FKB1A_RABIT
ID FKB1A_RABIT Reviewed; 108 AA.
AC P62943; P20071; Q9H103; Q9H566;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 25-MAY-2022, entry version 93.
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=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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], SUBCELLULAR LOCATION, AND INTERACTION
RP WITH RYR1.
RX PubMed=1374404; DOI=10.1016/s0021-9258(19)50114-4;
RA Jayaraman T., Brillantes A.M., Timerman A.P., Fleischer S.,
RA Erdjument-Bromage H., Tempst P., Marks A.R.;
RT "FK506 binding protein associated with the calcium release channel
RT (ryanodine receptor).";
RL J. Biol. Chem. 267:9474-9477(1992).
RN [2]
RP INTERACTION WITH RYR1, AND TISSUE SPECIFICITY.
RX PubMed=7669046; DOI=10.1006/bbrc.1995.2283;
RA Xin H.B., Timerman A.P., Onoue H., Wiederrecht G.J., Fleischer S.;
RT "Affinity purification of the ryanodine receptor/calcium release channel
RT from fast twitch skeletal muscle based on its tight association with
RT FKBP12.";
RL Biochem. Biophys. Res. Commun. 214:263-270(1995).
RN [3]
RP INTERACTION WITH RYR1, AND FUNCTION.
RX PubMed=10603943; DOI=10.1111/j.1749-6632.1998.tb08263.x;
RA Ondrias K., Marx S.O., Gaburjakova M., Marks A.R.;
RT "FKBP12 modulates gating of the ryanodine receptor/calcium release
RT channel.";
RL Ann. N. Y. Acad. Sci. 853:149-156(1998).
RN [4] {ECO:0007744|PDB:3J8H}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) IN COMPLEX WITH RYR1.
RX PubMed=25517095; DOI=10.1038/nature14063;
RA Yan Z., Bai X.C., Yan C., Wu J., Li Z., Xie T., Peng W., Yin C.C., Li X.,
RA Scheres S.H., Shi Y., Yan N.;
RT "Structure of the rabbit ryanodine receptor RyR1 at near-atomic
RT resolution.";
RL Nature 517:50-55(2015).
RN [5] {ECO:0007744|PDB:5GKY, ECO:0007744|PDB:5GKZ, ECO:0007744|PDB:5GL0, ECO:0007744|PDB:5GL1}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) IN COMPLEX WITH RYR1,
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=27468892; DOI=10.1038/cr.2016.89;
RA Bai X.C., Yan Z., Wu J., Li Z., Yan N.;
RT "The central domain of RyR1 is the transducer for long-range allosteric
RT gating of channel opening.";
RL Cell Res. 26:995-1006(2016).
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 ECO:0000269|PubMed:10603943}.
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). Interacts
CC directly with RYR2 and RYR3 (By similarity). Interacts directly with
CC RYR1 (PubMed:1374404, PubMed:10603943, PubMed:25517095,
CC PubMed:27468892). 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:Q62658, ECO:0000269|PubMed:10603943,
CC ECO:0000269|PubMed:1374404, ECO:0000269|PubMed:25517095,
CC ECO:0000269|PubMed:27468892, ECO:0000269|PubMed:7669046}.
CC -!- INTERACTION:
CC P62943; P11716: RYR1; NbExp=2; IntAct=EBI-16134925, EBI-6477441;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P62942}. Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:1374404, ECO:0000269|PubMed:27468892}; Peripheral
CC membrane protein {ECO:0000269|PubMed:27468892}; Cytoplasmic side
CC {ECO:0000269|PubMed:27468892}.
CC -!- TISSUE SPECIFICITY: Detected in fast twitch skeletal muscle (at protein
CC level). {ECO:0000269|PubMed:7669046}.
CC -!- SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1 subfamily.
CC {ECO:0000305}.
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DR EMBL; M89928; AAA31252.1; -; Genomic_RNA.
DR PIR; A42657; A42657.
DR RefSeq; NP_001164597.1; NM_001171126.1.
DR PDB; 3J8H; EM; 3.80 A; B/D/F/H=2-108.
DR PDB; 5GKY; EM; 3.80 A; B/D/F/H=1-108.
DR PDB; 5GKZ; EM; 4.00 A; B/D/F/H=1-108.
DR PDB; 5GL0; EM; 4.20 A; B/D/F/H=1-108.
DR PDB; 5GL1; EM; 5.70 A; B/D/F/H=1-108.
DR PDBsum; 3J8H; -.
DR PDBsum; 5GKY; -.
DR PDBsum; 5GKZ; -.
DR PDBsum; 5GL0; -.
DR PDBsum; 5GL1; -.
DR AlphaFoldDB; P62943; -.
DR BMRB; P62943; -.
DR SMR; P62943; -.
DR DIP; DIP-61479N; -.
DR IntAct; P62943; 1.
DR GeneID; 100328942; -.
DR KEGG; ocu:100328942; -.
DR CTD; 2280; -.
DR eggNOG; KOG0544; Eukaryota.
DR InParanoid; P62943; -.
DR OrthoDB; 1328688at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0098562; C:cytoplasmic side of membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0031312; C:extrinsic component of organelle membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:AgBase.
DR GO; GO:1990425; C:ryanodine receptor complex; IDA:UniProtKB.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0014802; C:terminal cisterna; IDA:BHF-UCL.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IMP:AgBase.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; IMP: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; Isomerase; Membrane;
KW Reference proteome; Rotamase; Sarcoplasmic reticulum.
FT CHAIN 1..108
FT /note="Peptidyl-prolyl cis-trans isomerase FKBP1A"
FT /id="PRO_0000075291"
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"
SQ SEQUENCE 108 AA; 11951 MW; 9CC8493C802540B4 CRC64;
MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFM LGKQEVIRGW
EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPHATLVF DVELLKLE
