocytes. Defects in the AK1 gene are the cause of a form of hemolytic anemia.

Aldolase C Fructose-Bisphosphate (ALDOC) belongs to the class I fructose-bisphosphate aldolase family. ALDOC is a glycolytic enzyme which catalyzes the reversible aldol cleavage of fructose-1,6-biphosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceraldehyde-3-phosphate or glyceraldehydes respectively. ALDOC is expressed exclusively in the hippocampus and Purkinje cells of the brain.

Pyruvate Dehydrogenase Complex, Component X, also known as PDHX, encodes the E3 binding protein subunit of the PDH complex which contains 3 catalytic subunits. PDHX tethers E3 dimers to the E2 core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is critical for a functional PDH complex.

Phosphoglycerate mutase 2 (PGAM2) is a member of the phosphoglycerate mutase family. PGAM is a dimeric enzyme which contains in separate tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). PGAM (Phosphoglycerate mutase) catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. PGAM2 gene mutations cause muscle phosphoglycerate mutase efficiency, otherwise known as glycogen storage disease X.

Phosphoglucomutase-1 also known as PGM1 is a member of the phosphohexose mutase family. There are more than a few PGM isozymes, which catalyze the transfer of phosphate between the 1&6positions of glucose. In nearly all cell types, PGM1 isozymes predominate, representing around 90% of total PGM activity.It has been found that defects in PGM1 are the cause of glycogen storage disease type 14.

GNMT is an enzyme that catalyzes the conversion of S-adenosyl-L-methionine with glycine to S-adenosyl-L-homocysteine and sarcosine. GNMT is located in the cytoplasm and acts as a homotetramer. Defects in the GNMT gene causes of GNMT deficiency (hypermethioninemia). GNMT affects DNA methylation by regulating the ratio of S-adenosylmethionine to S-adenosylhomocystine and is involved in the detoxification pathway in liver cells. GNMT expression is diminished in human hepatocellular carcinoma (HCC). GNMT catalyzes the methylation of glycine by using s- adenosylmethionine (adomet) to form n-methylglycine (sarcosine) with the concomitant production of s-adenosylhomocysteine (adohcy). GNMT plays an essential role in the regulation of tissue concentration of adomet and of metabolism of methionine.

NUDT3 is a 172 amino acid cytoplasmic protein which is a member of the nudix hydrolase family and DIPP subfamily. NUDT3 functions as a negative regulator of the ERK 1/2 pathway and hydrolyzes 5-phosphoribose 1-diphosphate. NUDT3 is a monomer which binds magnesium as a cofactor. In addition, NUDT3 is widely expressed but can be found at highest levels in the liver, pancreas, brain and heart.

Cyclophilin B (also known as PPIB, peptidylpropyl isomerase B) is a cyclosporine-binding protein and is mainly located within the endoplasmic reticulum. It is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression.

GMFB is part of the GMF subfamily of the larger actin-binding protein ADF family. GMFB is phosphorylated after phorbol ester stimulation, and is crucial for the nervous system. GMFB causes brain cell differentiation, stimulates neural regeneration and inhibits tumor cell proliferation. GMFB overexpression in astrocytes results in the increase of BDNF production. GMFB expression is increased by exercise, thus BDNF is important for exercise-induction of BDNF.

Ubiquitin-conjugating enzyme E2 F (UBE2F) is a member of the ubiquitin-conjugating enzyme family and UBE2F subfamily. Ubiquitin-conjugating enzymes or sometimes as ubiquitin-carrier enzymes, run the second step in the ubiquitination reaction which targets a protein for degradation using the proteasome. The UBE2F receives the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins.
RBX2-UBE2F complex neddylates specific target proteins, for example CUL5 as can be seen from the specific interaction with the E3 ubiquitin ligase RBX2, but not RBX1.