Peptidyl-prolyl cis-trans isomerase FKBP1A

Details

Name
Peptidyl-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 Name
FKBP1A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010486|Peptidyl-prolyl cis-trans isomerase FKBP1A
MGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPFKFMLGKQEVIRGW
EEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLE
Number of residues
108
Molecular Weight
11950.665
Theoretical pI
8.48
GO Classification
Functions
activin binding / FK506 binding / ion channel binding / macrolide binding / peptidyl-prolyl cis-trans isomerase activity / signal transducer activity / SMAD binding / transforming growth factor beta receptor binding / type I transforming growth factor beta receptor binding
Processes
'de novo' protein folding / amyloid fibril formation / calcium ion transmembrane transport / chaperone-mediated protein folding / extracellular fibril organization / heart morphogenesis / heart trabecula formation / negative regulation of protein phosphatase type 2B activity / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of protein binding / positive regulation of protein ubiquitination / protein folding / protein maturation by protein folding / protein peptidyl-prolyl isomerization / protein refolding / regulation of activin receptor signaling pathway / regulation of amyloid precursor protein catabolic process / regulation of immune response / regulation of protein localization / regulation of ryanodine-sensitive calcium-release channel activity / SMAD protein complex assembly / T cell activation / transforming growth factor beta receptor signaling pathway / ventricular cardiac muscle tissue morphogenesis
Components
cytoplasm / cytosol / endoplasmic reticulum membrane / extracellular exosome / extracellular matrix / membrane / terminal cisterna / Z disc
General Function
Type i transforming growth factor beta receptor binding
Specific Function
Keeps 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 Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010487|Peptidyl-prolyl cis-trans isomerase FKBP1A (FKBP1A)
ATGGGAGTGCAGGTGGAAACCATCTCCCCAGGAGACGGGCGCACCTTCCCCAAGCGCGGC
CAGACCTGCGTGGTGCACTACACCGGGATGCTTGAAGATGGAAAGAAATTTGATTCCTCC
CGGGACAGAAACAAGCCCTTTAAGTTTATGCTAGGCAAGCAGGAGGTGATCCGAGGCTGG
GAAGAAGGGGTTGCCCAGATGAGTGTGGGTCAGAGAGCCAAACTGACTATATCTCCAGAT
TATGCCTATGGTGCCACTGGGCACCCAGGCATCATCCCACCACATGCCACTCTCGTCTTC
GATGTGGAGCTTCTAAAACTGGAATGA
Chromosome Location
20
Locus
20p13
External Identifiers
ResourceLink
UniProtKB IDP62942
UniProtKB Entry NameFKB1A_HUMAN
GenBank Protein ID182628
GenBank Gene IDM34539
GenAtlas IDFKBP1A
HGNC IDHGNC:3711
General 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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:12665801]
  10. Chen YG, Liu F, Massague J: Mechanism of TGFbeta receptor inhibition by FKBP12. EMBO J. 1997 Jul 1;16(13):3866-76. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10656803]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00864Tacrolimusapproved, investigationalyesinhibitorDetails
DB01723{3-[3-(3,4-Dimethoxy-Phenyl)-1-(1-{1-[2-(3,4,5-Trimethoxy-Phenyl)-Butyryl]-Piperidin-2yl}-Vinyloxy)-Propyl]-Phenoxy}-Acetic AcidexperimentalunknownDetails
DB02311Methyl Methylsulfinylmethyl SulfideexperimentalunknownDetails
DB02888FKB-001experimentalunknownDetails
DB03621L-709,587experimentalunknownDetails
DB040944-Hydroxy-2-ButanoneexperimentalunknownDetails
DB00877Sirolimusapproved, investigationalyesotherDetails
DB00337Pimecrolimusapproved, investigationalunknownpotentiatorDetails
DB05814GPI-1485investigationalunknownDetails
DB03338Heptyl-Beta-D-GlucopyranosideexperimentalunknownDetails
DB01951Gpi-1046experimentalunknownDetails
DB08231Myristic acidexperimentalunknownDetails
DB08520(21S)-1AZA-4,4-DIMETHYL-6,19-DIOXA-2,3,7,20-TETRAOXOBICYCLO[19.4.0] PENTACOSANEexperimentalunknownDetails
DB01712(3r)-4-(P-Toluenesulfonyl)-1,4-Thiazane-3-Carboxylicacid-L-Phenylalanine Ethyl EsterexperimentalunknownDetails
DB085976-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidineexperimentalunknownDetails
DB04012(3r)-4-(P-Toluenesulfonyl)-1,4-Thiazane-3-Carboxylicacid-L-LeucineexperimentalunknownDetails