Biology:FKBP1A
 Generic protein structure example |
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene.[1] 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 protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed.[2]
Interactions
FKBP1A has been shown to interact with:
- GLMN,[3][4]
- ITPR1[5][6]
- KIAA1303,[7][8]
- Mammalian target of rapamycin,[7][8][9][10][11][12]
- RYR1,[13][14][15] and
- TGF beta receptor 1.[16][17]
References
- ↑ "Chromosomal assignment of the human immunophilin FKBP-12 gene". Biochemical and Biophysical Research Communications 179 (3): 1427–33. Sep 1991. doi:10.1016/0006-291X(91)91732-R. PMID 1930186.
- ↑ "Entrez Gene: FKBP1A FK506 binding protein 1A, 12kDa". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2280.
- ↑ "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 271 (51): 32923–9. Dec 1996. doi:10.1074/jbc.271.51.32923. PMID 8955134.
- ↑ "Mutation of FKBP associated protein 48 (FAP48) at proline 219 disrupts the interaction with FKBP12 and FKBP52". Regulatory Peptides 97 (2–3): 147–52. Mar 2001. doi:10.1016/s0167-0115(00)00206-8. PMID 11164950.
- ↑ "In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin". Journal of Cell Science 118 (Pt 23): 5443–51. Dec 2005. doi:10.1242/jcs.02657. PMID 16278292.
- ↑ "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 272 (44): 27582–8. Oct 1997. doi:10.1074/jbc.272.44.27582. PMID 9346894.
- ↑ 7.0 7.1 "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive". Nature Cell Biology 6 (11): 1122–8. Nov 2004. doi:10.1038/ncb1183. PMID 15467718.
- ↑ 8.0 8.1 "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Current Biology 14 (14): 1296–302. Jul 2004. doi:10.1016/j.cub.2004.06.054. PMID 15268862.
- ↑ "Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP". Science 273 (5272): 239–42. Jul 1996. doi:10.1126/science.273.5272.239. PMID 8662507. Bibcode: 1996Sci...273..239C.
- ↑ "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 101 (33): 12288–93. Aug 2004. doi:10.1073/pnas.0404041101. PMID 15284440. Bibcode: 2004PNAS..10112288L.
- ↑ "Characterization of the FKBP.rapamycin.FRB ternary complex". Journal of the American Chemical Society 127 (13): 4715–21. Apr 2005. doi:10.1021/ja043277y. PMID 15796538.
- ↑ "Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells". The Journal of Biological Chemistry 270 (2): 815–22. Jan 1995. doi:10.1074/jbc.270.2.815. PMID 7822316.
- ↑ "FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes". The Journal of Biological Chemistry 278 (25): 22600–8. Jun 2003. doi:10.1074/jbc.M205866200. PMID 12704193.
- ↑ "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 354 (Pt 2): 413–22. Mar 2001. doi:10.1042/bj3540413. PMID 11171121.
- ↑ "FKBP12 binding modulates ryanodine receptor channel gating". The Journal of Biological Chemistry 276 (20): 16931–5. May 2001. doi:10.1074/jbc.M100856200. PMID 11279144.
- ↑ "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science 265 (5172): 674–6. Jul 1994. doi:10.1126/science.7518616. PMID 7518616. Bibcode: 1994Sci...265..674W.
- ↑ "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Molecular and Cellular Biology 15 (7): 3479–86. Jul 1995. doi:10.1128/mcb.15.7.3479. PMID 7791754.
Further reading
- "Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases". FEBS Letters 495 (1–2): 1–6. Apr 2001. doi:10.1016/S0014-5793(01)02326-2. PMID 11322937.
- "Chromosomal band assignments of the genes encoding human FKBP12 and FKBP13". Biochemical and Biophysical Research Communications 189 (2): 819–23. Dec 1992. doi:10.1016/0006-291X(92)92276-4. PMID 1281998.
- "FK506 binding protein associated with the calcium release channel (ryanodine receptor)". The Journal of Biological Chemistry 267 (14): 9474–7. May 1992. doi:10.1016/S0021-9258(19)50114-4. PMID 1374404.
- "Solution structure of FK506 bound to FKBP-12". FEBS Letters 302 (1): 89–96. May 1992. doi:10.1016/0014-5793(92)80292-O. PMID 1375171.
- "Complementary DNA encoding the human T-cell FK506-binding protein, a peptidylprolyl cis-trans isomerase distinct from cyclophilin". Proceedings of the National Academy of Sciences of the United States of America 87 (14): 5440–3. Jul 1990. doi:10.1073/pnas.87.14.5440. PMID 1695378. Bibcode: 1990PNAS...87.5440M.
- "Molecular cloning and overexpression of the human FK506-binding protein FKBP". Nature 346 (6285): 671–4. Aug 1990. doi:10.1038/346671a0. PMID 1696686. Bibcode: 1990Natur.346..671S.
- "The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase". The Journal of Biological Chemistry 265 (34): 21011–5. Dec 1990. doi:10.1016/S0021-9258(17)45319-1. PMID 1701173.
- "Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin". Science 252 (5007): 836–9. May 1991. doi:10.1126/science.1709301. PMID 1709301. Bibcode: 1991Sci...252..836M.
- "Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex". Science 252 (5007): 839–42. May 1991. doi:10.1126/science.1709302. PMID 1709302. Bibcode: 1991Sci...252..839V.
- "Proton and nitrogen sequential assignments and secondary structure determination of the human FK506 and rapamycin binding protein". Biochemistry 30 (19): 4774–89. May 1991. doi:10.1021/bi00233a020. PMID 1709363.
- "Molecular cloning of a membrane-associated human FK506- and rapamycin-binding protein, FKBP-13". Proceedings of the National Academy of Sciences of the United States of America 88 (15): 6677–81. Aug 1991. doi:10.1073/pnas.88.15.6677. PMID 1713687. Bibcode: 1991PNAS...88.6677J.
- "Exon organization of the human FKBP-12 gene: correlation with structural and functional protein domains". Biochemistry 30 (35): 8512–7. Sep 1991. doi:10.1021/bi00099a002. PMID 1716149.
- "A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase". Nature 341 (6244): 758–60. Oct 1989. doi:10.1038/341758a0. PMID 2477715. Bibcode: 1989Natur.341..758H.
- "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science 265 (5172): 674–6. Jul 1994. doi:10.1126/science.7518616. PMID 7518616. Bibcode: 1994Sci...265..674W.
- "Three distinct messenger RNAs can encode the human immunosuppressant-binding protein FKBP12". Gene 150 (2): 251–7. Dec 1994. doi:10.1016/0378-1119(94)90434-0. PMID 7529739.
- "Cyclophilin A and FKBP12 interact with YY1 and alter its transcriptional activity". The Journal of Biological Chemistry 270 (25): 15187–93. Jun 1995. doi:10.1074/jbc.270.25.15187. PMID 7541038.
- "Interaction of FKBP12-FK506 with calcineurin A at the B subunit-binding domain". The Journal of Biological Chemistry 270 (26): 15463–6. Jun 1995. doi:10.1074/jbc.270.26.15463. PMID 7541044.
- "X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex". Cell 82 (3): 507–22. Aug 1995. doi:10.1016/0092-8674(95)90439-5. PMID 7543369.
- "Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin". Journal of Molecular Biology 229 (1): 105–24. Jan 1993. doi:10.1006/jmbi.1993.1012. PMID 7678431.
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