Cyclophilin A, the major intracellular receptor for the immunosuppressant cyclosporin A, maps to chromosome 7p11.2-p13: four pseudogenes map to chromosomes 3, 10, 14, and 18.
Cyclophilin A (CyP-A), the major intracellular receptor for the immunosuppressant cyclosporin A (CsA), is a member of the immunophilin class of proteins, which all possess peptidyl-prolyl cis-trans isomerase activity and, therefore, are believed to be involved in protein folding and/or intracellular protein transport. The CyP-A protein is encoded by a single gene; in addition, 15 pseudogenes have been identified. Recently, specific binding of CyP-A to the human immunodeficiency virus type 1 (HIV-1) gag protein has been reported. Interestingly, this interaction can be inhibited by the immunosuppressant CsA and also by nonimmunosuppressive, CyP-A-binding CsA derivatives, which were also shown to exhibit potent anti-HIV-1 activity. Results thus indicate that CyP-A may have an essential function in HIV-1 replication. Using a panel of somatic rodent-human cell hybrids and PCR technology, we localized the coding cyclophilin A gene (PPIA) on chromosome 7 and four pseudogenes (PPIP2, PPIP3, PPIP4, and PPIP6) on chromosomes 14, 10, 18, and 3, respectively. Using chromosome 7 and chromosome 10 deletion hybrid panels, we were able to localize further the coding gene to the region 7p11.2-p13, as confirmed by fluorescence in situ hybridization analysis, and one pseudogene (PPIP3) to the region 10q11.2-q23. This is the first report on the regional mapping of members of the CyP-A gene family.
Willenbrink
W
W
Sandoz Research Institute, Vienna, Austria.
Halaschek
J
J
Schuffenhauer
S
S
Kunz
J
J
Steinkasserer
A
A
D000591:Amino Acid Isomerases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D016572:Cyclosporine / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D007166:Immunosuppressive Agents / Q000378:metabolism; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D011544:Pseudogenes
D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase