Peptidyl-prolyl cis-trans isomerase FKBP1A


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
  • type I transforming growth factor beta receptor binding
  • activin binding
  • SMAD binding
  • transforming growth factor beta receptor binding
  • FK506 binding
  • macrolide binding
  • ion channel binding
  • peptidyl-prolyl cis-trans isomerase activity
  • signal transducer activity
Processes
  • protein refolding
  • 'de novo' protein folding
  • regulation of activin receptor signaling pathway
  • amyloid fibril formation
  • protein folding
  • regulation of amyloid precursor protein catabolic process
  • T cell activation
  • chaperone-mediated protein folding
  • regulation of protein localization
  • positive regulation of protein ubiquitination
  • extracellular fibril organization
  • regulation of ryanodine-sensitive calcium-release channel activity
  • heart trabecula formation
  • heart morphogenesis
  • SMAD protein complex assembly
  • ventricular cardiac muscle tissue morphogenesis
  • negative regulation of protein phosphatase type 2B activity
  • regulation of immune response
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • calcium ion transmembrane transport
  • positive regulation of protein binding
  • protein maturation by protein folding
  • protein peptidyl-prolyl isomerization
  • transforming growth factor beta receptor signaling pathway
Components
  • extracellular matrix
  • endoplasmic reticulum membrane
  • cytosol
  • extracellular exosome
  • terminal cisterna
  • cytoplasm
  • Z disc
  • membrane
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.
Transmembrane Regions
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 IDNone
GenAtlas IDFKBP1A
HGNC IDHGNC:3711
Chromosome Location20
Locus20p13
References
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  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 ]
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  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 ]
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  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 ]
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  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 ]
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