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Immunophilin
In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPI) that catalyze the interconversion between the cis and trans isomers of peptide bonds containing the amino acid proline (Pro). They are chaperone molecules that generally assist in the proper folding of diverse "client" proteins. Immunophilins are traditionally classified into two families that differ in sequence and biochemical characteristics. These two families are: "cyclosporin-binding cyclophilins (CyPs)" and "FK506-binding proteins (FKBPs)". In 2005, a group of dual-family immunophilins (DFI) has been discovered, mostly in unicellular organisms; these DFIs are natural chimera of CyP and FKBPs, fused in either order (CyP-FKBP or FKBP-CyP). Immunophilins act as receptors for immunosuppressive drugs such as sirolimus (rapamycin), cyclosporin (such as CsA) and tacrolimus (FK506), which inhibit the prolyl isomerase activity of the immunophilins. The drug-immunophilin complexes (CsA-Cy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP4
FK506-binding protein 4 is a protein that in humans is encoded by the ''FKBP4'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B lymphocyte, B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP5
FK506 binding protein 5, also known as FKBP5, is a protein which in humans is encoded by the ''FKBP5'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants tacrolimus (FK506) and sirolimus (rapamycin). It is thought to mediate calcineurin inhibition. It also interacts functionally with mature corticoid receptor hetero-complexes (i.e. progesterone-, glucocorticoid-, mineralocorticoid-receptor complexes) along with the 90 kDa heat shock protein and PTGES3 (P23 protein). As an Hsp90-associated co-chaperone that regulates the responsiveness of steroid hormone receptors, FKBP51 plays an important role in stress endocrinology and glucocorticoid signaling. Structure FKBP5 is part of the FKBP protein family and contains several funct ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP12
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' gene. It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins ( FKBPs). Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 (tacrolimus) and rapamycin (sirolimus). It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels including the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same prote ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunosuppressive Drug
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified into five groups: * glucocorticoids * cytostatics * antibodies * drugs acting on immunophilins * other drugs Glucocorticoids In pharmacologic (supraphysiologic) doses, glucocorticoids, such as prednisone, dexamethasone, and hydrocortisone are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Immunosuppressive mechanism Glucocorticoids suppress cell-mediated immunity. They act by inhibiting gene expression of cytokines including Interleukin 1 (IL-1), IL-2, IL-3, IL-4, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Calcineurin
Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates nuclear factor of activated T cell cytoplasmic (NFATC1, NFATc), a transcription factor, by dephosphorylation, dephosphorylating it. The activated NFATc is then Protein targeting#Post-translational translocation, translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of the Cell immunity, T cell response. Calcineurin is the target of a class of drugs called Immunosuppressive drug#Drugs acting on immunophilins, calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus. Structure Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP
The FKBPs, or FK506 binding proteins, constitute a family of proteins that have prolyl isomerase activity and are related to the cyclophilins in function, though not in amino acid sequence. FKBPs have been identified in many eukaryotes, ranging from yeast to humans, and function as protein folding chaperones for proteins containing proline residues. Along with cyclophilin, FKBPs belong to the immunophilin family. FKBP1A (also known as FKBP12) is notable in humans for binding the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and patients with autoimmune disorders. Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin, which binds cyclophilin. Both the FKBP-tacrolimus complex and the cyclosporin-cyclophilin complex inhibit a phosphatase called calcineurin, thus blocking signal transduction in the T-lymphocyte transduction pathway. This ther ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP3
FK506-binding protein 3 also known as FKBP25 is a protein that in humans is encoded by the ''FKBP3'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It has a higher affinity for rapamycin than for FK506 and thus may be an important target molecule for immunosuppression by rapamycin. Interactions FKBP3 has been shown to interact with YY1, HDAC1, Histone deacetylase 2, DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ..., and Mdm2. Both crystal structure of FKBP25 with FK506 and the NMR structure of full lengt ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclophilin
Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin (cyclosporin A), an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of life. These proteins have peptidyl prolyl isomerase activity, which catalyzes the isomerization of peptide bonds from ''trans'' form to ''cis'' form at proline residues and facilitates protein folding. Cyclophilin A is a cytosolic and highly abundant protein. The protein belongs to a family of isozymes, including cyclophilins B and C, and natural killer cell cyclophilin-related protein. Major isoforms have been found within single cells, including inside the Endoplasmic reticulum, and some are even secreted. Mammalian cyclophilins Human genes encoding proteins containing the cyclophilin domain include: * PPIA, PPIB, PPIC, PPID, PPIE, PPIF, PPIG, PPIH * PPIL1, PPIL2, PPIL3, PPIL4, PPIAL4, PPIL6 * PPWD1 Cyclophilin A Cy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chaperone Molecule
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis. The first molecular chaperones discovered were a type of assembly chaperones which assist in the assembly of nucleosomes from folded histones and DNA. One major function of molecular chaperones is to prevent the aggregation of misfolded proteins, thus many chaperone proteins are classified as heat shock proteins, as the tendency for protein aggregation is increased by heat stress. The majority of molecular chaperones do not convey any steric information for protein folding, and instead assist in protein folding by binding to and stabilizing folding intermediat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, eczema, and in organ transplants to prevent rejection. It is also used as eye drops for keratoconjunctivitis sicca (dry eyes). Common side effects include high blood pressure, headache, kidney problems, increased hair growth, and vomiting. Other severe side effects include an increased risk of infection, liver problems, and an increased risk of lymphoma. Blood levels of the medication should be checked to decrease the risk of side effects. Use during pregnancy may result in preterm birth; however, ciclosporin does not appear to cause birth defects. Ciclosporin is believed to work by decreasing the function of lymphocytes. It does this by forming a complex with cyclophilin to block the phosphatase activity of calcineurin, which in turn ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T cell-mediated diseases such as atopic dermatitis, eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat Dry eye syndrome#Other, dry eye syndrome in cats and dogs. Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and cell proliferation, proliferation of T cells, as part of the body's learned (or adaptive immune response, adaptive) immune response. Chemically, it is a macrolide lactone that was first discovered in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inositol Trisphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals. Properties Chemical formula and molecular weight IP3 is an organic molecule with a molecular mass of 420.10 g/mol. Its empirical formula is C6H15O15P3. It is composed of an inositol ring with three phosphate groups bound at the 1, 4, and 5 carbon positions, and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
