Full text data of FKBP1A
FKBP1A
(FKBP1, FKBP12)
[Confidence: low (only semi-automatic identification from reviews)]
Peptidyl-prolyl cis-trans isomerase FKBP1A; PPIase FKBP1A; 5.2.1.8 (12 kDa FK506-binding protein; 12 kDa FKBP; FKBP-12; Calstabin-1; FK506-binding protein 1A; FKBP-1A; Immunophilin FKBP12; Rotamase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Peptidyl-prolyl cis-trans isomerase FKBP1A; PPIase FKBP1A; 5.2.1.8 (12 kDa FK506-binding protein; 12 kDa FKBP; FKBP-12; Calstabin-1; FK506-binding protein 1A; FKBP-1A; Immunophilin FKBP12; Rotamase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P62942
ID FKB1A_HUMAN Reviewed; 108 AA.
AC P62942; D3DVW6; P20071; Q4VC47; Q6FGD9; Q6LEU3; Q9H103; Q9H566;
read moreDT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP1A;
DE Short=PPIase FKBP1A;
DE EC=5.2.1.8;
DE AltName: Full=12 kDa FK506-binding protein;
DE Short=12 kDa FKBP;
DE Short=FKBP-12;
DE AltName: Full=Calstabin-1;
DE AltName: Full=FK506-binding protein 1A;
DE Short=FKBP-1A;
DE AltName: Full=Immunophilin FKBP12;
DE AltName: Full=Rotamase;
GN Name=FKBP1A; Synonyms=FKBP1, FKBP12;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1695378; DOI=10.1073/pnas.87.14.5440;
RA Maki N., Sekiguchi F., Nishimaki J., Miwa K., Hayano T., Takahashi N.,
RA Suzuki M.;
RT "Complementary DNA encoding the human T-cell FK506-binding protein, a
RT peptidylprolyl cis-trans isomerase distinct from cyclophilin.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5440-5443(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1696686; DOI=10.1038/346671a0;
RA Standaert R.F., Galat A., Verdine G.L., Schreiber S.L.;
RT "Molecular cloning and overexpression of the human FK506-binding
RT protein FKBP.";
RL Nature 346:671-674(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1716149; DOI=10.1021/bi00099a002;
RA Dilella A.G., Craig R.J.;
RT "Exon organization of the human FKBP-12 gene: correlation with
RT structural and functional protein domains.";
RL Biochemistry 30:8512-8517(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Placenta;
RX PubMed=7529739; DOI=10.1016/0378-1119(94)90434-0;
RA Peattie D.A., Hsiao K., Benasutti M., Lippke J.A.;
RT "Three distinct messenger RNAs can encode the human immunosuppressant-
RT binding protein FKBP12.";
RL Gene 150:251-257(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-52.
RX PubMed=1701173;
RA Siekierka J.J., Widerrecht G., Greulich H., Boulton D., Hung S.H.Y.,
RA Cryan J., Hodges P.J., Sigal N.H.;
RT "The cytosolic-binding protein for the immunosuppressant FK-506 is
RT both a ubiquitous and highly conserved peptidyl-prolyl cis-trans
RT isomerase.";
RL J. Biol. Chem. 265:21011-21015(1990).
RN [11]
RP PROTEIN SEQUENCE OF 2-17.
RX PubMed=2477715; DOI=10.1038/341758a0;
RA Harding M.W., Galat A., Uehling D.E., Schreiber S.L.;
RT "A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-
RT prolyl isomerase.";
RL Nature 341:758-760(1989).
RN [12]
RP PROTEIN SEQUENCE OF 2-14.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [13]
RP FUNCTION IN TGFBR1 INHIBITION, AND INTERACTION WITH TGFBR1.
RX PubMed=9233797; DOI=10.1093/emboj/16.13.3866;
RA Chen Y.G., Liu F., Massague J.;
RT "Mechanism of TGFbeta receptor inhibition by FKBP12.";
RL EMBO J. 16:3866-3876(1997).
RN [14]
RP INTERACTION WITH RYR3.
RX PubMed=10358090; DOI=10.1074/jbc.274.24.17297;
RA Murayama T., Oba T., Katayama E., Oyamada H., Oguchi K., Kobayashi M.,
RA Otsuka K., Ogawa Y.;
RT "Further characterization of the type 3 ryanodine receptor (RyR3)
RT purified from rabbit diaphragm.";
RL J. Biol. Chem. 274:17297-17308(1999).
RN [15]
RP INTERACTION WITH ACVR1B AND SMAD7, AND FUNCTION.
RX PubMed=16720724; DOI=10.1677/jme.1.01966;
RA Yamaguchi T., Kurisaki A., Yamakawa N., Minakuchi K., Sugino H.;
RT "FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin
RT type I receptor.";
RL J. Mol. Endocrinol. 36:569-579(2006).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP INTERACTION WITH RYR3.
RX PubMed=22100703; DOI=10.1016/j.abb.2011.11.004;
RA Wen H., Kang S., Song Y., Song Y., Yang H.J., Kim M.H., Park S.;
RT "Characterization of the binding sites for the interactions between
RT FKBP12 and intracellular calcium release channels.";
RL Arch. Biochem. Biophys. 517:37-42(2012).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP STRUCTURE BY NMR.
RX PubMed=1709363; DOI=10.1021/bi00233a020;
RA Rosen M.K., Michnick S.W., Karplus M., Schreiber S.L.;
RT "Proton and nitrogen sequential assignments and secondary structure
RT determination of the human FK506 and rapamycin binding protein.";
RL Biochemistry 30:4774-4789(1991).
RN [23]
RP STRUCTURE BY NMR.
RX PubMed=1709301; DOI=10.1126/science.1709301;
RA Michnick S.W., Rosen M.K., Wandless T.J., Karplus M., Schreiber S.L.;
RT "Solution structure of FKBP, a rotamase enzyme and receptor for FK506
RT and rapamycin.";
RL Science 252:836-839(1991).
RN [24]
RP STRUCTURE BY NMR.
RX PubMed=1375171; DOI=10.1016/0014-5793(92)80292-O;
RA Lepre C.A., Thomson J.A., Moore J.M.;
RT "Solution structure of FK506 bound to FKBP-12.";
RL FEBS Lett. 302:89-96(1992).
RN [25]
RP STRUCTURE BY NMR OF COMPLEX WITH ASCOMYCIN.
RX PubMed=7682113; DOI=10.1002/bip.360330404;
RA Xu R.X., Nettesheim D., Olejniczak E.T., Meadows R., Gemmecker G.,
RA Fesik S.W.;
RT "1H, 13C, and 15N assignments and secondary structure of the FK506
RT binding protein when bound to ascomycin.";
RL Biopolymers 33:535-550(1993).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=1709302; DOI=10.1126/science.1709302;
RA van Duyne G.D., Standaert R.F., Karplus P.A., Schreiber S.L.,
RA Clardy J.;
RT "Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant
RT complex.";
RL Science 252:839-842(1991).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RA van Duyne G.D., Standaert R.F., Schreiber S.L., Clardy J.;
RT "Atomic structure of the rapamycin human immunophilin FKBP-12
RT complex.";
RL J. Am. Chem. Soc. 113:7433-7434(1991).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
RX PubMed=7678431; DOI=10.1006/jmbi.1993.1012;
RA van Duyne G.D., Standaert R.F., Karplus P.A., Schreiber S.L.,
RA Clardy J.;
RT "Atomic structures of the human immunophilin FKBP-12 complexes with
RT FK506 and rapamycin.";
RL J. Mol. Biol. 229:105-124(1993).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 2-107 IN COMPLEX WITH
RP TGFBR1.
RX PubMed=10025408; DOI=10.1016/S0092-8674(00)80555-3;
RA Huse M., Chen Y.-G., Massague J., Kuriyan J.;
RT "Crystal structure of the cytoplasmic domain of the type I TGF beta
RT receptor in complex with FKBP12.";
RL Cell 96:425-436(1999).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
RX PubMed=10656803; DOI=10.1006/jmbi.1999.3411;
RA Burkhard P., Taylor P., Walkinshaw M.D.;
RT "X-ray structures of small ligand-FKBP complexes provide an estimate
RT for hydrophobic interaction energies.";
RL J. Mol. Biol. 295:953-962(2000).
CC -!- FUNCTION: Keeps in an inactive conformation TGFBR1, the TGF-beta
CC type I serine/threonine kinase receptor, preventing TGF-beta
CC receptor activation in absence of ligand. Recruites SMAD7 to
CC ACVR1B which prevents the association of SMAD2 and SMAD3 with the
CC activin receptor complex, thereby blocking the activin signal. May
CC modulate the RYR1 calcium channel activity. PPIases accelerate the
CC folding of proteins. It catalyzes the cis-trans isomerization of
CC proline imidic peptide bonds in oligopeptides.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Inhibited by both FK506 and rapamycin.
CC -!- SUBUNIT: Interacts directly with RYR1, RYR2 and RYR3. Identified
CC in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein
CC phosphatase 1 (PP1) (By similarity). Interacts with TGFBR1;
CC prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the
CC inactive conformation. Interacts with ACVR1B and SMAD7.
CC -!- INTERACTION:
CC P36896:ACVR1B; NbExp=2; IntAct=EBI-1027571, EBI-1384128;
CC O15105:SMAD7; NbExp=3; IntAct=EBI-1027571, EBI-3861591;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1
CC subfamily.
CC -!- SIMILARITY: Contains 1 PPIase FKBP-type domain.
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DR EMBL; M34539; AAA35844.1; -; mRNA.
DR EMBL; M92423; AAA58476.1; -; Genomic_DNA.
DR EMBL; M92422; AAA58476.1; JOINED; Genomic_DNA.
DR EMBL; M93060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X55741; CAA39272.1; -; Genomic_DNA.
DR EMBL; M80199; AAA58472.1; -; Genomic_DNA.
DR EMBL; X52220; CAA36462.1; -; mRNA.
DR EMBL; BT007066; AAP35729.1; -; mRNA.
DR EMBL; CR407613; CAG28541.1; -; mRNA.
DR EMBL; CR542168; CAG46965.1; -; mRNA.
DR EMBL; AL136531; CAH72382.1; -; Genomic_DNA.
DR EMBL; AL109658; CAH72382.1; JOINED; Genomic_DNA.
DR EMBL; AL109658; CAI22728.1; -; Genomic_DNA.
DR EMBL; AL136531; CAI22728.1; JOINED; Genomic_DNA.
DR EMBL; CH471133; EAX10633.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10634.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10635.1; -; Genomic_DNA.
DR EMBL; BC001925; AAH01925.3; -; mRNA.
DR EMBL; BC005147; AAH05147.1; -; mRNA.
DR PIR; I65284; A35780.
DR RefSeq; NP_000792.1; NM_000801.4.
DR RefSeq; NP_463460.1; NM_054014.3.
DR RefSeq; XP_005260730.1; XM_005260673.1.
DR UniGene; Hs.471933; -.
DR UniGene; Hs.700839; -.
DR PDB; 1A7X; X-ray; 2.00 A; A/B=2-108.
DR PDB; 1B6C; X-ray; 2.60 A; A/C/E/G=2-107.
DR PDB; 1BKF; X-ray; 1.60 A; A=2-108.
DR PDB; 1BL4; X-ray; 1.90 A; A/B=2-107.
DR PDB; 1D6O; X-ray; 1.85 A; A/B=2-108.
DR PDB; 1D7H; X-ray; 1.90 A; A/B=2-108.
DR PDB; 1D7I; X-ray; 1.90 A; A/B=2-108.
DR PDB; 1D7J; X-ray; 1.85 A; A/B=2-108.
DR PDB; 1EYM; X-ray; 2.00 A; A/B=2-108.
DR PDB; 1F40; NMR; -; A=2-108.
DR PDB; 1FAP; X-ray; 2.70 A; A=2-107.
DR PDB; 1FKB; X-ray; 1.70 A; A=2-108.
DR PDB; 1FKD; X-ray; 1.72 A; A=2-107.
DR PDB; 1FKF; X-ray; 1.70 A; A=2-108.
DR PDB; 1FKG; X-ray; 2.00 A; A=2-108.
DR PDB; 1FKH; X-ray; 1.95 A; A=2-108.
DR PDB; 1FKI; X-ray; 2.20 A; A/B=2-108.
DR PDB; 1FKJ; X-ray; 1.70 A; A=2-107.
DR PDB; 1FKR; NMR; -; A=2-108.
DR PDB; 1FKS; NMR; -; A=2-108.
DR PDB; 1FKT; NMR; -; A=2-108.
DR PDB; 1J4H; X-ray; 1.80 A; A=2-107.
DR PDB; 1J4I; X-ray; 1.80 A; A=2-107.
DR PDB; 1J4R; X-ray; 1.80 A; A/B/D=2-107.
DR PDB; 1NSG; X-ray; 2.20 A; A=2-107.
DR PDB; 1QPF; X-ray; 2.50 A; A/D=2-107.
DR PDB; 1QPL; X-ray; 2.90 A; A/C=2-107.
DR PDB; 2DG3; X-ray; 1.70 A; A=2-108.
DR PDB; 2DG4; X-ray; 1.70 A; A=2-108.
DR PDB; 2DG9; X-ray; 1.70 A; A=2-108.
DR PDB; 2FAP; X-ray; 2.20 A; A=2-107.
DR PDB; 2FKE; X-ray; 1.72 A; A=2-107.
DR PDB; 2PPN; X-ray; 0.92 A; A=2-108.
DR PDB; 2PPO; X-ray; 1.29 A; A=2-108.
DR PDB; 2PPP; X-ray; 0.94 A; A=2-108.
DR PDB; 2RSE; NMR; -; A=2-108.
DR PDB; 3FAP; X-ray; 1.85 A; A=2-107.
DR PDB; 3H9R; X-ray; 2.35 A; B=1-108.
DR PDB; 3MDY; X-ray; 2.05 A; B/D=1-108.
DR PDB; 4DH0; X-ray; 2.10 A; A=2-108.
DR PDB; 4FAP; X-ray; 2.80 A; A=2-107.
DR PDB; 4IPX; X-ray; 1.70 A; A=2-108.
DR PDBsum; 1A7X; -.
DR PDBsum; 1B6C; -.
DR PDBsum; 1BKF; -.
DR PDBsum; 1BL4; -.
DR PDBsum; 1D6O; -.
DR PDBsum; 1D7H; -.
DR PDBsum; 1D7I; -.
DR PDBsum; 1D7J; -.
DR PDBsum; 1EYM; -.
DR PDBsum; 1F40; -.
DR PDBsum; 1FAP; -.
DR PDBsum; 1FKB; -.
DR PDBsum; 1FKD; -.
DR PDBsum; 1FKF; -.
DR PDBsum; 1FKG; -.
DR PDBsum; 1FKH; -.
DR PDBsum; 1FKI; -.
DR PDBsum; 1FKJ; -.
DR PDBsum; 1FKR; -.
DR PDBsum; 1FKS; -.
DR PDBsum; 1FKT; -.
DR PDBsum; 1J4H; -.
DR PDBsum; 1J4I; -.
DR PDBsum; 1J4R; -.
DR PDBsum; 1NSG; -.
DR PDBsum; 1QPF; -.
DR PDBsum; 1QPL; -.
DR PDBsum; 2DG3; -.
DR PDBsum; 2DG4; -.
DR PDBsum; 2DG9; -.
DR PDBsum; 2FAP; -.
DR PDBsum; 2FKE; -.
DR PDBsum; 2PPN; -.
DR PDBsum; 2PPO; -.
DR PDBsum; 2PPP; -.
DR PDBsum; 2RSE; -.
DR PDBsum; 3FAP; -.
DR PDBsum; 3H9R; -.
DR PDBsum; 3MDY; -.
DR PDBsum; 4DH0; -.
DR PDBsum; 4FAP; -.
DR PDBsum; 4IPX; -.
DR ProteinModelPortal; P62942; -.
DR SMR; P62942; 2-108.
DR DIP; DIP-29710N; -.
DR IntAct; P62942; 8.
DR MINT; MINT-87893; -.
DR STRING; 9606.ENSP00000371138; -.
DR BindingDB; P62942; -.
DR ChEMBL; CHEMBL2221341; -.
DR DrugBank; DB00337; Pimecrolimus.
DR DrugBank; DB00877; Sirolimus.
DR DrugBank; DB00864; Tacrolimus.
DR PhosphoSite; P62942; -.
DR DMDM; 51702264; -.
DR PaxDb; P62942; -.
DR PRIDE; P62942; -.
DR DNASU; 2280; -.
DR Ensembl; ENST00000381719; ENSP00000371138; ENSG00000088832.
DR Ensembl; ENST00000400137; ENSP00000383003; ENSG00000088832.
DR GeneID; 2280; -.
DR KEGG; hsa:2280; -.
DR UCSC; uc002wey.3; human.
DR CTD; 2280; -.
DR GeneCards; GC20M001349; -.
DR HGNC; HGNC:3711; FKBP1A.
DR HPA; CAB004639; -.
DR HPA; HPA051798; -.
DR MIM; 186945; gene.
DR neXtProt; NX_P62942; -.
DR PharmGKB; PA28153; -.
DR eggNOG; COG0545; -.
DR HOVERGEN; HBG051623; -.
DR InParanoid; P62942; -.
DR KO; K09568; -.
DR OMA; FQCNIGV; -.
DR OrthoDB; EOG7ZGX5T; -.
DR PhylomeDB; P62942; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; P62942; -.
DR EvolutionaryTrace; P62942; -.
DR GeneWiki; FKBP1A; -.
DR GenomeRNAi; 2280; -.
DR NextBio; 9269; -.
DR PMAP-CutDB; P62942; -.
DR PRO; PR:P62942; -.
DR ArrayExpress; P62942; -.
DR Bgee; P62942; -.
DR CleanEx; HS_FKBP1A; -.
DR Genevestigator; P62942; -.
DR GO; GO:0030424; C:axon; IBA:RefGenome.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IBA:RefGenome.
DR GO; GO:0014802; C:terminal cisterna; ISS:BHF-UCL.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0005528; F:FK506 binding; IDA:BHF-UCL.
DR GO; GO:0044325; F:ion channel binding; ISS:BHF-UCL.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:BHF-UCL.
DR GO; GO:0004871; F:signal transducer activity; IMP:UniProtKB.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISS:BHF-UCL.
DR GO; GO:0006458; P:'de novo' protein folding; TAS:BHF-UCL.
DR GO; GO:0034205; P:beta-amyloid formation; IDA:BHF-UCL.
DR GO; GO:0043206; P:extracellular fibril organization; IDA:BHF-UCL.
DR GO; GO:0060347; P:heart trabecula formation; ISS:BHF-UCL.
DR GO; GO:0032513; P:negative regulation of protein phosphatase type 2B activity; IDA:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0022417; P:protein maturation by protein folding; TAS:BHF-UCL.
DR GO; GO:0042026; P:protein refolding; TAS:BHF-UCL.
DR GO; GO:0032925; P:regulation of activin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0050776; P:regulation of immune response; IMP:BHF-UCL.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0007183; P:SMAD protein complex assembly; IDA:BHF-UCL.
DR GO; GO:0042110; P:T cell activation; NAS:BHF-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR InterPro; IPR023566; PPIase_FKBP.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR PANTHER; PTHR10516; PTHR10516; 1.
DR Pfam; PF00254; FKBP_C; 1.
DR PROSITE; PS50059; FKBP_PPIASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Isomerase; Phosphoprotein;
KW Reference proteome; Rotamase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 108 Peptidyl-prolyl cis-trans isomerase
FT FKBP1A.
FT /FTId=PRO_0000075289.
FT DOMAIN 20 108 PPIase FKBP-type.
FT MOD_RES 2 2 N-acetylglycine.
FT MOD_RES 9 9 Phosphoserine.
FT CONFLICT 60 60 W -> R (in Ref. 6; CAG28541).
FT CONFLICT 91 91 I -> V (in Ref. 6; CAG28541).
FT STRAND 3 9
FT STRAND 22 31
FT STRAND 36 39
FT HELIX 40 43
FT STRAND 47 50
FT TURN 51 54
FT HELIX 58 64
FT STRAND 72 77
FT HELIX 79 81
FT TURN 82 86
FT TURN 89 91
FT STRAND 98 108
SQ SEQUENCE 108 AA; 11951 MW; 9CC8493C802540B4 CRC64;
MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFM LGKQEVIRGW
EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPHATLVF DVELLKLE
//
ID FKB1A_HUMAN Reviewed; 108 AA.
AC P62942; D3DVW6; P20071; Q4VC47; Q6FGD9; Q6LEU3; Q9H103; Q9H566;
read moreDT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP1A;
DE Short=PPIase FKBP1A;
DE EC=5.2.1.8;
DE AltName: Full=12 kDa FK506-binding protein;
DE Short=12 kDa FKBP;
DE Short=FKBP-12;
DE AltName: Full=Calstabin-1;
DE AltName: Full=FK506-binding protein 1A;
DE Short=FKBP-1A;
DE AltName: Full=Immunophilin FKBP12;
DE AltName: Full=Rotamase;
GN Name=FKBP1A; Synonyms=FKBP1, FKBP12;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1695378; DOI=10.1073/pnas.87.14.5440;
RA Maki N., Sekiguchi F., Nishimaki J., Miwa K., Hayano T., Takahashi N.,
RA Suzuki M.;
RT "Complementary DNA encoding the human T-cell FK506-binding protein, a
RT peptidylprolyl cis-trans isomerase distinct from cyclophilin.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5440-5443(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1696686; DOI=10.1038/346671a0;
RA Standaert R.F., Galat A., Verdine G.L., Schreiber S.L.;
RT "Molecular cloning and overexpression of the human FK506-binding
RT protein FKBP.";
RL Nature 346:671-674(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1716149; DOI=10.1021/bi00099a002;
RA Dilella A.G., Craig R.J.;
RT "Exon organization of the human FKBP-12 gene: correlation with
RT structural and functional protein domains.";
RL Biochemistry 30:8512-8517(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Placenta;
RX PubMed=7529739; DOI=10.1016/0378-1119(94)90434-0;
RA Peattie D.A., Hsiao K., Benasutti M., Lippke J.A.;
RT "Three distinct messenger RNAs can encode the human immunosuppressant-
RT binding protein FKBP12.";
RL Gene 150:251-257(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-52.
RX PubMed=1701173;
RA Siekierka J.J., Widerrecht G., Greulich H., Boulton D., Hung S.H.Y.,
RA Cryan J., Hodges P.J., Sigal N.H.;
RT "The cytosolic-binding protein for the immunosuppressant FK-506 is
RT both a ubiquitous and highly conserved peptidyl-prolyl cis-trans
RT isomerase.";
RL J. Biol. Chem. 265:21011-21015(1990).
RN [11]
RP PROTEIN SEQUENCE OF 2-17.
RX PubMed=2477715; DOI=10.1038/341758a0;
RA Harding M.W., Galat A., Uehling D.E., Schreiber S.L.;
RT "A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-
RT prolyl isomerase.";
RL Nature 341:758-760(1989).
RN [12]
RP PROTEIN SEQUENCE OF 2-14.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [13]
RP FUNCTION IN TGFBR1 INHIBITION, AND INTERACTION WITH TGFBR1.
RX PubMed=9233797; DOI=10.1093/emboj/16.13.3866;
RA Chen Y.G., Liu F., Massague J.;
RT "Mechanism of TGFbeta receptor inhibition by FKBP12.";
RL EMBO J. 16:3866-3876(1997).
RN [14]
RP INTERACTION WITH RYR3.
RX PubMed=10358090; DOI=10.1074/jbc.274.24.17297;
RA Murayama T., Oba T., Katayama E., Oyamada H., Oguchi K., Kobayashi M.,
RA Otsuka K., Ogawa Y.;
RT "Further characterization of the type 3 ryanodine receptor (RyR3)
RT purified from rabbit diaphragm.";
RL J. Biol. Chem. 274:17297-17308(1999).
RN [15]
RP INTERACTION WITH ACVR1B AND SMAD7, AND FUNCTION.
RX PubMed=16720724; DOI=10.1677/jme.1.01966;
RA Yamaguchi T., Kurisaki A., Yamakawa N., Minakuchi K., Sugino H.;
RT "FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin
RT type I receptor.";
RL J. Mol. Endocrinol. 36:569-579(2006).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP INTERACTION WITH RYR3.
RX PubMed=22100703; DOI=10.1016/j.abb.2011.11.004;
RA Wen H., Kang S., Song Y., Song Y., Yang H.J., Kim M.H., Park S.;
RT "Characterization of the binding sites for the interactions between
RT FKBP12 and intracellular calcium release channels.";
RL Arch. Biochem. Biophys. 517:37-42(2012).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP STRUCTURE BY NMR.
RX PubMed=1709363; DOI=10.1021/bi00233a020;
RA Rosen M.K., Michnick S.W., Karplus M., Schreiber S.L.;
RT "Proton and nitrogen sequential assignments and secondary structure
RT determination of the human FK506 and rapamycin binding protein.";
RL Biochemistry 30:4774-4789(1991).
RN [23]
RP STRUCTURE BY NMR.
RX PubMed=1709301; DOI=10.1126/science.1709301;
RA Michnick S.W., Rosen M.K., Wandless T.J., Karplus M., Schreiber S.L.;
RT "Solution structure of FKBP, a rotamase enzyme and receptor for FK506
RT and rapamycin.";
RL Science 252:836-839(1991).
RN [24]
RP STRUCTURE BY NMR.
RX PubMed=1375171; DOI=10.1016/0014-5793(92)80292-O;
RA Lepre C.A., Thomson J.A., Moore J.M.;
RT "Solution structure of FK506 bound to FKBP-12.";
RL FEBS Lett. 302:89-96(1992).
RN [25]
RP STRUCTURE BY NMR OF COMPLEX WITH ASCOMYCIN.
RX PubMed=7682113; DOI=10.1002/bip.360330404;
RA Xu R.X., Nettesheim D., Olejniczak E.T., Meadows R., Gemmecker G.,
RA Fesik S.W.;
RT "1H, 13C, and 15N assignments and secondary structure of the FK506
RT binding protein when bound to ascomycin.";
RL Biopolymers 33:535-550(1993).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=1709302; DOI=10.1126/science.1709302;
RA van Duyne G.D., Standaert R.F., Karplus P.A., Schreiber S.L.,
RA Clardy J.;
RT "Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant
RT complex.";
RL Science 252:839-842(1991).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RA van Duyne G.D., Standaert R.F., Schreiber S.L., Clardy J.;
RT "Atomic structure of the rapamycin human immunophilin FKBP-12
RT complex.";
RL J. Am. Chem. Soc. 113:7433-7434(1991).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
RX PubMed=7678431; DOI=10.1006/jmbi.1993.1012;
RA van Duyne G.D., Standaert R.F., Karplus P.A., Schreiber S.L.,
RA Clardy J.;
RT "Atomic structures of the human immunophilin FKBP-12 complexes with
RT FK506 and rapamycin.";
RL J. Mol. Biol. 229:105-124(1993).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 2-107 IN COMPLEX WITH
RP TGFBR1.
RX PubMed=10025408; DOI=10.1016/S0092-8674(00)80555-3;
RA Huse M., Chen Y.-G., Massague J., Kuriyan J.;
RT "Crystal structure of the cytoplasmic domain of the type I TGF beta
RT receptor in complex with FKBP12.";
RL Cell 96:425-436(1999).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
RX PubMed=10656803; DOI=10.1006/jmbi.1999.3411;
RA Burkhard P., Taylor P., Walkinshaw M.D.;
RT "X-ray structures of small ligand-FKBP complexes provide an estimate
RT for hydrophobic interaction energies.";
RL J. Mol. Biol. 295:953-962(2000).
CC -!- FUNCTION: Keeps in an inactive conformation TGFBR1, the TGF-beta
CC type I serine/threonine kinase receptor, preventing TGF-beta
CC receptor activation in absence of ligand. Recruites SMAD7 to
CC ACVR1B which prevents the association of SMAD2 and SMAD3 with the
CC activin receptor complex, thereby blocking the activin signal. May
CC modulate the RYR1 calcium channel activity. PPIases accelerate the
CC folding of proteins. It catalyzes the cis-trans isomerization of
CC proline imidic peptide bonds in oligopeptides.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Inhibited by both FK506 and rapamycin.
CC -!- SUBUNIT: Interacts directly with RYR1, RYR2 and RYR3. Identified
CC in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein
CC phosphatase 1 (PP1) (By similarity). Interacts with TGFBR1;
CC prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the
CC inactive conformation. Interacts with ACVR1B and SMAD7.
CC -!- INTERACTION:
CC P36896:ACVR1B; NbExp=2; IntAct=EBI-1027571, EBI-1384128;
CC O15105:SMAD7; NbExp=3; IntAct=EBI-1027571, EBI-3861591;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1
CC subfamily.
CC -!- SIMILARITY: Contains 1 PPIase FKBP-type domain.
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DR EMBL; M34539; AAA35844.1; -; mRNA.
DR EMBL; M92423; AAA58476.1; -; Genomic_DNA.
DR EMBL; M92422; AAA58476.1; JOINED; Genomic_DNA.
DR EMBL; M93060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X55741; CAA39272.1; -; Genomic_DNA.
DR EMBL; M80199; AAA58472.1; -; Genomic_DNA.
DR EMBL; X52220; CAA36462.1; -; mRNA.
DR EMBL; BT007066; AAP35729.1; -; mRNA.
DR EMBL; CR407613; CAG28541.1; -; mRNA.
DR EMBL; CR542168; CAG46965.1; -; mRNA.
DR EMBL; AL136531; CAH72382.1; -; Genomic_DNA.
DR EMBL; AL109658; CAH72382.1; JOINED; Genomic_DNA.
DR EMBL; AL109658; CAI22728.1; -; Genomic_DNA.
DR EMBL; AL136531; CAI22728.1; JOINED; Genomic_DNA.
DR EMBL; CH471133; EAX10633.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10634.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10635.1; -; Genomic_DNA.
DR EMBL; BC001925; AAH01925.3; -; mRNA.
DR EMBL; BC005147; AAH05147.1; -; mRNA.
DR PIR; I65284; A35780.
DR RefSeq; NP_000792.1; NM_000801.4.
DR RefSeq; NP_463460.1; NM_054014.3.
DR RefSeq; XP_005260730.1; XM_005260673.1.
DR UniGene; Hs.471933; -.
DR UniGene; Hs.700839; -.
DR PDB; 1A7X; X-ray; 2.00 A; A/B=2-108.
DR PDB; 1B6C; X-ray; 2.60 A; A/C/E/G=2-107.
DR PDB; 1BKF; X-ray; 1.60 A; A=2-108.
DR PDB; 1BL4; X-ray; 1.90 A; A/B=2-107.
DR PDB; 1D6O; X-ray; 1.85 A; A/B=2-108.
DR PDB; 1D7H; X-ray; 1.90 A; A/B=2-108.
DR PDB; 1D7I; X-ray; 1.90 A; A/B=2-108.
DR PDB; 1D7J; X-ray; 1.85 A; A/B=2-108.
DR PDB; 1EYM; X-ray; 2.00 A; A/B=2-108.
DR PDB; 1F40; NMR; -; A=2-108.
DR PDB; 1FAP; X-ray; 2.70 A; A=2-107.
DR PDB; 1FKB; X-ray; 1.70 A; A=2-108.
DR PDB; 1FKD; X-ray; 1.72 A; A=2-107.
DR PDB; 1FKF; X-ray; 1.70 A; A=2-108.
DR PDB; 1FKG; X-ray; 2.00 A; A=2-108.
DR PDB; 1FKH; X-ray; 1.95 A; A=2-108.
DR PDB; 1FKI; X-ray; 2.20 A; A/B=2-108.
DR PDB; 1FKJ; X-ray; 1.70 A; A=2-107.
DR PDB; 1FKR; NMR; -; A=2-108.
DR PDB; 1FKS; NMR; -; A=2-108.
DR PDB; 1FKT; NMR; -; A=2-108.
DR PDB; 1J4H; X-ray; 1.80 A; A=2-107.
DR PDB; 1J4I; X-ray; 1.80 A; A=2-107.
DR PDB; 1J4R; X-ray; 1.80 A; A/B/D=2-107.
DR PDB; 1NSG; X-ray; 2.20 A; A=2-107.
DR PDB; 1QPF; X-ray; 2.50 A; A/D=2-107.
DR PDB; 1QPL; X-ray; 2.90 A; A/C=2-107.
DR PDB; 2DG3; X-ray; 1.70 A; A=2-108.
DR PDB; 2DG4; X-ray; 1.70 A; A=2-108.
DR PDB; 2DG9; X-ray; 1.70 A; A=2-108.
DR PDB; 2FAP; X-ray; 2.20 A; A=2-107.
DR PDB; 2FKE; X-ray; 1.72 A; A=2-107.
DR PDB; 2PPN; X-ray; 0.92 A; A=2-108.
DR PDB; 2PPO; X-ray; 1.29 A; A=2-108.
DR PDB; 2PPP; X-ray; 0.94 A; A=2-108.
DR PDB; 2RSE; NMR; -; A=2-108.
DR PDB; 3FAP; X-ray; 1.85 A; A=2-107.
DR PDB; 3H9R; X-ray; 2.35 A; B=1-108.
DR PDB; 3MDY; X-ray; 2.05 A; B/D=1-108.
DR PDB; 4DH0; X-ray; 2.10 A; A=2-108.
DR PDB; 4FAP; X-ray; 2.80 A; A=2-107.
DR PDB; 4IPX; X-ray; 1.70 A; A=2-108.
DR PDBsum; 1A7X; -.
DR PDBsum; 1B6C; -.
DR PDBsum; 1BKF; -.
DR PDBsum; 1BL4; -.
DR PDBsum; 1D6O; -.
DR PDBsum; 1D7H; -.
DR PDBsum; 1D7I; -.
DR PDBsum; 1D7J; -.
DR PDBsum; 1EYM; -.
DR PDBsum; 1F40; -.
DR PDBsum; 1FAP; -.
DR PDBsum; 1FKB; -.
DR PDBsum; 1FKD; -.
DR PDBsum; 1FKF; -.
DR PDBsum; 1FKG; -.
DR PDBsum; 1FKH; -.
DR PDBsum; 1FKI; -.
DR PDBsum; 1FKJ; -.
DR PDBsum; 1FKR; -.
DR PDBsum; 1FKS; -.
DR PDBsum; 1FKT; -.
DR PDBsum; 1J4H; -.
DR PDBsum; 1J4I; -.
DR PDBsum; 1J4R; -.
DR PDBsum; 1NSG; -.
DR PDBsum; 1QPF; -.
DR PDBsum; 1QPL; -.
DR PDBsum; 2DG3; -.
DR PDBsum; 2DG4; -.
DR PDBsum; 2DG9; -.
DR PDBsum; 2FAP; -.
DR PDBsum; 2FKE; -.
DR PDBsum; 2PPN; -.
DR PDBsum; 2PPO; -.
DR PDBsum; 2PPP; -.
DR PDBsum; 2RSE; -.
DR PDBsum; 3FAP; -.
DR PDBsum; 3H9R; -.
DR PDBsum; 3MDY; -.
DR PDBsum; 4DH0; -.
DR PDBsum; 4FAP; -.
DR PDBsum; 4IPX; -.
DR ProteinModelPortal; P62942; -.
DR SMR; P62942; 2-108.
DR DIP; DIP-29710N; -.
DR IntAct; P62942; 8.
DR MINT; MINT-87893; -.
DR STRING; 9606.ENSP00000371138; -.
DR BindingDB; P62942; -.
DR ChEMBL; CHEMBL2221341; -.
DR DrugBank; DB00337; Pimecrolimus.
DR DrugBank; DB00877; Sirolimus.
DR DrugBank; DB00864; Tacrolimus.
DR PhosphoSite; P62942; -.
DR DMDM; 51702264; -.
DR PaxDb; P62942; -.
DR PRIDE; P62942; -.
DR DNASU; 2280; -.
DR Ensembl; ENST00000381719; ENSP00000371138; ENSG00000088832.
DR Ensembl; ENST00000400137; ENSP00000383003; ENSG00000088832.
DR GeneID; 2280; -.
DR KEGG; hsa:2280; -.
DR UCSC; uc002wey.3; human.
DR CTD; 2280; -.
DR GeneCards; GC20M001349; -.
DR HGNC; HGNC:3711; FKBP1A.
DR HPA; CAB004639; -.
DR HPA; HPA051798; -.
DR MIM; 186945; gene.
DR neXtProt; NX_P62942; -.
DR PharmGKB; PA28153; -.
DR eggNOG; COG0545; -.
DR HOVERGEN; HBG051623; -.
DR InParanoid; P62942; -.
DR KO; K09568; -.
DR OMA; FQCNIGV; -.
DR OrthoDB; EOG7ZGX5T; -.
DR PhylomeDB; P62942; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; P62942; -.
DR EvolutionaryTrace; P62942; -.
DR GeneWiki; FKBP1A; -.
DR GenomeRNAi; 2280; -.
DR NextBio; 9269; -.
DR PMAP-CutDB; P62942; -.
DR PRO; PR:P62942; -.
DR ArrayExpress; P62942; -.
DR Bgee; P62942; -.
DR CleanEx; HS_FKBP1A; -.
DR Genevestigator; P62942; -.
DR GO; GO:0030424; C:axon; IBA:RefGenome.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IBA:RefGenome.
DR GO; GO:0014802; C:terminal cisterna; ISS:BHF-UCL.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0005528; F:FK506 binding; IDA:BHF-UCL.
DR GO; GO:0044325; F:ion channel binding; ISS:BHF-UCL.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:BHF-UCL.
DR GO; GO:0004871; F:signal transducer activity; IMP:UniProtKB.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISS:BHF-UCL.
DR GO; GO:0006458; P:'de novo' protein folding; TAS:BHF-UCL.
DR GO; GO:0034205; P:beta-amyloid formation; IDA:BHF-UCL.
DR GO; GO:0043206; P:extracellular fibril organization; IDA:BHF-UCL.
DR GO; GO:0060347; P:heart trabecula formation; ISS:BHF-UCL.
DR GO; GO:0032513; P:negative regulation of protein phosphatase type 2B activity; IDA:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0022417; P:protein maturation by protein folding; TAS:BHF-UCL.
DR GO; GO:0042026; P:protein refolding; TAS:BHF-UCL.
DR GO; GO:0032925; P:regulation of activin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0050776; P:regulation of immune response; IMP:BHF-UCL.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0007183; P:SMAD protein complex assembly; IDA:BHF-UCL.
DR GO; GO:0042110; P:T cell activation; NAS:BHF-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR InterPro; IPR023566; PPIase_FKBP.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR PANTHER; PTHR10516; PTHR10516; 1.
DR Pfam; PF00254; FKBP_C; 1.
DR PROSITE; PS50059; FKBP_PPIASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Isomerase; Phosphoprotein;
KW Reference proteome; Rotamase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 108 Peptidyl-prolyl cis-trans isomerase
FT FKBP1A.
FT /FTId=PRO_0000075289.
FT DOMAIN 20 108 PPIase FKBP-type.
FT MOD_RES 2 2 N-acetylglycine.
FT MOD_RES 9 9 Phosphoserine.
FT CONFLICT 60 60 W -> R (in Ref. 6; CAG28541).
FT CONFLICT 91 91 I -> V (in Ref. 6; CAG28541).
FT STRAND 3 9
FT STRAND 22 31
FT STRAND 36 39
FT HELIX 40 43
FT STRAND 47 50
FT TURN 51 54
FT HELIX 58 64
FT STRAND 72 77
FT HELIX 79 81
FT TURN 82 86
FT TURN 89 91
FT STRAND 98 108
SQ SEQUENCE 108 AA; 11951 MW; 9CC8493C802540B4 CRC64;
MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFM LGKQEVIRGW
EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPHATLVF DVELLKLE
//
MIM
186945
*RECORD*
*FIELD* NO
186945
*FIELD* TI
*186945 FK506-BINDING PROTEIN 1A; FKBP1A
;;FK506-BINDING PROTEIN 1; FKBP1;;
FK506-BINDING PROTEIN, 12-KD; FKBP12;;
read moreFK506-BINDING PROTEIN, T-CELL, 12-KD;;
CALSTABIN 1
*FIELD* TX
DESCRIPTION
Immunophilins are a family of highly conserved proteins that bind with
immunosuppressive drugs, such as FK506, rapamycin, and cyclosporin A
(CsA). The 2 major types of immunophilins are FK506-binding proteins
(FKBPs), most of which bind FK506 and rapamycin, and cyclophilins (e.g.,
PPIA; 123840), which bind CsA. Most FKBPs, including FKBP1A, exhibit
peptidyl-prolyl cis/trans isomerase (PPIase; EC 5.2.1.8) activity. FKBPs
are involved in numerous biologic processes, including protein folding,
receptor signaling, protein trafficking, transcription, apoptosis, and
T-cell activation (review by Kang et al., 2008).
CLONING
Maki et al. (1990) isolated and sequenced DNA coding for FKBP from human
peripheral blood T lymphocytes by using mixed 20-mer oligonucleotide
probes synthesized on the basis of the sequence of bovine Fkbp. They
found an ORF encoding 108 amino acids, the first 40 of which are
identical to those of the bovine sequence. Analysis showed no
significant sequence similarity to other proteins, including cyclophilin
(PPIA; 123840). Southern blot analysis of human genomic DNA suggested
the existence of only a few copies of the FKBP gene. This is in contrast
to results indicating as many as 20 copies of the cyclophilin gene, as
well as possible pseudogenes, in the mammalian genome. Standaert et al.
(1990) likewise isolated a cDNA for FKBP and reported the derived amino
acid sequence. The human FKBP cDNA sequence shares significant
similarity with an ORF in the genome of Neisseria meningitidis.
Peattie et al. (1994) identified 3 distinct mRNAs for FKBP12, designated
A, B, and C, that result from differential splicing or polyadenylation.
All 3 encode the same protein sequence.
GENE FUNCTION
Jin et al. (1991) noted that the 12-kD FKBP is a cytosolic receptor for
rapamycin and FK506, both of which are immunosuppressants.
Wang et al. (1994) reported that in a yeast genetic screen, FKBP1
interacted with various type I receptors, including the TGF-beta type I
receptor (190181). Deletion, point mutation, and coimmunoprecipitation
studies demonstrated the specificity of this interaction, and
competitive binding assays indicated that the type I receptor may be a
natural ligand for FKBP1. Wang et al. (1994) concluded that FKBP1 may
play a role in type I receptor-mediated signaling.
- Reviews
Kang et al. (2008) reviewed the molecular characteristics of FKBP family
members, including FKBP1A, and the biologic functions of their ligands
in performing neuroprotective and neurotrophic activities.
MAPPING
Using PCR to amplify an intron-containing region of the gene in purified
DNA isolated from human/rodent somatic cell hybrids, DiLella (1991)
assigned the FKBP1 gene to human chromosome 20. DiLella et al. (1992)
used fluorescence in situ hybridization to map the FKBP1 gene to
chromosome 20p13.
ANIMAL MODEL
To define the functions of FKBP12 in vivo, Shou et al. (1998) generated
mutant mice deficient in Fkpb12 using embryonic stem (ES) cell
technology. Fkbp12-deficient mice had normal skeletal muscle, but they
had severe dilated cardiomyopathy and ventricular septal defects that
mimicked a human congenital heart disorder, namely noncompaction of left
ventricular myocardium (see 302060 for an X-linked form of myocardial
noncompaction). About 9% of the mutants exhibited exencephaly secondary
to a defect in neural tube closure. Physiologic studies demonstrated
that Fkbp12 was dispensable for Tgf-beta-mediated signaling, but that it
modulated the calcium release activity of both skeletal and cardiac
ryanodine receptors.
HISTORY
Based on the similarity of the FKBP1 protein sequence with the amino
acid sequence of bovine protein kinase C inhibitor-2 (PKCI2) published
by Mozier et al. (1990), Goebl (1991) suggested that FKBP1 is the same
as PKCI2. In an erratum, Goebl (1991) stated that the PKCI2 sequence
published by Mozier et al. (1990) was incorrect and that FKBP1 is not a
protein kinase C inhibitor. This was demonstrated independently by Walsh
(1991), who found that pure recombinant FKBP1 does not have protein
kinase C inhibitory activity.
*FIELD* RF
1. DiLella, A. G.: Chromosomal assignment of the human immunophilin
FKBP-12 gene. Biochem. Biophys. Res. Commun. 179: 1427-1433, 1991.
2. DiLella, A. G.; Hawkins, A.; Craig, R. J.; Schreiber, S. L.; Griffin,
C. A.: Chromosomal band assignments of the genes encoding human FKBP12
and FKBP13. Biochem. Biophys. Res. Commun. 189: 819-823, 1992.
3. Goebl, M. G.: The peptidyl-prolyl isomerase, FK506-binding protein,
is most likely the 12 kd endogenous inhibitor 2 of protein kinase
C. (Letter) Cell 64: 1051-1052, 1991. Note: Erratum: Cell 66: 423
only, 1991.
4. Jin, Y.-J.; Albers, M. W.; Lane, W. S.; Bierer, B. E.; Schreiber,
S. L.; Burakoff, S. J.: Molecular cloning of a membrane-associated
human FK506- and rapamycin-binding protein, FKBP-13. Proc. Nat. Acad.
Sci. 88: 6677-6681, 1991.
5. Kang, C. B.; Hong, Y.; Dhe-Paganon, S.; Yoon, H. S.: FKBP family
proteins: immunophilins with versatile biological functions. Neurosignals 16:
318-325, 2008.
6. 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.
Nat. Acad. Sci. 87: 5440-5443, 1990.
7. Mozier, N. M.; Zurcher-Neely, H. A.; Guido, D. M.; Mathews, W.
R.; Heinrikson, R. L.; Fraser, E. D.; Walsh, M. P.; Pearson, D. J.
: Amino acid sequence of a 12-kDa inhibitor of protein kinase C. Europ.
J. Biochem. 194: 19-23, 1990. Note: Retraction: Europ. J. Biochem.
200: 811 only, 1991.
8. Peattie, D. A.; Hsaio, K.; Benasutti, M.; Lippke, J. A.: Three
distinct messenger RNAs can encode the human immunosuppressant-binding
protein FKBP12. Gene 150: 251-257, 1994.
9. Shou, W.; Aghdasi, B.; Armstrong, D. L.; Guo, Q.; Bao, S.; Charng,
M.-J.; Mathews, L. M.; Schneider, M. D.; Hamilton, S. L.; Matzuk,
M. M.: Cardiac defects and altered ryanodine receptor function in
mice lacking FKBP12. Nature 391: 489-492, 1998.
10. Standaert, R. F.; Galat, A.; Verdine, G. L.; Schreiber, S. L.
: Molecular cloning and overexpression of the human FK506-binding
protein FKBP. Nature 346: 671-674, 1990.
11. Walsh, M. P.: Retraction concerning Amino acid sequence of a
12-kDa inhibitor of protein kinase C [Mozier, N. M., Zurcher-Neely,
H. A., Guido, D. M., Mathews, W. R., Heinrikson, R. L., Fraser, E.
D., Walsh, M. P. and Pearson, D. J. (1990) Europ. J. Biochem. 194,
19-23]: Mistaken identity of a protein kinase C inhibitor. (Letter) Europ.
J. Biochem. 200: 811 only, 1991.
12. Wang, T.; Donahoe, P. K.; Zervos, A. S.: Specific interaction
of type I receptors of the TGF-beta family with the immunophilin FKBP-12. Science 265:
674-676, 1994.
*FIELD* CN
Matthew B. Gross - updated: 3/3/2011
Stylianos E. Antonarakis - updated: 6/7/2000
Victor A. McKusick - updated: 3/3/1998
*FIELD* CD
Victor A. McKusick: 8/20/1990
*FIELD* ED
carol: 09/30/2013
alopez: 6/10/2013
terry: 7/30/2012
carol: 6/20/2012
terry: 3/25/2011
mgross: 3/3/2011
mgross: 3/2/2011
wwang: 6/10/2009
mgross: 11/24/2004
ckniffin: 5/10/2002
carol: 7/10/2001
mgross: 6/7/2000
alopez: 2/24/1999
alopez: 9/3/1998
alopez: 3/9/1998
terry: 3/3/1998
mark: 4/30/1996
mark: 6/1/1995
carol: 2/23/1995
carol: 2/4/1993
carol: 12/18/1992
carol: 9/14/1992
supermim: 3/16/1992
*RECORD*
*FIELD* NO
186945
*FIELD* TI
*186945 FK506-BINDING PROTEIN 1A; FKBP1A
;;FK506-BINDING PROTEIN 1; FKBP1;;
FK506-BINDING PROTEIN, 12-KD; FKBP12;;
read moreFK506-BINDING PROTEIN, T-CELL, 12-KD;;
CALSTABIN 1
*FIELD* TX
DESCRIPTION
Immunophilins are a family of highly conserved proteins that bind with
immunosuppressive drugs, such as FK506, rapamycin, and cyclosporin A
(CsA). The 2 major types of immunophilins are FK506-binding proteins
(FKBPs), most of which bind FK506 and rapamycin, and cyclophilins (e.g.,
PPIA; 123840), which bind CsA. Most FKBPs, including FKBP1A, exhibit
peptidyl-prolyl cis/trans isomerase (PPIase; EC 5.2.1.8) activity. FKBPs
are involved in numerous biologic processes, including protein folding,
receptor signaling, protein trafficking, transcription, apoptosis, and
T-cell activation (review by Kang et al., 2008).
CLONING
Maki et al. (1990) isolated and sequenced DNA coding for FKBP from human
peripheral blood T lymphocytes by using mixed 20-mer oligonucleotide
probes synthesized on the basis of the sequence of bovine Fkbp. They
found an ORF encoding 108 amino acids, the first 40 of which are
identical to those of the bovine sequence. Analysis showed no
significant sequence similarity to other proteins, including cyclophilin
(PPIA; 123840). Southern blot analysis of human genomic DNA suggested
the existence of only a few copies of the FKBP gene. This is in contrast
to results indicating as many as 20 copies of the cyclophilin gene, as
well as possible pseudogenes, in the mammalian genome. Standaert et al.
(1990) likewise isolated a cDNA for FKBP and reported the derived amino
acid sequence. The human FKBP cDNA sequence shares significant
similarity with an ORF in the genome of Neisseria meningitidis.
Peattie et al. (1994) identified 3 distinct mRNAs for FKBP12, designated
A, B, and C, that result from differential splicing or polyadenylation.
All 3 encode the same protein sequence.
GENE FUNCTION
Jin et al. (1991) noted that the 12-kD FKBP is a cytosolic receptor for
rapamycin and FK506, both of which are immunosuppressants.
Wang et al. (1994) reported that in a yeast genetic screen, FKBP1
interacted with various type I receptors, including the TGF-beta type I
receptor (190181). Deletion, point mutation, and coimmunoprecipitation
studies demonstrated the specificity of this interaction, and
competitive binding assays indicated that the type I receptor may be a
natural ligand for FKBP1. Wang et al. (1994) concluded that FKBP1 may
play a role in type I receptor-mediated signaling.
- Reviews
Kang et al. (2008) reviewed the molecular characteristics of FKBP family
members, including FKBP1A, and the biologic functions of their ligands
in performing neuroprotective and neurotrophic activities.
MAPPING
Using PCR to amplify an intron-containing region of the gene in purified
DNA isolated from human/rodent somatic cell hybrids, DiLella (1991)
assigned the FKBP1 gene to human chromosome 20. DiLella et al. (1992)
used fluorescence in situ hybridization to map the FKBP1 gene to
chromosome 20p13.
ANIMAL MODEL
To define the functions of FKBP12 in vivo, Shou et al. (1998) generated
mutant mice deficient in Fkpb12 using embryonic stem (ES) cell
technology. Fkbp12-deficient mice had normal skeletal muscle, but they
had severe dilated cardiomyopathy and ventricular septal defects that
mimicked a human congenital heart disorder, namely noncompaction of left
ventricular myocardium (see 302060 for an X-linked form of myocardial
noncompaction). About 9% of the mutants exhibited exencephaly secondary
to a defect in neural tube closure. Physiologic studies demonstrated
that Fkbp12 was dispensable for Tgf-beta-mediated signaling, but that it
modulated the calcium release activity of both skeletal and cardiac
ryanodine receptors.
HISTORY
Based on the similarity of the FKBP1 protein sequence with the amino
acid sequence of bovine protein kinase C inhibitor-2 (PKCI2) published
by Mozier et al. (1990), Goebl (1991) suggested that FKBP1 is the same
as PKCI2. In an erratum, Goebl (1991) stated that the PKCI2 sequence
published by Mozier et al. (1990) was incorrect and that FKBP1 is not a
protein kinase C inhibitor. This was demonstrated independently by Walsh
(1991), who found that pure recombinant FKBP1 does not have protein
kinase C inhibitory activity.
*FIELD* RF
1. DiLella, A. G.: Chromosomal assignment of the human immunophilin
FKBP-12 gene. Biochem. Biophys. Res. Commun. 179: 1427-1433, 1991.
2. DiLella, A. G.; Hawkins, A.; Craig, R. J.; Schreiber, S. L.; Griffin,
C. A.: Chromosomal band assignments of the genes encoding human FKBP12
and FKBP13. Biochem. Biophys. Res. Commun. 189: 819-823, 1992.
3. Goebl, M. G.: The peptidyl-prolyl isomerase, FK506-binding protein,
is most likely the 12 kd endogenous inhibitor 2 of protein kinase
C. (Letter) Cell 64: 1051-1052, 1991. Note: Erratum: Cell 66: 423
only, 1991.
4. Jin, Y.-J.; Albers, M. W.; Lane, W. S.; Bierer, B. E.; Schreiber,
S. L.; Burakoff, S. J.: Molecular cloning of a membrane-associated
human FK506- and rapamycin-binding protein, FKBP-13. Proc. Nat. Acad.
Sci. 88: 6677-6681, 1991.
5. Kang, C. B.; Hong, Y.; Dhe-Paganon, S.; Yoon, H. S.: FKBP family
proteins: immunophilins with versatile biological functions. Neurosignals 16:
318-325, 2008.
6. 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.
Nat. Acad. Sci. 87: 5440-5443, 1990.
7. Mozier, N. M.; Zurcher-Neely, H. A.; Guido, D. M.; Mathews, W.
R.; Heinrikson, R. L.; Fraser, E. D.; Walsh, M. P.; Pearson, D. J.
: Amino acid sequence of a 12-kDa inhibitor of protein kinase C. Europ.
J. Biochem. 194: 19-23, 1990. Note: Retraction: Europ. J. Biochem.
200: 811 only, 1991.
8. Peattie, D. A.; Hsaio, K.; Benasutti, M.; Lippke, J. A.: Three
distinct messenger RNAs can encode the human immunosuppressant-binding
protein FKBP12. Gene 150: 251-257, 1994.
9. Shou, W.; Aghdasi, B.; Armstrong, D. L.; Guo, Q.; Bao, S.; Charng,
M.-J.; Mathews, L. M.; Schneider, M. D.; Hamilton, S. L.; Matzuk,
M. M.: Cardiac defects and altered ryanodine receptor function in
mice lacking FKBP12. Nature 391: 489-492, 1998.
10. Standaert, R. F.; Galat, A.; Verdine, G. L.; Schreiber, S. L.
: Molecular cloning and overexpression of the human FK506-binding
protein FKBP. Nature 346: 671-674, 1990.
11. Walsh, M. P.: Retraction concerning Amino acid sequence of a
12-kDa inhibitor of protein kinase C [Mozier, N. M., Zurcher-Neely,
H. A., Guido, D. M., Mathews, W. R., Heinrikson, R. L., Fraser, E.
D., Walsh, M. P. and Pearson, D. J. (1990) Europ. J. Biochem. 194,
19-23]: Mistaken identity of a protein kinase C inhibitor. (Letter) Europ.
J. Biochem. 200: 811 only, 1991.
12. Wang, T.; Donahoe, P. K.; Zervos, A. S.: Specific interaction
of type I receptors of the TGF-beta family with the immunophilin FKBP-12. Science 265:
674-676, 1994.
*FIELD* CN
Matthew B. Gross - updated: 3/3/2011
Stylianos E. Antonarakis - updated: 6/7/2000
Victor A. McKusick - updated: 3/3/1998
*FIELD* CD
Victor A. McKusick: 8/20/1990
*FIELD* ED
carol: 09/30/2013
alopez: 6/10/2013
terry: 7/30/2012
carol: 6/20/2012
terry: 3/25/2011
mgross: 3/3/2011
mgross: 3/2/2011
wwang: 6/10/2009
mgross: 11/24/2004
ckniffin: 5/10/2002
carol: 7/10/2001
mgross: 6/7/2000
alopez: 2/24/1999
alopez: 9/3/1998
alopez: 3/9/1998
terry: 3/3/1998
mark: 4/30/1996
mark: 6/1/1995
carol: 2/23/1995
carol: 2/4/1993
carol: 12/18/1992
carol: 9/14/1992
supermim: 3/16/1992