Peattie D A, Harding M W, Fleming M A, DeCenzo M T, Lippke J A, Livingston D J, Benasutti M
Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139-4211.
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10974-8. doi: 10.1073/pnas.89.22.10974.
Using an FK506 affinity column to identify mammalian immunosuppressant-binding proteins, we identified an immunophilin with an apparent M(r) approximately 55,000, which we have named FKBP52. We used chemically determined peptide sequence and a computerized algorithm to search GenPept, the translated GenBank data base, and identified two cDNAs likely to encode the murine FKBP52 homolog. We amplified a murine cDNA fragment, used it to select a human FKBP52 (hFKBP52) cDNA clone, and then used the clone to deduce the hFKBP52 sequence (calculated M(r) 51,810) and to express hFKBP52 in Escherichia coli. Recombinant hFKBP52 has peptidyl-prolyl cis-trans isomerase activity that is inhibited by FK506 and rapamycin and an FKBP12-like consensus sequence that probably defines the immunosuppressant-binding site. FKBP52 is apparently common to several vertebrate species and associates with the 90-kDa heat shock protein (hsp90) in untransformed mammalian steroid receptor complexes. The putative immunosuppressant-binding site is probably distinct from the hsp90-binding site, and we predict that FKBP52 has different structural domains to accommodate these functions. hFKBP52 contains 12 protein kinase phosphorylation-site motifs and a potential calmodulin-binding site, implying that posttranslational phosphorylation could generate multiple isoforms of the protein and that calmodulin and intracellular Ca2+ levels could affect FKBP52 function. FKBP52 transcripts are present in a variety of human tissues and could vary in abundance and/or stability.
利用FK506亲和柱来鉴定哺乳动物免疫抑制剂结合蛋白，我们鉴定出一种表观分子量约为55,000的亲免素，我们将其命名为FKBP52。我们使用化学测定的肽序列和计算机算法搜索GenPept（翻译后的GenBank数据库），并鉴定出两个可能编码小鼠FKBP52同源物的cDNA。我们扩增了一个小鼠cDNA片段，用它来筛选人FKBP52（hFKBP52）cDNA克隆，然后用该克隆推导hFKBP52序列（计算分子量为51,810）并在大肠杆菌中表达hFKBP52。重组hFKBP52具有肽基脯氨酰顺反异构酶活性，该活性被FK506和雷帕霉素抑制，并且具有一个类似FKBP12的共有序列，该序列可能定义了免疫抑制剂结合位点。FKBP52显然在几种脊椎动物物种中都存在，并与未转化的哺乳动物类固醇受体复合物中的90 kDa热休克蛋白（hsp90）相关联。推测的免疫抑制剂结合位点可能与hsp90结合位点不同，并且我们预测FKBP52具有不同的结构域来适应这些功能。hFKBP52包含12个蛋白激酶磷酸化位点基序和一个潜在的钙调蛋白结合位点，这意味着翻译后磷酸化可能产生该蛋白的多种异构体，并且钙调蛋白和细胞内Ca2+水平可能影响FKBP52的功能。FKBP52转录本存在于多种人体组织中，其丰度和/或稳定性可能会有所不同。
