Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2001-05-08
2004-08-24
Carlson, Karen Cochrane (Department: 1653)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023100, C435S006120, C435S069100, C530S350000
Reexamination Certificate
active
06780983
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a novel, human adipose tissue-derived polypeptide having water channel activity and to a DNA sequence encoding for the polypeptide.
BACKGROUND ART
The permeation of water through a cell membrane generally occurs slowly by way of diffusion into the lipid bilayer which is the main structure of the cell membrane. Recently, however, it was discovered that, in certain kinds of cells, water is transferred rapidly through the cell membrane, suggesting the involvement in the above phenomenon of some membrane protein selectively permeable to water. Thereafter, such membrane proteins of various kinds have actually been isolated. Such membrane proteins are designated as water channels. In this specification, the function of the above water channels which has selective permeation of water through the cell membrane is referred to as “water channel activity”. The water channels may be permeable to water alone or permeable to not only water but also low-molecular-weight substances such as glycerol and urea.
As a membrane protein having such water channel activity, there have been isolated a group of membrane proteins known as aquapolins (AQPs). Furthermore, some aquapolin genes have so far been cloned, and aquapolins such as AQP1 through AQP5, FA-CHIP and AQP-&ggr;TIP have been discovered in mammals, amphibians, plants, etc. [cf. e.g. Akira Sasaki, Igaku no Ayumi (Advances in Medicine), vol. 173, No. 9, 1995].
P. Agre et al. reported, in Science (vol. 256, pp. 385 to 387, 1992) that
Xenopus laevis
oocytes in which the in vitro transcript RNA for CHIP28, the current designation of which is AQP1, had been introduced showed increased water permeability. In Science (vol. 264, pp. 92 to 95, 1994), B. A. van Oost et al. disclosed the amino acid sequence of human AQP2 and suggested that this should be involved in vasopressin-dependent urine concentration.
In Proc. Natl. Acad. Sci. USA (vol. 91, pp. 6269 to 6273, 1994), Ishibashi et al. disclosed the nucleotide sequence of the gene for renal collecting tubule-derived AQP3 and the amino acid sequence encoded thereof. Ishibashi et al. confirmed its water channel activity by injecting the AQP3 cRNA into
Xenopus laevis
oocytes and measuring the water permeability thereof. Ishibashi et al. reported that this AQP3 transported not only water but also nonionic small molecules such as urea and glycerol.
In Proc. Natl. Acad. Sci. USA (vol. 91, pp. 13052 to 13056, 1994), J. S. Jung et al. reported about the isolation of AQP4. This AQP4 is known to occur most abundantly in mammalian brains and have mercury resistance. In J. Biol. Chem. (vol. 270, pp. 1908 to 1912, 1995), S. Raina et al. who prepared rat salivary gland-derived AQP5 cDNA describe the nucleotide sequence of the cDNA and the amino acid sequence encoded thereby. S. Raina et al. cloned the cDNA by utilizing the occurrence of an NPA sequence and confirmed its function by observing that the cRNA enhances the water permeability of
Xenopus laevis
oocytes.
The aquapolin family mentioned above is considered to be involved in water metabolism in mammals and, for example, it has been confirmed that AQP2 is found only in the renal collecting tubule luminal membrane, which is indicative of its close association with the vasopressin-urea concentration system, and its involvement in renal diseases has become acknowledged. Therefore, such membrane proteins having water channel activity are of importance in any attempt to develop novel therapies for water-associated diseases.
Meanwhile, the expression of the aquapolin family mentioned above has been confirmed in such organs as kidney, brain, gall bladder, eye, intestine, salivary gland and bronchus but there is no report as yet about the occurrence of membrane proteins having water channel activity in other organs or tissues, particularly in adipose tissue.
SUMMARY OF THE INVENTION
In view of the above-mentioned state of the art, the present invention has for its object to provide a novel membrane protein having water channel activity and a DNA sequence encoding for the polypeptide.
The present invention is related to a novel polypeptide having water channel activity which has the amino acid sequence, within the molecule thereof, shown in the sequence listing under SEQ ID NO:1.
The present invention is also related to a nucleotide sequence itself which codes for a polypeptide having, within the molecule thereof, the amino acid sequence shown in the sequence listing under SEQ ID NO:1 and having water channel activity.
The present invention is further related to the DNA sequence shown in the sequence listing under SEQ ID NO:2.
The present invention is still further related to a polypeptide having water channel activity which has the amino acid sequence, within the molecule thereof, encoded by the nucleotide No. 173 to No. 1198 of the nucleotide sequence shown in the sequence listing under SEQ ID NO:2.
DETAILED DESCRIPTION OF THE INVENTION
In the following, the present invention is described in detail.
The polypeptide of the present invention has the amino acid sequence shown in the sequence listing under SEQ ID NO:1. This polypeptide has a sequence composed of three amino acids, namely asparagine-proline-alanine, as the amino acid Nos. 195 to 197. However, the characteristic feature common to the so-far known AQPs, that said asparagine-proline-alanine sequence occurs twice, is not found in the polypeptide of the present invention. That this polypeptide has water channel activity can be confirmed from the fact that it enhances the water permeability of
Xenopus laevis
oocytes.
The above polypeptide may be generated by translation by a protein synthesis system constituted, in vivo or in vitro, based on the nucleotide sequence coding for the amino acid sequence of said polypeptide. The nucleotide sequence of the present invention substantially has a region coding for the amino acid sequence of said polypeptide and, where necessary, may contain one or more other regions such as a promoter region. In the protein synthesis based on genetic information, the information carried by the gene DNA is transcribed into mRNA as the result of DNA-dependent RNA synthesis aided by RNA polymerase. And, this mRNA is translated into the amino acid sequence in a tRNA-containing protein synthesis system. Therefore, the nucleotide sequence of the present invention includes not only the DNA sequence but also the RNA sequence. Furthermore, since it is generally known that, for an amino acid, there is one or a plurality of codons corresponding thereto, it is a matter of course that the above-mentioned nucleotide sequence is not limited to only one sequence but may include nucleotide sequences resulting from substitution of another synomyous codon coding for the same amino acid.
The above polypeptide can be formed based on the genetic information carried by the DNA sequence shown in the sequence listing under SEQ ID NO:2. This polypeptide is encoded by that portion of the nucleotide sequence shown in the sequence listing under SEQ ID NO:2 which ranges from the nucleotide No. 173 to No. 1198. Of the DNA sequence shown in the sequence listing under SEQ ID NO:2, the nucleotide sequences other than the portion of said nucleotide numbers are noncoding regions, among which the polyadenylation consensus sequence AATAAA occurs at the nucleotide No. 1234 to No. 1239. Other possible reading frames of said DNA sequence shown under SEQ ID NO:2 can be excluded from consideration, since the polypeptides encoded are very small-sized, hence considered to be incapable of performing any water channel function.
It has been confirmed by the inventors that the full-length sequence of the above nucleic acid bases has no counterpart sequence either in GenBank or in dbEST.
The polypeptide of the present invention has water channel activity in adipose tissue. While adipose tissue is distributed in various parts of the living organism, the polypeptide of the present invention has an action to control the transfer of water in such adipose tissue and is e
Ishida Naruhiro
Kuriyama Hiroshi
Mita Shiro
Okubo Kousaku
Carlson Karen Cochrane
Connolly Bove & Lodge & Hutz LLP
Robinson Hope A.
Santen Pharmaceutical Co. Ltd.
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