FKBP1A

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 protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed.

Interactions

FKBP1A has been shown to interact with:

• GLMN,
• ITPR1
• KIAA1303,
• Mammalian target of rapamycin,
• RYR1, and
• TGF beta receptor 1.

References

References

1. (Sep 1991). "Chromosomal assignment of the human immunophilin FKBP-12 gene". Biochemical and Biophysical Research Communications.
2. "Entrez Gene: FKBP1A FK506 binding protein 1A, 12kDa".
3. (Dec 1996). "FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin". The Journal of Biological Chemistry.
4. (Mar 2001). "Mutation of FKBP associated protein 48 (FAP48) at proline 219 disrupts the interaction with FKBP12 and FKBP52". Regulatory Peptides.
5. (Dec 2005). "In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin". Journal of Cell Science.
6. (Oct 1997). "FKBP12 binds the inositol 1,4,5-trisphosphate receptor at leucine-proline (1400-1401) and anchors calcineurin to this FK506-like domain". The Journal of Biological Chemistry.
7. (Nov 2004). "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive". Nature Cell Biology.
8. (Jul 2004). "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Current Biology.
9. (Jul 1996). "Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP". Science.
10. (Aug 2004). "Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals". Proceedings of the National Academy of Sciences of the United States of America.
11. (Apr 2005). "Characterization of the FKBP.rapamycin.FRB ternary complex". Journal of the American Chemical Society.
12. (Jan 1995). "Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells". The Journal of Biological Chemistry.
13. (Jun 2003). "FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes". The Journal of Biological Chemistry.
14. (Mar 2001). "Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor". The Biochemical Journal.
15. (May 2001). "FKBP12 binding modulates ryanodine receptor channel gating". The Journal of Biological Chemistry.
16. (Jul 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science.
17. (Jul 1995). "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Molecular and Cellular Biology.