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   27-MAR-2024, entry version 210.
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   PDB; 7ZW0; EM; 2.40 A; sk=1-114.
DR   PDBsum; 1YAT; -.
DR   PDBsum; 7ZW0; -.
DR   AlphaFoldDB; P20081; -.
DR   EMDB; EMD-14990; -.
DR   SMR; P20081; -.
DR   BioGRID; 35691; 339.
DR   DIP; DIP-1263N; -.
DR   IntAct; P20081; 66.
DR   MINT; P20081; -.
DR   STRING; 4932.YNL135C; -.
DR   iPTMnet; P20081; -.
DR   MaxQB; P20081; -.
DR   PaxDb; 4932-YNL135C; -.
DR   PeptideAtlas; P20081; -.
DR   TopDownProteomics; P20081; -.
DR   EnsemblFungi; YNL135C_mRNA; YNL135C; YNL135C.
DR   GeneID; 855587; -.
DR   KEGG; sce:YNL135C; -.
DR   AGR; SGD:S000005079; -.
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; EQFDASW; -.
DR   OrthoDB; 25281at2759; -.
DR   BioCyc; YEAST:YNL135C-MONOMER; -.
DR   Reactome; R-SCE-166208; mTORC1-mediated signalling.
DR   Reactome; R-SCE-2025928; Calcineurin activates NFAT.
DR   BioGRID-ORCS; 855587; 6 hits in 10 CRISPR screens.
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:0006325; P:chromatin organization; IGI:SGD.
DR   GO; GO:0006457; P:protein folding; IMP:SGD.
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   PANTHER; PTHR10516; PEPTIDYL-PROLYL CIS-TRANS ISOMERASE; 1.
DR   PANTHER; PTHR10516:SF464; PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP12; 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   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
//