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 27-MAR-2024, entry version 176. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSBTAP00000060070; -. DR BindingDB; P18203; -. DR PaxDb; 9913-ENSBTAP00000010928; -. DR PeptideAtlas; P18203; -. DR Ensembl; ENSBTAT00000010928.5; ENSBTAP00000010928.4; ENSBTAG00000008303.5. DR GeneID; 614795; -. DR KEGG; bta:614795; -. DR CTD; 2280; -. DR VEuPathDB; HostDB:ENSBTAG00000008303; -. DR VGNC; VGNC:112449; FKBP1A. DR eggNOG; KOG0544; Eukaryota. DR GeneTree; ENSGT00940000153311; -. DR HOGENOM; CLU_013615_12_1_1; -. DR InParanoid; P18203; -. DR OMA; FTSMNNQ; -. DR OrthoDB; 25281at2759; -. DR TreeFam; TF105291; -. DR Reactome; R-BTA-166208; mTORC1-mediated signalling. DR Reactome; R-BTA-2025928; Calcineurin activates NFAT. DR Reactome; R-BTA-2173789; TGF-beta receptor signaling activates SMADs. DR EvolutionaryTrace; P18203; -. DR Proteomes; UP000009136; Chromosome 13. DR Bgee; ENSBTAG00000008303; Expressed in occipital lobe and 104 other cell types or 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: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: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 canonical NF-kappaB signal transduction; 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: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 PANTHER; PTHR10516; PEPTIDYL-PROLYL CIS-TRANS ISOMERASE; 1. DR PANTHER; PTHR10516:SF301; PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP1A-RELATED; 1. DR Pfam; PF00254; FKBP_C; 1. DR SUPFAM; SSF54534; FKBP-like; 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 //