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FKBP
FKBP, or FK506 binding protein, is 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. 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 therapeutic role is not related to prolyl isome ... [...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 r ... [...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. Clinical significance The FKBP5 gene has been found to have multiple polyadenylation ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP1A
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' 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 (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. There is evidence of multiple alternatively spliced transcript variants for this gene, but the full length nature of some variants has not been determined. Interactions FKBP1A has b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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-CyP an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP1B
Peptidyl-prolyl cis-trans isomerase FKBP1B is an enzyme that in humans is encoded by the ''FKBP1B'' 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 (tacrolimus) and rapamycin (sirolimus). It is highly similar to the FK506-binding protein 1A. Its physiological role is thought to be in excitation-contraction coupling in cardiac muscle. There are two alternatively spliced transcript variants of this gene encoding different isoforms. Clinical significance Defective interaction between FKB1B and the ryanodine receptor is thought to be a potential mechanism underlying the arrhythmias seen in those with the genetic condition catecholaminergic polymorphic ventricular tachycardia Catecholaminergic polymorphic ventricular tachycardia ... [...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 Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the co ..., DNA, and Mdm2. Both crystal structure of FKBP25 with FK506 and the NMR structure of full length F ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP2
FK506-binding protein 2 is a protein that in humans is encoded by the ''FKBP2'' 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 is thought to function as an ER chaperone and may also act as a component of membrane cytoskeletal scaffolds. This gene has two alternatively spliced transcript variants that encode the same isoform. Multiple polyadenylation sites have been described for this gene, but the full length nature of this gene has not been determined. Interactions FKBP2 has been shown to interact with ARFGEF1 and EPB41L2 Band 4.1-like protein 2 is a protein that in humans is encoded by the ''EPB41L2'' gene. Interactions EPB41L2 has been shown to interact with FKBP2 and GRIA1 Glutamate receptor 1 is a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBPL
FK506-binding protein like, also known as FKBPL, is a protein that in humans is encoded by the ''FKBPL'' gene. Function FKBPL has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. FKBPL is involved in cellular response to stress. It was first isolated in 1999 and was initially named DIR1. It was later reclassified because of its homology to the FKBP family of proteins and was renamed FKBP-like (FKBPL). A separate study that found it to be involved in the stabilisation of newly synthesised p21 termed it Wisp39. It is known to interact with Hsp90, glucocorticoid receptor and dynamitin and may play a role in signalling, like other FKBPs. FKBPL has also been shown to influence estrogen receptor signalling and ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemically Induced Dimerization
Chemically Induced Dimerization (CID) is a biological mechanism in which two proteins bind only in the presence of a certain small molecule, enzyme or other dimerizing agent. Genetically engineered CID systems are used in biological research to control protein localization, to manipulate signalling pathways and to induce protein activation. History The first small molecule CID system was developed in 1993 and used FK1012, a derivative of the drug tacrolimus (FK506), to induce homo-dimerization of FKBP. This system was used ''in vivo'' to induce binding between cell surface receptors which could not bind in the normal way because they lacked the transmembrane and extracellular domain. Addition of FK1012 to the cells caused signal transduction. Chemically induced dimerization systems Applications CID has been used for a number of applications in biomedical research. In most applications each dimerizing protein is expressed as part of a fusion construct with other proteins of inter ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ 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 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 in cats and dogs. Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and proliferation of T cells, as part of the body's learned (or adaptive) immune response. Chemically, it is a macrolide lactone that was first discovered in 1987, from the fermentation broth of a Japanese soil sample that contained the bacterium ''Streptomyces tsukubensis''. It is on ... [...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 (NFATc), a transcription factor, by dephosphorylating it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of the T cell response. Calcineurin is the target of a class of drugs called 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-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, each encoded by a separate gene (PPP3CA, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
AH Receptor-interacting Protein
AH receptor-interacting protein (AIP) also known as aryl hydrocarbon receptor-interacting protein, immunophilin homolog ARA9, or HBV X-associated protein 2 (XAP-2) is a protein that in humans is encoded by the ''AIP'' gene. The protein is a member of the FKBP family. Function AIP may play a positive role in aryl hydrocarbon receptor-mediated signalling possibly by influencing its receptivity for ligand and/or its nuclear targeting. AIP is the cellular negative regulator of the hepatitis B virus (HBV) X protein. Further, it's been known to suppress antiviral signaling and the induction of type I interferon by targeting IRF7, a key player in the antiviral signal pathways. AIP consists of an N-terminal FKBP52 like domain and a C-terminal TPR domain. Mutations and role in disease AIP mutations may be the cause of a familial form of acromegaly, familial isolated pituitary adenoma (FIPA). Somatotropinomas (i.e. GH-producing pituitary adenomas), sometimes associated with prolact ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
