FPR1/YNL135C Summary Help

Standard Name FPR1 1
Systematic Name YNL135C
Alias FKB1 , RBP1
Feature Type ORF, Verified
Description Peptidyl-prolyl cis-trans isomerase (PPIase); binds to the drugs FK506 and rapamycin; also binds to the nonhistone chromatin binding protein Hmo1p and may regulate its assembly or function; N-terminally propionylated in vivo (1, 2, 3, 4 and see Summary Paragraph)
Name Description Fk 506-sensitive Proline Rotamase 1
Chromosomal Location
ChrXIV:372226 to 371882 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -105 cM
Gene Ontology Annotations All FPR1 GO evidence and references
  View Computational GO annotations for FPR1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Regulators 5 genes
Classical genetics
reduction of function
Large-scale survey
175 total interaction(s) for 132 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 35
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 5
  • Biochemical Activity: 2
  • Co-localization: 1
  • PCA: 3
  • Reconstituted Complex: 2
  • Two-hybrid: 9

Genetic Interactions
  • Dosage Rescue: 2
  • Negative Genetic: 59
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 8
  • Positive Genetic: 31
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 6
  • Synthetic Rescue: 2

Expression Summary
Length (a.a.) 114
Molecular Weight (Da) 12,158
Isoelectric Point (pI) 5.87
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXIV:372226 to 371882 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -105 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..345 372226..371882 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005079

FPR1 encodes a peptidyl-prolyl cis-trans isomerase that helps mediate correct protein folding (2). Fpr1p is a member of a large group of prolyl isomerases comprised of three structurally unrelated families: the FKBPs (FK506 binding proteins), the cyclophilins, and the parvulins (reviewed in 5). S. cerevisiae contains 4 FKBPs (Fpr1p, 2p, 3p, and 4p), 8 cyclophilins (Cpr1p through Cpr8p), and one parvulin (Ess1p; reviewed in 5).

Fpr1p can bind the related macrolides rapamycin and the immunosuppressant FK506; binding to either inhibits its peptidyl-prolyl isomerase activity and is toxic to yeast (2, 6). Toxicity is not due to inhibition of activity, however, because fpr1 null mutants are viable (7). Rather, toxicity is caused by interaction of the bound Fpr1p with signaling proteins: FK506-bound Fpr1p binds to calcineurin A subunit (isoforms Cmp2p and Cna1p) and exerts a negative regulatory role in calcineurin function, and rapamycin-bound Fpr1p binds directly to Tor1p and Tor2p, leading to G1 arrest (8, 9, 10, 11).

In the absence of macrolide binding, Fpr1p appears to regulate the homoserine biosynthetic pathway by perturbing feedback inhibition of aspartokinase by threonine (12). Endogenous Fpr1p (not bound to FK506 or rapamycin) interacts directly with aspartokinase (Hom3p), the first enzyme in the pathway that converts aspartate to either threonine or methionine (13). Loss of Fpr1p function causes resistance to the toxic amino acid analog hydroxynorvaline, a phenotype also observed in cells that synthesize a feedback-resistant form of aspartokinase, suggesting that Fpr1p regulates feedback inhibition of Hom3p (14, 13). Another target of Fpr1p is Hmo1p, a nonhistone, chromatin-binding protein of the high mobility group (HMG) family (3). Hmo1p forms homodimers or homooligomers, and Fpr1p plays a role in regulating this self-association (reviewed in 5).

Fpr1p homologs have been identified in the fungal pathogens C. neoformans and C. albicans, and in S. pombe (reviewed in 5). The human Fpr1p ortholog, FKBP12, is the intracellular receptor for FK506; the FKBP12-FK506 complex mediates immunosuppression through inhibition of calcineurin (reviewed in 5).

Last updated: 2008-12-09 Contact SGD

References cited on this page View Complete Literature Guide for FPR1
1) Heitman J, et al.  (1991) FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 88(5):1948-52
2) Koltin Y, et al.  (1991) Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein. Mol Cell Biol 11(3):1718-23
3) Dolinski KJ and Heitman J  (1999) Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase. Genetics 151(3):935-44
4) Foyn H, et al.  (2013) Protein N-terminal acetyltransferases act as N-terminal propionyltransferases in vitro and in vivo. Mol Cell Proteomics 12(1):42-54
5) Arevalo-Rodriguez M, et al.  (2004) Prolyl isomerases in yeast. Front Biosci 9():2420-46
6) Nielsen JB, et al.  (1992) Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the nonessential gene FKB2. Proc Natl Acad Sci U S A 89(16):7471-5
7) Wiederrecht G, et al.  (1991) FKB1 encodes a nonessential FK 506-binding protein in Saccharomyces cerevisiae and contains regions suggesting homology to the cyclophilins. Proc Natl Acad Sci U S A 88(3):1029-33
8) Cardenas ME, et al.  (1994) Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands. EMBO J 13(24):5944-57
9) Cardenas ME, et al.  (1995) Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A. EMBO J 14(12):2772-83
10) Heitman J, et al.  (1991) Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253(5022):905-9
11) Lorenz MC and Heitman J  (1995) TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin. J Biol Chem 270(46):27531-7
12) Arevalo-Rodriguez M, et al.  (2004) FKBP12 controls aspartate pathway flux in Saccharomyces cerevisiae to prevent toxic intermediate accumulation. Eukaryot Cell 3(5):1287-96
13) Alarcon CM and Heitman J  (1997) FKBP12 physically and functionally interacts with aspartokinase in Saccharomyces cerevisiae. Mol Cell Biol 17(10):5968-75
14) Ramos C and Calderon IL  (1992) Overproduction of threonine by Saccharomyces cerevisiae mutants resistant to hydroxynorvaline. Appl Environ Microbiol 58(5):1677-82