FKBP_YEAST
ID FKBP_YEAST Reviewed; 114 AA.
AC P20081; D6W147;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=FK506-binding protein 1;
DE Short=FKBP;
DE AltName: Full=12-kDa cytosolic FK506-binding protein;
DE Short=FKBP-12;
DE AltName: Full=Peptidyl-prolyl cis-trans isomerase;
DE Short=PPIase;
DE EC=5.2.1.8 {ECO:0000269|PubMed:1996117};
DE AltName: Full=Rapamycin-binding protein {ECO:0000303|PubMed:1996117};
GN Name=FPR1; Synonyms=FKB1, RBP1 {ECO:0000303|PubMed:1996117};
GN OrderedLocusNames=YNL135C; ORFNames=N1213, N1845;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=1704127; DOI=10.1073/pnas.88.3.1029;
RA Wiederrecht G.J., Brizuela L., Elliston K.O., Sigal N.H., Siekierka J.J.;
RT "FKB1 encodes a nonessential FK 506-binding protein in Saccharomyces
RT cerevisiae and contains regions suggesting homology to the cyclophilins.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1029-1033(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1705713; DOI=10.1073/pnas.88.5.1948;
RA Heitman J., Movva R.N., Hiestand P.C., Hall M.N.;
RT "FK 506-binding protein proline rotamase is a target for the
RT immunosuppressive agent FK 506 in Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1948-1952(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CATALYTIC ACTIVITY.
RX PubMed=1996117; DOI=10.1128/mcb.11.3.1718-1723.1991;
RA Koltin Y., Faucette L., Bergsma D.J., Levy M.A., Cafferkey R., Koser P.L.,
RA Johnson R.K., Livi G.P.;
RT "Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a
RT peptidyl-prolyl cis-trans isomerase related to human FK506-binding
RT protein.";
RL Mol. Cell. Biol. 11:1718-1723(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8619318; DOI=10.1002/yea.320111210;
RA Mallet L., Bussereau F., Jacquet M.;
RT "A 43.5 kb segment of yeast chromosome XIV, which contains MFA2, MEP2,
RT CAP/SRV2, NAM9, FKB1/FPR1/RBP1, MOM22 and CPT1, predicts an adenosine
RT deaminase gene and 14 new open reading frames.";
RL Yeast 11:1195-1209(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(1997).
RN [6]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [8]
RP PROTEIN SEQUENCE OF 67-100.
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 [9]
RP INTERACTION WITH HMO1.
RX PubMed=10049913; DOI=10.1093/genetics/151.3.935;
RA Dolinski K.J., Heitman J.;
RT "Hmo1p, a high mobility group 1/2 homolog, genetically and physically
RT interacts with the yeast FKBP12 prolyl isomerase.";
RL Genetics 151:935-944(1999).
RN [10]
RP INTERACTION WITH FAP1, AND MUTAGENESIS OF PHE-43; ASP-44; ASP-48; ARG-49;
RP PHE-94 AND PHE-106.
RX PubMed=10998178; DOI=10.1046/j.1365-2958.2000.02105.x;
RA Kunz J., Loeschmann A., Deuter-Reinhard M., Hall M.N.;
RT "FAP1, a homologue of human transcription factor NF-X1, competes with
RT rapamycin for binding to FKBP12 in yeast.";
RL Mol. Microbiol. 37:1480-1493(2000).
RN [11]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16823961; DOI=10.1021/pr050477f;
RA Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A.;
RT "Toward the complete yeast mitochondrial proteome: multidimensional
RT separation techniques for mitochondrial proteomics.";
RL J. Proteome Res. 5:1543-1554(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=7681823; DOI=10.2210/pdb1yat/pdb;
RA Rotonda J., Burbaum J.J., Chan H.K., Marcy A.I., Becker J.W.;
RT "Improved calcineurin inhibition by yeast FKBP12-drug complexes.
RT Crystallographic and functional analysis.";
RL J. Biol. Chem. 268:7607-7609(1993).
CC -!- FUNCTION: PPIases accelerate the folding of proteins. It catalyzes the
CC cis-trans isomerization of proline imidic peptide bonds in
CC oligopeptides. {ECO:0000305|PubMed:1996117}.
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; Evidence={ECO:0000269|PubMed:1996117};
CC -!- SUBUNIT: Interacts with HMO1. Interacts with FAP1.
CC {ECO:0000269|PubMed:10049913, ECO:0000269|PubMed:10998178}.
CC -!- INTERACTION:
CC P20081; P43573: BUD27; NbExp=2; IntAct=EBI-6961, EBI-22787;
CC P20081; P10869: HOM3; NbExp=3; IntAct=EBI-6961, EBI-2430;
CC P20081; P35169: TOR1; NbExp=4; IntAct=EBI-6961, EBI-19374;
CC P20081; P32600: TOR2; NbExp=3; IntAct=EBI-6961, EBI-19385;
CC P20081; Q9FR53: TOR; Xeno; NbExp=3; IntAct=EBI-6961, EBI-1382370;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion
CC {ECO:0000269|PubMed:16823961}.
CC -!- MISCELLANEOUS: Binds to the immunosuppressant drug FK506 and also
CC mediates the sensitivity to rapamycin (PubMed:1996117). Rapamycin
CC disrupts interaction with FAP1. {ECO:0000269|PubMed:1996117}.
CC -!- MISCELLANEOUS: Present with 43300 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1 subfamily.
CC {ECO:0000305}.
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DR EMBL; Z46843; CAA86890.1; -; Genomic_DNA.
DR EMBL; M57967; AAA03564.1; -; Unassigned_DNA.
DR EMBL; M60877; AAA34607.1; -; Genomic_DNA.
DR EMBL; M63892; AAA34962.1; -; mRNA.
DR EMBL; Z71411; CAA96017.1; -; Genomic_DNA.
DR EMBL; AY557997; AAS56323.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10413.1; -; Genomic_DNA.
DR PIR; A37870; A33146.
DR RefSeq; NP_014264.1; NM_001182973.1.
DR PDB; 1YAT; X-ray; 2.50 A; A=2-114.
DR PDBsum; 1YAT; -.
DR AlphaFoldDB; P20081; -.
DR SMR; P20081; -.
DR BioGRID; 35691; 337.
DR DIP; DIP-1263N; -.
DR IntAct; P20081; 66.
DR MINT; P20081; -.
DR STRING; 4932.YNL135C; -.
DR iPTMnet; P20081; -.
DR MaxQB; P20081; -.
DR PaxDb; P20081; -.
DR PRIDE; P20081; -.
DR TopDownProteomics; P20081; -.
DR EnsemblFungi; YNL135C_mRNA; YNL135C; YNL135C.
DR GeneID; 855587; -.
DR KEGG; sce:YNL135C; -.
DR SGD; S000005079; FPR1.
DR VEuPathDB; FungiDB:YNL135C; -.
DR eggNOG; KOG0544; Eukaryota.
DR GeneTree; ENSGT00980000202019; -.
DR HOGENOM; CLU_013615_12_1_1; -.
DR InParanoid; P20081; -.
DR OMA; RVIAGWD; -.
DR BioCyc; YEAST:YNL135C-MON; -.
DR Reactome; R-SCE-166208; mTORC1-mediated signalling.
DR Reactome; R-SCE-2025928; Calcineurin activates NFAT.
DR EvolutionaryTrace; P20081; -.
DR PRO; PR:P20081; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P20081; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0005527; F:macrolide binding; IDA:SGD.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:SGD.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IGI:SGD.
DR GO; GO:0006457; P:protein folding; IMP:SGD.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; IBA:GO_Central.
DR GO; GO:1901710; P:regulation of homoserine biosynthetic process; IGI:SGD.
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 Mitochondrion; Phosphoprotein; Reference proteome; Rotamase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..114
FT /note="FK506-binding protein 1"
FT /id="PRO_0000075305"
FT DOMAIN 26..114
FT /note="PPIase FKBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 43
FT /note="F->Y: Reduces interaction with FAP1."
FT /evidence="ECO:0000269|PubMed:10998178"
FT MUTAGEN 44
FT /note="D->V: Abrogates interaction with FAP1."
FT /evidence="ECO:0000269|PubMed:10998178"
FT MUTAGEN 48
FT /note="D->V: Abrogates interaction with FAP1."
FT /evidence="ECO:0000269|PubMed:10998178"
FT MUTAGEN 49
FT /note="R->I: Abrogates interaction with FAP1."
FT /evidence="ECO:0000269|PubMed:10998178"
FT MUTAGEN 94
FT /note="F->V: Abrogates interaction with FAP1."
FT /evidence="ECO:0000269|PubMed:10998178"
FT MUTAGEN 106
FT /note="F->Y: Reduces interaction with FAP1."
FT /evidence="ECO:0000269|PubMed:10998178"
FT HELIX 6..8
FT /evidence="ECO:0007829|PDB:1YAT"
FT STRAND 10..15
FT /evidence="ECO:0007829|PDB:1YAT"
FT STRAND 28..37
FT /evidence="ECO:0007829|PDB:1YAT"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:1YAT"
FT TURN 47..50
FT /evidence="ECO:0007829|PDB:1YAT"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:1YAT"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:1YAT"
FT HELIX 64..69
FT /evidence="ECO:0007829|PDB:1YAT"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:1YAT"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:1YAT"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:1YAT"
FT TURN 88..92
FT /evidence="ECO:0007829|PDB:1YAT"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:1YAT"
FT STRAND 104..113
FT /evidence="ECO:0007829|PDB:1YAT"
SQ SEQUENCE 114 AA; 12158 MW; 65C134830D300C06 CRC64;
MSEVIEGNVK IDRISPGDGA TFPKTGDLVT IHYTGTLENG QKFDSSVDRG SPFQCNIGVG
QVIKGWDVGI PKLSVGEKAR LTIPGPYAYG PRGFPGLIPP NSTLVFDVEL LKVN
