Identification of a nuclear-specific cyclophilin which interacts with the proteinase inhibitor eglin c.
We have identified a novel human cyclophilin (hCyP-60) which interacts with the proteinase inhibitor eglin c using the yeast two-hybrid system. A cDNA isolated from a Raji B lymphocyte library reveals a domain showing sequence similarity to known cyclophilins flanked by unique N- and C-terminal residues. In addition, hCyP-60 contains a tyrosine residue (Tyr 389) instead of a tryptophan residue found in most eukaryotic cyclophilins at a position important for cyclosporin binding. Northern and Western analysis reveal widespread expression with considerable tissue-specific variation. Specifically, the highest levels of mRNA are detected in the thymus, pancreas, testis, and K-562 cell line, while the most protein is detected in the kidney. Immunohistochemistry indicates a nuclear-specific localization both in transfected cells and tissue sections. hCyP-60's specific subcellular localization and conserved amino acid sequence suggest that it may play a specific role in the nucleus.
Wang
B B
BB
Khepri Pharmaceuticals, South San Francisco, CA 94080, USA.
Hayenga
K J
KJ
Payan
D G
DG
Fisher
J M
JM
D000591:Amino Acid Isomerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry*; D003001:Cloning, Molecular; D021983:Cyclophilins; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000378:metabolism*
D002352:Carrier Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D000591:Amino Acid Isomerases; D021983:Cyclophilins; C099773:PPIL2 protein, human; D019696:Peptidylprolyl Isomerase