Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases

  title={Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases},
  author={C. Christine Trandinh and Gerald M. Pao and Milton H. Saier},
  journal={The FASEB Journal},
  pages={3410 - 3420}
The immunophilins, protein receptors for the immunosuppressing drugs cyclosporin A and FK506 and related proteins from plants, fungi, and bacteria, have been analyzed structurally and evolutionarily. The cyclosporin A binding proteins (cyclophilins) represent one ubiquitous family of homologous proteins, and the FK506‐ and rapamycin‐binding proteins (FKBPs) constitute a second, unrelated family. Multiple sequence alignments of members of each of these two protein families define the highly… 

Identification of all FK506-binding proteins from Neurospora crassa.

Genomic organization of mouse and human 65 kDa FK506-binding protein genes and evolution of the FKBP multigene family.

These analyses suggest that the FKBP multigene family emerged early in the evolutionary history of eukaryotes, and during that time some members have experienced gene elongation by means of PPIase domain duplication.

Neurospora crassa FK 506-binding proteins : Identification and analysis in Neurospora crassa

The results of this work showed that besides the involvement in protein folding these proteins present particular features, probably as a result of specific cellular functions, and that FKBP11 is located in cytoplasm.

Isolation, characterization and targeted disruption of mouse ppia: cyclophilin A is not essential for mammalian cell viability.

The isolation and characterization of mouse Ppia (mPpia), the gene encoding cyclophilin A, is described, indicating that CyPA is not essential for mammalian cell viability.

Mutational analysis of slyD, an Escherichia coli gene encoding a protein of the FKBP immunophilin family

Among the FKBP genes found in organisms across the evolutionary spectrum, slyD is unique in having three distinct drug‐independent phenotypes, which causes significant growth rate defects in Escherichia coli B and C backgrounds.


  • Si LiJin Fei Z. Lv
  • Biology
    Archives of insect biochemistry and physiology
  • 2016
The real-time quantitative reverse-transcription (qRT) PCR and Western blotting results showed that Bm-FKBP12B was present throughout all of the development stages, but it was abundant in the adult and embryo stages, suggesting that it might play important roles in regulating gene expression in the silk gland and during silk fiber formation.

Molecular cloning, structure and expression of a novel nuclear RNA-binding cyclophilin-like gene (PPIL4) from human fetal brain

RT-PCR analysis indicated that PPIL4 gene expression is abundant in kidney but has a ubiquitously low expression pattern in other human adult tissues.



Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding

At least two different classes of conformationally active enzymes (conformases13) exist that catalyse slow steps in protein folding that occur in a wide variety of cells and are inhibited by immunosupressive drugs.

Catalysis of protein folding by cyclophilins from different species.

Neisseria meningitidis encodes an FK506-inhibitable rotamase.

  • B. SampsonE. Gotschlich
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1992
Using the polymerase chain reaction, a homolog of an FK506-binding protein from Neisseria meningitidis is cloned and sequenced and expressed the gene product as a fusion protein with maltose-bindingprotein, which had rotamase activity comparable to that of human Fk506- binding protein.

S-cyclophilin. New member of the cyclophilin family associated with the secretory pathway.

Two distinct forms of peptidylprolyl-cis-trans-isomerase are expressed separately in periplasmic and cytoplasmic compartments of Escherichia coli cells.

It is proposed that the folding of some exported proteins may be catalyzed by the periplasmic proline isomerase and, in turn, that some proteins which have isomerized may not be translocated efficiently.

A second cyclophilin-related gene in Saccharomyces cerevisiae.

The nucleotide and deduced amino acid sequence of a second S. cerevisiae CyP-related gene is shown and it is shown that this gene contains a hydrophobic 34 amino acid N-terminal extension which may function as a signal sequence for subcellular compartmentalization.

Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins

The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA), which is thought to be linked to the immunosuppressive action of CsA.

The nucleotide sequence of a third cyclophilin‐homologous gene from Saccharomyces cerevisiae

The nucleotide sequence of a 1558 bp DNA fragment from the right arm of chromosome III of Saccharomyces cerevisiae contains an open reading frame of 954 nucleotides with coding potential for a protein with high similarity to the ubiquitous cyclophilins, which suggests that SCC3 could be a secretory or, more likely, a transmembrane protein.