Original Article

Journal of Molecular Medicine

, Volume 78, Issue 7, pp 389-394

First online:

Molecular cloning and expression of a novel klotho-related protein

  • Kensei YahataAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Kiyoshi MoriAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Hiroshi AraiAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Susumu KoideAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Yoshihiro OgawaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Masashi MukoyamaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Akira SugawaraAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Shoichi OzakiAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
  • , Issei TanakaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507
    • , Yo-ichi NabeshimaAffiliated withDepartment of Pathology and Tumor Biology, Faculty of Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501
    • , Kazuwa NakaoAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507

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Abstract

Klotho protein is a novel β-glucosidase-like protein produced predominantly in the kidney. The klotho mouse, which genetically lacks klotho gene expression, manifests various systemic phenotypes resembling aging. In the present study we succeeded in isolating a novel human protein structurally related to klotho protein. The protein possesses one β-glucosidase-like domain and is 42% identical with klotho protein at the amino acid level. Unlike klotho protein, it possesses neither a signal sequence nor a transmembrane domain, suggesting that it is a cytosolic protein, and thus was termed cytosolic β-glucosidase-like protein-1 (cBGL1). By Northern blot analysis cBGL1 mRNA was expressed most abundantly in the liver, followed by the small intestine, colon, spleen, and kidney. When klotho and cBGL1 gene expression was examined in renal cell carcinoma tissues, both klotho and cBGL1 mRNA levels in tumors were lower than those in nontumor regions, suggesting that renal epithelial cells may lose klotho and cBGL1 gene expression during the course of malignant transformation. In conclusion, we describe the primary structure and gene expression of a novel protein related to klotho protein.

Klotho β-Glucosidase Gene expression Kidney Renal cell carcinoma