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Guanosine monophosphate reductase (GMPR) catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. GMPR acts in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in upholding the intracellular balance of A and G nucleotides. In addition, the GMPR protein functions in the re-utilization of free intracellular bases and purine nucleosides.

Uroporphyrinogen III synthase (UROS) is an enzyme involved in the 4th step of porphyrin metabolism and in the conversion of hydroxymethyl bilane into uroporphyrinogen III. Defects in the UROS protein can cause molecular lesions which lead to the autosomal recessive Gunther disease, otherwise known as congenital erythropoietic porphyria (CEP).

Uromodulin is the most abundant protein in normal urine. Its secretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. Uromodulin plays a role as a constitutive inhibitor of calcium crystallization in renal fluids. Secretion of uromodulin in urine provides protection against urinary tract infections caused by uropathogenic bacteria. Defects in Uromodulin expression are associated with the autosomal dominant renal disorders medullary cystic kidney disease-2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN). These disorders are characterized by juvenile onset of hyperuricemia, gout, and progressive renal failure. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. UMOD is involved in regulating the circulating activity of cytokines as it binds to il-1, il-2 and tnf with high affinity.

The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of fas-mediated apoptosis using similar mechanisms.

CD40 is part of the TNF-receptor superfamily. CD40 is a necessary mediator for vast range of immune and inflammatory responses together with T cell-dependent immunoglobulin class switching, memory B cell growth, and germinal center formation. The transcription factor AKNA regulates the expression of CD40 and its ligand, which is vital for homotypic cell interactions. Adaptor protein TNFR2 interacts with CD40 and serves as a mediator of the signal transduction. The interaction of CD40 and its ligand is crucial for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. CD40 is the receptor for TNFSF5/CD40L.

Adenosylmethionine decarboxylase proenzyme (AMD1) is synthesized originally as an inactive proenzyme. Putrescine stimulates both the proenzyme processing and the catalytic activity. The catalytic activity is inhibited by iodoacetic acid. The active enzyme formation entails a self-maturation process in which the active site pyruvoyl group is produced from an internal serine residue using an autocatalytic post-translational modification.

DNA Cytosine-5--Methyltransferase 3-Like (DNMT3L) is a nuclear protein with similarity to DNA methyltransferases, but is not believed to act as a DNA methyltransferase since it doesn’t contain the amino acid residues needed for methyltransferase activity. Nevertheless, DNMT3L stimulates de novo methylation by DNA cytosine methyltransferase 3 alpha and is assumed to be required for the formation of maternal genomic imprints. DNMT3L also mediates transcriptional repression as a result of interaction with histone deacetylase 1. DNMT3L is a catalytically inactive regulatory factor of DNA methyltransferases, which is vital for the function of DNMT3A and DNMT3B. DNMT3L activates DNMT3A and DNMT3B by binding to their catalytic domain. Furthermore, DNMT3L accelerates the binding of DNA and AdoMet to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases.

D-Tyrosyl-tRNA Deacylase 1 (DTD1) is a member of the DTD family. DTD1 hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr). DTD1 may be a defense mechanism against a damaging effect of D-tyrosine. DTD1 is an ATPase involved in DNA replication, which may facilitate loading of CDC45 onto pre-replication complexes. The DTD1 protein localizes to the DUE (DNA unwinding elements) of active replication origins. DTD1 is expressed in numerous adult and fetal tissues, with the highest levels in the testis, ovary, spleen and in the adult and fetal brain. DTD1 might be a risk factor for AIA (aspirin-intolerant asthma) by catalyzing the hydrolysis of D-tryptophan and interacting with the tyrosyl-tRNA synthetase (tyrRS) enzyme that promotes a pro-inflammatory phenotype.

Neuron-specificenolase also caled NSE is a glycolytic isoenzyme which is situated in central and peripheral neurons and neuroendocrine cells. Enolase-2 is released into the CSF when neural tissue is injured. Neoplasms derived from neural or neuroendocrine tissue release Enolase-2 into the blood. Enolase-2 is a useful substance that has been detected in patients with certain tumors, such as neuroblastoma, small cell lung cancer, medullary thyroid cancer, carcinoid tumors, pancreatic endocrine tumors, and melanoma. ENO2 is 1 of the 3 enolase isoenzymes found in mammals. ENO2 isoenzyme, is found in mature neurons and cells of neuronal origin. An exchange from alpha enolase to gamma enolase occurs in neural tissue during development in rats and primates.

Beta-galactosidase or GLB1 is a B-galactosidase found in the lysosome. This enzyme hydrolyzes the finale B-galactose from the precursors ganglioside & keratin sulfate. GLB1 has a crucial part in the creation of elastogenesis (extracellular elastic fibers) and connective tissue development. This enzyme is similar to elastin-binding protein which is a key part in non-integrin cell surface receptor. In cells that extort elastin GLB1 is linked to tropoelastin intracellularly and act as recycling molecular chaperone.

Flavokinase is a transferases family member, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. Flavokinase is an enzyme that catalyzes the phosphorylation of riboflavin (vitamin B2) to form flavin-mononucleotide (FMN), which is an obligatory step in vitamin B2 utilization and flavin cofactor synthesis. It has been proposed that TNF, through the activation of the RFK gene, enhances the incorporation of FAD in NADPH oxidase enzymes, which is a critical step for the assembly and activation of NADPH oxidase.

Cathepsin D is synthesized as a 54kDa precursor, which is proteolytically processed to an intermediate 48kDa single chain, which matures into more stable 34kDa and 14kDa two chain form. It is an estrogen-regulated lysosomal protease that has been suggested to facilitate cancer cell migration and invasion by digesting the basement membrane, extracellular matrix, and xonnective tissue. Because of its mitogenic and proteolytic activities, it has been implicated as a prognostic marker in many tumor types. Cathepsin D is expressed in epithelial cells as well as in macrophages.

AKR1C4 is a member of the aldo/keto reductase superfamily that has over 40 known enzymes and proteins. AKR1C4 enables the conversion of aldehydes and ketones to their corresponding alcohols by using NADH and/or NADPH as cofactors. AKR1C4 takes part in the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver.

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.

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.

Spermine synthase (SMS) is amember of the spermidine/spermine synthase family. SMS is an enzyme which converts spermidine into spermine. The SMS enzyme is essential for normal viability, growth and fertility involved in polyamine metabolism. Defects in the SMS gene are the cause of Snyder-Robinson syndrome (SRS), also known as X-linked mental retardation Snyder-Robinson type. SRS is categorized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry, its transmission is X-linked recessive.

Branched Chain Amino-Acid Transaminase 2 (BCAT2) is a member of the class-IV pyridoxal-phosphate-dependent aminotransferase family. BCAT2 is a branched chain aminotransferase found in mitochondria. BCAT2 forms a dimer which catalyzes the first step in the production of the branched chain amino acids leucine, isoleucine, and valine. In addition, BCAT2 may actn as a transporter of branched chain alpha-keto acids.

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.

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.

Carbonic Anhydrase VIII or CA8 was previously called CA-related protein due to its sequence resemblance to additional recognized carbonic anhydrase genes. Nonetheless CA8 doesn’t have carbonic anhydrase function. This protein keeps bearing a carbonic anhydrase classification because of coherent sequence similarity to additional proteins in carbonic anhydrase family. Mutations in this protein may lead to cerebellar dysequilibrium syndrome type 3 or ataxia mental retardation.

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.

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.

DNA toposisomerase I is a key nuclear enzyme that interconverts supercoiled DNA to the required topological conformations for normal DNA replication and transcription. This enzyme is the target antigen for the so-called Scl-70 autoantibodies. Scl-70 antibodies are a specific marker in Scleroderma patients (specificity 98-100%) and are associated with the presence of diffuse skin involvement and pulmonary fibrosis.
In human tissues the DNA topoisomerase I is initially synthesized as a protein with 100 kDa molecular weight. Most of this precursor is then proteolytically processed to a species with 70 kDa molecular weight from which the Scl-70 antigen has derived its name.