FKB1A_BOVIN
ID FKB1A_BOVIN Reviewed; 108 AA.
AC P18203; Q5E945;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP1A;
DE Short=PPIase FKBP1A;
DE EC=5.2.1.8 {ECO:0000250|UniProtKB:P62942};
DE AltName: Full=12 kDa FK506-binding protein {ECO:0000303|PubMed:1706222};
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP RETRACTED PAPER.
RC TISSUE=Brain;
RX PubMed=2253615; DOI=10.1111/j.1432-1033.1990.tb19421.x;
RA Mozier N.M., Zuercher-Neely H.A., Guido D.M., Mathews W.R.,
RA Heinrikson R.L., Fraser E.D., Walsh M.P., Pearson J.D.;
RT "Amino acid sequence of a 12-kDa inhibitor of protein kinase C.";
RL Eur. J. Biochem. 194:19-23(1990).
RN [3]
RP RETRACTION NOTICE OF PUBMED:2253615.
RX PubMed=1915353; DOI=10.1111/j.1432-1033.1991.tb16249.x;
RA Walsh M.P.;
RT "Retraction concerning amino acid sequence of a 12-kDa inhibitor of protein
RT kinase C. Mistaken identity of a protein kinase C inhibitor.";
RL Eur. J. Biochem. 200:811-811(1991).
RN [4]
RP PROTEIN SEQUENCE OF 2-108.
RC TISSUE=Thymus;
RX PubMed=1718307; DOI=10.1007/bf01024778;
RA Lane W.S., Galat A., Harding M.W., Schreiber S.L.;
RT "Complete amino acid sequence of the FK506 and rapamycin binding protein,
RT FKBP, isolated from calf thymus.";
RL J. Protein Chem. 10:151-160(1991).
RN [5]
RP PROTEIN SEQUENCE OF 2-87.
RX PubMed=1701173; DOI=10.1016/s0021-9258(17)45319-1;
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 both a
RT ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase.";
RL J. Biol. Chem. 265:21011-21015(1990).
RN [6]
RP PROTEIN SEQUENCE OF 2-41.
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-prolyl
RT isomerase.";
RL Nature 341:758-760(1989).
RN [7]
RP IDENTITY OF FKBP AND PKCI-2.
RX PubMed=1706222; DOI=10.1016/0092-8674(91)90258-z;
RA Goebl M.G.;
RT "The peptidyl-prolyl isomerase, FK506-binding protein, is most likely the
RT 12 kd endogenous inhibitor 2 of protein kinase C.";
RL Cell 64:1051-1052(1991).
RN [8]
RP IDENTITY OF FKBP AND PKCI-2.
RX PubMed=1710319; DOI=10.1038/351195a0;
RA Tropschug A.M., Hofmann R.;
RT "FK506 and protein kinase C.";
RL Nature 351:195-195(1991).
RN [9]
RP SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
RX PubMed=1868545; DOI=10.1016/0092-8674(81)90004-0;
RA Goebl M.;
RT "The peptidyl-prolyl isomerase, FK506-binding protein, is not identical to
RT protein kinase C inhibitor 2.";
RL Cell 66:423-423(1991).
RN [10]
RP SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
RX PubMed=1710782; DOI=10.1038/351527c0;
RA Albers M.W., Liu J., Schreiber S.L.;
RT "Relationship of FKBP to PKCI-2.";
RL Nature 351:527-527(1991).
RN [11]
RP STRUCTURE BY NMR.
RX PubMed=2041572; DOI=10.1038/351248a0;
RA Moore J.M., Peattie D.A., Fitzgibbon M.J., Thomson J.A.;
RT "Solution structure of the major binding protein for the immunosuppressant
RT FK506.";
RL Nature 351:248-250(1991).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PPP3R1 AND PPP3CA.
RX PubMed=7543369; DOI=10.1016/0092-8674(95)90439-5;
RA Griffith J.P., Kim J.L., Kim E.E., Sintchak M.D., Thomson J.A.,
RA Fitzgibbon M.J., Fleming M.A., Caron P.R., Hsiao K., Navia M.A.;
RT "X-ray structure of calcineurin inhibited by the immunophilin-
RT immunosuppressant FKBP12-FK506 complex.";
RL Cell 82:507-522(1995).
CC -!- FUNCTION: Keeps in an inactive conformation TGFBR1, the TGF-beta type I
CC serine/threonine kinase receptor, preventing TGF-beta receptor
CC activation in absence of ligand. May modulate the RYR1 calcium channel
CC activity. PPIases accelerate the folding of proteins. It catalyzes the
CC cis-trans isomerization of proline imidic peptide bonds in
CC oligopeptides.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-peptidylproline (omega=180) = [protein]-
CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA-
CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833,
CC ChEBI:CHEBI:83834; EC=5.2.1.8;
CC Evidence={ECO:0000250|UniProtKB:P62942};
CC -!- ACTIVITY REGULATION: Inhibited by both FK506 and rapamycin.
CC -!- SUBUNIT: Interacts with TGFBR1; prevents TGFBR1 phosphorylation by
CC TGFBR2 and stabilizes it in the inactive conformation. Interacts with
CC ACVR1B and SMAD7 (By similarity). Identified in a complex composed of
CC RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By
CC similarity). Interacts directly with RYR2 and RYR3. Interacts with
CC GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose
CC dependent manner (By similarity). Interacts directly with RYR1 (By
CC similarity). {ECO:0000250|UniProtKB:P26883,
CC ECO:0000250|UniProtKB:P62942, ECO:0000250|UniProtKB:P62943}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P62942}. Sarcoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P62943}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P62943}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P62943}.
CC -!- SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be protein kinase C inhibitor 2
CC (PKCI-2 or 12 kDa inhibitor of protein kinase C). Later, was shown
CC experimentally not to inhibit protein kinase C (PubMed:1868545,
CC PubMed:1710782). {ECO:0000269|PubMed:1710782,
CC ECO:0000269|PubMed:1868545, ECO:0000305|PubMed:1915353,
CC ECO:0000305|PubMed:2253615}.
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DR EMBL; BT021075; AAX09092.1; -; mRNA.
DR PIR; A61431; A61431.
DR RefSeq; NP_001030533.1; NM_001035456.1.
DR PDB; 1FKK; X-ray; 2.20 A; A=2-108.
DR PDB; 1FKL; X-ray; 1.70 A; A=2-108.
DR PDB; 1TCO; X-ray; 2.50 A; C=2-108.
DR PDBsum; 1FKK; -.
DR PDBsum; 1FKL; -.
DR PDBsum; 1TCO; -.
DR AlphaFoldDB; P18203; -.
DR BMRB; P18203; -.
DR SMR; P18203; -.
DR STRING; 9913.ENSBTAP00000010928; -.
DR BindingDB; P18203; -.
DR PaxDb; P18203; -.
DR PeptideAtlas; P18203; -.
DR PRIDE; P18203; -.
DR Ensembl; ENSBTAT00000010928; ENSBTAP00000010928; ENSBTAG00000008303.
DR GeneID; 614795; -.
DR KEGG; bta:614795; -.
DR CTD; 2280; -.
DR VEuPathDB; HostDB:ENSBTAG00000008303; -.
DR eggNOG; KOG0544; Eukaryota.
DR GeneTree; ENSGT00940000153311; -.
DR HOGENOM; CLU_013615_12_1_1; -.
DR InParanoid; P18203; -.
DR OMA; FTSMNNQ; -.
DR OrthoDB; 1328688at2759; -.
DR TreeFam; TF105291; -.
DR Reactome; R-BTA-166208; mTORC1-mediated signalling.
DR Reactome; R-BTA-2025928; Calcineurin activates NFAT.
DR EvolutionaryTrace; P18203; -.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000008303; Expressed in occipital lobe and 104 other tissues.
DR ExpressionAtlas; P18203; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISA:AgBase.
DR GO; GO:0098562; C:cytoplasmic side of membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; ISA:AgBase.
DR GO; GO:0031312; C:extrinsic component of organelle membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISA:AgBase.
DR GO; GO:1990425; C:ryanodine receptor complex; ISS:UniProtKB.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISA:AgBase.
DR GO; GO:0030018; C:Z disc; ISA:AgBase.
DR GO; GO:0048185; F:activin binding; ISA:AgBase.
DR GO; GO:0019855; F:calcium channel inhibitor activity; ISA:AgBase.
DR GO; GO:0005528; F:FK506 binding; ISA:AgBase.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISA:AgBase.
DR GO; GO:0046332; F:SMAD binding; ISA:AgBase.
DR GO; GO:0044325; F:transmembrane transporter binding; ISA:AgBase.
DR GO; GO:1990000; P:amyloid fibril formation; ISA:AgBase.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISA:AgBase.
DR GO; GO:0003007; P:heart morphogenesis; ISA:AgBase.
DR GO; GO:0060347; P:heart trabecula formation; ISA:AgBase.
DR GO; GO:0006936; P:muscle contraction; ISA:AgBase.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; ISA:AgBase.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISA:AgBase.
DR GO; GO:0051280; P:negative regulation of release of sequestered calcium ion into cytosol; ISA:AgBase.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; ISA:AgBase.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISA:AgBase.
DR GO; GO:0032092; P:positive regulation of protein binding; ISA:AgBase.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISA:AgBase.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; ISA:AgBase.
DR GO; GO:0032925; P:regulation of activin receptor signaling pathway; ISA:AgBase.
DR GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; ISA:AgBase.
DR GO; GO:0050776; P:regulation of immune response; ISA:AgBase.
DR GO; GO:0032880; P:regulation of protein localization; ISA:AgBase.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; ISA:AgBase.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISA:AgBase.
DR GO; GO:0031000; P:response to caffeine; ISA:AgBase.
DR GO; GO:0007183; P:SMAD protein complex assembly; ISA:AgBase.
DR GO; GO:0097435; P:supramolecular fiber organization; ISA:AgBase.
DR GO; GO:0042110; P:T cell activation; NAS:BHF-UCL.
DR GO; GO:0042098; P:T cell proliferation; ISA:AgBase.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISA:AgBase.
DR Gene3D; 3.10.50.40; -; 1.
DR InterPro; IPR046357; PPIase_dom_sf.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR Pfam; PF00254; FKBP_C; 1.
DR PROSITE; PS50059; FKBP_PPIASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Isomerase;
KW Membrane; Reference proteome; Rotamase; Sarcoplasmic reticulum.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1701173,
FT ECO:0000269|PubMed:1718307, ECO:0000269|PubMed:2253615,
FT ECO:0000269|PubMed:2477715"
FT CHAIN 2..108
FT /note="Peptidyl-prolyl cis-trans isomerase FKBP1A"
FT /id="PRO_0000075288"
FT DOMAIN 20..108
FT /note="PPIase FKBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT MOD_RES 53
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26883"
FT MOD_RES 53
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26883"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:1FKL"
FT STRAND 22..31
FT /evidence="ECO:0007829|PDB:1FKL"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:1FKL"
FT TURN 41..44
FT /evidence="ECO:0007829|PDB:1FKL"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:1FKL"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:1FKL"
FT HELIX 58..65
FT /evidence="ECO:0007829|PDB:1FKL"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:1FKL"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:1FKL"
FT TURN 82..86
FT /evidence="ECO:0007829|PDB:1FKL"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:1FKL"
FT STRAND 98..108
FT /evidence="ECO:0007829|PDB:1FKL"
SQ SEQUENCE 108 AA; 11910 MW; 9CD0F1278039C5B4 CRC64;
MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFV LGKQEVIRGW
EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPNATLIF DVELLKLE
