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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.

GSTT1 belongs to a superfamily of proteins which catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds. GSTT1 is one of the GSTs’ four main classes: alpha, mu, pi and theta (which includes GSTT1 and GSTT2). GSTT1 is involved in activation and detoxification reactions and catalyzes the conjugation of industrial chemicals, such as epoxybutane, ethylene oxides, halomethane with glutathione. GSTT1 is found in erythrocytes, at low levels in the liver as well as in Clara and ciliated cells at the alveolar/bronchiolar junction in the lung.
The GSTT1 gene is deficient in 38% of the population. The GSTTI enzyme deficiency might influence the individual risk for development of acquired aplastic anemia and acute myeloid leukemia. The presence or absence of the GSTT1 gene is concurrent with GSST1+ (the conjugator) and GSTT1- (the non-conjugator) phenotypes correspondingly. The GSTT1+ phenotype is able to catalyze the glutathione conjugation of dichloromethane. GSTT1-null genotypes are seen as having a higher risk of developing leukoplakia. Germline genetic polymorphism in GSTT1 is linked to breast cancer.

Leukotriene A-4 hydrolase (LTA4H) is a bifunctional enzyme that converts leukotriene A4 to leukotriene B4 and functions as an aminopeptidase. The LTA4H enzyme is a member of the family of hydrolases, specifically those acting on ether bonds (ether hydrolases). LTA4H participates in arachidonic acid metabolism.

IMP2 Inner Mitochondrial Membrane Peptidase-Like (IMMP2L) is implicated in processing the signal peptide sequences, IMMP2L is used to direct mitochondrial proteins to the mitochondria. IMMP2L resides in the mitochondria and is one of the essential proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants which encode the same protein have been found for IMMP2L.

Ectonucleotide Pyrophosphatase-2, aka ENPP2, a part of the ectonucleotide pyrophosphatasefamily. ENPP2 is able to cut the phosphodiester bond between the alpha and the beta position of triphosphate nucleotides, acting as an ectonucleotide phosphodiesterase producing pyrophosphate, as most members of the ENPP family. It is unlike ENPP-1 and ENPP-3, has weak activity against nucleotides, but shows a lysophospholipase D activity which allows the formation of LPA and choline from lysophosphatidylcholine. As well, ENPP-2 and LPA are involved in several inflammatory-driven diseases such as arthritis and asthma.

PHPT1 is a member of the Janus protein familyand is 125 amino acid long. PHPT1 appears as a monomer in the cytoplasm and is an EDTA-insensitive phosphohistidine phosphatase. Overexpression of PHPT1 resolts in specific phosphohistidine phosphatase activity towards phosphopeptide I, with no activity detected towards phosphotyrosine, phosphothreonine and phosphoserine peptides.

N-alpha-acetyltransferase 30 (NAA30) is catalytic subunit of the N-terminal acetyltransferase C (NatC) complex. NAA30 catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Leu-Ala and Met-Leu-Gly. In addition, NAA30 is essential for the lysosomal localization and function of ARL8B. The disease Eastern equine encephalitis has been associated with NAA30.

ABHD14B is a member of the AB hydrolase superfamily. ABHD14B has an alpha/beta hydrolase fold - a catalytic domain found in a large number of enzymes. In molecular biology, the alpha/beta hydrolase fold is common to a number of hydrolytic enzymes of broad differing phylogenetic source and catalytic function. The Ab hydrolase domain containing gene subfamily includes 15 mostly uncharacterized members. ABHD14B has hydrolase activity with p-nitrophenyl butyrate (in vitro) and is able to activate transcription.

Dual specificity phosphatase 18 (DUSP18) belongs to the dual-specificity phosphatase (DSP) family, which catalyzes dephosphorylation of phosphotyrosine and phosphothreonine residues. DUSP18 has a preferential enzymatic activity for phosphorylated tyrosine residues over threonine residues, in addition DUSP18 dephosphorylates p-nitrophenyl phosphate (pNPP) in vitro. Furthermore, DUSP18 is inhibited by iodoarectic acid and is activated by manganese ions. DUSP18 is extensively expressed with the highest levels in the liver, brain, ovary and testis.

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.

SULT2B1 catalyzes the sulfate conjugation of numerous hormones, neurotransmitters, drugs and xenobiotic compounds. Sulfonation enhances the water solubility of molecules, and therefore their renal excretion, however it can also result in bioactivation to form active metabolites. SULT2B1b is localized in the cytosol and nuclei of human cells. SULT2B1b is selective for the sulfation of 3beta-hydroxysteroids such as dehydroepiandrosterone and pregnenolone, and participates in cholesterol sulfation in human skin.

FEN1 removes 5'' overhanging flaps in DNA repair and processes the 5'' ends of Okazaki fragments in lagging strand DNA synthesis. The interaction between FEN1 and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, therefore passing the substrate from one enzyme to another. FEN1 is part of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5'' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions.

Lysine Methyltransferase 5A (KMT5A) is an enzyme which catalyzes both histones and non-histone proteins. KMT5A contributes to the maintenance of proper higher-order structure of DNA during mitosis. KMT5A takes part in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans. KMT5A plays a role as a barrier to prevent cellular senescence through chromatinmediated regulation of senescence-associated metabolic remodeling. KMT5A mediates monomethylation of p53/TP53 at 'Lys-382', which leads to repress p53/TP53-target genes. The loss of KMT5A simultaneously stimulate nucleolar function and retinoblastoma protein-mediated mitochondrial metabolism.

NUDT1 is an enzyme that hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates, thereby preventing misincorporation of 8-oxo-dGTP into DNA thus preventing A:T to C:G transversions. NUDT1 is found mostly in the cytoplasm, with some in the mitochondria, suggesting that it is involved in the sanitization of nucleotide pools both for nuclear and mitochondrial genomes. Moreover, NUDT1 is expressed at much higher levels in proliferating cells than in resting cells. Misincorporation of oxidized nucleoside triphosphates into DNA/RNA during replication and transcription can cause mutations which may result in carcinogenesis or neurodegeneration.

Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1) is a member of the purine/pyrimidine phosphoribosyltransferase family. PRTFDC1 has a low, barely measurable phosphoribosyltransferase activity (in vitro). PRTFDC1 can bind GMP, IMP and alpha-D-5-phosphoribosyl 1-pyrophosphate (PRPP). PRTFDC1 is not expected to impact purine metabolism or GMP salvage.

Human Pin 1 is a peptidyl-prolyl cis/trans isomerase (PPIase) that 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.

Ubiquitin-conjugating enzyme E2 H (UBE2H) is a member of the ubiquitin-conjugating enzyme family. Protein modification with ubiquitin is a vital cellular apparatus for directing abnormal or short-lived proteins for degradation. Ubiquitination requires at least 3 classes of enzymes: ubiquitin-activating enzymes (E1s) ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). UBE2H receives ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. UBE2H protein sequence is 100% identical to the mouse homolog and 98% identical to the frog and zebrafish homologs.

UBE2E3 or Ubiquitin-conjugating enzyme E2 E3 is part of the E2 ubiquitinconjugating enzyme family. UBE2E3 is needed for the destruction of mitotic cyclins and for cell cycle progression. The ubiquitination process covalently attaches to a short protein of 76 amino acids called ubiquitin, to a lysine residue on the target protein. When a protein has been tagged with one ubiquitin molecule, other rounds of ubiquitination form a polyubiquitin chain that is recognized by the proteasome's 19S regulatory particle, triggering the ATP-dependent unfolding of the target protein which grants passage into the proteasome's 20S core particle, where proteases degrade the target into short peptide fragments for recycling by the cell.

Acyl-CoA synthetase family member 2, also known as ACSF2 is a member of the ATP-dependent AMP-binding enzyme family. Acyl-CoA synthetases are a family of enzymes which catalyze the thioesterification of fatty acids with coenzymeA to form activated intermediates, which play a basic part in lipid metabolism as well as homeostasis of lipid-related processes. ACSF2 is required for the complex of lipid synthesis, energy production via beta-oxidation, protein acylation and fatty-acid dependent transcriptional regulation. Moreover, ACSF2 is required for fatty acid import into cells by the process of vectorial acylation.

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.

Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) is a member of the FAH family. FAHD1 is considered to have hydrolase activity and it uses Magnesium and Calcium as cofactors. It seems quite likely that the metal binding sites are involved in an enzymatic activity connected to the catabolism of aromatic amino acids.

Plasma protease C1 inhibitor (SERPING1) is a part of the serpin superfamily of serine protease inhibitors. SERPING1 plays an important role in regulating activation of both the complement and contact systems. SERPING1 is also activating C1 by coupling with the active catalytic site at the light chains of C1r and C1s. SERPING1 insufficiency results in hereditary angioedema, which is characterized by recurrent episodes of localized angioedema of the skin, gastrointestinal mucosa or upper respiratory mucosa.

BLMH is affiliate to the papain superfamily of the cysteine protease and the peptidase C1 family. BLMH is a cytoplasmic cysteinepeptidase usually found as a homohexamer. The standard physiological role of BLMH has not been determined, but it shields normal and malignant cells from the glycopeptide antitumor drug BLM. BLMH catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxyamide bond of its B-aminoalaninamide moiety and in addition demonstrates general aminopeptidase activity.