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Coagulation factor VIII participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder.

LDHA catalyzes the conversion of L-lactate and NAD to pyruvate and NADH in the final step of anaerobic glycolysis. LDHA is localized primarily in muscle tissue and is part of the lactate dehydrogenase family. Mutations in LDHA have been linked to exertional myoglobinuria. LDH1 is decreased in essential thrombocythemia. LDHA is induced through a non-genomic pathway of estrogen action. Reduction in LDH-A activity results in stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential.

SAE1 and SAE2 form heterodimers which take part in the posttranslational modification of proteins (sumoylation). This process regulates protein structure as well as intracellular localization of the target. SAE1/SAE2 may indicate on dermatomyositis (DM) as autoantibodies against those 2 proteins have been found in patients.

DAAO is a peroxisomal enzyme which uses FAD (flavin adenine dinucleotide) as a cofactor and oxidizes D-amino acids to the corresponding amino acids, producing ammonia and hydrogen peroxide. DAAO substrates include an extensive array of D-amino acids, but it is inactive on the naturally occurring L-amino acids. DAAO acts on a variety of D-amino acids especially on those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups; however it doesn’t act on acidic amino acids. DAAO may be involved in acid base balance in the kidney or it could act as a detoxifying agent which removes D-amino acids accumulated during aging. DAAO regulates the neuromodulator D-serine level in the brain. DAAO is highly active towards D-DOPA. Creatinine inhibits the DAAO in uremia. DAAO may also have a role in the pathophysiology of schizophrenia, but not in bipolar disorder.

GCDH is part of the acyl-CoA dehydrogenase family. GCDH is localized in the mitochondrial matrix as a homotetramer of 45-kD subunits. GCDH catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. GCDH uses electron transfer flavoprotein as its electron acceptor.

UBE2K belongs to the ubiquitin-conjugating enzymes family which take part in many cellular processes such as selective protein degradation, DNA repair, cell cycle control, and sporulation. In this mechanism, the ATP-coupled activation and subsequent ligation of ubiquitin are catalyzed by separate enzymes functionally linked by ubiquitin carrier protein UBC1. In addition, UBE2K is involved in Alzheimer's disease, Huntington's disease and antigen processing through its interaction with amyloid-?, huntingtin, and MHC-heavy chain proteins.

Glutathione reductase (Gor) is a member of the class-I pyridine nucleotide disulfide oxidoreductase family. The main role of the Gor protein is to uphold high levels of reduced glutathione in the cytosol. With the associated oxidation of NADPH, Gor transforms oxidized glutathione to the reduced form. The active site of the Gor protein is a redox-active disulfide bond.

HADH is part of the 3-hydroxyacyl-CoA dehydrogenase enzyme family. HADH is involved in mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. HADH enzymatic activity is at its peak with medium-chain-length fatty acids. Mutations in HADH cause familial hyperinsulinemic hypoglycemia. HADH participates in fatty acid oxidation, where some enzymes work in a step-wise fashion to break metabolize fats and convert them to energy.

Mitochondrial rRNA methyltransferase 1 homolog (MRM1) is a part of the RNA methyltransferase TrmH family. MRM1 methylates the ribose of guanosine G-2270 in the peptidyl transferase center of the mitochondrial large ribosomal RNA (21S).

ATPaseTransporting Beta 2 (ATP1B2) is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na+ and K+ ions across the plasma membrane. The precise function of the beta-2 subunit is not known. The ATP1B2 protein is composed of 3 subunits: alpha (catalytic), beta and gamma.

PDIA6 belongs to the protein disulfide isomerase family (PDI). PDIA6 is an enzyme in the endoplasmic reticulum in eukaryotes or periplasmic space of prokaryotes which catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold. PDIA6 functions as a chaperone that inhibits aggregation of misfolded proteins. PDIA6, also has a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin.

PDXP is the active form of vitamin B6 that functions as a coenzyme in preserving biochemical homeostasis. The desired degradation route from PLP to 4-pyridoxic acid involves the dephosphorylation of PLP by PDXP. PDXP shows activity to pyridoxal 5''-phosphate (PLP), pyridoxine 5''-phosphate (PMP) and Pyridoxine 5''-phosphate (PNP), with a highest activity with PLP followed by PNP.

Carbonic anhydrase (carbonate dehydratase) is a family of metalloenzymes (enzymes that contain one or more metal atoms as a functional component of the enzyme) that catalyze the rapid (and reversible) conversion of carbon dioxide to bicarbonate and protons, a reaction that occurs rather slowly in the absence of a catalyst. Carbonic anhydrase greatly increases the rate of the reaction, with typical catalytic rates of the different forms of this enzyme ranging between 104 and 106 reactions per second. The active site of most carbonic anhydrases contains a zincion. CAIII is a cytoplasmic isoenzyme, but is released into the circulation following injury.

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.

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.

Proteasome subunit beta type-2 (PSMB2) belongs to the proteasome T1B family, which is a 20S core beta subunit. The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. Proteasomes are spread throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. A crucial function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. PSMB2 is up-regulated in ovarian cancer cell lines.

Glutathione reductase (GSR) belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. The GSR enzyme is a homodimeric flavoprotein and has a role in maintaining glutathione (GSH) in its reduced form by catalyzing the reduction of glutathione disulfide (GSSG): GSSG + NADPH + H+ ->2GSH + NADP+. In the majority of eukaryotic cells, GSR upholds the ratio of [GSH] / [GSSG], and partakes in quite a few critical functions such as the detoxification of reactive oxygen species as well as protein and DNA biosynthesis.

Dopa decarboxylase is a homodimeric, pyridoxal phosphate dependent enzyme.
Dopa decarboxylase is involved in 2 metabolic pathways, synthesizing 2 significant neurotransmitters the take part in numerous clinical disorders, including Parkinson’s disease. Dopa decarboxylase is located in different areas of the brain and is mostly found in basal ganglia. Dopa decarboxylase catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopa, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. Defects in Dopa decarboxylase leads to aromatic L-amino-acid decarboxylase deficiency (AADCD). AADCD deficiency is an inborn error in neurotransmitter metabolism that causes combined serotonin and catecholamine deficiency.

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.

Matrix Metallopeptidase 23B (MMP23B) belongs to the matrix metalloproteinase (MMP) family, and it is section of a duplicated region of chromosome 1p36.3. MMP23B is a protease. MMP23B regulates the surface expression of some potassium channels by holding them in the endoplasmic reticulum. Members of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis.

HMOX2 cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently transferred to bilirubin by biliverdin reductase. Under physiological conditions, the activity of HMOX2 is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. HMOX2 participates in the production of carbon monoxide in the brain where it operates as a neurotransmitter. HMOX2 is an essential enzyme in heme catabolism and is involved in cellular response to oxidative stress.

Serine/threonine-protein kinase 16 (STK16) is a membrane-associated protein kinase which phosphorylates on serine and threonine residues. STK16 is involved in secretory vesicle trafficking or intracellular signaling. Furthermore, the STK16 protein may have a role in regulating stromal-epithelial interactions which occur during ductal morphogenesis in the mammary gland. STK16 can autophosphorylate on Tyr residue; it is however unclear whether STK16 has tyrosine-protein kinase toward other proteins. STK16 may also be involved in TGF-beta signaling.