You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
NamePeptidyl-prolyl cis-trans isomerase FKBP1A
Synonyms
  • 12 kDa FK506-binding protein
  • 12 kDa FKBP
  • 5.2.1.8
  • Calstabin-1
  • FK506-binding protein 1A
  • FKBP-12
  • FKBP-1A
  • FKBP1
  • FKBP12
  • Immunophilin FKBP12
  • PPIase FKBP1A
  • Rotamase
Gene NameFKBP1A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0010486|Peptidyl-prolyl cis-trans isomerase FKBP1A
MGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPFKFMLGKQEVIRGW
EEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLE
Number of residues108
Molecular Weight11950.665
Theoretical pI8.48
GO Classification
Functions
  • signal transducer activity
  • FK506 binding
  • macrolide binding
  • transforming growth factor beta receptor binding
  • peptidyl-prolyl cis-trans isomerase activity
  • type I transforming growth factor beta receptor binding
  • ion channel binding
  • activin binding
  • SMAD binding
Processes
  • protein maturation by protein folding
  • positive regulation of protein ubiquitination
  • protein peptidyl-prolyl isomerization
  • heart trabecula formation
  • ventricular cardiac muscle tissue morphogenesis
  • protein refolding
  • regulation of activin receptor signaling pathway
  • protein folding
  • regulation of amyloid precursor protein catabolic process
  • regulation of protein localization
  • regulation of ryanodine-sensitive calcium-release channel activity
  • SMAD protein complex assembly
  • 'de novo' protein folding
  • regulation of immune response
  • amyloid fibril formation
  • calcium ion transmembrane transport
  • chaperone-mediated protein folding
  • extracellular fibril organization
  • heart morphogenesis
  • transforming growth factor beta receptor signaling pathway
  • negative regulation of protein phosphatase type 2B activity
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • positive regulation of protein binding
  • T cell activation
Components
  • membrane
  • extracellular matrix
  • terminal cisterna
  • endoplasmic reticulum membrane
  • cytosol
  • extracellular exosome
  • Z disc
  • cytoplasm
General FunctionType i transforming growth factor beta receptor binding
Specific FunctionKeeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID182628
UniProtKB IDP62942
UniProtKB Entry NameFKB1A_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0010487|Peptidyl-prolyl cis-trans isomerase FKBP1A (FKBP1A)
ATGGGAGTGCAGGTGGAAACCATCTCCCCAGGAGACGGGCGCACCTTCCCCAAGCGCGGC
CAGACCTGCGTGGTGCACTACACCGGGATGCTTGAAGATGGAAAGAAATTTGATTCCTCC
CGGGACAGAAACAAGCCCTTTAAGTTTATGCTAGGCAAGCAGGAGGTGATCCGAGGCTGG
GAAGAAGGGGTTGCCCAGATGAGTGTGGGTCAGAGAGCCAAACTGACTATATCTCCAGAT
TATGCCTATGGTGCCACTGGGCACCCAGGCATCATCCCACCACATGCCACTCTCGTCTTC
GATGTGGAGCTTCTAAAACTGGAATGA
GenBank Gene IDM34539
GeneCard IDNot Available
GenAtlas IDFKBP1A
HGNC IDHGNC:3711
Chromosome Location20
Locus20p13
References
  1. Maki N, Sekiguchi F, Nishimaki J, Miwa K, Hayano T, Takahashi N, Suzuki M: Complementary DNA encoding the human T-cell FK506-binding protein, a peptidylprolyl cis-trans isomerase distinct from cyclophilin. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5440-3. 1695378
  2. Standaert RF, Galat A, Verdine GL, Schreiber SL: Molecular cloning and overexpression of the human FK506-binding protein FKBP. Nature. 1990 Aug 16;346(6285):671-4. 1696686
  3. DiLella AG, Craig RJ: Exon organization of the human FKBP-12 gene: correlation with structural and functional protein domains. Biochemistry. 1991 Sep 3;30(35):8512-7. 1716149
  4. Peattie DA, Hsiao K, Benasutti M, Lippke JA: Three distinct messenger RNAs can encode the human immunosuppressant-binding protein FKBP12. Gene. 1994 Dec 15;150(2):251-7. 7529739
  5. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. 11780052
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Siekierka JJ, Wiederrecht G, Greulich H, Boulton D, Hung SH, Cryan J, Hodges PJ, Sigal NH: The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. J Biol Chem. 1990 Dec 5;265(34):21011-5. 1701173
  8. Harding MW, Galat A, Uehling DE, Schreiber SL: A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature. 1989 Oct 26;341(6244):758-60. 2477715
  9. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. 12665801
  10. Chen YG, Liu F, Massague J: Mechanism of TGFbeta receptor inhibition by FKBP12. EMBO J. 1997 Jul 1;16(13):3866-76. 9233797
  11. Murayama T, Oba T, Katayama E, Oyamada H, Oguchi K, Kobayashi M, Otsuka K, Ogawa Y: Further characterization of the type 3 ryanodine receptor (RyR3) purified from rabbit diaphragm. J Biol Chem. 1999 Jun 11;274(24):17297-308. 10358090
  12. Yamaguchi T, Kurisaki A, Yamakawa N, Minakuchi K, Sugino H: FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type I receptor. J Mol Endocrinol. 2006 Jun;36(3):569-79. 16720724
  13. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  14. Wen H, Kang S, Song Y, Song Y, Yang HJ, Kim MH, Park S: Characterization of the binding sites for the interactions between FKBP12 and intracellular calcium release channels. Arch Biochem Biophys. 2012 Jan 1;517(1):37-42. doi: 10.1016/j.abb.2011.11.004. Epub 2011 Nov 11. 22100703
  15. Rosen MK, Michnick SW, Karplus M, Schreiber SL: Proton and nitrogen sequential assignments and secondary structure determination of the human FK506 and rapamycin binding protein. Biochemistry. 1991 May 14;30(19):4774-89. 1709363
  16. Michnick SW, Rosen MK, Wandless TJ, Karplus M, Schreiber SL: Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin. Science. 1991 May 10;252(5007):836-9. 1709301
  17. Lepre CA, Thomson JA, Moore JM: Solution structure of FK506 bound to FKBP-12. FEBS Lett. 1992 May 4;302(1):89-96. 1375171
  18. Xu RX, Nettesheim D, Olejniczak ET, Meadows R, Gemmecker G, Fesik SW: 1H, 13C, and 15N assignments and secondary structure of the FK506 binding protein when bound to ascomycin. Biopolymers. 1993 Apr;33(4):535-50. 7682113
  19. Van Duyne GD, Standaert RF, Karplus PA, Schreiber SL, Clardy J: Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex. Science. 1991 May 10;252(5007):839-42. 1709302
  20. Van Duyne GD, Standaert RF, Karplus PA, Schreiber SL, Clardy J: Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin. J Mol Biol. 1993 Jan 5;229(1):105-24. 7678431
  21. Huse M, Chen YG, Massague J, Kuriyan J: Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12. Cell. 1999 Feb 5;96(3):425-36. 10025408
  22. Burkhard P, Taylor P, Walkinshaw MD: X-ray structures of small ligand-FKBP complexes provide an estimate for hydrophobic interaction energies. J Mol Biol. 2000 Jan 28;295(4):953-62. 10656803