Table 1.
Tags/Clusters from discovery approach selected for further analysis
| Genomic region | Tag/Cluster name | Gene/Proteome description |
|---|---|---|
| CYP3A4 (PXRE) | Control (literature) | |
| CYP2B6 | Control (literature) | |
| UGT1A1 | Control (literature) | |
| MDR1 | Control (literature) | |
| CARS | GP0059_02_B04-frag008 | Encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the 20 aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. Alterations in this region have been associated with the Beckwith–Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancer. |
| OSBP2 | GP0059_06_B06-frag009 | Oxysterols are byproducts of cholesterol that can have cytotoxic effects on many cell types. The membrane-bound protein encoded by this gene contains a pleckstrin homology domain and an oxysterol-binding region. It binds oxysterols such as 7-ketocholesterol and may inhibit their cytotoxicity. |
| PFAS | GP0059_03_A11-frag004 | The enzyme encoded by this gene catalyzes the fourth step of inosine monophosphate biosynthesis. |
| CD59 | GP0059_06_C01-frag008 | This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. |
| CEACAM6 | GP0059_05_C06-frag011 | Carcinoembryonic antigen is one of the most widely used tumor markers in serum immunoassay determinations of carcinoma. An apparent lack of absolute cancer specificity for CEA probably results in part from the presence in normal and neoplastic tissues of antigens that share antigenic determinants with the 180 kDa form of CEA. |
| DOCK1 | GP0059_08_D04-frag004 | Dedicator of cytokinesis 1, member of the CDM family, contains an SH3 domain, binds phosphatidylinositol-3,4,5-triphosphate, integrin receptor-mediated complex formation with BCAR1 and CRK leads to RAC1 activation and phagocytosis of apoptotic cells. |
| FLJ10986 | GP0059_06_D06-frag004 | |
| CYP4F12 | Cluster 19 153 (GP0059_07_F05-frag007; GP0059_06_D09-frag005) | Cytochrome P450 family 4 subfamily F polypeptide 12, metabolizes arachidonic acid by omega 3-hydroxylation, metabolizes docosahexanoic acid, docosapentaenoic acid, leukotrienes and the antihistamine drug ebastine. |
| CYP3A5 | GP0059_02_H05-frag007 | This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. The enzyme metabolizes drugs such as nifedipine and cyclosporine as well as the steroid hormones testosterone, progesterone and androstenedione. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. This cluster includes a pseudogene, CYP3A5P1, which is very similar to CYP3A5. This similarity has caused some difficulty in determining whether cloned sequences represent the gene or the pseudogene. |
| CYP3A5P2/CYP3A4 | Cluster 7 170 (GP0059_04_A01-frag006; GP0059_01_D05-frag007) | |
| ABCC4 | GP0059_10_C11-frag004 | The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. This protein is a member of the MRP subfamily which is involved in multi-drug resistance. The specific function of this protein has not yet been determined; however, this protein may play a role in cellular detoxification as a pump for its substrate, organic anions. |
| SULT1B1 | GP0059_01_B02-frag007 | Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. |
| SLC40A1 | Cluster 2 215 (GP0059_10_F11-frag006; GP0059_01_C04-frag005) | Solute carrier family 40 (iron-regulated transporter) member 1, an iron transporter involved in iron homeostasis and regulation of translation initiation, possibly involved in development; gene mutations are a cause of autosomal dominant hemochromatosis. |
| KCNK5 | Cluster 6 129 (GP0059_03_F09-frag006; GP0059_10_A04-frag005) | Potassium channel subfamily K member 5, mediates a pH and acid sensitive, noninactivating, outwardly rectifying K+ conductance, involved in potassium ion transport, inhibited by amide anesthetics. |
| UGT1A5 | GP0059_07_C01-frag002 | Encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones and drugs, into water-soluble, excretable metabolites. |
| AKR1C1 | GP0059_01_B10-frag003 | Aldo-keto reductase family 1 member C1 acts in xenobiotic and progesterone metabolism, increased expression is observed in lung cancer, glaucoma and polycystic ovary syndrome. |
| AKR1C2 | GP0059_02_C12-frag007 | Aldo-keto reductase family 1 member C2 (dihydrodiol dehydrogenase), functions in bile transport, steroid metabolism and xenobiotic metabolism, expression is decreased in prostate and breast cancer but upregulated in esophageal squamous cell carcinoma. |
| CYP2C8 (gene) | GP0059_03_D11-frag004 | Cytochrome P450 family 2 subfamily C polypeptide 8, a member of heme-binding mono-oxygenase superfamily, metabolizes steroids, fatty acids and xenobiotics, altered expression may contribute to colon cancer development. |
| CYP2C8 (downstream) | GP0059_05_C04-frag010 | |
| PAPSS2 | GP0059_01_A08-frag002 | 3′-phosphoadenosine 5′-phosphosulfate synthase 2, involved in skeletal development; mutation in the corresponding gene correlates with spondyloepimetaphyseal dysplasia, mouse Papss2 gene is associated with brachymorphism. |
| HDAC7A | GP0059_06_H02-frag002 | Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene has sequence homology to members of the histone deacetylase family. This gene is orthologous to mouse HDAC7 gene whose protein promotes repression mediated via the transcriptional corepressor SMRT. |
| TEAD2 | GP0059_01_B06-frag007 | TEA domain family member 2, a member of the TEA DNA-binding domain family of transcription factors, regulates transcription, may be involved in organ morphogenesis and central nervous system development. |
| HIST1H1E | GP0059_06_E12-frag008 | The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a member of the histone H1 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. |
| BMP1 | GP0059_06_G08-frag002 | Encodes a protein that is capable of inducing formation of cartilage in vivo. Although other bone morphogenetic proteins are members of the TGF-β superfamily, this gene encodes a protein that is not closely related to other known growth factors. |
| CFL1 | GP0059_09_F09-frag0005 | Cofilin 1 (non-muscle), plays a role in actin filament depolymerization and lymphocyte chemotaxis, involved in the G protein-coupled receptor protein and Rho protein signaling pathways. |
| EIF5 | GP0059_05_G08-frag003 | |
| TGIF2 | GP0059_03_G06-frag003 | This gene is a DNA-binding homeobox protein and a transcriptional repressor. The encoded protein appears to repress transcription by recruiting histone deacetylases to TGF-β-responsive genes. This gene is amplified and overexpressed in some ovarian cancers, and mutations in this gene can cause holoprosencephaly. |
| BBC3 | Cluster 19-76 | Bcl-2 binding component 3, regulates p53 (TP53)-dependent and independent apoptosis, increased expression of BBC3 plays a role in chronic lymphocytic leukemia and lung neoplasms and is used in the treatment of glioma and colorectal neoplasms. |
| CLG | Cluster 19-185 | |
| GLDC | Cluster 9-228 | Glycine decarboxylase (glycine dehydrogenase, P-protein), part of the glycine cleavage system that catalyzes the decarboxylation of glycine; mutation of the corresponding gene causes nonketotic hyperglycinemia. |
| ABCB4 | GP0059_06_D02-frag005 | This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a full transporter and member of the P-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. |
| CENTD2 | Cluster 11-186 | Centaurin delta 2, functions as a GTPase activating protein (GAP) for both Arf and Rho family proteins, mediates PIP3 phosphoinositide-dependent Golgi apparatus membrane changes, filopodia formation and cell spreading. |
| ZNF281 | Cluster 1-52 | Zinc finger protein 281, a transcriptional repressor, member of the ZBP family, contains four Kruppel-type zinc fingers. |
| BCL9L | Cluster 11-267 | B-cell CLL/lymphoma 9-like, a BCL9-related protein that acts as a transcriptional regulator, induces β-catenin (CTNNB1) nuclear translocation epithelial to mesenchymal transition, enhances cell migration, expression is upregulated in colorectal tumors. |
| ARNT2 | Cluster 15-179 | Aryl-hydrocarbon receptor nuclear translocator 2, a protein that heterodimerizes with HIF-1alpha (HIF1A) and is involved in hypoxia-induced erythropoietin (EPO) expression. |
| ASS1 | Cluster 9-86 | The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10–14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase. Mutations in the chromosome 9 copy of ASS cause citrullinemia. Two transcript variants encoding the same protein have been found for this gene. |
| CTNNA1 | GF0059_10_B02-frag003 | |
| ELK1 | GP0059_02_G12-frag003 | This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum reponse element in the promoter of the c-fos proto-oncogene. The protein encoded by this gene is a nuclear target for the ras-raf-MAPK signaling cascade. |
| MTL5 | GP0059_04_G12-frag010 | Metallothionein proteins are highly conserved low-molecular-weight cysteine-rich proteins that are induced by and bind to heavy metal ions and have no enzymatic activity. They may play a central role in the regulation of cell growth and differentiation and are involved in spermatogenesis. This gene encodes a metallothionein-like protein which has been shown to be expressed differentially in mouse testes and ovary. |
| WT | GP0059_05_B10-frag005 | |
| XRCC5 | GP0059_01_D07-frag005 | The protein encoded by this gene is the 80 kDa subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. |