The immunophilin FKBP4 (FKBP52/ FKBP59) maps to the distal short arm of human Chromosome 12

The immunophilin FKBP4 (FKBP52/ FKBP59) maps to the distal short arm of human Chromosome 12 268 Mammalian Genome 9, Brief Data Report Mouse Genome Database (MGD), Mouse Genome Informatics, The region is unlikely to be interrupted by an intron, and thus we Jackson Laboratory, Bar Harbor, Maine. World Wibe Web (URL: increase our chance of mapping the cognate gene rather than a (10/97). processed pseudogene. To further exclude this possibility, we am- 13. Mathew S, Murty VVVS, Cheifetz S, George D, Massague J, Chaganti plified a second set of primers, Set 2 FKBP4/2/f (TGGGGAAT- RSK. (1994) Genomics 20, 114-115 CATTTTAGCTGG), FKBP4/2/r (TTTTTCCCATGTCCCTAG- Bonyadi M, Cui W, Nagase H, Akhurst RJ. (1996) Genomics 33, CAC) that span 276 bp from a different and non-overlapping re- 328-329 gion of the 3' UTR, bp 1751-1926. In the monochromosomal cell 15. Imbeaud S, Faure E, Lamarre I, Mattei MG, di Clemente N, Tizard R, hybrid panel, a product of 276 bp amplified in I aA9602+ and total Carre-Eusebe D, Belville C, Tragethon L, Tonkin C, Nelson J, McAu- human only, corroborating our previous mapping results. There- liffe M, Bidart, J-M, Lababidi A, Josso N, Cate RL, Picard J-Y. (1995) fore, FKBP4 maps to the distal telomere of HSAl2p. Nat Genet 11, 382-388 Discussion: FKBP4 (also known as FKBP52 or FKBP59) is one of 16. Visser JA, McLuskey A, van Beers T, Weghuis DO, van Kessel AG, Grootegoed JA, Themmen AP. (1995) Biochem Biophys Res Com- a group of proteins, known as the immunophilins, that act as re- mun 215, 1029-1036 ceptors for the immunosuppressant drugs, cyclosporin A, FK506 17. Mishina Y, Tizard R, Deng JM, Pathak BG, Copeland NG, Jenkins (both of which affect calcium-dependent steps between the T cell NA, Cate RL, Behringer RR. (1997) Biochem Biophys Res Common receptor and gene transcription) and rapamycin (which acts at a 237,741-746 calcium-independent step to inhibit IL-2-dependent proliferation of T cells) [4]. In addition to this role, the immunophilins have highest levels of expression within the brain and have been impli- The immunophilin FKBP4 (FKBP52/ cated in neuronal cell function, particularly signal transduction [4]. The immunophilins divide into two families: (i) the cyclophilins FKBP59) maps to the distal short arm of and (ii) the FK506- and rapamycin-binding proteins (FKBPs). human Chromosome 12 FKBP4 is a peptidyl prolyl isomerase that binds to HSP90 and forms separate complexes with steroid receptors; in these com- N.A. Bermingham,' S. Rauf, 1 ' 2 N. Katsanis, l plexes, FKBP4 is thought to be involved in targeted protein traf- J.E. Martin, 2 A.J. Hunter, 3 E.M.C. Fisher' ricking and to function as a molecular chaperone [5,6]. We found that FKBP4 maps near the telomere of HSAl2p. 'Neurogenetics Unit, Imperial College School of Medicine at St. Recently, one EST (from THC 124209) that appears to be derived Mary's, Norfolk Place, London W2 IPG, UK from FKBP4 was mapped to within -4 cM of our position for 2Department of Histopathology, The Royal London Hospital, FKBP4, thus further corroborating our mapping data. Whitechapel, London El 1BB, UK The effect of mutation in FKBP4 is unknown but potentially 'SmithKline Beecham, The Pinnacles, Harlow, Essex CM19 SAD, UK could alter cellular homeostasis; we note that acute myeloid leu- kemia, myelodysplastic syndrome, acute lymphoblastic leukemia, Received: 26 August 1997 / Accepted: 30 October 1997 and chronic lymphoproliferative disease have all been mapped to Species: Human unknown loci on 12p13 [7]. Locus name: FK506 binding protein 4 Acknowledgments: We acknowledge the support of Techne in providing Locus symbols: FKBP4 (otherwise known as FKBP52, FKBP59) Techne GeneE thermal cyclers. This work was funded by Smithkline Map position: FKBP4 maps to telomeric human Chromosome Beecham, the UK Medical Research Council, the Motor Neurone Disease (Chr) 12p13, 5.4cR from the marker WI6086, 10.7cR from Association of Great Britain, and the John Hitt Foundation. D 12S 100 in the Genebridge 4 radiation hybrid panel; equivalent to References approximately 2 cM from D 12S 100 [ 1 1. 1. Gyapay G, Schmitt K, Fizames C, Jones H, Vega-Czarny N, Spillett D, Method of mapping: We designed two sets of PCR primers to the Muselet D, Prud'Homme J-F, Dib C, Auffray C, Morissette J, Weis- human FKBP4 3'untranslated region (accession number M88279). senbach J, Goodfellow PN (1996) A radiation hybrid map of the human Set 1, FKBP4/1/f (TCTGTTCCCTTCCTCACCC), FKBP4/l/r genome. Hum Mol Genet 5, 339-346 (AGGCTGAGGGGATTTTGG) span bp 1950-2089 and amplify 2. Hernandez D, Egan SE, Yulug IG, Fisher EMC (1994) Mapping the gene which encodes phosphatidylinositol specific phospholipase C-'y2 the expected 140-bp product in human genomic DNA. We ampli- in the human and mouse. Genomics, in press fied this product in a monochromosomal cell hybrid panel with Zhong S, Wolf CR, Spurr NK (1992) Chromosomal assignment and suitable rodent controls, as described in [2]. Only DNAs from total linkage analysis of the human glutathione S-transferase p. gene human and cell hybrid 1aA9602+ amplified, and both produced (GSTM1) using intron specific polymerase chain reaction. Hum Genet the 140-bp product. laA9602+ contains human Chr 12 with traces 90, 435-439 of HSA21 and X [3], as no other cell hybrid amplified, including 4. Snyder SH, Sabatini DM (1995) Immunophilins and the nervous sys- those containing HSA21 and X, we concluded that FKBP4 most tem. Nat Med 1, 32-37 likely maps to HSAl2. We then amplified the 140-bp product in 5. Bose S, Weikl T, Bugl H, Buchner J (1996) Chaperone function of the Genebridge 4 radiation hybrid panel [ 11 and independently Hsp90-associated proteins. Science 274, 1715-1717 determined that our sequence maps 5.3cR from WI6086 and 6. Owens-Grillo JK, Czar MJ, Hutchison KA, Hoffmann K, Perdew GH, Pratt WB (1996) A model of protein targeting mediated by immuno- 10.7cR from D 12S 100, a marker which is within 5 cM of the 12p philins and other proteins that bind to hsp90 via tetratricopeptide repeat telomere. domains. J Biol Chem 271, 13468-13475 We chose PCR primers from the 3' UTR primarily because this 7. Mitelman F, Mertens F, Johansson B (1997) A breakpoint map of recurrent chromosomal rearrangements in human neoplasia. Nat Genet Correspondence to: E.M.C. Fisher 15, 417-474 Mammalian Genome Springer Journals

The immunophilin FKBP4 (FKBP52/ FKBP59) maps to the distal short arm of human Chromosome 12

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