Molecular cloning of a membrane-associated human FK506- and rapamycin-binding protein, FKBP-13.
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.
Jin
Y J
YJ
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Albers
M W
MW
Lane
W S
WS
Bierer
B E
BE
Schreiber
S L
SL
Burakoff
S J
SJ
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000935:Antifungal Agents / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011090:Polyenes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D020123:Sirolimus; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D012333:RNA, Messenger; C070133:FKBP-13; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus; D016559:Tacrolimus