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The epidermal growth factor receptor (EGF R) subfamily of receptor tyrosine kinases comprises four members: EGF R (also known as HER1, ErbB1 or ErbB), ErbB2 (Neu, HER-2), ErbB3 (HER-3), and ErbB4 (HER-4). All family members are type I transmembrane glycoprotein that has an extracellular domain which contains two cysteine-rich domains separated by a spacer region that is involved in ligand-binding, and a cytoplasmic domain which has a membrane-proximal tyrosine kinase domain and a C-terminal tail with multiple tyrosine autophosphorylation sites. The human EGF R gene encodes a 1210 amino acid (aa) residue precursor with a 24 aa putative signal peptide, a 621 aa extracellular domain, a 23 aa transmembrane domain, and a 542 aa cytoplasmic domain. EGF R has been shown to bind a subset of the EGF family ligands, including EGF, amphiregulin, TGF-a , betacellulin, epiregulin, heparin-binding EGF and neuregulin-2 in the absence of a co-receptor. Ligand binding induces EGF R homodimerization as well as heterdimerization with ErbB2, resulting in kinase activation, tyrosine phosphorylation and cell signaling. EGF R can also be recruited to form heterodimers with the ligand-activated ErbB3 or ErbB4. EGF R signaling has been shown to regulate multiple biological functions including cell proliferation, differentiation, motility and apoptosis. In addition, EGF R signaling has also been shown to play a role in carcinogenesis.

Hexokinases phosphorylate glucose to produce glucose-6-phosphate, thus committing glucose to the glycolytic pathway. Hexokinase 2 is the predominant form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells.

Dickkopf-related protein 3 (DKK3) belongs to the DKK protein family including Dkk-1, 2, 3 and -4. DKK3 is a 350 amino acid secreted glycoprotein which is comprised of an N-terminal signal peptide and 2 conserved cysteine-rich domains that are separated by a 12 amino acid linker region. DKK3 is involved in embryonic development through its inhibition of the WNT signaling pathway. DKK3 gene expression is decreased in a variety of cancer cell lines and it may act as a tumor suppressor gene.

KLF4 (aka the gut-enriched Kruppel-like factor-GKLF), is a zinc finger-containing transcription factor which is a member of the Kruppel-like family of transcription factors. KLF4 plays key roles during the proliferation and differentiation of epithelial cells. Particularly, it is found mainly in the gut and has been shown to be expressed during growth arrest. KLF4 is also involved in cell cycle control since expression of KLF4 inhibits DNA synthesis by blocking the G1/S phase of the cell cycle.

CD3 has four peptide chains (gamma, delta, epsilon and zeta) that form CD3. Defects in CD3 are associated with T cell immunodeficiency CD3 complex mediates signal transduction.

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.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of growth hormone (GH; MIM 139250). Early studies showed that growth hormone did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as 'somatomedin' (Daughaday et al., 1972). Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

EPH Receptor A2 (EPHA2) is a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPHA2 is a protein which binds ephrin-A ligands. EPH and EPH-related receptors are associated with mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily normally have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. EPHA2 gene mutations are the cause of certain genetically-related cataract disorders.

Myeloid differentiation primary response gene 88 (MYD88) is a cytosolic adapter protein, which has a central role in the innate and adaptive immune response. MYD88 functions as a vital signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. MYD88 acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. The MYD88 protein increases IL-8 transcription. MYD88 is involved in IL-18-mediated signaling pathway. MYD88 activates IRF1, resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. MYD88 is comprised of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in the MYD88 gene have an increased susceptibility to pyogenic bacterial infections.

CD-90 plays a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain.
Thy-1 is the designation for a major cell surface glycoprotein characteristic to T cells,. The Thy-1 glycoproteins are constituents of thymocytes and neurons and probably are involved in cell-cell interactions. Human Thy-1 homolog maps to chromosome 11 because that is where T3D is found, in the mouse T3D and Thy-1 map to chromosome 9 along with certain other loci that are on human 11q.

HER-2/neu (erbB-2) encodes an 185-kDa orphan receptor tyrosine kinase that is constitutively active as a dimer and displays potent oncogenic activity when overexpressed. Herstatin, as the product of alternative HER-2 transcript, retains intron 8. The herstatin mRNA is expressed in normal human fetal kidney and liver, but is at reduced levels relative to p185HER-2 mRNA in carcinoma cells that contain an amplified HER-2 gene. Herstatin appears to be an inhibitor of p185HER-2, because it disrupts dimers, reduces tyrosine phosphorylation of p185, and inhibits the anchorage-independent growth of transformed cells that overexpress HER-2.

Caseine Kinase 1 alpha belongs is a member of the protein kinase superfamily, CK1 Ser/Thr protein kinase family, Casein kinase I subfamily. The CK1 isoforms - alpha, beta, gamma, delta, epsilon and their splice variants are involved in diverse cellular processes including membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular differentiation. Possibly CSNK1A1 can phosphorylate a large number of proteins and is involved in Wnt signaling where it phosphorylates CTNNB1 on Ser45. CSNK1A1 also interacts with the Axin complex.

The transcription of heat-shock genes is rapidly induced after temperature stress in response to environmental changes, and it is also involved in oogenesis, spermatogenesis, and placental development. Hsp90, is a major repressor of HSF1 gene. HSF1 is known for its participation in heat shock response. HSF1 protein regulates the transcription of hundreds of targets, such as genes involved in protein folding, detoxification, energy generation, carbohydrate metabolism, and cell wall organization. HSF1 binds to MTA1 in vitro & in breast carcinoma. Suppression of estrogen-dependent transcription may contribute to role of HSF1 in cancer. Human cancer lines of diverse origins express higher dependence on HSF1 function to maintain proliferation and survival than their non-transformed counterparts. HSF1 induces anticoagulation and relaxation factors in vascular endothelial cells and could therefore be used to treat cardiovascular disease. HSF1 is directly involved in the regulation of HO1 havi

Human immunodeficiency virus (HIV) is a retrovirusthat can lead to a condition in which the immune systembegins to fail, leading to opportunistic infections. HIV primarily infects vital cells in the humanimmune systemsuch as helper T cells(specifically CD4+ T cells), macrophagesand dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: firstly, direct viral killing of infected cells; secondly, increased rates of apoptosisin infected cells; and thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytesthat recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunityis lost, and the body becomes progressively more susceptible to opportunistic infections. HIV was classified as a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses have many common morphologies and biological properties. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry of the target cell, the viral RNA genomeis converted to double-stranded DNAby a virally encoded reverse transcriptasethat is present in the virus particle. This viral DNA is then integrated into the cellular DNA by a virally encoded integraseso that the genome can be transcribed. Once the virus has infected the cell, two pathways are possible: either the virus becomes latentand the infected cell continues to function, or the virus becomes active and replicates, and a large number of virus particles are liberated that can then infect other cells.

NME2 takes an important part in the synthesis of nucleoside triphosphates other than ATP. NME2 negatively controls Rho activity by interacting with AKAP13/LBC. NME2 acts as a transcriptional activator of the MYC gene. NME2 binds DNA non-specifically. NME2 is a heterodimeric enzyme functioning as a nucleoside diphosphate kinase. NME1 and NME2 contain 152 amino acids, A and B polypeptide chains of the NM23 enzyme, respectively. NME2 is identical to the beta subunit of human erythrocyte NDP kinase. NDP kinases participate in the synthesis of nucleoside triphosphates, and NM23 is involved in the regulation of signal transduction by complexing with G proteins, causing activation/inactivation of developmental pathways.

WHSC1L1 gene is related to the Wolf-Hirschhorn syndrome candidate-1 gene and encodes a protein with PWWP (proline-tryptophan-tryptophan-proline) domains. The function of the WHSC1L1 protein has not been determined. WHSC1L1 is highly expressed in brain, heart and skeletal muscle; however it is expressed at lower level in the liver and the lung.

Cytokeratin 8 (KRT8) belongs to the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. KRT8 typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. KRT8 has a role in retaining cellular structural integrity and also functions in signal transduction and cellular differentiation. KRT8 gene mutations cause cryptogenic cirrhosis.

Rubella virus is an enveloped positive-strand RNA virus of the family TOGAVIRIDAE: Virions are composed of three structural proteins: a capsid and two membrane-spanning glycoproteins, E2 and E1. During virus assembly, the capsid interacts with genomic RNA to form nucleocapsids. The rubella virus (RV) structural proteins: capsid, E2, and E1 are synthesized as a polyprotein precursor. The signal peptide that initiates translocation of E2 into the lumen of the endoplasmic reticulum remains attached to the carboxy terminus of the capsid protein after cleavage by signal peptidase.

Japanese encephalitis previously known as Japanese B encephalitis is a virus from the family Flaviviridae. it is closely related to the West Nile virus and St. Louis encephalitis virus. Positive sense single stranded RNA genome is packaged in the capsid, formed by the capsid protein. The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several nonstructural proteins also (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). NS1 is produced as secretory form also. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that the Japanese encephalitis virus (JEV) infects the lumen of the endoplasmic reticulum (ER) and rapidly accumulates substantial amounts of viral proteins for the JEV. Japanese Encephalitis is diagnosed by detection of antibodies in serum and CSF (cerebrospinal fluid) by IgM capture ELISA.

Proteasomal ubiquitin receptor ADRM1 (ADRM1) functions as a proteasomal ubiquitin receptor. ADRM1 is an integral plasma membrane protein which promotes cell adhesion. ADRM1 is assumed to undergo O-linked glycosylation. ADRM1 gene expression is induced by gamma interferon in some cancer cells. ADRM1 employs the deubiquitinating enzyme UCHL5 at the 26S proteasome and promotes its activity.

HERVK is related with several tumors such as passenger virus, and anti-Retroviral therapy against amyotrophic lateral sclerosis/ALS has exhibited to decrease the symptoms of amyotrophic lateral sclerosis/ALS. High counts of viral sequences exist in the human genome but stay silent. Though, in pathological conditions, these viruses are produced. Human Endogenous Retrovirus-K, is produced in neurons of a subpopulation of patients with amyotrophic lateral sclerosis/ALS, a progressive neurodegenerative disease. The envelope protein of this HERV results in degeneration of neurons, and transgenic animals producing this protein advance an ALS-like syndrome triggered by nucleolar dysfunction in motor neurons. Reactivation of the HERVK is controlled by the transcription factor TDP-43. Therefore, therapeutic tactics against this virus alter the course of the disease.

HIV-1 protease is very significant in the life cycle of the HIV virus. It is expressed in the infected cells as a part of Gag-Pol polyprotein from which it is auto-catalytycaly released after formation of an immature viral particle. The enzyme subsequently cleaves the other parts of viral polyproteins resulting in the maturation of the virus. In HIV-infected patients the enzyme is subjected to intensive mutagenesis and mutants resistant to applied medicines are produced as a result of the selection pressure.

EIF2S1 participates in the premature steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA which binds to a 40S ribosomal subunit, followed by mRNA binding to create a 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 should exchange with GTP by way of a reaction catalyzed by eIF-2B.