The precursor form of the nerve growth factor (proNGF) like its mature form is characterized by the cystin knot motif consisting of three cystine bridges; whereas proneurotrophins and mature neurotrophins elicit opposite biological effects. ProNGF functions preferentially via the complex of pan-neurotrophin receptor p75 (p75NTR) and vps10p domain-containing receptor sortilin inducing neuronal apoptosis and contributing to age- and disease-related neurodegeneration.
Gamma-Synuclein (SNCG) is a member of the Synuclein protein family. Gamma-Synuclein is mostly expressed in the peripheral nervous system and retina. Gamma-Synuclein plays a role in neurofilament network integrity and may be involved in modulating axonal architecture during development and in the adult. In addition, it may also function in modulating the keratin network in skin. SNCG expression in breast tumors has been as a marker for tumor progression. SNCG is also believed to be involved in the pathogenesis of neurodegenerative diseases.
CD81, also known as TAPA-1, belongs to the transmembrane 4 superfamily, also known as the tetraspanin family. Members of this family mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility.CD81 is a widely expressed cell-surface protein involved in an astonishing variety of biologic responses. It is related to adhesion, morphology, activation, proliferation, and differentiation of B, T, and other cells. On B cells CD81 is part of a complex with CD21, CD19, and Leu13. This complex reduces the threshold for B cell activation via the B cell receptor by bridging Ag specific recognition and CD21-mediated complement recognition.
Aminoglycoside 3'-phosphotransferase (APH(3')), also known as aminoglycoside kinase, is an aminoglycoside-modifying enzyme and widely presented in resistant bacteria. These ATP-dependent enzymes phosphorylate the 3'-hydroxyl of a variety of aminoglycosides including kanamycins, neomycins, paromomycins, neamine, ribostamycin, geneticin, and paromamine. These phosphorylated aminoglycosides fail to bind to their respective ribosomal binding sites with high affinity; hence resistance is conferred to the drugs that are phosphorylated. APH(3') is primarily found in certain species of gram-positive bacteria.
Alpha-2-HS-glycoprotein (AHSG) is a glycoprotein that is composed of two subunits, the A and B chains, belongs to the Cystatin family of proteases inhibitors. It is highly expressed in embryonic cells and adult hepatocytes, and is expressed to a lesser extent in monocytes/macrophages. AHSG is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response. It is involved in several functions, such as endocytosis, brain development and the formation of bone tissue. In addition, AHSG may influence the resolution of inflammation by modulating the phagocytosis of apoptotic cells by macrophages. ASHG blocks TGF-beta-dependent signaling in osteoblastic cells.
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a secretory subtilase belonging to the proteinase K subfamily. PCSK9 is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular processing in the ER , the pro domain and mature chain secrete together through noncovalent interactions. PCSK9 binds with low-density lipoprotein receptor (LDLR) and plays a major regulatory role in cholesterol homeostasis. PCSK9 also plays a role in the neural development.
T cell immunoglobulin and mucin domain-3 (TIM3), also called hepatitis A virus cellular receptor 2 (HAVCR2), is a transmembrane glycoprotein of the TIM family of immune regulating molecules and plays an important role in the Th1-mediated immune response. TIM3 is expressed on the Th1 cells, CD8 T-cells, monocytes, and dendritic cells, but not on Th2 cells. TIM3 expressed by monocytes and dendritic cells facilitates phagocytosis of apoptotic cells and up-regulates cross-presentation of apoptotic cell-associated antigens through interaction with phosphatidylserine. Engagement of TIM3 by its ligand galectin-9 induces a range of immunosuppressive functions which enhance immune tolerance and inhibit anti-tumor immunity. Stimulation of TIM3 with an agonistic antibody promotes inflammation through the activation of innate immune cells. TIM3 is also regarded as a potential target molecule for immunotherapy. TIM3 and programmed cell death 1 (PD-1) as two important coinhibitory regulators of T cell responses, have been implicated with the T-cell dysfunction or exhaustion associated with chronic HBV infection including HBV-related HCC.
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