Molecular cloning of a membrane-associated human FK506- and rapamycin-binding protein, FKBP-13

Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6677-81. doi: 10.1073/pnas.88.15.6677.

Abstract

The 12-kDa FK506-binding protein (FKBP-12) is a cytosolic receptor for the immunosuppressants FK506 and rapamycin. Here we report the molecular cloning and subcellular localization of a 13-kDa FKBP (FKBP-13), which has a 21-amino acid signal peptide and appears to be membrane-associated. Although no internal hydrophobic region, and thus no transmembrane domain, is apparent within the 120 amino acids of mature FKBP-13, a potential endoplasmic reticulum retention sequence (Arg-Thr-Glu-Leu) is found at its C terminus. FKBP-13 has 51% nucleotide sequence identity and 43% amino acid sequence identity to FKBP-12; the N-terminal sequences are divergent, but the 92-amino acid C-terminal sequence of FKBP-13 has 46 identical and 20 related residues when compared with FKBP-12. The conserved residues that comprise the drug binding site and rotamase active site of FKBP-12 are completely conserved in FKBP-13. Therefore, the three-dimensional structures of FKBP-12 and the FKBP-12/FK506 complex are likely to be excellent models of the corresponding FKBP-13 structure.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / metabolism*
  • Antifungal Agents / metabolism
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Line
  • Cloning, Molecular / methods
  • Humans
  • Immunosuppressive Agents / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Polyenes / metabolism*
  • Polymerase Chain Reaction
  • Protein Conformation
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Sequence Homology, Nucleic Acid
  • Sirolimus
  • Tacrolimus
  • Tacrolimus Binding Proteins*

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Carrier Proteins
  • Immunosuppressive Agents
  • Polyenes
  • RNA, Messenger
  • FKBP-13
  • Tacrolimus Binding Proteins
  • Sirolimus
  • Tacrolimus

Associated data

  • GENBANK/M65128
  • GENBANK/M66858
  • GENBANK/M66859
  • GENBANK/M66860
  • GENBANK/M66861
  • GENBANK/M66862
  • GENBANK/M75099
  • GENBANK/S45955
  • GENBANK/S45957
  • GENBANK/S45959
  • GENBANK/S45963