FKB1A_RAT
ID FKB1A_RAT Reviewed; 108 AA.
AC Q62658; A0JN04; P97533;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 163.
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;
DE Short=12 kDa FKBP;
DE Short=FKBP-12;
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=7518616; DOI=10.1126/science.7518616;
RA Wang T., Donahoe P.K., Zervos A.S.;
RT "Specific interaction of type I receptors of the TGF-beta family with the
RT immunophilin FKBP-12.";
RL Science 265:674-676(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Aortic smooth muscle;
RA Marx S.O., Jayaraman T., Mehran R., Go L.O., Wiederrecht G.J., Marks A.R.;
RT "Identification of a novel FK506-binding protein in rat aortic smooth
RT muscle cells.";
RL Circulation 92:297-297(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Pancreatic islet;
RX PubMed=9013543; DOI=10.1074/jbc.272.6.3133;
RA Noguchi N., Takasawa S., Nata K., Tohgo A., Kato I., Ikehata F.,
RA Yonekura H., Okamoto H.;
RT "Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from
RT islet microsomes.";
RL J. Biol. Chem. 272:3133-3136(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Heart;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH RYR2, AND TISSUE SPECIFICITY.
RX PubMed=20431056; DOI=10.1161/circresaha.110.219816;
RA Guo T., Cornea R.L., Huke S., Camors E., Yang Y., Picht E., Fruen B.R.,
RA Bers D.M.;
RT "Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized
RT cardiac myocytes and effects on Ca sparks.";
RL Circ. Res. 106:1743-1752(2010).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Recruits SMAD7 to ACVR1B which
CC prevents the association of SMAD2 and SMAD3 with the activin receptor
CC complex, thereby blocking the activin signal. May modulate the RYR1
CC calcium channel activity. PPIases accelerate the folding of proteins.
CC It catalyzes the cis-trans isomerization of proline imidic peptide
CC bonds in oligopeptides (By similarity). {ECO:0000250}.
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 (By similarity).
CC Interacts with ACVR1B and SMAD7. Identified in a complex composed of
CC RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By
CC similarity). Interacts directly with RYR2 (PubMed:20431056). Interacts
CC directly with RYR3 (By similarity). Interacts directly with RYR1 (By
CC similarity). Interacts with GLMN; rapamycin and FK506 abolish the
CC interaction with GLMN in a dose dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:P26883, ECO:0000250|UniProtKB:P62942,
CC ECO:0000250|UniProtKB:P62943, ECO:0000269|PubMed:20431056}.
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 -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:20431056}.
CC -!- SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1 subfamily.
CC {ECO:0000305}.
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DR EMBL; U09386; AAA19163.1; -; mRNA.
DR EMBL; U69485; AAB48933.1; -; mRNA.
DR EMBL; D86641; BAA13153.1; -; mRNA.
DR EMBL; BC070519; AAH70519.3; -; mRNA.
DR EMBL; BC126071; AAI26072.1; -; mRNA.
DR RefSeq; NP_037234.2; NM_013102.3.
DR AlphaFoldDB; Q62658; -.
DR BMRB; Q62658; -.
DR SMR; Q62658; -.
DR BioGRID; 247668; 4.
DR CORUM; Q62658; -.
DR IntAct; Q62658; 1.
DR MINT; Q62658; -.
DR STRING; 10116.ENSRNOP00000012608; -.
DR ChEMBL; CHEMBL2095; -.
DR DrugCentral; Q62658; -.
DR GuidetoPHARMACOLOGY; 2609; -.
DR iPTMnet; Q62658; -.
DR PhosphoSitePlus; Q62658; -.
DR jPOST; Q62658; -.
DR PaxDb; Q62658; -.
DR PRIDE; Q62658; -.
DR GeneID; 25639; -.
DR KEGG; rno:25639; -.
DR UCSC; RGD:2617; rat.
DR CTD; 2280; -.
DR RGD; 2617; Fkbp1a.
DR VEuPathDB; HostDB:ENSRNOG00000008822; -.
DR eggNOG; KOG0544; Eukaryota.
DR HOGENOM; CLU_013615_12_1_1; -.
DR InParanoid; Q62658; -.
DR OMA; FTSMNNQ; -.
DR OrthoDB; 1328688at2759; -.
DR PhylomeDB; Q62658; -.
DR Reactome; R-RNO-166208; mTORC1-mediated signalling.
DR Reactome; R-RNO-2025928; Calcineurin activates NFAT.
DR Reactome; R-RNO-2173789; TGF-beta receptor signaling activates SMADs.
DR PRO; PR:Q62658; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000008822; Expressed in Ammon's horn and 20 other tissues.
DR Genevisible; Q62658; RN.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0098562; C:cytoplasmic side of membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0031312; C:extrinsic component of organelle membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0048185; F:activin binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0005528; F:FK506 binding; IDA:RGD.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISO:RGD.
DR GO; GO:0046332; F:SMAD binding; ISO:RGD.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IDA:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IDA:BHF-UCL.
DR GO; GO:1990000; P:amyloid fibril formation; ISO:RGD.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR GO; GO:0060347; P:heart trabecula formation; ISO:RGD.
DR GO; GO:0006936; P:muscle contraction; ISO:RGD.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; ISO:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; ISO:RGD.
DR GO; GO:0032925; P:regulation of activin receptor signaling pathway; ISO:RGD.
DR GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0050776; P:regulation of immune response; ISO:RGD.
DR GO; GO:0032880; P:regulation of protein localization; ISO:RGD.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; ISO:RGD.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:0031000; P:response to caffeine; ISO:RGD.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0007183; P:SMAD protein complex assembly; ISO:RGD.
DR GO; GO:0097435; P:supramolecular fiber organization; ISO:RGD.
DR GO; GO:0042098; P:T cell proliferation; ISO:RGD.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
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 Acetylation; Cytoplasm; Isomerase; Membrane; Phosphoprotein;
KW Reference proteome; Rotamase; Sarcoplasmic reticulum.
FT CHAIN 1..108
FT /note="Peptidyl-prolyl cis-trans isomerase FKBP1A"
FT /id="PRO_0000075292"
FT DOMAIN 20..108
FT /note="PPIase FKBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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 CONFLICT 89
FT /note="P -> T (in Ref. 3; BAA13153)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 108 AA; 11923 MW; 1C195C2A52C17666 CRC64;
MGVQVETISS GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFT LGKQEVIRGW
EEGVAQMSVG QRAKLIISPD YAYGATGHPG IIPPHATLVF DVELLKLE
