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Beta-lactamase is a type of enzyme (EC 3.5.2.6) produced by some bacteria that is responsible for their resistance to beta-lactam antibiotics like penicillins, cephalosporins, cephamycins and carbapenems. These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam. The lactamase enzyme breaks that ring open, deactivating the molecule's antibacterial properties.

Interleukin-35 is a glycosylated, disulfide-linked, heterodimeric protein comprised of the p35 subunit of IL-12 (IL-12 alpha) and the beta subunit of IL-27 (EBI3). IL35 is expressed by regulatory T-cells (Tregs), macrophages and some trophoblast and dendritic cells. IL-35 is produced in response to inflammation and generally serves as an inflammation suppressor. Interleukin-35 curbs inflammation by applying multiple activities, including the stimulation of regulatory T-cells and the inhibition of Th17 cells.

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.

Thyroglobulin (TG) represents one of the main autoantigenic targets in autoimmune thyroid disease of humans. TG is a large globular dimeric glycoprotein with a total molecular weight of 660 kDa, which occupies a key precursor role in the biosynthesis of the thyroid hormones. Approximately 75% of the total protein content of the thyroid follicle consists of TG. The thyroid gland uses the Thyroglobulin in order to produce the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Thyroglobulin is produced by the thyroid epithelial cells (thyrocytes) which form spherical follicles. Thyroglobulin is subsequently secreted and stored in the follicular lumen.
Patients with Hashimoto's thyroiditis or Graves' disease, frequently develop antibodies against Thyroglobulin. Tg-specific antibodies help in the diagnosis of the above diseases, however they also may be present in apparently healthy euthyroid individuals. Blood Thyroglobulin levels can be used as a tumor marker for certain kinds of thyroid cancer, and the may also be elevated in cases of Graves' disease.

EBI3 has an induced expression in B lymphocytes in reaction to Epstein-Barr virus infection. EBI3 encodes a secreted glycoprotein belonging to the hematopoietin receptor family, and heterodimerizes with a 28 kDa protein to form iIL-27. EBI3 drives rapid clonal expansion of naive cd4(+) t-cells. EBI3 strongly synergizes with IL-12 to activate IFN-gamma production of naive cd4(+) t-cells. EBI3 mediates its biologic effects through the cytokine receptor wsx-1/tccr.

IL-21 is produced by CD4+ T cells in response to antigenic stimulation. Its action enhances antigen-specific responses of immune cells. The biological effects of IL-21 include induction of differentiation of T-cells-stimulated B-cells into plasma cells and memory B-cells, stimulation (in conjuction) with IL-4 of IgG production, and induction of apoptotic effects in naive B-cells and stimulated B-cells in the absence of T-cell signaling. Additionally, IL-21 promotes the anti-tumor activity of CD8+ T-cells and NK cells. IL-21 exerts its effect through binding to a specific type I cytokine receptor, IL-21R, which also contains the gamma chain (°C) found in other cytokine receptors including IL-2, IL-4, IL-7, IL-9 and IL-15. The IL-21/IL-21R interaction triggers a cascade of events which includes activation of the tyrosine kinases JAK1 and JAK3, followed by activation of the transcription factors STAT1 and STAT3.

IL-32 is part of the cytokine family and contains a tyrosine sulfation site, 3 potential N-myristoylation sites, multiple putative phosphorylation sites, and an RGD cell-attachment sequence. IL-32 expression is elevated after the activation of T-cells by mitogens or the activation of NK cells by IL-2. IL-32 induces the production of TNF-a from macrophage cells. IL-32 pro-inflammatory pathway is activated in response to influenza A virus infection. Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function.
Induction of TNF, IL-1beta, and IL-6 by IL-32 is intervened by p38-MAPK. IL-32 induced monocyte-to-macrophage differentiation is mediated through nonapoptotic, caspase-3-dependent mechanisms. IL32 plays an important role in the pathogenesis of rheumatoid arthritis. IL-32 is involved in activation-induced cell death in T cells, through its intracellular actions. IL-32 is a cell-associated proinflammatory cytokine, which is particularly stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of IFNgamma.
IL-32 is associated with TNF-a, IL-1beta, and IL-18. IL32 is involved in human rheumatoid arthritis and is a novel target in autoimmune diseases.

IL-1 alpha is produced by activated macrophages.IL-1 alpha stimulates thymocyte proliferation by inducing il-2 release, b-cell maturation and proliferation, and fibroblast growth factor activity. IL1A proteins take part in the inflammatory response, being identified as endogenous pyrogens, and stimulate the release of prostaglandin and collagenase from synovial cells.

Interleukin-21 isoform 1 or IL21, categorized as a T helper cytokine. IL21 is part of the regulation of immune responses, haematopoiesis and cell-mediated responses. IL21 takes a main part in haematopoiesis and immune responses regulation, therefore can affect lymphocyte development. Activation of T cells leads to production of the IL21 which has an important role in the viral infections persistence.

IL36RA belongs to the IL-1 family of proteins. IL36RA is produced as a 156 aa protein which holds no signal sequence, no prosegment and no potential N-linked glycosylation site but, IL36RA is secreted as a 17 kDa monomer. Cells known to express IL36Ra/IL1F5 include monocytes, B cells, keratinocytes, dendritic cells/Langerhans cells and gastric fundus Parietal and Chief cells.

Placental Lactogen is a polypeptide hormone that is produced by the Syncytiotrophoblasts of the Placenta.Placental Lactogen has both GH and Prolactin activities on growth, lactation, and luteal steroid production. In women, placental lactogen secretion begins soon after implantation and increases to 1 g or more a day in late pregnancy. Placental Lactogen Bovine is also capable of activating human and other heterologous GH receptors.

Ubiquitin-conjugating enzyme E2 R2 (UBE2R2) is a member of the ubiquitin-conjugating enzyme family. Protein kinase CK2 is a ubiquitous and pleiotropic Ser/Thr protein kinase implicated in cell growth andtransformation. This protein is a protein similar to the E2 ubiquitin conjugating enzyme UBC3/CDC34. Studies propose that CK2-dependent phosphorylation of this ubiquitin-conjugating enzyme functions by regulating beta-TrCP substrate recognition and induces its interaction with beta-TrCP, enhancing beta-catenin degradation. UBE2R2 receives ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes monoubiquitination and 'Lys-48'-linked polyubiquitination. UBE2R2 may be implicated in degradation of katenin. Among the diseases associated with UBE2R2 are cblc, and herpes simplex.

UPK3A is a member of the uroplakin-3 family. Uroplakins (UP) which are transmembrane proteins are important components of the urothelium that pass the lipid bilayer once (UPII, UPIIIa, and UPIIIb) or four times (UPIa and UPIb; both members of the "tetraspanin" family). All hold great luminal/extracellular domains, but only UPIIIa and UPIIIb have significant cytoplasmic shares in their C-termini. UPK3A is an extremely specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas. Alterations in this gene are related to renal adysplasia.

Gastroenteritis which has been identified as caused by Yersinia Enterocolitica has been discovered by virulent isolates of the bacteria. During infection, pores are being formed in the presence of adapter protein Yersiniosis. YopB's Interaction with the target membrane to form pores enables the entrance of YopE effectors to the cytoplasmic space of the host’s cell.

Polypeptide hormones secreted by the parathyroid glands, which promote release of calcium from bone to extracellular fluid by activating osteoblasts and inhibiting osteoclasts, indirectly promote increased intestinal absorption of calcium, and promote renal tubular reabsorption of calcium and increased renal excretion of phosphates. It is a major regulator of bone metabolism. Secretion of parathyroid hormone increases when the level of calcium in the extracellular fluid is low. Its action is opposed by calcitonin.
PTH (7-34), which is a PTH/PTHrP receptor antagonist, can stimulate hair growth and epidermal proliferation in mice.

Apoptosis-Inducing Factor, Mitochondrion-Associated, 1 (AIFM1) is a mitochondrial protein which translocates to the nucleus once apoptosis has been initiated. AIFM1 causes DNA fragmentation and chromatin condensation and also triggers the release of cytochrome c and caspase-9 from mitochondria. Bcl-2 overexpression prevents the release of AIFM1 from mitochondria, but doesn’t block its apoptogenic activity.

Interferon alpha-14 (IFNA14) is a member of the alpha/beta interferon family. IFNA14 is produced by macrophages (IFN-alpha have antiviral activities). The interferon stimulates the production of 2 enzymes: a protein kinase and an oligoadenylate synthetase.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

IL2 is a secreted cytokine that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine is a heterotrimeric protein complex whose gamma chain is also shared by interleukin 4 (IL4) and interleukin 7 (IL7). The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli.

UbcH12 is functional in in vitro NEDDylation reactions. It has been shown to form a thioester linkage with NEDD8 in the presence of the NEDD8 activating enzyme complex Uba3/APP-BP1. APP-BP1 binds to the amyloid precursor protein (APP) carboxy terminal domain and is important in conjunction with Uba3 and UbcH12 in driving cells through the S to M checkpoint. It was demonstrated to be the E2 responsible for the NEDDylation of the Cul-1 component of the SCF (?-TRCP) complex which is important as the E3-ligase in the ubiquitinylation of I?B?. NEDDylation of Cul-1 is essential for conjugation and processing of NF-?B p105 by SCF (?-TRCP) following phosphorylation of the complex. A dominant negative form of UbcH12, previously demonstrated to sequester NEDD8 and inhibit its conjugation, inhibits both conjugation and processing of p105, which is alleviated by wild-type UbcH12.

Ubiquilin-2, also known as UBQLN2 contains an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. UBQLN2 is physically linked with proteasomes as well as ubiquitin ligases, and therefore is considered to functionally connect the ubiquitination machinery to the proteasome in order to affect in vivo protein degradation. Furthermore, UBQLN2 binds the ATPase domain of the Hsp70-like Stch protein. Among the diseases which are associated with UBQLN2: Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia as well as Amyotrophic lateral sclerosis type 15.

HP-NAP protects DNA from oxidative damage by sequestering intracellular Fe2+ ion and storing it in the form of Fe3+ oxyhydroxide mineral. One hydrogen peroxide oxidizes two Fe2+ ions, thus preventing hydroxyl radical production by the Fenton reaction. HP-NAP is necessary for the survival in the presence of oxidative stress. Dps is also a virulence factor which activates neutrophils, mast cells and monocytes. HP-NAP binds to neutrophil-glycosphingolipids and to sulfated carbohydrates on mucin. HP-NAP might play a part in the accumulation of neutrophils and monocytes at the site of infection. HP-NAP induces superoxide anion generation, adhesion and chemotaxis of neutrophils, via a pertussis toxin-sensitive pathway involving MAP kinases.

SERPINI1 (Neuroserpin) is an inhibitory serpin which is expressed primarily in the central nervous system. Even though the physiological target of SERPINI1 is still vague, amassed evidence suggest that SERPINI1 has an imperative role in controlling proteolytic degradation of extracellular matrix (ECM) during synaptogenesis and the subsequent development of neuronal plasticity. The neuroprotective role of SERPINI1 has been demonstrated in transgenic mice lacking SERPINI1 expression. The deficiency of SERPINI1 in these mice is linked with motor neuron disease characterized by axonal degradation. In humans, defects in SERPINI1, caused by point mutations in the neuroserpin gene, trigger a hereditary disorder known as the familial encephalopathy with neuroserpin inclusion bodies (FENIB).