Peptidyl-Prolyl Cis-Trans Isomerase FKBP1A (FKBP1A) Antibody – Rabbit Polyclonal

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. The protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels, and coordinates multi-protein complex formation of 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 protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed. [provided by RefSeq, Sep 2008]

FKBP12: an immunophilin and peptidyl-prolyl cis-trans isomerase that binds to the immunosuppressant drugs FK506 (a.k.a. tacrolimus or Fujimycin) and rapamycin (a.k.a. Sirolimus). The FKBP12/rapamycin complex binds NFAT transcription factors and inhibits the induction of T cell genes including IL-2, IL-3, IL-4, TNF-alpha and GM-CSF. FK506 is used in treating patients after organ transplant and those suffering from autoimmune disorders. The immunosuppressant activity of FKBP12 is not apparently related to its prolyl isomerase activity. The FKBP12/rapamycin complex inhibits the mammalian target of rapamycin (mTOR) pathway by directly binding the mTOR Complex1 (mTORC1). mTORC1 contains Raptor, mLST8, and PRAS40, and interacts with DEPTOR, which inhibits its activity. mTOR, a S/T protein kinase, is a central regulator of cellular growth and metabolism. Its inhibition enhances the dependence on aerobic glycolysis in leukemic cells.

Protein type: EC 5.2.1.8; Isomerase

Chromosomal Location of Human Ortholog: 20p13

Cellular Component: cytoplasm; cytosol; endoplasmic reticulum membrane; extracellular matrix; membrane; nerve terminal; sarcoplasmic reticulum membrane; Z disc

Molecular Function: activin binding; calcium channel inhibitor activity; enzyme binding; FK506 binding; Hsp70 protein binding; macrolide binding; peptidyl-prolyl cis-trans isomerase activity; protein binding; protein homodimerization activity; signal transducer activity; SMAD binding; transforming growth factor beta receptor binding

Biological Process: 'de novo' protein folding; cytokine and chemokine mediated signaling pathway; fibril organization and biogenesis; heart morphogenesis; muscle contraction; negative regulation of protein amino acid phosphorylation; negative regulation of protein phosphatase type 2B activity; negative regulation of release of sequestered calcium ion into cytosol; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of protein binding; positive regulation of protein ubiquitination; protein folding; protein maturation via protein folding; protein peptidyl-prolyl isomerization; protein refolding; regulation of activin receptor signaling pathway; regulation of immune response; regulation of protein localization; release of sequestered calcium ion into cytosol; response to caffeine; response to iron ion; SMAD protein complex assembly; T cell activation; T cell proliferation; transforming growth factor beta receptor signaling pathway; ventricular cardiac muscle morphogenesis